Co-reporter:Laia Davin;Ross McLellan;Alberto Hernán-Gómez;William Clegg;Alan R. Kennedy;Maria Mertens;Iain A. Stepek
Chemical Communications 2017 vol. 53(Issue 26) pp:3653-3656
Publication Date(Web):2017/03/28
DOI:10.1039/C6CC09675A
Using a specially designed magnesium metallating manifold, combining kinetically activated TMP amide base with a sterically amplified β-diketiminate ligand, this study has established a new regioselective strategy for magnesiation of challenging N-heterocyclic molecules. The broad scope of the approach is illustrated through reactions of pyrazine, triazoles and substituted pyridines by isolation and structural elucidation of their magnesiated intermediates.
Co-reporter:Lewis C. H. Maddock;Ivana Borilovic;Jamie McIntyre;Alan R. Kennedy;Guillem Aromí
Dalton Transactions 2017 vol. 46(Issue 20) pp:6683-6691
Publication Date(Web):2017/05/23
DOI:10.1039/C7DT01319A
Using a transamination approach to access novel Fe(II) complexes, this study presents the synthesis, X-ray crystallographic and magnetic characterisation of a series of new iron complexes containing the multifunctional 2,2-dipyridylamide (DPA) ligand using iron bis(amide) [{Fe(HMDS)2}2] and sodium ferrate [{NaFe(HMDS)3}∞] (1) as precursors (HMDS = 1,1,1,3,3,3-hexamethyldisilazide). Reactions of DPA(H) with 1 show exceptionally good stoichiometric control, allowing access to heteroleptic [(THF)2·NaFe(DPA)(HMDS)2] (3) and homoleptic [{THF·NaFe(DPA)3}∞] (4) by using 1 and 3 equivalents of DPA(H), respectively. Linking this methodology and co-complexation, which is a more widely used approach to prepare heterobimetallic complexes, 3 can also be prepared by combining NaHMDS with heteroleptic [{Fe(DPA)(HMDS)}2] (2). In turn, 2 has been also synthesised and structurally defined by reacting [{Fe(HMDS)2}2] with two equivalents of DPA(H). Structural studies demonstrate the coordination flexibility of the N-bridged bis(heterocycle) ligand DPA, with 2 and 3 exhibiting discrete monomeric motifs, whereas 4 displays a much more intricate supramolecular structure, with one of its DPA ligands coordinating in an anti/anti fashion (as opposed to 2 and 3 where DPA shows a syn/syn conformation), which facilitates propagation of the structure via its central amido N. Magnetic studies confirmed the high-spin electron configuration of the iron(II) centres in all three compounds and revealed the existence of weak ferromagnetic interactions in dinuclear compound 2 (J = 1.01 cm−1).
Co-reporter:Laia Davin;Ross McLellan;Alan R. Kennedy
Chemical Communications 2017 vol. 53(Issue 85) pp:11650-11653
Publication Date(Web):2017/10/24
DOI:10.1039/C7CC07193K
Using β-diketiminate Mg(II) complexes containing either alkyl, aryl or amide groups, the regioselective functionalization of a wide range of fluoroarenes is accomplished but in uniquely different ways. Overcoming common limitations of traditional s-block bases, kinetically activated [(DippNacnac)Mg(TMP)] (1) deprotonates these molecules at room temperature, trapping sensitive fluoroaryl anions that can then engage in Negishi cross-coupling; whereas [(DippNacnac)Mg(R)THF] (R = nBu, Ph, benzofuryl) have proved to be effective reagents for C–F bond alkylation/arylation via pyridine directed C–F bond cleavage.
Co-reporter:Dr. Alberto Hernán-Gómez;Dr. Alan R. Kennedy; Eva Hevia
Angewandte Chemie International Edition 2017 Volume 56(Issue 23) pp:6632-6635
Publication Date(Web):2017/06/01
DOI:10.1002/anie.201702246
AbstractCombining alkali-metal-mediated metalation (AMMM) and N-heterocyclic carbene (NHC) chemistry, a novel C−N bond activation and ring-opening process is described for these increasingly important NHC molecules, which are generally considered robust ancillary ligands. Here, mechanistic investigations on reactions of saturated NHC SIMes (SIMes=[:C{N(2,4,6-Me3C6H2)CH2}2]) with Group 1 alkyl bases suggest this destructive process is triggered by lateral metalation of the carbene. Exploiting co-complexation and trans-metal-trapping strategies with lower polarity organometallic reagents (Mg(CH2SiMe3)2 and Al(TMP)iBu2), key intermediates in this process have been isolated and structurally defined.
Co-reporter:Dr. Alberto Hernán-Gómez;Dr. Alan R. Kennedy; Eva Hevia
Angewandte Chemie 2017 Volume 129(Issue 23) pp:6732-6735
Publication Date(Web):2017/06/01
DOI:10.1002/ange.201702246
AbstractCombining alkali-metal-mediated metalation (AMMM) and N-heterocyclic carbene (NHC) chemistry, a novel C−N bond activation and ring-opening process is described for these increasingly important NHC molecules, which are generally considered robust ancillary ligands. Here, mechanistic investigations on reactions of saturated NHC SIMes (SIMes=[:C{N(2,4,6-Me3C6H2)CH2}2]) with Group 1 alkyl bases suggest this destructive process is triggered by lateral metalation of the carbene. Exploiting co-complexation and trans-metal-trapping strategies with lower polarity organometallic reagents (Mg(CH2SiMe3)2 and Al(TMP)iBu2), key intermediates in this process have been isolated and structurally defined.
Co-reporter:Zoe Livingstone, Alberto Hernán-Gómez, Sharon E. Baillie, David R. Armstrong, Luca M. Carrella, William Clegg, Ross W. Harrington, Alan R. Kennedy, Eva Rentschler and Eva Hevia
Dalton Transactions 2016 vol. 45(Issue 14) pp:6175-6182
Publication Date(Web):2015/11/20
DOI:10.1039/C5DT04044B
By exploring the reactivity of sodium butyl-magnesiate (1) supported by the bulky chelating silyl(bisamido) ligand {Ph2Si(NAr*)2}2− (Ar* = 2,6-iPr2-C6H3) towards Quinoxaline (Qx), the ability of this bimetallic system to effectively promote SET processes has been disclosed. Thus 1 executes the single-electron reduction of Qx affording complex (2) whose structure in the solid state contains two quinaxolyl radical anions Qx˙ stabilised within a dimeric magnesiate framework. Combining multinuclear NMR and EPR measurements with DFT calculations, new insights into the constitution of 2 in solution and its magnetic behaviour have been gained. Further evidence on the SET reactivity of 1 was found when it was reacted with nitroxyl radical TEMPO which furnished contacted ion pair sodium magnesiate [(Ph2Si(NAr*)2)Mg(TEMPO−)Na(THF)3] (4) where both metals are connected by an alkoxide bridge, resulting from reduction of TEMPO. The role that the different ligands present in 1 can play in these new SET reactions has also been assessed. Using an amination approach, the Bu group in 1 can be replaced by the more basic amide TMP allowing the isolation of (3) which was characterised by multinuclear NMR and X-ray crystallography. 1H NMR monitoring of the reaction of 3 with Qx showed its conversion to 2, leaving the hydrogen atoms of the heterocycle untouched. Contrastingly, using sodium homoalkyl magnesiate [NaMg(CH2SiMe3)3] (5) led to the chemoselective C2 alkylation of this heterocycle, suggesting that the presence of the steric stabiliser {Ph2Si(NAr*)2}2− on the mixed-metal reagent is required in order to facilitate the Qx reduction.
Co-reporter:Marina Uzelac, Alberto Hernán-Gómez, David R. Armstrong, Alan R. Kennedy and Eva Hevia
Chemical Science 2015 vol. 6(Issue 10) pp:5719-5728
Publication Date(Web):03 Jul 2015
DOI:10.1039/C5SC02086G
Advancing the rational design of main-group N-heterocyclic carbene complexes, this study reports the synthesis, X-ray crystallographic and NMR spectroscopic characterisation of a novel series of Ga complexes containing neutral or anionic NHC ligands using the unsaturated carbene IPr (IPr = 1,3-bis-(2,6-di-isopropylphenyl)imidazol-2-ylidene). Starting from normal adduct GaR3·IPr (1) (R = CH2SiMe3), the addition of polar LiR led to the formation of NHC-stabilised gallate species IPr·LiGaR4 (2), resulting from co-complexation of the single-metal species. Contrastingly, reversing the order of addition of these organometallic reagents, by treating unsaturated free IPr, first with LiR followed by GaR3, furnished novel heteroleptic gallate (THF)2Li[:C{[N(2,6-iPr2C6H3)]2CHCGa(CH2SiMe3)3}] (3), which contains an anionic NHC ligand acting as an unsymmetrical bridge between the two metals, coordinating through its abnormal C4 position to Ga and through its normal C2 position to Li. Electrophilic interception studies of 3 using methyl triflate (MeOTf), methanol and imidazolium salt (IMes·HCl) led to the isolation and structural elucidation of the two novel neutral abnormal NHC (aNHC) complexes [CH3C{[N(2,6-iPr2C6H3)]2CHCGa(CH2SiMe3)3}] (4) and aIPr·GaR3 (5) (aIPr = HC{[N(2,6-iPr2C6H3)]2CHC}). These studies disclose the preference of the anionic IPr ligand present in 3 to react with electrophiles via its C2 position, leaving its Ga–C4 bond intact. Abnormal complex 5 can also be accessed by a thermally induced rearrangement of its normal isomer 1. Combining NMR spectroscopic and kinetic studies with DFT calculations, new light has been shed on this intriguing transformation, which suggests that it occurs via a dissociative mechanism, highlighting the importance of the donor ability of the solvent used in these thermal isomerizations as well as the steric bulk of the substituents on the NHC and the Ga reagent. These findings intimate that relief of the steric hindrance around Ga by forming an abnormal complex is a key driving force behind these rearrangements.
Co-reporter:Lewis C. H. Maddock; Thomas Cadenbach; Alan R. Kennedy; Ivana Borilovic; Guillem Aromí
Inorganic Chemistry 2015 Volume 54(Issue 18) pp:9201-9210
Publication Date(Web):September 2, 2015
DOI:10.1021/acs.inorgchem.5b01638
This study reports the synthesis and single-crystal X-ray crystallographic, NMR spectroscopic, and magnetic characterization of a series of sodium ferrates using bis(amide) Fe(HMDS)2 as a precursor (HMDS = 1,1,1,3,3,3-hexamethyldisilazide). Reaction with sodium reagents NaHMDS and NaCH2SiMe3 in hexane afforded donor-solvent-free sodium ferrates [{NaFe(HMDS)3}∞] (1) and [{NaFe(HMDS)2(CH2SiMe3)}∞] (2), respectively, which exhibit contacted ion pair structures, giving rise to new polymeric chain arrangements made up of a combination of inter- and intramolecular Na···Me(HMDS) electrostatic interactions. Addition of the unsaturated NHC IPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) to 1 and 2 caused deaggregation of their polymeric structures to form discrete NHC-stabilized solvent-separated ion pairs [Na(IPr)2]+[Fe(HMDS)3]− (3) and [(THF)3·NaIPr]+[Fe(HMDS)2CH2SiMe3]− (4), where in both cases, the NHC ligand coordinates preferentially to Na. In contrast, when IPr is sequentially reacted with the single-metal reagents NaCH2SiMe3 and Fe(HMDS)2, the novel heteroleptic ferrate (THF)3Na[:C{[N(2,6-iPr2C6H3)]2CHCFe(HMDS)2}] (5) is obtained. This contains an anionic NHC ligand acting as an unsymmetrical bridge between the two metals, coordinating through its abnormal C4 position to Fe and its normal C2 position to Na. The formation of 5 can be described as an indirect ferration process where IPr is first metalated at the C4 position by the polar sodium alkyl reagent, which in turn undergoes transmetalation to the more electronegative Fe(HMDS)2 fragment. Treatment of 5 with 1 molar equiv of methyl triflate (MeOTf) led to the isolation and structural elucidation of the neutral abnormal NHC (aNHC) tricoordinate iron complex [CH3C{[N(2,6-iPr2C6H3)]2CHCFe(HMDS)2}] (6) with the subsequent elimination of NaOTf, disclosing the selectivity of complex 5 to react with this electrophile via its C2 position, leaving its Fe–C4 and Fe–N bonds intact. The magnetic susceptibility properties of compounds 1–6 have been examined. This study revealed a drastic change of magnetic susceptibility in replacing a pure σ donor from an idealized trigonal coordination environment by an NHC π donating character.
Co-reporter:Andrew J. Roberts, William Clegg, Alan R. Kennedy, Michael R. Probert, Stuart D. Robertson and Eva Hevia
Dalton Transactions 2015 vol. 44(Issue 17) pp:8169-8177
Publication Date(Web):27 Mar 2015
DOI:10.1039/C5DT00312A
Using bis(amide) Zn(HMDS)2 (HMDS = 1,1,1,3,3,3-hexamethyldisilazide) as a precursor, this study explores the synthesis of N-heterocyclic carbene stabilized mixed amido-hydride zinc complexes using two alternative hydride sources, namely dimethylamine borane (DMAB) and phenylsilane PhSiH3. Hydride-rich zinc cluster Zn4(HMDS)2H6·2IPr (1) (IPr = 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidene), which can be envisaged as a co-complex of IPr·ZnH2 and (HMDS)ZnH, is obtained when DMAB is employed, with the concomitant formation of heteroleptic bis(amido)borane [HB(NMe2)(HMDS)] and H2 evolution. NMR studies in d8-THF show that although the bulky carbene IPr does not bind to the zinc bis(amide), its presence in the reaction media is required in order to stabilise 1. Reactions using the slightly less sterically demanding NHC IXy (IXy = 1,3-bis-(2,6-dimethylphenyl)imidazol-2-ylidene) led to the isolation and structural elucidation of the carbene adduct Zn(HMDS)2·IXy (2). Contrastingly, mixtures of equimolar amounts of PhSiH3 and the zinc bis(amide) (60 °C, 3 h, hexane) afforded monomeric heteroleptic hydride (HMDS)ZnH·IPr (3). NMR studies, including DOSY experiments, revealed that while the integrity of 3 is retained in polar d8-THF solutions, in lower polarity C6D6 it displays a much more complex solution behaviour, being in equilibrium with the homoleptic species ZnH2·IPr, Zn(HMDS)2 and IPr.
Co-reporter:Alberto Hernán-Gómez, Emma Herd, Marina Uzelac, Thomas Cadenbach, Alan R. Kennedy, Ivana Borilovic, Guillem Aromı́, and Eva Hevia
Organometallics 2015 Volume 34(Issue 11) pp:2614-2623
Publication Date(Web):February 13, 2015
DOI:10.1021/om501251q
This study explores the synthetic utility of homo(aryl) lithum zincate reagents [LiZnPh3] (2) and [Li2ZnPh4] (3), made by cocomplexation of variable amounts of their monometallic components LiPh and ZnPh2 (1), as chemoselective nucleophilic arylating reagents. Lithium zincates 2 and 3 were both characterized by multinuclear (1H, 13C, and 7Li) NMR spectroscopy, and in the case of 2, a classical reagent in heterobimetallic chemistry, the molecular structure of its OnBu2 solvate [LiZnPh3(OnBu2)2] 2·2OBu2 has been established by X-ray crystallography. Using the synthetically relevant N-heterocyclic molecule acridine (acr, NC13H9), a new zincate-mediated arylating approach is demonstrated which allows the chemoselective arylation of acr at its C9 position, affording 9,10-dihydro-9-phenylacridine (4) in 95% yield using microwave irradiation (125 °C, 20 min). These conditions are in contrast with previous transition-metal-catalyzed methodologies using ZnPh2 as an arylating reagent, which require significantly longer reaction times (130 °C, 20 h). Oxidation of 4 with DDQ furnished 9-phenylacridine (5) in a 71% yield. New insights into the constitution of the intermediate organometallic species involved in these reactions prior to the hydrolysis step have been gained by trapping homometallic [(THF)3Li(NC13H9-Ph)] (6). Interestingly the reaction of acr with 3 equiv of PhLi/TMEDA led to the isolation of a different product, namely the novel paramagnetic [(THF)(TMEDA)Li{NC13H8-Ph}•–] (7), which contains a radical anion of 9-phenylacridine. The structure of the donor–acceptor complex [(acr)ZnPh2] (8) has also been included as a result of the reaction of 1 with acr.
Co-reporter:Tobias D. Bluemke, William Clegg, Pablo García-Alvarez, Alan R. Kennedy, Konrad Koszinowski, Matthew D. McCall, Luca Russo and Eva Hevia
Chemical Science 2014 vol. 5(Issue 9) pp:3552-3562
Publication Date(Web):16 Jun 2014
DOI:10.1039/C4SC01263A
Expanding the synthetic potential of Mg–Zn hybrid organyl reagents (generated via transmetallation reactions), this study uncovers a versatile approach, involving a sequence of direct Zn–I exchange and Pd catalysed cross-coupling reactions which grants access to a wide range of asymmetric bis(aryls). By combining X-ray crystallography with ESI-MS and non-deuterium NMR spectroscopic studies, new light is shed on the heterobimetallic constitution of the intriguing organometallic species [(THF)4MgCl2Zn(tBu)Cl] (1) and [{Mg2Cl3(THF)6}+{ZntBu3}−] (2), formed through transmetallation of tBuMgCl with n equivalent amounts of ZnCl2 (n = 1 and 3 respectively). Operating by cooperative effects, alkyl-rich hybrid 2 can effectively promote direct Zn–I exchange reactions with aromatic halides in short periods of time at room temperature in THF solution. The structural elucidation of key organometallic intermediates involved in some of these Zn–I exchanges, provides new reactivity insights into how these bimetallic systems operate. Thus, while the reaction of 2 with 3 equivalents of 2-iodoanisole (3b) gives magnesium dizincate [{Mg(THF)6}2+{Zn(o-C6H4-OMe)3}2−] (4) which demonstrates the 3-fold activation of the tBu groups attached to Zn in 2, using 2-iodobenzonitrile (3i), only two tBu groups react with the substrate, affording [(THF)4MgCl(NC-o-C6H4)ZnI(o-C6H4-CN)(THF)] (7). In 7 Mg and Zn are connected by an aryl bridge, suggesting that the formation of contacted ion-pair hybrids may have a deactivating effect on the outcome of the Zn–I exchange process. A wide range of homoleptic tris(aryl) zincate intermediates have been prepared in situ and used as precursors in Pd catalysed cross-coupling reactions, affording bis(aryls) 6a–s in excellent yields under mild reaction conditions without the need of any additive or polar cosolvent such as NMP or DMI.
Co-reporter:Sharon E. Baillie, Tobias D. Bluemke, William Clegg, Alan R. Kennedy, Jan Klett, Luca Russo, Marco de Tullio and Eva Hevia
Chemical Communications 2014 vol. 50(Issue 85) pp:12859-12862
Publication Date(Web):03 Sep 2014
DOI:10.1039/C4CC05305B
Using structurally well-defined dipotassium-tetra(alkyl)magnesiates, a new straightforward methodology to promote regioselective Mg–H exchange reactions of a wide range of aromatic and heteroaromatic substrates is disclosed. Contacted ion pair intermediates are likely to be involved, with K being the key to facilitate the magnesiation processes.
Co-reporter:David R. Armstrong, William Clegg, Alberto Hernán-Gómez, Alan R. Kennedy, Zoe Livingstone, Stuart D. Robertson, Luca Russo and Eva Hevia
Dalton Transactions 2014 vol. 43(Issue 11) pp:4361-4369
Publication Date(Web):25 Oct 2013
DOI:10.1039/C3DT52639A
Exploring the reactivity of sodium butylmagnesiate reagent [{Na(THF)6}+{(Ph2Si(NAr*)2)Mg(Bu)(THF)}−] (1) supported by the bulky chelating silyl(bisamido) ligand {Ph2Si(NAr*)2}2− (Ar* = 2,6-iPr2-C6H3) towards N-methylbenzimidazole (bImMe), pyrrole and 2,6-diisopropylaniline (NH2Ar*), this study provides new insights into the ability of this bimetallic base to facilitate direct Mg–H exchange reactions as well as to exhibit polybasicity. Thus 1 effectively promotes the deprotomagnesiation of bImMe under mild reaction conditions to give the α-metallated intermediate [{Na(THF)5}2+{(Ph2Si(NAr*)2)Mg(bImMe*)}2−] (2) (bImMe* = 2-N-methylbenzimidazolyl). Analysis of crystallographic and NMR data of 2 combined with DFT calculations show that the metallated C in the bImMe* ligands possesses a significant carbenic character. Contrasting with previous studies of benzothiazole (btz), 1 does not react with an excess of bImMe even under forcing refluxing conditions. Contrastingly, the amination reactions of equimolar amounts of 1 with pyrrole and 2,6-diisopropylaniline allowed the isolation of [{(Ph2Si(NAr*)(NHAr*))Mg(NC4H4)2(THF)Na(THF)2}] (3) and [{Na(THF)6}+{(Ph2Si(NAr*)(NHAr*))Mg(NHAr*)2(THF)}−] (4) respectively as crystalline solids. Highlighting the ability of 1 to act as a polybasic reagent, 3 and 4 are formed as the result of the deprotonation of two molecules of the relevant amine via its butyl group and one amido arm of the silyl(bisamido) ligand. Similarly, the reactions of 1 with 3 molar equivalents of the relevant amine yielded homoleptic tris(amido) compounds [(THF)2NaMg(NC4H4)3] (5) and [{Na(THF)6}+{Mg(NHAr*)3}−] (7), with the concomitant formation of bis(amine) Ph2Si(NHAr)2, as a result of the complete amination of 1 using its three basic sites. The structures in the solid state of 3 and 4 were elucidated by X-ray crystallography. Despite their similar constitution, these heteroleptic tris(amido)magnesiates adopt contrasting structures, with the former displaying a contacted ion-pair structure, where Na and Mg are connected by two bridging pyrrolyl anions, whereas the latter gives rise to a solvent-separated ion pair motif. To the best of our knowledge 3 represents the first crystallographically characterized magnesium compound containing an anionic non-substituted form of pyrrole. Noticeably, Mg interacts exclusively with the N atoms of the pyrrolyl ligands, forming strong σ-bonds, whereas Na prefers to engage with the π-systems of both NC4-rings.
Co-reporter:David R. Armstrong, Helena S. Emerson, Alberto Hernán-Gómez, Alan R. Kennedy and Eva Hevia
Dalton Transactions 2014 vol. 43(Issue 38) pp:14229-14238
Publication Date(Web):15 May 2014
DOI:10.1039/C4DT01131G
Using an interlocking co-complexation approach, a homologous series of unsolvated alkali-metal zincates [MZn(CH2SiMe3)3] (M = Li 1, Na 2, K 3) was prepared by reacting equimolar amounts of Zn(CH2SiMe3)2 with the relevant alkali-metal alkyl M(CH2SiMe3) employing non-coordinating hexane as a solvent. X-ray crystallographic studies reveal that these heterobimetallic compounds exhibit unprecedented supramolecular assemblies made up exclusively of a three-fold combination of M–CH2, Zn–CH2 and M⋯Me interactions. Revealing an important alkali-metal effect, 1 displays a linear chain structure; whereas 2 and 3 form much more intricate 3D and 2D coordination networks respectively. Shedding new light into the formation of these solvent-free zincates, DFT calculations indicate that the infinite degree of aggregation observed in 1–3 plays a major role in thermodynamically driving the co-complexation reactions of their homometallic precursors. NMR spectroscopic studies suggest that in C6D6 solution 1–3 exist as discrete contacted ion-pair species, where the alkali-metal is partially solvated by molecules of deuterated solvent. The supramolecular assemblies of 1–3 can be easily deaggregated by adding the polydentate N-donors PMDETA (N,N,N′,N′′,N′′-pentamethyldiethylenetriamine) or TMEDA (N,N,N′,N′-tetramethylethylenediamine), affording monomeric [(PMDETA)LiZn(CH2SiMe3)3] (4) and [(TMEDA)2NaZn(CH2SiMe3)3] (5).
Co-reporter:Cristian Vidal;Dr. Joaquín García-Álvarez;Dr. Alberto Hernán-Gómez;Dr. Alan R. Kennedy; Eva Hevia
Angewandte Chemie International Edition 2014 Volume 53( Issue 23) pp:5969-5973
Publication Date(Web):
DOI:10.1002/anie.201400889
Abstract
Despite their enormous synthetic relevance, the use of polar organolithium and Grignard reagents is greatly limited by their requirements of low temperatures in order to control their reactivity as well as the need of dry organic solvents and inert atmosphere protocols to avoid their fast decomposition. Breaking new ground on the applications of these commodity organometallics in synthesis under more environmentally friendly conditions, this work introduces deep eutetic solvents (DESs) as a green alternative media to carry out chemoselective additions of ketones in air at room temperature. Comparing their reactivities in DES with those observed in pure water suggest that a kinetic activation of the alkylating reagents is taking place, favoring nucleophilic addition over the competitive hydrolysis, which can be rationalized through formation of halide-rich magnesiate or lithiate species.
Co-reporter:Sharon E. Baillie, Victoria L. Blair, Tyne D. Bradley, William Clegg, Jemma Cowan, Ross W. Harrington, Alberto Hernán-Gómez, Alan R. Kennedy, Zoe Livingstone and Eva Hevia
Chemical Science 2013 vol. 4(Issue 4) pp:1895-1905
Publication Date(Web):14 Feb 2013
DOI:10.1039/C3SC22326D
Opening-up new synthetic applications of β-diketiminate stabilised magnesium complexes, this case study compares the ability of the alkyl [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(THF)] (1) and the amido reagent [{Ar*NC(Me)CHC(Me)NAr*}Mg(TMP)] (2) (Ar* = 2,6-i-Pr2-C6H3) to promote direct Mg–H exchange towards the series of 1,3-benzoazoles: benzoxazole (boz), benzothiazole (btz) and N-methyl benzimidazole (bImMe). Both reagents deprotonate boz at room temperature to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{O(o-C6H4)NC}(THF)] (3) via the C–O bond cleavage of a putative C2-magnesiated-benzoxazolyl intermediate. Structurally tracking the reactivity of 1 and 2 towards less acidic btz and bImMe showed that the behaviour of reagents 1 and 2 diverged dramatically. Kinetically activated TMP-reagent 2 effectively promotes the deprotonative magnesiation of btz and bImMe under mild reaction conditions, giving the alpha-metallated intermediates [{Ar*NC(Me)CHC(Me)NAr*}2Mg2{btz*}2] (4) and [{Ar*NC(Me)CHC(Me)NAr*}2Mg2{bImMe*}2] (7) (btz* = 2-benzothiazolyl; bImMe* = 2-N-methylbenzimidazolyl). Analysis of crystallographic and NMR data revealed that in 4 and 7 the metallated carbon atoms display a markedly carbenic character and that in solution these species exist at room temperature solely as the ring-closed products, without any observable equilibration to the acyclic isomers. Contrastingly, alkyl reagent 1 decreases the magnesiation rate of btz facilitating an intriguing new cascade activation process of two molecules of substrate involving a sequence of deprotonation/coordination/C–C coupling and ring-opening reactions to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{(btz*)C(H)N(o-C6H4)S}] (5). Hydrolysis of 5 followed by addition of the radical oxidant TEMPO ultimately produces the homocoupled product bis(benzothiazole) 6 in a 72% isolated yield. Thus, this establishes a novel transition-metal-free method to prepare homocoupled thiazoles. More straightforwardly, the coordination product [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(bImMe)] (8) was obtained when equimolar amounts of bImMe and 1 were reacted, illustrating the kinetic stubbornness of the Mg–C bond in butyl derivative 1. Complex 8 can be envisaged as a valuable guide to the constitution of a premetallation complex (in relation to the complex-induced proximity effect, CIPE).
Co-reporter:David R. Armstrong, Sharon E. Baillie, Victoria L. Blair, Nicolas G. Chabloz, Josefina Diez, Joaquin Garcia-Alvarez, Alan R. Kennedy, Stuart D. Robertson and Eva Hevia
Chemical Science 2013 vol. 4(Issue 11) pp:4259-4266
Publication Date(Web):14 Aug 2013
DOI:10.1039/C3SC52101J
Merging two evolving areas in synthesis, namely cooperative bimetallics and N-heterocyclic carbenes (NHCs), this study reports the isolation of the first intermediates of alkali-metal-mediated zincation (AMMZn) of a free NHC and a Zn–NHC complex using sodium zincate [(TMEDA)NaZn(TMP)(tBu)2] (1) as a metallating reagent. The structural authentication of (THF)3Na[:C{[N(2,6-iPr2C6H3)]2CHCZn(tBu2)}] (2) and [Na(THF)6]+[tBu2Zn:C{[N(2,6-iPr2C6H3)]2CHCZn(tBu2)}]− (4), resulting from the reactions of 1 with unsaturated free NHC IPr (IPr = 1,3-bis(2,6-di-isopropylphenylimidazole-2-ylidene) and NHC complex ZntBu2IPr (3) respectively demonstrates that in both cases, this mixed-metal approach can easily facilitate the selective C4 zincation of the unsaturated backbone of the NHC ligand. Furthermore, the generation of anionic NHC fragments enables dual coordination through their normal (C2) and abnormal (C4) positions to the bimetallic system, stabilising the kinetic AMMZn intermediates which normally go undetected and provides new mechanistic insights in to how these mixed-metal reagents operate. In stark contrast to this bimetallic approach when NHC-complex 3 is reacted with a more conventional single-metal base such as tBuLi, the deprotonation of the coordinated carbene is inhibited, favouring instead, co-complexation to give NHC-stabilised [IPr·LiZntBu3] (5). Showing the potential of 2 to act as a transfer agent of its anionic NHC unit to transition metal complexes, this intermediate reacts with two molar equivalents of [ClAu(PPh3)] to afford the novel digold species [ClAu:C{[N(2,6-iPr2C6H3)]2CHCAu(PPh3)}] (6) resulting from an unprecedented double transmetallation reaction which involves the simultaneous exchange of both cationic (Na+) and neutral (ZntBu2) entities on the NHC framework.
Co-reporter:Alberto Hernán-Gómez, Tyne D. Bradley, Alan R. Kennedy, Zoe Livingstone, Stuart D. Robertson and Eva Hevia
Chemical Communications 2013 vol. 49(Issue 77) pp:8659-8661
Publication Date(Web):22 Jul 2013
DOI:10.1039/C3CC45167D
Mixed-metal reagents [NaMg(CH2SiMe3)3] (1) and [(THF)NaMg(NPh2)3(THF)] [3-(THF)2] can act as precatalysts to selectively promote the hydroamination/trimerization of isocyanates (RNCO) depending on the steric bulk of the R substituent.
Co-reporter:Jennifer A. Garden ; David R. Armstrong ; William Clegg ; Joaquin García-Alvarez ; Eva Hevia ; Alan R. Kennedy ; Robert E. Mulvey ; Stuart D. Robertson ;Luca Russo
Organometallics 2013 Volume 32(Issue 19) pp:5481-5490
Publication Date(Web):September 16, 2013
DOI:10.1021/om4007664
Aiming to shed new light on the stability and constitution of the organometallic intermediates involved in direct ortho-metalation processes, using trifluoromethylbenzene (1) as a case study, this paper investigates the deprotonation of 1 using group 1 alkyl bases tBuLi and nBuNa in the presence of the Lewis donors TMEDA (N,N,N′,N′-tetramethylethylenediamine), THF, and PMDETA (N,N,N′,N″,N″-pentamethyldiethylenetriamine). A systematic and comprehensive study combining structural, spectroscopic, and theoretical studies reveals that these donors strongly influence the final outcome of the reactions, not only by activating the alkali-metal bases and facilitating deprotonation of 1 but also by tuning the regioselectivity of the reaction. Thus, while using tBuLi/TMEDA, ortho-metalation of 1 is preferred, switching to THF gives a complex mixture of products with the meta-regioisomer being the major species crystallizing from hexane solution. This donor effect is significantly reduced when nBuNa is employed, as ortho-regioselectivity is observed almost exclusively using THF, TMEDA, or PMDETA. DFT calculations computing the relative energies of the ortho-, meta-, and para-regioisomers obtained from these metalating systems have also been carried out. Reinforcing the experimental findings, these theoretical studies show that although in all cases the product of ortho-metalation is the most thermodynamically preferred, the energy difference between the three possible modeled regioisomers is much larger for the Na systems than for the Li ones. The structures of key reaction intermediates [(TMEDA)·Li(C6H4-CF3)]2 (2), [(TMEDA)·Na(C6H4-CF3)]2 (3), and [(PMDETA)·Na(C6H4-CF3)]2 (4) have been elucidated by X-ray crystallographic studies. All compounds exhibit a similar dimeric arrangement with a four-atom core constituting a {MCMC} ring. Interestingly for Na derivatives 3 and 4 unusual Na···F dative interactions are found, which appear to contribute to the overall stability of these compounds, therefore favoring ortho-metalation of 1, as the meta or para structures do not contain these additional interactions.
Co-reporter:David R. Armstrong, Elanor Brammer, Thomas Cadenbach, Eva Hevia, and Alan R. Kennedy
Organometallics 2013 Volume 32(Issue 2) pp:480-489
Publication Date(Web):January 11, 2013
DOI:10.1021/om3009469
Exploring the co-complexation reactions between the gallium alkyl Ga(CH2SiMe3)3 and alkali-metal alkyl MCH2SiMe3 (M = Li, Na, or K) using an arene/hexane solvent mixture has allowed the isolation of solvent-free alkali-metal tetraorganogallates [{MGa(CH2SiMe3)4}∞] (M = Li, 1; Na, 2) and related benzene adduct [{(C6H6)2KGa(CH2SiMe3)4}∞] (3). By combining X-ray crystallography, NMR spectroscopy, and DFT calculations, this study sheds new light on the constitution of these mixed-metal species. X-ray crystallographic studies reveal that all gallates exhibit novel polymeric arrangements, with 1 and 2 sharing the same linear chain structure, made up exclusively of M–C and Ga–C bonds, whereas 3 displays a significantly more open structural motif, where the K and Ga atoms are connected by a single alkyl bridge and propagation occurs via weaker K···Me electrostatic interactions of a methyl from a SiMe3 group of an alkyl ligand from one monomer to the potassium from a neighboring monomeric unit. Multinuclear NMR spectroscopic studies suggest that in deuterated benzene solutions 1–3 exist as discrete solvent-separated ion-pair species where the alkali-metal is solvated by the arene solvent. DFT calculations show that while the infinite aggregation of these polymeric structures is key for thermodynamically favoring the formation of 1 and 2, in the case of 3 the solvation of unsaturated potassium by two molecules of benzene, via π-electrostatic interactions, appears to be the major contributor to its overall stability.
Co-reporter:Sharon E. Baillie, Victoria L. Blair, David C. Blakemore, Duncan Hay, Alan R. Kennedy, David C. Pryde and Eva Hevia
Chemical Communications 2012 vol. 48(Issue 14) pp:1985-1987
Publication Date(Web):20 Dec 2011
DOI:10.1039/C2CC16959B
Comparing the reactivity of the related lithium zincates [(THF)LiZn(TMP)tBu2] (1) and [(PMDETA)LiZntBu3] (2) towards pyrazine discloses two new bimetallic approaches for the selective 2,5-dideprotonation and room temperature C–H alkylation of this sensitive heterocycle.
Co-reporter:Eva Hevia, Alan R. Kennedy and Matthew D. McCall
Dalton Transactions 2012 vol. 41(Issue 1) pp:98-103
Publication Date(Web):24 Oct 2011
DOI:10.1039/C1DT11465D
Exploring the reactivity of the mixed-metal reagent [(TMEDA)Na(TMP)ZntBu2] (1) towards substituted metallocenebenzoylferrocene 2, this study has found that two competing reactivity pathways are available for the sodium TMP-zincate, namely (i) remote 1,6-nucleophilic addition of a tert-butyl group to the phenyl ring of 2, and (ii) simultaneous alpha-deprotonation of the substituted cyclopentadienyl ring of the metallocene and alkylation (1,2-addition) across the CO bond of the carbonyl group. A key organometallic intermediate [(TMEDA)Na(μ-TMP)Zn{OC(tBu)(Ph)(η5-C5H3)Fe(η5-C5H5)}] (3), resulting from the latter reaction has been trapped and characterised by X-ray crystallography and multinuclear (1H and 13C) NMR spectroscopy. Its molecular structure revealed a unique two-fold activation of the tert-butyl groups bonded to zinc in the bimetallic base 1, showing for the first time that each alkyl group can exhibit markedly different reactivities (deprotonation vs.1,2-addition) towards the same substrate molecule. Iodine interception of the organometallic intermediates of the reaction between 1 and 2 allowed the isolation and characterization (1H, 13C NMR and X-ray crystallography) of the ferrocenyl derivatives [PhC(OH)(tBu)(η5-C5H3I)Fe(η5-C5H5)] (4) and [4-tBu-C6H4C(O)(η5-C5H4)Fe(η5-C5H5)] (5) in a 29% and 24% isolated yield respectively. The low yield observed for the formation of 5 (resulting from the 1,6-addition reaction followed by spontaneous aerobic oxidation during aqueous workup) could be increased to 41% when the reaction mixture was hydrolysed in the presence of the radical oxidant TEMPO.
Co-reporter:Sharon E. Baillie, William Clegg, Pablo García-Álvarez, Eva Hevia, Alan R. Kennedy, Jan Klett and Luca Russo
Chemical Communications 2011 vol. 47(Issue 1) pp:388-390
Publication Date(Web):31 Aug 2010
DOI:10.1039/C0CC02164D
The study of co-complexation reactions between NaCH2SiMe3 and Mg(CH2SiMe3)2 has allowed the isolation and structural elucidation of the first solvent-free alkali-metal alkylmagnesiate [{NaMg(CH2SiMe3)3}∞] (1) as well as the related solvent-free sodium alkyl [{(NaCH2SiMe3)4}∞] (3).
Co-reporter:Victoria L. Blair, David C. Blakemore, Duncan Hay, Eva Hevia, David C. Pryde
Tetrahedron Letters 2011 Volume 52(Issue 36) pp:4590-4594
Publication Date(Web):7 September 2011
DOI:10.1016/j.tetlet.2011.06.090
This study investigates the ability of the mixed-metal reagent [Li(TMP)Zn(tBu)2] 1 to promote direct Zn–H exchange reactions (zincations) of a wide range of N-heterocyclic molecules. The generated metallated intermediates from these reactions are intercepted with I2 and some of them are also employed as precursors in Pd-catalysed Negishi cross-coupling applications. A comparison with recent precedents in metallation chemistry reveals that for some of these heterocycles, 1 allows improved conversions, under milder conditions and in certain cases, even gives unique regioselectivities.
Co-reporter:Dr. David R. Armstrong; William Clegg;Dr. Pablo García-Alvarez;Matthew D. McCall;Lorraine Nuttall;Dr. Alan R. Kennedy;Dr. Luca Russo;Dr. Eva Hevia
Chemistry - A European Journal 2011 Volume 17( Issue 16) pp:4470-4479
Publication Date(Web):
DOI:10.1002/chem.201002544
Abstract
Building on recent advances in synthesis showing that the addition of inorganic salts to Grignard reagents can greatly enhance their performance in alkylation reactions to ketones, this study explores the reactions of EtMgCl with benzophenone in the presence of stoichiometric or catalytic amounts of ZnCl2 with the aim of furthering the understanding of the role and constitution of the organometallic species involved in these transformations. Investigations into the metathesis reactions of three molar equivalents of EtMgCl with ZnCl2 led to the isolation and characterisation (X-ray crystallography and 1H and 13C NMR spectroscopy) of novel magnesium “zinc-rich” zincate [{(THF)6Mg2Cl3}+{Zn2Et5}−] (1), whose complicated constitution in THF solutions was assessed by variable-temperature 1H DOSY NMR studies. Compound 1 reacted with one equivalent of benzophenone to yield magnesium magnesiate [{(THF)6Mg2Cl3}+{Mg2(OC(Et)Ph2)2Cl3(THF)}−] (3), whose structure was determined by X-ray crystallography. 1H NMR monitoring of this reaction showed two equivalents of ZnEt2 formed as a co-product, which together with the “magnesium only constitution” of 3 provides experimental insights into how zinc can be efficiently recycled in these reactions, and therefore used catalytically. The chemoselectivity of this reaction can be rationalised in terms of the synergic effect of magnesium and zinc and contrasts with the results obtained when benzophenone was allowed to react with EtMgCl in the absence of ZnCl2, where the reduction of the ketone takes place preferentially. The reduction product [{(THF)5Mg3Cl4{OC(H)Ph(CF3)}2] (4) obtained from the reaction of EtMgCl with 2,2,2-trifluoroacetophenone was established by X-ray crystallography and multinuclear (1H, 13C and 19F) NMR spectroscopy. Compounds 3 and 4 exhibit new structural motifs in magnesium chemistry having MgCl2 integrated within their constitution, which highlights the new role of this inorganic salt in providing structural support for the newly generated alkoxide ligand.
Co-reporter:Dr. David R. Armstrong; William Clegg;Dr. Pablo García-Álvarez;Dr. Alan R. Kennedy;Matthew D. McCall;Dr. Luca Russo;Dr. Eva Hevia
Chemistry - A European Journal 2011 Volume 17( Issue 30) pp:8333-8341
Publication Date(Web):
DOI:10.1002/chem.201100866
Abstract
Numerous organic transformations rely on organozinc compounds made through salt-metathesis (exchange) reactions from organolithium or Grignard reagents with a suitable zinc precursor. By combining X-ray crystallography, NMR spectroscopy and DFT calculations, this study sheds new light on the constitution of the organometallic species involved in this important synthetic tool. Investigations into the metathesis reactions of equimolar amounts of Grignard reagents (RMgX) and ZnCl2 in THF led to the isolation of novel magnesium–zinc hybrids, [{(thf)2Mg(μ-Cl)3ZnR}2] (R=Et, tBu, nBu or o-OMe-C6H4), which exhibit an unprecedented structural motif in mixed magnesium–zinc chemistry. Furthermore, theoretical modelling of the reaction of EtMgCl with ZnCl2 reveals that formation of the mixed-metal compound is thermodynamically preferred to that of the expected homometallic products, RZnCl and MgCl2. This study also assesses the alkylating ability of hybrid 3 towards the sensitive ketone trifluoroacetophenone, revealing a dramatic increase in the chemoselectivity of the reaction when LiCl is introduced as an additive. This observation, combined with recent related breakthroughs in synthesis, points towards the existence of a trilateral Li/Mg/Zn synergistic effect.
Co-reporter:Dr. Eva Hevia; Robert E. Mulvey
Angewandte Chemie International Edition 2011 Volume 50( Issue 29) pp:6448-6450
Publication Date(Web):
DOI:10.1002/anie.201102054
Co-reporter:Dr. Victoria L. Blair; William Clegg;Dr. Alan R. Kennedy;Zoe Livingstone;Dr. Luca Russo;Dr. Eva Hevia
Angewandte Chemie International Edition 2011 Volume 50( Issue 42) pp:
Publication Date(Web):
DOI:10.1002/anie.201105347
Co-reporter:Dr. Victoria L. Blair; William Clegg;Dr. Alan R. Kennedy;Zoe Livingstone;Dr. Luca Russo;Dr. Eva Hevia
Angewandte Chemie International Edition 2011 Volume 50( Issue 42) pp:9857-9860
Publication Date(Web):
DOI:10.1002/anie.201103275
Co-reporter:Dr. Victoria L. Blair; William Clegg;Dr. Alan R. Kennedy;Zoe Livingstone;Dr. Luca Russo;Dr. Eva Hevia
Angewandte Chemie 2011 Volume 123( Issue 42) pp:
Publication Date(Web):
DOI:10.1002/ange.201105347
Co-reporter:Dr. Victoria L. Blair; William Clegg;Dr. Alan R. Kennedy;Zoe Livingstone;Dr. Luca Russo;Dr. Eva Hevia
Angewandte Chemie 2011 Volume 123( Issue 42) pp:10031-10034
Publication Date(Web):
DOI:10.1002/ange.201103275
Co-reporter:Dr. Eva Hevia; Robert E. Mulvey
Angewandte Chemie 2011 Volume 123( Issue 29) pp:6576-6578
Publication Date(Web):
DOI:10.1002/ange.201102054
Co-reporter:David R. Armstrong ; Victoria L. Blair ; William Clegg ; Sophie H. Dale ; Joaquin Garcia-Alvarez ; Gordon W. Honeyman ; Eva Hevia ; Robert E. Mulvey ;Luca Russo
Journal of the American Chemical Society 2010 Volume 132(Issue 27) pp:9480-9487
Publication Date(Web):June 22, 2010
DOI:10.1021/ja1038598
Performed with a desire to advance knowledge of the structures and mechanisms governing alkali-metal-mediated zincation, this study monitors the reaction between the TMP-dialkylzincate reagent [(TMEDA)Na(TMP)(tBu)Zn(tBu)] 1 and trifluoromethyl benzene C6H5CF3 2. A complicated mixture of products is observed at room temperature. X-ray crystallography has identified two of these products as ortho- and meta-regioisomers of heterotrianionic [(TMEDA)Na(TMP)(C6H4-CF3)Zn(tBu)], 3-ortho and 3-meta, respectively. Multinuclear NMR data of the bulk crystalline product confirm the presence of these two regioisomers as well as a third isomer, 3-para, in a respective ratio of 20:11:1, and an additional product 4, which also exhibits ortho-zincation of the aryl substrate. Repeating the reaction at 0 °C gave exclusively 4, which was crystallographically characterized as [{(TMEDA)2Na}+{Zn(C6H4-CF3)(tBu)2}−]. Mimicking the original room-temperature reaction, this kinetic product was subsequently reacted with TMP(H) to afford a complicated mixture of products, including significantly the three regioisomers of 3. Surprisingly, 4 adopts a solvent-separated ion pair arrangement in contrast to the contacted ion variants of 3-ortho and 3-meta. Aided by DFT calculations on model systems, discussion focuses on the different basicities, amido or alkyl, and steps, exhibited in these reactions, and how the structures and bonding within these isolated key metallic intermediates (prior to any electrophilic interception step), specifically the interactions involving the alkali metal, influence the regioselectivity of the Zn−H exchange process.
Co-reporter:Eva Hevia, Alan R. Kennedy, Jan Klett, Zoe Livingstone and Matthew D. McCall
Dalton Transactions 2010 vol. 39(Issue 2) pp:520-526
Publication Date(Web):10 Sep 2009
DOI:10.1039/B911818G
A systematic study of the stoichiometric alkylation reactions of 2,2,2-trifluoroacetophenone 1 with [ZnR2(TMEDA)] (R= Me, Et, tBu, CH2SiMe3; TMEDA= N,N,N′,N′-tetramethylethylenediamine) monitored by 1H and 19F NMR spectroscopy is presented. For R = Me, Et the alkylation products alkyl(alkoxides) [(TMEDA)Zn(R){OC(CF3)(R)Ph}] (R = Me, 2: Et, 3) are obtained as the single products of the reaction. When the steric bulk of the dialkylzinc reagent is increased the alkylation reaction is inhibited. Thus, for R = tBu, the reduction product [(TMEDA)Zn(tBu){OC(CF3)(H)Ph}] is obtained as a result of β-hydride elimination from one of the tBu groups of the organometallic reagent. 1H NMR spectroscopic monitoring of the reaction allowed the detection of isobutene as a side product of this reduction process. For the highly sterically demanding group R = CH2SiMe3 which lacks hydrogen atoms at the β position, no reaction is observed even under refluxing conditions. Two important intermediates from these reactions have been structurally elucidated: [(TMEDA)Zn(Me){OC(CF3)(Me)Ph}] (2) which could be involved in the previously reported alkylation reaction of trifluoromethyl ketones by ZnR2 catalysed by TMEDA and unprecedented tetranuclear [(tBu)2Zn4{OC(CF3)(H)Ph}6] (5) resulting from the reduction of 1 when reacted with tBu2Zn, which displays a rare Zn⋯Zn⋯Zn⋯Zn linear chain arrangement for a zinc alkyl(alkoxide).
Co-reporter:Eva Hevia;Jonathan Z. Chua;Matthew D. McCall;Pablo García-Álvarez;Alan R. Kennedy
PNAS 2010 Volume 107 (Issue 12 ) pp:5294-5299
Publication Date(Web):2010-03-23
DOI:10.1073/pnas.0913307107
Studying seemingly simple metathesis reactions between ZnCl2 and tBuMgCl has, surprisingly, revealed a much more complex chemistry involving mixed magnesium-zinc compounds that could be regarded
as Mg-Zn hybrids. Thus, the reaction of equimolar amounts of ZnCl2 and tBuMgCl reveals the formation of the unprecedented mixed Mg-Zn complex [(THF)4Mg(μ-Cl)2Zn(tBu)(Cl)] (1), as a result of the co-complexation of the two anticipated exchange products of the metathesis. This magnesium zincate adopts
a contacted ion-pair structure, closely related to Knochel’s pioneering “Turbo” Grignard reagents. Furthermore, a second coproduct
identified in this reaction is the solvent-separated mixed magnesium-zinc chloride complex [{Mg(THF)6}2+{Zn2Cl6}2-] (3) that critically diminishes the amount of ZnCl2 available for the intended metathesis reaction to take place. In another surprising result, when the reaction is carried
out by using an excess of 3 M equivalents of the Grignard reagent (closer to the catalytic conditions employed by synthetic
chemists), solvent-separated magnesium trialkyl zincate [{Mg2Cl3(THF)6}+{Zn(tBu)3}-] (4) is obtained that can be viewed as a model for the active species involved in the increasingly important organic transformations
of Grignard reagents catalysed by ZnCl2. Furthermore, preliminary reactivity studies reveal that complex 4 can be used as an effective new reagent for direct Zn-I exchange reactions that allow the preparation and structural identification
of the magnesium tris(aryl) zincate [{Mg2Cl3(THF)6}+{Zn(p-Tol)3}-] (5) that represents the first example of complete 3-fold activation of a zincate in a Zn-I exchange reaction which, in turn,
can efficiently be used as a precursor for Negishi cross-coupling reactions.
Co-reporter:Eva Hevia, Alan R. Kennedy, Jan Klett and Matthew D. McCall
Chemical Communications 2009 (Issue 22) pp:3240-3242
Publication Date(Web):20 Apr 2009
DOI:10.1039/B903592C
A new application of zincate [(THF)Li(TMP)(tBu)Zn(tBu)] (1) in alkali-metal mediated zincation (AMMZn) is reported by isolating and structurally defining the first intermediates of direct lateral zincation (DlZn) of trimethyl(phenoxy)silane (2) both of which adopt novel six-element {ZnCSiOLiN} ring structures.
Co-reporter:William Clegg, David V. Graham, Emma Herd, Eva Hevia, Alan R. Kennedy, Matthew D. McCall and Luca Russo
Inorganic Chemistry 2009 Volume 48(Issue 12) pp:5320-5327
Publication Date(Web):May 1, 2009
DOI:10.1021/ic900313b
A systematic study of the interlocking co-complexation reactions between the primary lithium amide LiNHDipp (Dipp = 2,6-diisopropylphenyl) and dimethylzinc in the presence of different donor ligands is presented which concludes that the final outcome of these reactions is largely dictated by the type of structure that is formed when the donor is coordinated to the lithium amide. When chelating diamine TMEDA (N,N,N′,N′-tetramethylethylenediamine) is employed [{Li2(NHDipp)2(TMEDA)}∞] (1) is obtained, where Li2N2 rings are connected by TMEDA bridges generating a polymeric chain arrangement which does not form a co-complex with Me2Zn even in the presence of an excess of TMEDA. The tridentate ligand PMDETA (N,N,N′,N′′,N′′-pentamethyldiethylenetriamine) when reacted with LiNHDipp forms monomeric [(PMDETA)Li(NHDipp)](4) which successfully forms a mixed-metal co-complex with Me2Zn affording dialkyl(amido)zincate [(PMDETA)LiZn(NHDipp)(Me)2] (2). When the co-complexation reaction is carried out in the presence of monodentate tetrahydrofuran (THF), zincate [(THF)3LiZn(NHDipp)(Me)2] (3) is obtained which was found to partially decompose in hexane solution after long periods of time at room temperature (2 weeks) to afford the unprecedented “zinc-rich” zincate [(THF)3LiZn2(Me)3(NHDipp)2] (5). This compound presents a unique structure in the solid state previously unknown in organozincate chemistry with a trinuclear Li···Zn···Zn chain arrangement where the metals are connected by only two amido bridges and therefore both zinc centers exhibit trigonal planar geometries. 5 can be prepared in good yields by the rational reaction of LiNHDipp with a 2:1:3 mixture of Me2Zn, NH2Dipp and THF. The different solid-state structural motifs of compounds 1, 2, 4, and 5 have been revealed by X-ray crystallographic studies. Multinuclear NMR (1H, 13C and 7Li) spectroscopic data recorded in C6D6 solution are also reported for compounds 1−6. Mixed-metal compounds 2 and 5 constitute the first examples of crystallographically characterized alkyl(amido)zincates containing a primary amide.
Co-reporter:DavidR. Armstrong Dr.;Joaquín García-Álvarez Dr.;DavidV. Graham;GordonW. Honeyman Dr., Dr.;AlanR. Kennedy Dr. ;RobertE. Mulvey
Chemistry - A European Journal 2009 Volume 15( Issue 15) pp:3800-3807
Publication Date(Web):
DOI:10.1002/chem.200801928
Co-reporter:David R. Armstrong, William Clegg, Sophie H. Dale, Joaquín García-Álvarez, Ross W. Harrington, Eva Hevia, Gordon W. Honeyman, Alan R. Kennedy, Robert E. Mulvey and Charles T. O'Hara
Chemical Communications 2008 (Issue 2) pp:187-189
Publication Date(Web):13 Nov 2007
DOI:10.1039/B713987J
In a new type of reactivity for sodium TMP-zincate [(TMEDA)NaZn(tBu)2(TMP)] (1), transamination reactions with the amines diisopropylamine, DA(H), hexamethyldisilazane, HMDS(H) and chiral (R)-N-benzyl-α-methylbenzylamine have produced new sodium amido-di-tert-butyl zincates (all structurally characterised) with concomitant loss of TMP(H).
Co-reporter:David R. Armstrong, Christine Dougan, David V. Graham, Eva Hevia and Alan R. Kennedy
Organometallics 2008 Volume 27(Issue 23) pp:6063-6070
Publication Date(Web):November 5, 2008
DOI:10.1021/om800786n
The solution and solid-state characterization of the tetraorganozincates [(TMEDA)2Li2ZnMe(NMe2)3] (2) and [(TMEDA)2Li2ZnMe4] (4) and the all-amido triorganozincate [{(TMEDA)LiZn(NMe2)3}2] (3) are reported. X-ray crystallographic studies reveal that 2 and 4 exhibit similar structural motifs, namely trinuclear Li···Zn···Li chain arrangements held together by a methyl and three amido ligands in the former and exclusively by methyl groups in the latter, whereas 3 adopts a longer tetranuclear Li···Zn···Zn···Li chain arrangement with all NMe2 ligands. The zinc coordination in all these structures is distorted tetrahedral. DFT calculations revealed that the formation of tetraorganozincate 4 by cocomplexation of 2 equiv of MeLi and Me2Zn is thermodynamically preferred over the parent triorganozincate [(TMEDA)LiZnMe3]. Preliminary studies show that the tris(amido)alkyl zincate 2 is a poor Brønsted base for metalation (zincation) of functionalized aromatic substrates such as anisole, N,N-diisopropylbenzamide, and benzonitrile.
Co-reporter:David R. Armstrong, Allison M. Drummond, Liam Balloch, David V. Graham, Eva Hevia and Alan R. Kennedy
Organometallics 2008 Volume 27(Issue 22) pp:5860-5866
Publication Date(Web):October 15, 2008
DOI:10.1021/om800658s
The new mixed lithium−zinc enolate compounds [(TMEDA)2Li2Zn{OC(═CH2)Mes}4] (2) and [{TMP(H)}2Li2Zn{OC(═CH2)Mes}4] (3) were prepared by reaction of the sterically demanding ketone 2,4,6-trimethylacetophenone (1) with the all-amido homoleptic zincate [LiZn(TMP)3] (TMP = 2,2,6,6-tetramethylpiperidide). X-ray crystallographic studies revealed that these compounds adopt a trinuclear Li···Zn···Li chain arrangement with enolate O bridges. In contrast, the metalation of 1 with heteroleptic [(TMEDA)LiZn(TMP)Me2] afforded the dimeric lithium enolate [(TMEDA)2Li2{OC(═CH2)Mes}2] (4) as a crystalline solid, which has been characterized in the solid state by X-ray crystallography, and Me2Zn·TMEDA and TMP(H) as coproducts, showing that the dimethylamido zincate behaves as an amide base. The homoleptic zinc enolate [(TMEDA)Zn{OC(═CH2)Mes}2] (5) was obtained by reaction of 1 with the zinc amide Zn(TMP)2, and its structure was determined by X-ray crystallography. 5 adopts a rarely observed monomeric arrangement where the two enolate groups bind terminally to the zinc. New enolates 2−5 have also been characterized by 1H, 13C, and 7Li NMR spectroscopy in C6D6 solution. DFT studies of the metalation of 1 by Zn(TMP)2 and Et2Zn revealed that the former amide has a much greater kinetic basicity than the latter alkyl reagent.
Co-reporter:Prokopis C. Andrikopoulos, David R. Armstrong, Eva Hevia, Alan R. Kennedy, Robert E. Mulvey and Charles T. O'Hara
Chemical Communications 2005 (Issue 9) pp:1131-1133
Publication Date(Web):18 Jan 2005
DOI:10.1039/B416636A
Toluene is metallated by DABCO-activated disodium tetrabutylmagnesiate, but not by DABCO-activated monosodium tributylmagnesiate; this distinction is rationalised by DFT calculations on model systems, and the crystal structure of the main non-metallated product, which shows interstitial MgBu42− dianions within a polycationic network, is reported.
Co-reporter:Helen R. L. Barley;William Clegg ;Sophie H. Dale Dr. Dr.;Gordon W. Honeyman;Alan R. Kennedy Dr.;Robert E. Mulvey
Angewandte Chemie 2005 Volume 117(Issue 37) pp:
Publication Date(Web):26 AUG 2005
DOI:10.1002/ange.200501560
Durch deprotonierende Metallierung von Ferrocen mit einem Lithiumzincat-Reagens waren der neutrale Zinkkomplex [(Fc)2Zn(tmeda)] und das anionische Zincat [Li(thf)4][(Fc)3Zn] zugänglich (siehe Schema; tmp=2,2,6,6-Tetramethylpiperidin, TMEDA=N,N,N′,N′-Tetramethylethylendiamin). Das Lithiumzincat-Reagens [LinBu2Zn(tmp)(tmeda)] ließ sich durch Mischen von TMEDA, Li(tmp) und nBu2Zn im Verhältnis 1:1:1 einfach in situ erzeugen.
Co-reporter:Helen R. L. Barley, William Clegg, Sophie H. Dale, Eva Hevia, Gordon W. Honeyman, Alan R. Kennedy,Robert E. Mulvey
Angewandte Chemie International Edition 2005 44(37) pp:6018-6021
Publication Date(Web):
DOI:10.1002/anie.200501560
Co-reporter:David R. Armstrong, Helena S. Emerson, Alberto Hernán-Gómez, Alan R. Kennedy and Eva Hevia
Dalton Transactions 2014 - vol. 43(Issue 38) pp:NaN14238-14238
Publication Date(Web):2014/05/15
DOI:10.1039/C4DT01131G
Using an interlocking co-complexation approach, a homologous series of unsolvated alkali-metal zincates [MZn(CH2SiMe3)3] (M = Li 1, Na 2, K 3) was prepared by reacting equimolar amounts of Zn(CH2SiMe3)2 with the relevant alkali-metal alkyl M(CH2SiMe3) employing non-coordinating hexane as a solvent. X-ray crystallographic studies reveal that these heterobimetallic compounds exhibit unprecedented supramolecular assemblies made up exclusively of a three-fold combination of M–CH2, Zn–CH2 and M⋯Me interactions. Revealing an important alkali-metal effect, 1 displays a linear chain structure; whereas 2 and 3 form much more intricate 3D and 2D coordination networks respectively. Shedding new light into the formation of these solvent-free zincates, DFT calculations indicate that the infinite degree of aggregation observed in 1–3 plays a major role in thermodynamically driving the co-complexation reactions of their homometallic precursors. NMR spectroscopic studies suggest that in C6D6 solution 1–3 exist as discrete contacted ion-pair species, where the alkali-metal is partially solvated by molecules of deuterated solvent. The supramolecular assemblies of 1–3 can be easily deaggregated by adding the polydentate N-donors PMDETA (N,N,N′,N′′,N′′-pentamethyldiethylenetriamine) or TMEDA (N,N,N′,N′-tetramethylethylenediamine), affording monomeric [(PMDETA)LiZn(CH2SiMe3)3] (4) and [(TMEDA)2NaZn(CH2SiMe3)3] (5).
Co-reporter:Eva Hevia, Alan R. Kennedy and Matthew D. McCall
Dalton Transactions 2012 - vol. 41(Issue 1) pp:NaN103-103
Publication Date(Web):2011/10/24
DOI:10.1039/C1DT11465D
Exploring the reactivity of the mixed-metal reagent [(TMEDA)Na(TMP)ZntBu2] (1) towards substituted metallocenebenzoylferrocene 2, this study has found that two competing reactivity pathways are available for the sodium TMP-zincate, namely (i) remote 1,6-nucleophilic addition of a tert-butyl group to the phenyl ring of 2, and (ii) simultaneous alpha-deprotonation of the substituted cyclopentadienyl ring of the metallocene and alkylation (1,2-addition) across the CO bond of the carbonyl group. A key organometallic intermediate [(TMEDA)Na(μ-TMP)Zn{OC(tBu)(Ph)(η5-C5H3)Fe(η5-C5H5)}] (3), resulting from the latter reaction has been trapped and characterised by X-ray crystallography and multinuclear (1H and 13C) NMR spectroscopy. Its molecular structure revealed a unique two-fold activation of the tert-butyl groups bonded to zinc in the bimetallic base 1, showing for the first time that each alkyl group can exhibit markedly different reactivities (deprotonation vs.1,2-addition) towards the same substrate molecule. Iodine interception of the organometallic intermediates of the reaction between 1 and 2 allowed the isolation and characterization (1H, 13C NMR and X-ray crystallography) of the ferrocenyl derivatives [PhC(OH)(tBu)(η5-C5H3I)Fe(η5-C5H5)] (4) and [4-tBu-C6H4C(O)(η5-C5H4)Fe(η5-C5H5)] (5) in a 29% and 24% isolated yield respectively. The low yield observed for the formation of 5 (resulting from the 1,6-addition reaction followed by spontaneous aerobic oxidation during aqueous workup) could be increased to 41% when the reaction mixture was hydrolysed in the presence of the radical oxidant TEMPO.
Co-reporter:Sharon E. Baillie, Victoria L. Blair, David C. Blakemore, Duncan Hay, Alan R. Kennedy, David C. Pryde and Eva Hevia
Chemical Communications 2012 - vol. 48(Issue 14) pp:NaN1987-1987
Publication Date(Web):2011/12/20
DOI:10.1039/C2CC16959B
Comparing the reactivity of the related lithium zincates [(THF)LiZn(TMP)tBu2] (1) and [(PMDETA)LiZntBu3] (2) towards pyrazine discloses two new bimetallic approaches for the selective 2,5-dideprotonation and room temperature C–H alkylation of this sensitive heterocycle.
Co-reporter:Alberto Hernán-Gómez, Tyne D. Bradley, Alan R. Kennedy, Zoe Livingstone, Stuart D. Robertson and Eva Hevia
Chemical Communications 2013 - vol. 49(Issue 77) pp:NaN8661-8661
Publication Date(Web):2013/07/22
DOI:10.1039/C3CC45167D
Mixed-metal reagents [NaMg(CH2SiMe3)3] (1) and [(THF)NaMg(NPh2)3(THF)] [3-(THF)2] can act as precatalysts to selectively promote the hydroamination/trimerization of isocyanates (RNCO) depending on the steric bulk of the R substituent.
Co-reporter:Marina Uzelac, Alberto Hernán-Gómez, David R. Armstrong, Alan R. Kennedy and Eva Hevia
Chemical Science (2010-Present) 2015 - vol. 6(Issue 10) pp:NaN5728-5728
Publication Date(Web):2015/07/03
DOI:10.1039/C5SC02086G
Advancing the rational design of main-group N-heterocyclic carbene complexes, this study reports the synthesis, X-ray crystallographic and NMR spectroscopic characterisation of a novel series of Ga complexes containing neutral or anionic NHC ligands using the unsaturated carbene IPr (IPr = 1,3-bis-(2,6-di-isopropylphenyl)imidazol-2-ylidene). Starting from normal adduct GaR3·IPr (1) (R = CH2SiMe3), the addition of polar LiR led to the formation of NHC-stabilised gallate species IPr·LiGaR4 (2), resulting from co-complexation of the single-metal species. Contrastingly, reversing the order of addition of these organometallic reagents, by treating unsaturated free IPr, first with LiR followed by GaR3, furnished novel heteroleptic gallate (THF)2Li[:C{[N(2,6-iPr2C6H3)]2CHCGa(CH2SiMe3)3}] (3), which contains an anionic NHC ligand acting as an unsymmetrical bridge between the two metals, coordinating through its abnormal C4 position to Ga and through its normal C2 position to Li. Electrophilic interception studies of 3 using methyl triflate (MeOTf), methanol and imidazolium salt (IMes·HCl) led to the isolation and structural elucidation of the two novel neutral abnormal NHC (aNHC) complexes [CH3C{[N(2,6-iPr2C6H3)]2CHCGa(CH2SiMe3)3}] (4) and aIPr·GaR3 (5) (aIPr = HC{[N(2,6-iPr2C6H3)]2CHC}). These studies disclose the preference of the anionic IPr ligand present in 3 to react with electrophiles via its C2 position, leaving its Ga–C4 bond intact. Abnormal complex 5 can also be accessed by a thermally induced rearrangement of its normal isomer 1. Combining NMR spectroscopic and kinetic studies with DFT calculations, new light has been shed on this intriguing transformation, which suggests that it occurs via a dissociative mechanism, highlighting the importance of the donor ability of the solvent used in these thermal isomerizations as well as the steric bulk of the substituents on the NHC and the Ga reagent. These findings intimate that relief of the steric hindrance around Ga by forming an abnormal complex is a key driving force behind these rearrangements.
Co-reporter:Sharon E. Baillie, William Clegg, Pablo García-Álvarez, Eva Hevia, Alan R. Kennedy, Jan Klett and Luca Russo
Chemical Communications 2011 - vol. 47(Issue 1) pp:NaN390-390
Publication Date(Web):2010/08/31
DOI:10.1039/C0CC02164D
The study of co-complexation reactions between NaCH2SiMe3 and Mg(CH2SiMe3)2 has allowed the isolation and structural elucidation of the first solvent-free alkali-metal alkylmagnesiate [{NaMg(CH2SiMe3)3}∞] (1) as well as the related solvent-free sodium alkyl [{(NaCH2SiMe3)4}∞] (3).
Co-reporter:Andrew J. Roberts, William Clegg, Alan R. Kennedy, Michael R. Probert, Stuart D. Robertson and Eva Hevia
Dalton Transactions 2015 - vol. 44(Issue 17) pp:NaN8177-8177
Publication Date(Web):2015/03/27
DOI:10.1039/C5DT00312A
Using bis(amide) Zn(HMDS)2 (HMDS = 1,1,1,3,3,3-hexamethyldisilazide) as a precursor, this study explores the synthesis of N-heterocyclic carbene stabilized mixed amido-hydride zinc complexes using two alternative hydride sources, namely dimethylamine borane (DMAB) and phenylsilane PhSiH3. Hydride-rich zinc cluster Zn4(HMDS)2H6·2IPr (1) (IPr = 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidene), which can be envisaged as a co-complex of IPr·ZnH2 and (HMDS)ZnH, is obtained when DMAB is employed, with the concomitant formation of heteroleptic bis(amido)borane [HB(NMe2)(HMDS)] and H2 evolution. NMR studies in d8-THF show that although the bulky carbene IPr does not bind to the zinc bis(amide), its presence in the reaction media is required in order to stabilise 1. Reactions using the slightly less sterically demanding NHC IXy (IXy = 1,3-bis-(2,6-dimethylphenyl)imidazol-2-ylidene) led to the isolation and structural elucidation of the carbene adduct Zn(HMDS)2·IXy (2). Contrastingly, mixtures of equimolar amounts of PhSiH3 and the zinc bis(amide) (60 °C, 3 h, hexane) afforded monomeric heteroleptic hydride (HMDS)ZnH·IPr (3). NMR studies, including DOSY experiments, revealed that while the integrity of 3 is retained in polar d8-THF solutions, in lower polarity C6D6 it displays a much more complex solution behaviour, being in equilibrium with the homoleptic species ZnH2·IPr, Zn(HMDS)2 and IPr.
Co-reporter:Sharon E. Baillie, Victoria L. Blair, Tyne D. Bradley, William Clegg, Jemma Cowan, Ross W. Harrington, Alberto Hernán-Gómez, Alan R. Kennedy, Zoe Livingstone and Eva Hevia
Chemical Science (2010-Present) 2013 - vol. 4(Issue 4) pp:NaN1905-1905
Publication Date(Web):2013/02/14
DOI:10.1039/C3SC22326D
Opening-up new synthetic applications of β-diketiminate stabilised magnesium complexes, this case study compares the ability of the alkyl [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(THF)] (1) and the amido reagent [{Ar*NC(Me)CHC(Me)NAr*}Mg(TMP)] (2) (Ar* = 2,6-i-Pr2-C6H3) to promote direct Mg–H exchange towards the series of 1,3-benzoazoles: benzoxazole (boz), benzothiazole (btz) and N-methyl benzimidazole (bImMe). Both reagents deprotonate boz at room temperature to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{O(o-C6H4)NC}(THF)] (3) via the C–O bond cleavage of a putative C2-magnesiated-benzoxazolyl intermediate. Structurally tracking the reactivity of 1 and 2 towards less acidic btz and bImMe showed that the behaviour of reagents 1 and 2 diverged dramatically. Kinetically activated TMP-reagent 2 effectively promotes the deprotonative magnesiation of btz and bImMe under mild reaction conditions, giving the alpha-metallated intermediates [{Ar*NC(Me)CHC(Me)NAr*}2Mg2{btz*}2] (4) and [{Ar*NC(Me)CHC(Me)NAr*}2Mg2{bImMe*}2] (7) (btz* = 2-benzothiazolyl; bImMe* = 2-N-methylbenzimidazolyl). Analysis of crystallographic and NMR data revealed that in 4 and 7 the metallated carbon atoms display a markedly carbenic character and that in solution these species exist at room temperature solely as the ring-closed products, without any observable equilibration to the acyclic isomers. Contrastingly, alkyl reagent 1 decreases the magnesiation rate of btz facilitating an intriguing new cascade activation process of two molecules of substrate involving a sequence of deprotonation/coordination/C–C coupling and ring-opening reactions to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{(btz*)C(H)N(o-C6H4)S}] (5). Hydrolysis of 5 followed by addition of the radical oxidant TEMPO ultimately produces the homocoupled product bis(benzothiazole) 6 in a 72% isolated yield. Thus, this establishes a novel transition-metal-free method to prepare homocoupled thiazoles. More straightforwardly, the coordination product [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(bImMe)] (8) was obtained when equimolar amounts of bImMe and 1 were reacted, illustrating the kinetic stubbornness of the Mg–C bond in butyl derivative 1. Complex 8 can be envisaged as a valuable guide to the constitution of a premetallation complex (in relation to the complex-induced proximity effect, CIPE).
Co-reporter:Tobias D. Bluemke, William Clegg, Pablo García-Alvarez, Alan R. Kennedy, Konrad Koszinowski, Matthew D. McCall, Luca Russo and Eva Hevia
Chemical Science (2010-Present) 2014 - vol. 5(Issue 9) pp:NaN3562-3562
Publication Date(Web):2014/06/16
DOI:10.1039/C4SC01263A
Expanding the synthetic potential of Mg–Zn hybrid organyl reagents (generated via transmetallation reactions), this study uncovers a versatile approach, involving a sequence of direct Zn–I exchange and Pd catalysed cross-coupling reactions which grants access to a wide range of asymmetric bis(aryls). By combining X-ray crystallography with ESI-MS and non-deuterium NMR spectroscopic studies, new light is shed on the heterobimetallic constitution of the intriguing organometallic species [(THF)4MgCl2Zn(tBu)Cl] (1) and [{Mg2Cl3(THF)6}+{ZntBu3}−] (2), formed through transmetallation of tBuMgCl with n equivalent amounts of ZnCl2 (n = 1 and 3 respectively). Operating by cooperative effects, alkyl-rich hybrid 2 can effectively promote direct Zn–I exchange reactions with aromatic halides in short periods of time at room temperature in THF solution. The structural elucidation of key organometallic intermediates involved in some of these Zn–I exchanges, provides new reactivity insights into how these bimetallic systems operate. Thus, while the reaction of 2 with 3 equivalents of 2-iodoanisole (3b) gives magnesium dizincate [{Mg(THF)6}2+{Zn(o-C6H4-OMe)3}2−] (4) which demonstrates the 3-fold activation of the tBu groups attached to Zn in 2, using 2-iodobenzonitrile (3i), only two tBu groups react with the substrate, affording [(THF)4MgCl(NC-o-C6H4)ZnI(o-C6H4-CN)(THF)] (7). In 7 Mg and Zn are connected by an aryl bridge, suggesting that the formation of contacted ion-pair hybrids may have a deactivating effect on the outcome of the Zn–I exchange process. A wide range of homoleptic tris(aryl) zincate intermediates have been prepared in situ and used as precursors in Pd catalysed cross-coupling reactions, affording bis(aryls) 6a–s in excellent yields under mild reaction conditions without the need of any additive or polar cosolvent such as NMP or DMI.
Co-reporter:Eva Hevia, Alan R. Kennedy, Jan Klett, Zoe Livingstone and Matthew D. McCall
Dalton Transactions 2010 - vol. 39(Issue 2) pp:NaN526-526
Publication Date(Web):2009/09/10
DOI:10.1039/B911818G
A systematic study of the stoichiometric alkylation reactions of 2,2,2-trifluoroacetophenone 1 with [ZnR2(TMEDA)] (R= Me, Et, tBu, CH2SiMe3; TMEDA= N,N,N′,N′-tetramethylethylenediamine) monitored by 1H and 19F NMR spectroscopy is presented. For R = Me, Et the alkylation products alkyl(alkoxides) [(TMEDA)Zn(R){OC(CF3)(R)Ph}] (R = Me, 2: Et, 3) are obtained as the single products of the reaction. When the steric bulk of the dialkylzinc reagent is increased the alkylation reaction is inhibited. Thus, for R = tBu, the reduction product [(TMEDA)Zn(tBu){OC(CF3)(H)Ph}] is obtained as a result of β-hydride elimination from one of the tBu groups of the organometallic reagent. 1H NMR spectroscopic monitoring of the reaction allowed the detection of isobutene as a side product of this reduction process. For the highly sterically demanding group R = CH2SiMe3 which lacks hydrogen atoms at the β position, no reaction is observed even under refluxing conditions. Two important intermediates from these reactions have been structurally elucidated: [(TMEDA)Zn(Me){OC(CF3)(Me)Ph}] (2) which could be involved in the previously reported alkylation reaction of trifluoromethyl ketones by ZnR2 catalysed by TMEDA and unprecedented tetranuclear [(tBu)2Zn4{OC(CF3)(H)Ph}6] (5) resulting from the reduction of 1 when reacted with tBu2Zn, which displays a rare Zn⋯Zn⋯Zn⋯Zn linear chain arrangement for a zinc alkyl(alkoxide).
Co-reporter:David R. Armstrong, Sharon E. Baillie, Victoria L. Blair, Nicolas G. Chabloz, Josefina Diez, Joaquin Garcia-Alvarez, Alan R. Kennedy, Stuart D. Robertson and Eva Hevia
Chemical Science (2010-Present) 2013 - vol. 4(Issue 11) pp:NaN4266-4266
Publication Date(Web):2013/08/14
DOI:10.1039/C3SC52101J
Merging two evolving areas in synthesis, namely cooperative bimetallics and N-heterocyclic carbenes (NHCs), this study reports the isolation of the first intermediates of alkali-metal-mediated zincation (AMMZn) of a free NHC and a Zn–NHC complex using sodium zincate [(TMEDA)NaZn(TMP)(tBu)2] (1) as a metallating reagent. The structural authentication of (THF)3Na[:C{[N(2,6-iPr2C6H3)]2CHCZn(tBu2)}] (2) and [Na(THF)6]+[tBu2Zn:C{[N(2,6-iPr2C6H3)]2CHCZn(tBu2)}]− (4), resulting from the reactions of 1 with unsaturated free NHC IPr (IPr = 1,3-bis(2,6-di-isopropylphenylimidazole-2-ylidene) and NHC complex ZntBu2IPr (3) respectively demonstrates that in both cases, this mixed-metal approach can easily facilitate the selective C4 zincation of the unsaturated backbone of the NHC ligand. Furthermore, the generation of anionic NHC fragments enables dual coordination through their normal (C2) and abnormal (C4) positions to the bimetallic system, stabilising the kinetic AMMZn intermediates which normally go undetected and provides new mechanistic insights in to how these mixed-metal reagents operate. In stark contrast to this bimetallic approach when NHC-complex 3 is reacted with a more conventional single-metal base such as tBuLi, the deprotonation of the coordinated carbene is inhibited, favouring instead, co-complexation to give NHC-stabilised [IPr·LiZntBu3] (5). Showing the potential of 2 to act as a transfer agent of its anionic NHC unit to transition metal complexes, this intermediate reacts with two molar equivalents of [ClAu(PPh3)] to afford the novel digold species [ClAu:C{[N(2,6-iPr2C6H3)]2CHCAu(PPh3)}] (6) resulting from an unprecedented double transmetallation reaction which involves the simultaneous exchange of both cationic (Na+) and neutral (ZntBu2) entities on the NHC framework.
Co-reporter:David R. Armstrong, William Clegg, Sophie H. Dale, Joaquín García-Álvarez, Ross W. Harrington, Eva Hevia, Gordon W. Honeyman, Alan R. Kennedy, Robert E. Mulvey and Charles T. O'Hara
Chemical Communications 2008(Issue 2) pp:NaN189-189
Publication Date(Web):2007/11/13
DOI:10.1039/B713987J
In a new type of reactivity for sodium TMP-zincate [(TMEDA)NaZn(tBu)2(TMP)] (1), transamination reactions with the amines diisopropylamine, DA(H), hexamethyldisilazane, HMDS(H) and chiral (R)-N-benzyl-α-methylbenzylamine have produced new sodium amido-di-tert-butyl zincates (all structurally characterised) with concomitant loss of TMP(H).
Co-reporter:Eva Hevia, Alan R. Kennedy, Jan Klett and Matthew D. McCall
Chemical Communications 2009(Issue 22) pp:NaN3242-3242
Publication Date(Web):2009/04/20
DOI:10.1039/B903592C
A new application of zincate [(THF)Li(TMP)(tBu)Zn(tBu)] (1) in alkali-metal mediated zincation (AMMZn) is reported by isolating and structurally defining the first intermediates of direct lateral zincation (DlZn) of trimethyl(phenoxy)silane (2) both of which adopt novel six-element {ZnCSiOLiN} ring structures.
Co-reporter:Laia Davin, Ross McLellan, Alberto Hernán-Gómez, William Clegg, Alan R. Kennedy, Maria Mertens, Iain A. Stepek and Eva Hevia
Chemical Communications 2017 - vol. 53(Issue 26) pp:NaN3656-3656
Publication Date(Web):2017/01/09
DOI:10.1039/C6CC09675A
Using a specially designed magnesium metallating manifold, combining kinetically activated TMP amide base with a sterically amplified β-diketiminate ligand, this study has established a new regioselective strategy for magnesiation of challenging N-heterocyclic molecules. The broad scope of the approach is illustrated through reactions of pyrazine, triazoles and substituted pyridines by isolation and structural elucidation of their magnesiated intermediates.
Co-reporter:Sharon E. Baillie, Tobias D. Bluemke, William Clegg, Alan R. Kennedy, Jan Klett, Luca Russo, Marco de Tullio and Eva Hevia
Chemical Communications 2014 - vol. 50(Issue 85) pp:NaN12862-12862
Publication Date(Web):2014/09/03
DOI:10.1039/C4CC05305B
Using structurally well-defined dipotassium-tetra(alkyl)magnesiates, a new straightforward methodology to promote regioselective Mg–H exchange reactions of a wide range of aromatic and heteroaromatic substrates is disclosed. Contacted ion pair intermediates are likely to be involved, with K being the key to facilitate the magnesiation processes.
Co-reporter:Lewis C. H. Maddock, Ivana Borilovic, Jamie McIntyre, Alan R. Kennedy, Guillem Aromí and Eva Hevia
Dalton Transactions 2017 - vol. 46(Issue 20) pp:NaN6691-6691
Publication Date(Web):2017/04/26
DOI:10.1039/C7DT01319A
Using a transamination approach to access novel Fe(II) complexes, this study presents the synthesis, X-ray crystallographic and magnetic characterisation of a series of new iron complexes containing the multifunctional 2,2-dipyridylamide (DPA) ligand using iron bis(amide) [{Fe(HMDS)2}2] and sodium ferrate [{NaFe(HMDS)3}∞] (1) as precursors (HMDS = 1,1,1,3,3,3-hexamethyldisilazide). Reactions of DPA(H) with 1 show exceptionally good stoichiometric control, allowing access to heteroleptic [(THF)2·NaFe(DPA)(HMDS)2] (3) and homoleptic [{THF·NaFe(DPA)3}∞] (4) by using 1 and 3 equivalents of DPA(H), respectively. Linking this methodology and co-complexation, which is a more widely used approach to prepare heterobimetallic complexes, 3 can also be prepared by combining NaHMDS with heteroleptic [{Fe(DPA)(HMDS)}2] (2). In turn, 2 has been also synthesised and structurally defined by reacting [{Fe(HMDS)2}2] with two equivalents of DPA(H). Structural studies demonstrate the coordination flexibility of the N-bridged bis(heterocycle) ligand DPA, with 2 and 3 exhibiting discrete monomeric motifs, whereas 4 displays a much more intricate supramolecular structure, with one of its DPA ligands coordinating in an anti/anti fashion (as opposed to 2 and 3 where DPA shows a syn/syn conformation), which facilitates propagation of the structure via its central amido N. Magnetic studies confirmed the high-spin electron configuration of the iron(II) centres in all three compounds and revealed the existence of weak ferromagnetic interactions in dinuclear compound 2 (J = 1.01 cm−1).
Co-reporter:Zoe Livingstone, Alberto Hernán-Gómez, Sharon E. Baillie, David R. Armstrong, Luca M. Carrella, William Clegg, Ross W. Harrington, Alan R. Kennedy, Eva Rentschler and Eva Hevia
Dalton Transactions 2016 - vol. 45(Issue 14) pp:NaN6182-6182
Publication Date(Web):2015/11/20
DOI:10.1039/C5DT04044B
By exploring the reactivity of sodium butyl-magnesiate (1) supported by the bulky chelating silyl(bisamido) ligand {Ph2Si(NAr*)2}2− (Ar* = 2,6-iPr2-C6H3) towards Quinoxaline (Qx), the ability of this bimetallic system to effectively promote SET processes has been disclosed. Thus 1 executes the single-electron reduction of Qx affording complex (2) whose structure in the solid state contains two quinaxolyl radical anions Qx˙ stabilised within a dimeric magnesiate framework. Combining multinuclear NMR and EPR measurements with DFT calculations, new insights into the constitution of 2 in solution and its magnetic behaviour have been gained. Further evidence on the SET reactivity of 1 was found when it was reacted with nitroxyl radical TEMPO which furnished contacted ion pair sodium magnesiate [(Ph2Si(NAr*)2)Mg(TEMPO−)Na(THF)3] (4) where both metals are connected by an alkoxide bridge, resulting from reduction of TEMPO. The role that the different ligands present in 1 can play in these new SET reactions has also been assessed. Using an amination approach, the Bu group in 1 can be replaced by the more basic amide TMP allowing the isolation of (3) which was characterised by multinuclear NMR and X-ray crystallography. 1H NMR monitoring of the reaction of 3 with Qx showed its conversion to 2, leaving the hydrogen atoms of the heterocycle untouched. Contrastingly, using sodium homoalkyl magnesiate [NaMg(CH2SiMe3)3] (5) led to the chemoselective C2 alkylation of this heterocycle, suggesting that the presence of the steric stabiliser {Ph2Si(NAr*)2}2− on the mixed-metal reagent is required in order to facilitate the Qx reduction.
Co-reporter:David R. Armstrong, William Clegg, Alberto Hernán-Gómez, Alan R. Kennedy, Zoe Livingstone, Stuart D. Robertson, Luca Russo and Eva Hevia
Dalton Transactions 2014 - vol. 43(Issue 11) pp:NaN4369-4369
Publication Date(Web):2013/10/25
DOI:10.1039/C3DT52639A
Exploring the reactivity of sodium butylmagnesiate reagent [{Na(THF)6}+{(Ph2Si(NAr*)2)Mg(Bu)(THF)}−] (1) supported by the bulky chelating silyl(bisamido) ligand {Ph2Si(NAr*)2}2− (Ar* = 2,6-iPr2-C6H3) towards N-methylbenzimidazole (bImMe), pyrrole and 2,6-diisopropylaniline (NH2Ar*), this study provides new insights into the ability of this bimetallic base to facilitate direct Mg–H exchange reactions as well as to exhibit polybasicity. Thus 1 effectively promotes the deprotomagnesiation of bImMe under mild reaction conditions to give the α-metallated intermediate [{Na(THF)5}2+{(Ph2Si(NAr*)2)Mg(bImMe*)}2−] (2) (bImMe* = 2-N-methylbenzimidazolyl). Analysis of crystallographic and NMR data of 2 combined with DFT calculations show that the metallated C in the bImMe* ligands possesses a significant carbenic character. Contrasting with previous studies of benzothiazole (btz), 1 does not react with an excess of bImMe even under forcing refluxing conditions. Contrastingly, the amination reactions of equimolar amounts of 1 with pyrrole and 2,6-diisopropylaniline allowed the isolation of [{(Ph2Si(NAr*)(NHAr*))Mg(NC4H4)2(THF)Na(THF)2}] (3) and [{Na(THF)6}+{(Ph2Si(NAr*)(NHAr*))Mg(NHAr*)2(THF)}−] (4) respectively as crystalline solids. Highlighting the ability of 1 to act as a polybasic reagent, 3 and 4 are formed as the result of the deprotonation of two molecules of the relevant amine via its butyl group and one amido arm of the silyl(bisamido) ligand. Similarly, the reactions of 1 with 3 molar equivalents of the relevant amine yielded homoleptic tris(amido) compounds [(THF)2NaMg(NC4H4)3] (5) and [{Na(THF)6}+{Mg(NHAr*)3}−] (7), with the concomitant formation of bis(amine) Ph2Si(NHAr)2, as a result of the complete amination of 1 using its three basic sites. The structures in the solid state of 3 and 4 were elucidated by X-ray crystallography. Despite their similar constitution, these heteroleptic tris(amido)magnesiates adopt contrasting structures, with the former displaying a contacted ion-pair structure, where Na and Mg are connected by two bridging pyrrolyl anions, whereas the latter gives rise to a solvent-separated ion pair motif. To the best of our knowledge 3 represents the first crystallographically characterized magnesium compound containing an anionic non-substituted form of pyrrole. Noticeably, Mg interacts exclusively with the N atoms of the pyrrolyl ligands, forming strong σ-bonds, whereas Na prefers to engage with the π-systems of both NC4-rings.
![Pyridine, 3-[(tetrahydro-2H-pyran-2-yl)oxy]-](http://img.cochemist.com/ccimg/870200/870150-50-8.png)
![Pyridine, 3-[(tetrahydro-2H-pyran-2-yl)oxy]-](http://img.cochemist.com/ccimg/870200/870150-50-8_b.png)
![[1,1'-Biphenyl]-4-carboxylic acid, 3'-(trifluoromethyl)-, ethyl ester](http://img.cochemist.com/ccimg/199500/199465-48-0.png)
![[1,1'-Biphenyl]-4-carboxylic acid, 3'-(trifluoromethyl)-, ethyl ester](http://img.cochemist.com/ccimg/199500/199465-48-0_b.png)
![SILANEDIAMINE, N,N'-BIS[2,6-BIS(1-METHYLETHYL)PHENYL]-1,1-DIPHENYL-](http://img.cochemist.com/ccimg/587100/587023-11-8.png)
![SILANEDIAMINE, N,N'-BIS[2,6-BIS(1-METHYLETHYL)PHENYL]-1,1-DIPHENYL-](http://img.cochemist.com/ccimg/587100/587023-11-8_b.png)
![PYRIDINE, 4-IODO-3-[(TETRAHYDRO-2H-PYRAN-2-YL)OXY]-](http://img.cochemist.com/ccimg/915300/915298-29-2.png)
![PYRIDINE, 4-IODO-3-[(TETRAHYDRO-2H-PYRAN-2-YL)OXY]-](http://img.cochemist.com/ccimg/915300/915298-29-2_b.png)
![2'-chloro-[1,1'-biphenyl]-4-carbonitrile](http://img.cochemist.com/ccimg/5800/5728-38-1.png)
![2'-chloro-[1,1'-biphenyl]-4-carbonitrile](http://img.cochemist.com/ccimg/5800/5728-38-1_b.png)
![Ethyl 4'-cyano-[1,1'-biphenyl]-4-carboxylate](http://img.cochemist.com/ccimg/89500/89409-89-2.png)
![Ethyl 4'-cyano-[1,1'-biphenyl]-4-carboxylate](http://img.cochemist.com/ccimg/89500/89409-89-2_b.png)
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![Chromium,bis[(1,2,3,4,5,6-h)-methylbenzene]-](http://img.cochemist.com/ccimg/12100/12087-58-0_b.png)
![Potassium, [(trimethylsilyl)methyl]-](http://img.cochemist.com/ccimg/53200/53127-82-5.png)
![Potassium, [(trimethylsilyl)methyl]-](http://img.cochemist.com/ccimg/53200/53127-82-5_b.png)
![Magnesium, bis[(trimethylsilyl)methyl]-](http://img.cochemist.com/ccimg/51400/51329-17-0.png)
![Magnesium, bis[(trimethylsilyl)methyl]-](http://img.cochemist.com/ccimg/51400/51329-17-0_b.png)
![4'-Chloro-[1,1'-biphenyl]-4-carbonitrile](http://img.cochemist.com/ccimg/57800/57774-36-4.png)
![4'-Chloro-[1,1'-biphenyl]-4-carbonitrile](http://img.cochemist.com/ccimg/57800/57774-36-4_b.png)
![Benzo[b]thiophene,2-iodo-](http://img.cochemist.com/ccimg/36800/36748-89-7.png)
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