Iron complexes bound by redox-active pyridine dialdimine (PDAI) ligands catalyze the cycloaddition of two terminal alkynes and one cyanamide. The reaction is both chemo- and regioselective, as only 4,6-disubstituted 2-aminopyridine products are formed in moderate to high yields. Isolation of an iron azametallacycle (4) suggests that catalyst deactivation occurs with a large excess of cyanamide over longer reaction times. Fe-catalyzed cycloaddition allowed for a straightforward synthesis of a variety of aminopyridines, including known estrogen receptor ligands.

A family of 2D coordination polymers were successfully synthesized through “bottom-up” techniques using Ni2+, Cu2+, Co2+, and hexaaminobenzene. Liquid–liquid and air–liquid interfacial reactions were used to realize thick (∼1–2 μm) and thin (<10 nm) stacked layers of nanosheet, respectively. Atomic-force microscopy and scanning electron microscopy both revealed the smooth and flat nature of the nanosheets. Selected area diffraction was used to elucidate the hexagonal crystal structure of the framework. Electronic devices were fabricated on thin samples of the Ni analogue and they were found to be mildly conducting and also showed back gate dependent conductance.

A series of (dppf)Ni(ketene) complexes were synthesized and fully characterized. In the solid state, the complexes possess η2-(C,O) coordination of the ketene in an overall planar configuration. They display similar structure in solution, except in some cases, the η2-(C,C) coordination mode is also detected. A combination of kinetic analysis and DFT calculations reveals the complexes undergo thermal decomposition by isomerization from η2-(C,O) to η2-(C,C) followed by scission of the C═C bond, which is usually rate limiting and results in an intermediate carbonyl carbene complex. Subsequent rearrangement of the carbene ligand is rate limiting for electron poor and sterically large ketenes, and results in a carbonyl alkene complex. The alkene readily dissociates, affording alkenes and (dppf)Ni(CO)2. Computational modeling of the decarbonylation pathway with partial phosphine dissociation reveals the barrier is reduced significantly, explaining the instability of ketene complexes with monodentate phosphines.

Transition-metal catalysis has revolutionized the field of organic synthesis by facilitating the construction of complex organic molecules in a highly efficient manner. Although these catalysts are typically based on precious metals, researchers have made great strides in discovering new base metal catalysts over the past decade.This Account describes our efforts in this area and details the development of versatile Ni complexes that catalyze a variety of cycloaddition reactions to afford interesting carbocycles and heterocycles. First, we describe our early work in investigating the efficacy of N-heterocyclic carbene (NHC) ligands in Ni-catalyzed cycloaddition reactions with carbon dioxide and isocyanate. The use of sterically hindered, electron donating NHC ligands in these reactions significantly improved the substrate scope as well as reaction conditions in the syntheses of a variety of pyrones and pyridones. The high reactivity and versatility of these unique Ni(NHC) catalytic systems allowed us to develop unprecedented Ni-catalyzed cycloadditions that were unexplored due to the inefficacy of early Ni catalysts to promote hetero-oxidative coupling steps. We describe the development and mechanistic analysis of Ni/NHC catalysts that couple diynes and nitriles to form pyridines. Kinetic studies and stoichiometric reactions confirmed a hetero-oxidative coupling pathway associated with this Ni-catalyzed cycloaddition. We then describe a series of new substrates for Ni-catalyzed cycloaddition reactions such as vinylcyclopropanes, aldehydes, ketones, tropones, 3-azetidinones, and 3-oxetanones. In reactions with vinycyclopropanes and tropones, DFT calculations reveal noteworthy mechanistic steps such as a C–C σ-bond activation and an 8π-insertion of vinylcyclopropane and tropone, respectively. Similarly, the cycloaddition of 3-azetidinones and 3-oxetanones also requires Ni-catalyzed C–C σ-bond activation to form N- and O-containing heterocycles.

An efficient and convenient procedure that generates the active Ni(0) catalyst in situ from cheap, air stable Ni(II) precursors is developed for the [4 + 2]-cycloaddition of alkynes and 3-azetidinones. The reaction affords useful 3-dehydropiperidinones in comparable yields to the reported Ni(0) procedure. Additionally, the cycloaddition with 3-oxetanone afforded the 3-dehydropyranone product. Chiral 2-substituted azetidinones were also tolerated to form substituted dehydropiperidinones in high yield and enantiomeric excess.

A Ni/N-heterocyclic carbene catalyst couples diynes to the C(α)–C(β) double bond of tropone, a type of reaction that is unprecedented for metal-catalyzed cycloadditions with aromatic tropone. Many different diynes were efficiently coupled to afford [5–6–7] fused tricyclic products, while [5–7–6] fused tricyclic compounds were obtained as minor byproducts in a few cases. The reaction has broad substrate scope and tolerates a wide range of functional groups, and excellent regioselectivity is found with unsymmetrical diynes. Theoretical calculations show that the apparent enone cycloaddition occurs through a distinctive 8π insertion of tropone. The initial intramolecular oxidative cyclization of diyne produces the nickelacyclopentadiene intermediate. This intermediate undergoes an 8π insertion of tropone, and subsequent reductive elimination generates the [5–6–7] fused tricyclic product. This initial product undergoes two competing isomerizations, leading to the observed [5–6–7] and [5–7–6] fused tricyclic products.

A general synthetic route to the first Xantphos nickel alkyne and alkene complexes has been discovered. Various Ni π-complexes were prepared and characterized. NMR experiments indicate benzonitrile undergoes ligand exchange with a Xantphos ligand of (Xant)2Ni, a compound that was previously believed to be unreactive. The Ni π-complexes were also shown to be catalytically competent in cross coupling and cycloaddition reactions. (Xant)2Ni is also catalytically active for these reactions when activated by a nitrile or coordinating solvent.

Several cycloaddition catalysts and reagents were surveyed for their effectiveness toward cyclizing alkynenitriles with cyanamides. Catalytic amounts of FeI2, iPrPDAI and Zn were found to effectively catalyze the [2+2+2] cycloaddition of a variety of cyanamides and alkynenitriles to afford bicyclic 2-aminopyrimidines.

A detailed mechanistic evaluation of the Ni(IPr)2-catalyzed [2 + 2 + 2] cycloaddition of diynes and nitriles was conducted. Through kinetic analysis of these reactions, observed regioselectivities of the products, and stoichiometric reactions, Ni(IPr)2-catalyzed cycloadditions of diynes and nitriles appear to proceed by a heterooxidative coupling mechanism, in contrast to other common cycloaddition catalysts. Reaction profiles demonstrated strong dependence on nitrile, resulting in variable nitrile-dependent resting states. The strong coordination and considerable steric bulk of the carbene ligands facilitate selective initial binding of nitrile, thereby forcing a heterocoupling pathway. In situ IR data suggest that the initial binding of the nitrile resides in a rare, η1-bound conformation. Following nitrile coordination are a rate-determining hapticity shift of the nitrile and subsequent loss of carbene. Alkyne coordination then leads to heterooxidative coupling, insertion of the pendant alkyne, and reductive elimination to afford pyridine products.

The reaction of Ni(COD)2, IPr, and nitrile affords dimeric [Ni(IPr)RCN]2 in high yields. X-ray analysis revealed these species display simultaneous η1- and η2-nitrile binding modes. These dimers are catalytically competent in the formation of pyridines from the cycloaddition of diynes and nitriles. Kinetic analysis showed the reaction to be first order in [Ni(IPr)RCN]2, zeroth order in added IPr, zeroth order in nitrile, and zeroth order in diyne. Extensive stoichiometric competition studies were performed, and selective incorporation of the exogenous, not dimer bound, nitrile was observed. Post cycloaddition, the dimeric state was found to be largely preserved. Nitrile and ligand exchange experiments were performed and found to be inoperative in the catalytic cycle. These observations suggest a mechanism whereby the catalyst is activated by partial dimer-opening followed by binding of exogenous nitrile and subsequent oxidative heterocoupling.

A protocol for the Suzuki-Miyaura coupling of heteroaryl boronic acids and vinyl chlorides that minimizes protodeboronation is described. A combination of catalytic amounts of Pd(OAc)2 and SPhos in conjunction with CsF in isopropanol effectively affords a variety of coupled products. Surprisingly, a dramatic temperature dependence in product selectivity was observed.

The cross-coupling of alkyl cyanamides with a number of aryl, heteroaryl, and vinyl halide and pseudohalide coupling partners has been developed via a modification of Pd-catalyzed amidation methods. The reactions proceed selectively under mild conditions with reasonable reaction times in moderate to excellent yields.

An easy and expeditious route to substituted piperidines is described. A Ni-phosphine complex was used as catalyst for [4 + 2] cycloaddition of 3-azetidinone and alkynes. The reaction has broad substrate scope and affords piperidines in excellent yields and excellent regioselectivity. In the reaction of an enantiopure azetidinone, complete retention of stereochemistry was observed.

Diynes and cyanamides undergo an iron-catalyzed [2 + 2 + 2] cycloaddition to form highly substituted 2-aminopyridines in an atom-efficient manner that is both high yielding and regioselective. This system was also used to cyclize two terminal alkynes and a cyanamide to afford a 2,4,6-trisubstituted pyridine product regioselectively.

Ni–phosphine complexes were used as catalysts for the cycloaddition of various ketenes and diynes. In general, 2,4-cyclohexadienones were formed instead of products arising from decarbonylation of the ketenes.

The combination of Fe(OAc)2 and an electron-donating, sterically hindered pyridyl bisimine ligand catalyzes the cycloaddition of alkynenitriles and alkynes. A variety of substituted pyridines were obtained in good yields.

The new paramagnetic complexes NiI(IMes)2X (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) were prepared from the reaction of Ni(IMes)2 with aryl halides. Products that would arise from oxidative addition were not observed. In contrast, NiII(tmiy)2(X)(Ar) complexes were formed from the oxidative addition of aryl halides to Ni bound by a sterically less hindered NHC ligand, tmiy (tetramethylimidazol-2-ylidene). The paramagnetic NiI(IMes)2X complexes were compared to known Ni(0) and Ni(II) catalysts for Kumada and Suzuki coupling reactions. Stoichiometric reactions between the NiI(IMes)2X complexes with aryl halides and transmetalating agents were also evaluated.

A convenient method for preparing substituted anilines via a Rh-catalyzed [2 + 2 + 2] cycloaddition reaction of diynes and 2-oxazolone was discovered. The initial cycloaddition adducts undergo facile decarboxylation of carbon dioxide to afford aniline products. Reaction conditions are mild, and only 3 mol % Rh catalyst is required. High regioselectivity was observed when an unsymmetrical diyne was used as a starting material.

Combination of 1,3-bis(2,6-diisopropylphenyl)imidazolum-2-carboxylate (IPrCO2) with the Lewis acids MBPh4, where M = Li or Na, provided two separate complexes. The crystal structures of these complexes revealed that coordination to NaBPh4 yielded a dimeric species, yet coordination of IPrCO2 with LiBPh4 yielded a monomeric species. Combination of 1,3-bis(2,4,6-trimethylphenyl)imidazolum-2-carboxylate (IMesCO2) with LiBPh4 also afforded a dimeric species that was similar in global structure to that of the IPrCO2+NaBPh4 dimer. In all three cases, the cation of the organic salt was coordinated to the oxyanion of the zwitterionic carboxylate. Thermogravimetric analysis of the crystals demonstrated that decarboxylation occurred at lower temperatures than the decarboxylation temperature of the parent NHC·CO2 (NHC = N-heterocyclic carbene). Kinetic analysis of the transcarboxylation of IPrCO2 to acetophenone with NaBPh4 to yield sodium benzoylacetate was performed. First-order dependences were observed for IPrCO2 and acetophenone, whereas zero -order dependence was observed for NaBPh4. Direct dicarboxylation was observed when ItBuCO2 was added to MeCN in the absence of added MBPh4.

A mild and general route for preparing dienamides is described. Nickel imidazolylidene complexes were used to mediate cycloadditive coupling between enynes and isocyanates. Dienamides were prepared in excellent yields and with good E:Z selectivity. These dienamides can be further manipulated through oxidative cyclization methods. When a terminal enyne is employed, cyclization affords a lactam rather than a dienamide.

A series of 1,3-disubstituted-2-imidazolium carboxylates, an adduct of CO2 and N-heterocyclic carbenes, were synthesized and characterized using single crystal X-ray, thermogravimetric, IR, and NMR analysis. The TGA analysis of the NHC-CO2’s shows that as steric bulk on the N-substituent increases, the ability of the NHC-CO2 to decarboxylate increases. The comparison of NHC-CO2’s with and without methyls at the 4,5-position indicate that extra electron density in the imidazolium ring enhances the stability of an NHC-CO2 thereby making it less prone to decarboxylation. Single crystal X-ray analysis shows that the torsional angle of the carboxylate group and the C−CO2 bond length with respect to the imidazolium ring is dependent on the steric bulk of the N-substituent. Rotamers in the unit cell of a single crystal of ItBuPrCO2 (2f) indicate that the C−CO2 bond length increases as the N-substituents rotate toward the carboxylate moiety, which suggests that rotation of the N-substituents through the plane of the C−CO2 bond may be involved in the bond breaking event to release CO2.

The regioselectivity of Ni(0)-catalyzed cycloadditions of various isocyanates and asymmetrical alkynes to afford pyridones was explored. The use of PEt3 provided, in most cases, two of the four possible pyridone regioisomers in high overall yields. Mechanistic rationale for the product distribution is provided.The regioselectivity of Ni(0)-catalyzed cycloadditions of various isocyanates and asymmetrical alkynes to afford pyridones was explored. The use of PEt3 provided, in most cases, two of the four possible pyridone regioisomers in high overall yields. Mechanistic rationale for the product distribution is provided.

Spectroscopic analysis, thermogravimetric analysis, and crossover experiments performed on a series of imidazolium carboxylates revealed carboxylation was reversible with N-aryl substituted adducts.

A general synthetic route to the first Xantphos nickel alkyne and alkene complexes has been discovered. Various Ni π-complexes were prepared and characterized. NMR experiments indicate benzonitrile undergoes ligand exchange with a Xantphos ligand of (Xant)2Ni, a compound that was previously believed to be unreactive. The Ni π-complexes were also shown to be catalytically competent in cross coupling and cycloaddition reactions. (Xant)2Ni is also catalytically active for these reactions when activated by a nitrile or coordinating solvent.

Several cycloaddition catalysts and reagents were surveyed for their effectiveness toward cyclizing alkynenitriles with cyanamides. Catalytic amounts of FeI2, iPrPDAI and Zn were found to effectively catalyze the [2+2+2] cycloaddition of a variety of cyanamides and alkynenitriles to afford bicyclic 2-aminopyrimidines.

A protocol for the Suzuki-Miyaura coupling of heteroaryl boronic acids and vinyl chlorides that minimizes protodeboronation is described. A combination of catalytic amounts of Pd(OAc)2 and SPhos in conjunction with CsF in isopropanol effectively affords a variety of coupled products. Surprisingly, a dramatic temperature dependence in product selectivity was observed.