Structural probes used to help elucidate mechanistic information of the organocatalyzed asymmetric ketimine hydrosilylation have revealed a new catalyst with unprecedented catalytic activity, maintaining adequate performance at 0.01 mol% loading. A new ‘dual activation’ model has been proposed that relies on the presence of both a Lewis basic and Brønsted acidic site within the catalyst architecture.

An efficient synthesis of [3-13C]-2,3-dihydroxy-4-methoxybenzaldehyde, an isotopically labelled probe of a common intermediate used in the synthesis of a number of biologically relevant molecules, has been achieved in 9 steps from an acyclic, non-aromatic precursor. A 13C label for molecular imaging was introduced in a linear synthesis from the reaction of [13C]-labelled methyl iodide with glutaric monomethyl ester chloride. Cyclisation then aromatisation gave 1,3-dimethoxybenzene and an additional methoxy group was introduced by a formylation/Baeyer–Villiger/hydrolysis/methylation sequence. Subsequent ortho-formylation and selective demethylation yielded the desired [3-13C]-2,3-dihydroxy-4-methoxybenzaldehyde.

Twelve P-chiral phosphine oxides were screened for their ability to act as a chiral Lewis base catalyst for the asymmetric hydrosilylation of ketimines, providing chiral amines in good conversion and yield, but relatively poor enantioselectivity (ee <30%). Mechanistic studies paralleling work on chiral sulfinamides have shown a non-linear relationship of catalyst enantioselectivity and the chiral amine product.Figure optionsDownload full-size imageDownload as PowerPoint slide(SP)-(2-Isopropylphenyl)methylphenylphosphine oxideC16H19OP>99% ee[α]D25 = −34.0 (c 0.1, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (SP)(SP)-Methylphenyl(2,4,6-trimethoxyphenyl)phosphine oxideC16H19O4P>99% ee[α]D25 = −28.1 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (SP)(SP)-(2-Methyl-4-fluorophenyl)methylphenylphosphine oxideC14H14FOP>99% ee[α]D24 = −24.2 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (SP)(SP)-(−)-(4-Methoxyphenyl)methylphenylphosphine oxideC14H15O2P>99% ee[α]D25 = −8.1 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (SP)(SP)-(2-Methyl-4-methoxyphenyl)methylphenylphosphine oxideC15H17O2P>99% ee[α]D25 = −21.6 (c 0.95, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (SP)(Sp)-N-Benzyl-methylphenyl-phosphinic amideC14H16NOP98% ee[α]D25 = −6.1 (c 0.9, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (SP)(SP)-[2-(2-Benzyloxyphenyl)ethynyl]methylphenylphosphine oxideC22H19O2P53% ee[α]D24 = −1.6 (c 0.6, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (SP)

Several 9-(2-aminoethyl)anthracene derivatives were prepared with different nitrogen substitutents including alkyl, acetamide, trifluoroacaeamide and t-butyl carbamate. The selectivity in Diels–Alder cyclodaddition reaction with N-methyl maleimide was evaluated through single crystal X-ray analysis of the products. Models for the change in selectivity with hydrogen bond acceptor are proposed, supported by DFT level calculations.

Enantioselective reductive desymmetrization of glutarimides has been achieved employing an oxazaborolidine catalyst derived from cis-1-amino-indan-2-ol. The reaction was found to proceed through a stereoablative process that upgraded the enantioselectivity of an intermediate hydroxy-lactam. The reaction was generally tolerant of a number of substituents in the 4-position, giving enantiomeric excesses of greater than 82%.

A highly enantioselective (>95% ee) strategy to affect the desymmetrization of a maleimide has been performed by temporary attachment to an anthracene template followed by asymmetric reduction with an oxazaborolidine catalyst. A stereoablative over-reduction process was partially responsible for the high levels of enantioselectivity. Exemplification of the strategy by stereoselective functionalization and retro-Diels–Alder reaction provided the natural product pyrrolam A.

Attempts at performing dynamic kinetic resolution on a series of cyclic ketimines by making use of an asymmetric organocatalysed hydrosilylation gave modest conversion and moderate to good enantioselectivities. In the case of α-tetralone derivatives, the use of an N-benzyl protecting group was found to be crucial in obtaining enhanced levels of selectivity.N-[(1R,2S)-2-Methylcyclohexyl]-benzenemethanamineC14H21Nee = 77%[α]D25=-3.6 (c 1.1 EtOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,2S)(1R,2S)-1-Amino-2-methylcyclohexane hydrochlorideC7H16ClNee = 77%[α]D20=+3.6 (c 0.65, EtOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,2S)(1S,2S)-N-Benzyl-1-amino-2-methyl-1,2,3,4-tetrahydronaphthaleneC18H21Nee = 61%[α]D20=-17.0 (c 0.4, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S)(S)-N-Benzyl-1,2,3,4-tetrahydronaphthalen-1-amineC17H19Nee = 55%[α]D20=-6.0 (c 0.66, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

A range of known and novel N-phosphoryl oxazolidinones and imidazolidinones were prepared and screened in the kinetic resolution of a range of racemic magnesium chloroalkoxides. Models are proposed to account for the enantioselectivity achieved based on a combination of chiral relay effects, generation of transient stereochemistry and the structure of the intermediate magnesium alkoxide.Figure optionsDownload full-size imageDownload as PowerPoint slide(4S)-4-tert-Butyldimethylsilyloxymethyl-2-oxazolidinoneC22H29NO3Si[α]D22 = −324.0 (c 0.25, CHCl3)Source of chirality: l-SerineAbsolute configuration: (4S)(4S)-3-Diethyl phosphoryl 4-t-butyldimethylsilyloxymethyl-2-oxazolidinoneC26H38NO6PSi[α]D22 = −105.5 (c 0.55, CHCl3)Source of chirality: l-SerineAbsolute configuration: (4S)(1S,2S)-N-Benzyl-1-amino-2-methyl-1,2,3,4-tetrahydronaphthaleneC15H23N2O4P[α]D22 = −19.0 (c 1.0, CHCl3)Source of chirality: (4S,5S)-1,5-Dimethyl-4-phenyl-2-imidazolidinoneAbsolute configuration: (1S,2S)(4S,5R)-3-Diethyl phosphoryl 4-phenyl-5-methyl-2-oxazolidinoneC14H20NO5P[α]D22 = +62.1 (c 0.95, CHCl3)Source of chirality: (4S,5R)-4-Phenyl-5-methyl-2-oxazolidinoneAbsolute configuration: (4S,5R)(4S)-3-Diethyl phosphoryl 4-benzyl-5,5-dimethyl-2-oxazolidinoneC16H24NO5P[α]D22 = −20.0 (c 0.5, CHCl3)Source of chirality: l-PhenylalanineAbsolute configuration: (4S)(4S)-3-Diethyl phosphoryl 4-isopropyl-5,5-diphenyl-2-oxazolidinoneC22H28NO5P[α]D22 = −170.0 (c 0.5, CHCl3)Source of chirality: l-ValineAbsolute configuration: (4S)Diethyl 1-phenylethyl phosphateC12H19O4Pee = 15%[α]D22 = −7.9 (c 0.9, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)Diethyl (phenyl cyclohexylcarbinyl) phosphateC17H27O4Pee = 19%[α]D22 = −10.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisDiethyl 2-methyl-1-phenyl-1-propyl phosphateC14H23O4Pee = 20%[α]D22 = −6.6 (c 1.5, CHCl3)Source of chirality: Asymmetric synthesisDiethyl 3-methyl-1-phenyl-2-butyl phosphateC15H25O4Pee = 28%[α]D22 = −10.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisDiethyl 3-[5-phenyl-2-methylpentyl] phosphateC16H27O4Pee = 14%[α]D22 = −8.3 (c 1.2, CHCl3)Source of chirality: Asymmetric synthesis

Chiral amines are key components in numerous bioactive molecules. The development of efficient and economical ways to access molecules containing this functional group still remains a challenge at the forefront of synthetic chemistry. Of the methods that do exist, the trichlorosilane mediated organocatalytic reduction of ketimines offers significant potential as an alternative strategy. In this perspective, we wish to highlight the progress made in the past decade in this field and offer a direct quantitative comparison to transition-metal mediated process.

A highly efficient chiral auxiliary-based strategy for the asymmetric synthesis of P-chiral phosphine oxides in >98:2 er has been developed. The methodology involves the highly stereoselective formation of P-chiral oxazolidinones that then undergo displacement with a variety of Grignard reagents to prepare the desired phosphine oxides.

A highly active organocatalyst has been shown to affect the asymmetric reductive amination of ketones producing both aromatic and aliphatic amines. At 1 mol% catalyst loading, a series of structurally diverse chiral amines were quickly and economically prepared with good enantioselectivity and generally useful yield. The efficient synthesis of the calcimimetic (+)-NPS R-568 (67%, 89% ee) demonstrated the synthetic applicability of this methodology.

Highly stereoselective Friedel–Crafts reactions have been performed using a chiral anthracene template to control the selectivity of the reaction. In the case of additions to fully substituted N-acyliminium ions, competitive elimination and condensation reactions were observed. Retro-Diels–Alder reaction of one of the reaction products led to a precursor that could be used for the construction of pyroglutamic acids bearing quaternary stereogenic centres.

Excellent regio- and diastereoselectivity were achieved in the microwave assisted Diels–Alder reaction between (S)-9-(1-methoxyethyl) anthracene and 2-cyclopenten-1-one. The addition of Grignard reagents to the ketone cycloadduct gave poor levels of diastereoselectivity, however, the reduction was significantly more stereoselective. Flash vacuum pyrolysis of the reduced material furnished the corresponding allylic alcohol in good yield and ee.(12S,13S)-9,10,12,13,14,15-Hexahydro-9-[(1S)-1-methoxyethyl]-9,10[2′,3′]cyclopentanthracen-11-oneC22H22O2[α]D = −151 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (12S,13S)(1S)(12R,13R)-9,10,12,13,14,15-Hexahydro-9-[(1S)-1-methoxyethyl]-9,10[2′,3′]cyclopentanthracen-11-oneC22H22O2[α]D = −160 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (12R,13R)(1S)(12S,13R)-9,10,12,13,14,15-Hexahydro-9-[(1S)-1-methoxyethyl]-9,10[3′,2′]cyclopentanthracen-11-oneC22H22O2[α]D = +96 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (12S,13R)(1S)(11S,12R,13R)-9,10,12,13,14,15-Hexahydro-9-[(1S)-1-methoxyethyl]-11-hydroxy-9,10[2′,3′]cyclopentanthraceneC22H24O2[α]D = −11 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (11S,12R,13R) (1S)(−)-(S)-2-Cyclopenten-1-olC5H8O[α]D = −77 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

An approach for the asymmetric synthesis of pyroglutamic acid derivatives is described based on an anthracene chiral auxiliary. The introduction of a furan ring as a masked carboxylic acid moiety proceeded with excellent levels of diastereo-selectivity, followed by conversion into a carboxylate ester. The ensuing retro-Diels–Alder procedure using flash vacuum pyrolysis (FVP) followed by reduction gave pyroglutamate esters in good yield but poor enantioselectivity, the latter of which was found to be dependant on the electronic nature of the N-protecting group.(3aS,9aS)-3a,4,9,9a-Tetrahydro-4-[(1S)-1-methoxyethyl]-2-(N-4′-methoxyphenylmethyl)-4,9-[1′,2′]benzeno-1H-benzo[f]isoindole-1,3-(2H)-dioneC29H27NO4[α]D = −42 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR) (1R)(3aS,9aS)-3a,4,9,9a-Tetrahydro-4-[(1S)-1-methoxyethyl]-2-(N-phenylmethyl)-4,9-[1′,2′]benzeno-1H-benzo[f]isoindole-1,3-(2H)-dioneC28H25NO3[α]D = −36 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR) (1R)(3S,3aS,9aS)-9-[(1S)-1-Methoxyethyl]-2,3,3a,4,9,9a-hexahydro-3-hydroxy-2-methyl-4,9 [1′,2′]-benzeno-1H-benz[f]isoindol-1-oneC22H23NO3[α]D = −24 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,3aR,9aR) (1R)(3S,3aS,9aS)-9-[(1S)-1-Methoxyethyl]-2,3,3a,4,9,9a-hexahydro-3-hydroxy-2-[N-4′-methoxyphenyl]-4,9 [1′,2′]-benzeno-1H-benz[f]isoindol-1-oneC22H23NO3[α]D = −44 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,3aR,9aR) (1R)(3S,3aS,9aS)-9-[(1S)-1-Methoxyethyl]-2,3,3a,4,9,9a-hexahydro-3-hydroxy-2-[N-4′-methoxyphenylmethyl]-4,9 [1′,2′]-benzeno-1H-benz[f]isoindol-1-oneC29H29NO4[α]D = +8 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,3aR,9aR) (1R)(3S,3aS,9aS)-9-[(1S)-1-Methoxyethyl]-2,3,3a,4,9,9a-hexahydro-3-hydroxy-2-[N-phenylmethyl]-4,9 [1′,2′]-benzeno-1H-benz[f]isoindol-1-oneC28H27NO3[α]D = +9 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,3aR,9aR) (1R)(3aS,9aS,3S)-2,3,3a,4,9,9a-Hexahydro-4-[(1S)-1-methoxyethyl]-3-(2-furanyl)-2-methyl-4,9-[1′,2′]benzeno-1H-benz[f]isoindol-1-oneC26H25NO3[α]D = +59 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR,3R) (1R)(3aS,9aS,3S)-2,3,3a,4,9,9a-Hexahydro 4-[(1S)-1-methoxyethyl]-3-(2-furanyl)-2-(N-4′-methoxyphenyl)-4,9[1′,2′]benzeno-1H-benz[f]isoindol-1-oneC32H29NO4[α]D = +8 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR,3R) (1R)(3aS,9aS,3S)-2,3,3a,4,9,9a-Hexahydro 4-[(1S)-1-methoxyethyl]-3-(2-furanyl)-2-(N-4′-methoxyphenylmethyl)-4,9[1′,2′]benzeno-1H-benz[f]isoindol-1-oneC33H31NO4[α]D = +8 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR,3R) (1R)(3aS,9aS,3S)-2,3,3a,4,9,9a-Hexahydro-4-[(1S)-1-methoxyethyl]-2-(N-phenylmethyl)-3-(2-furanyl)-2-methyl-4,9[1′,2′]benzeno-1H-benz[f]isoindol-1-oneC32H29NO3[α]D = +21 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR,3R) (1R)(3aS,9aS,3S)-2,3,3a,4,9,9a-Hexahydro-4-[(1S)-1-methoxyethyl]-2-methyl-4,9-[1′,2′]benzeno-1H-benz[f]isoindol-1-one-3-carboxylic acid methyl esterC24H25NO4[α]D = +21 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR,3R) (1R)(3aS,9aS,3S)-2,3,3a,4,9,9a-Hexahydro-4-[(1S)-1-methoxyethyl]-2-(N-4′-methoxyphenyl)-4,9-[1′,2′]benzeno-1H-benz[f]isoindol-1-one-3-carboxylic acid methyl esterC30H29NO5[α]D = +13 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR,3R) (1R)(3aS,9aS,3S)-2,3,3a,4,9,9a-Hexahydro-4-[(1S)-1-methoxyethyl]-2-(N-4′-methoxyphenylmethyl)-4,9-[1′,2′]benzeno-1H-benz[f]isoindol-1-one-3-carboxylic acid methyl esterC31H31NO5[α]D = +10 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR,3R) (1R)(3aS,9aS,3S)-2,3,3a,4,9,9a-Hexahydro-4-[(1S)-1-methoxyethyl]-2-(N-phenylmethyl)-4,9-[1′,2′]benzeno-1H-benz[f]isoindol-1-one-3-carboxylic acid methyl esterC30H29NO4[α]D = +2 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,9aR,3R) (1R)(S)-1-(4-Methoxyphenyl)-5-oxo-proline methyl esterC13H15NO4Ee 23%[α]D = −6 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

A triflimide-activated oxazaborolidine catalyst successfully promoted the asymmetric Diels−Alder reaction of 9-methylanthracene with methacrolein in high regio- and enantioselectivity. The cycloadduct obtained was subsequently used as a chiral template to access secondary and tertiary allylic alcohols in good to high enantiomeric excess via a cycloreversion by flash vacuum pyrolysis.

Organocatalysts for the asymmetric reduction of ketimines are presented that function well at low catalyst loadings providing chiral amines in good yield and enantioselectivity, the latter appearing to be independent of the ketimine substrate geometry.

Kinetic resolution of racemic C-3 substituted pyrrolidine-2,5-diones has been achieved for the first time using highly efficient oxazaborolidine catalysts derived from cis-1-amino-indan-2-ol.

Two approaches to the synthesis of chiral 9-amino anthracenes are described. The first, by nucleophilic addition of organolithium reagents to imines promoted by BF3·OEt2, unexpectedly provided stable aminoboranes as products. The second approach, using palladium catalysed cross coupling, was more successful for primary amines, and the key 9-(α-methylbenzylamino)anthracene subjected to cycloadditions with N-methyl maleimide and maleic anhydride. Excellent reactivity was achieved with good levels of diastereoselectivity, through a favourable combination of electrostatic and hydrogen bonding effects. Trial studies of the retro Diels–Alder reaction of these cycloadducts were also performed.(R)-9-(N-α-Methylbenzylamino)anthraceneC22H19NEe = 93%[α]D = +198 (c 0.5, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)(R)-(+)-α-Methylbenzyl formamideC9H11NO[α]D = +168.6 (c 1, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)(R)-(+)-N-Methyl-α-methylbenzylamineC9H13N[α]D = +77.7 (c 1, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)9-[N-Methyl-N-(R)-α-methylbenzylamino]anthraceneC23H21N[α]D = +70 (c 1, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)(3aS,9aS)-3a,4,9,9a-Tetrahydro-4-[(R)-α-methylbenzylamino]-2-methyl-4,9-[1′,2′]benzeno-1H-benzo[f]isoindole-1,3-(2H)-dioneC27H24N2O2[α]D = +50 (c 0.5, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (3S,9S,αR)(11S,15S)-9,10,11,15-Tetrahydro-9-[(R)-α-methylbenzylamino]-9,10[3′,4′]-furanoanthracene-12,14-dioneC26H21NO3[α]D = +26 (c 1, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (3S,9S,αR)1-Methyl-(3R)-(10-oxo-9,10-dihydroanthracen-9-yl) pyrrolidine-2,5-dioneC19H15NO3[α]D = +125 (c 0.08, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)

Diels–Alder cycloadditions of p-benzoquinone with 9R-(1-methoxyethyl)anthracene provides a 60 : 40 ratio of cycloadducts when heated at reflux in xylene. Mechanistic studies to explore the origins of this selectivity have shown that at lower temperatures the kinetic product predominates, giving a 96 : 4 ratio of cycloadducts.

Chiral 9-oxazolidinyl anthracene derivatives have been prepared as single diastereoisomers by condensation of 9-anthraldehyde with the appropriate N-alkyl amino alcohol. Asymmetric Diels–Alder cycloadditions of these with N-methyl maleimide proceeds in good yield and in good diastereoselectivity, the sense of which may be controlled by judicious choice of the N-alkyl group.

A bifunctional catalyst containing a polyether backbone and a nucleophilic imidazole moiety has been prepared that demonstrates cooperative catalysis in the presence of added group 1 and 2 salts for the phosphorylation of alcohols.

A number of chiral N-phosphoryl oxazolidinones have been prepared and evaluated as asymmetric phosphoryl transfer agents with the magnesium alkoxide of 1-phenyl ethanol. The reaction proceeded with little stereoselection, which was shown to be a consequence of the reaction mechanism that occurs with inversion of configuration at phosphorus consistent with in-line attack opposite the leaving group.Figure optionsDownload full-size imageDownload as PowerPoint slide(1S)-Phenylethanol diethyl phosphateC12H19O4P[α]D = −20.2 (c 1, CHCl3)Source of chirality = asymmetric synthesis[(4R)-4-Benzyl-2-oxo-oxazolidin-3-yl]-phosphonic acid diphenyl esterC22H20NO5P[α]D = +58.1 (c 1, CHCl3)Source of chirality = (4R)-4-benzyl-oxazolidin-2-one[(4R)-4-Benzyl-2-oxo-oxazolidin-3-yl]-phosphonic acid diethyl esterC14H20NO5P[α]D = −33.7 (c 1, CHCl3)Source of chirality = (4R)-benzyl-oxazolidin-2-one[(4S)-4-Phenyl-2-oxo-oxazolidin-3-yl]-phosphonic acid diethyl esterC13H18NO5P[α]D = −45.3 (c 1, CHCl3)Source of chirality = (4S)-Phenyl-oxazolidin-2-one[(4R,5S)-Indano[1,2-d]-2-oxo-oxazolidin-3-yl]-phosphonic acid diethyl esterC14H18NO5P[α]D = −13.5 (c 1, CHCl3)Source of chirality = (4R,5S)-indano[1,2-d]oxazolidin-2-one[(4S)-4-Isopropyl-5,5-dimethyl-2-oxo-oxazolidin-3-yl]-phosphonic acid diethyl esterC12H24NO5P[α]D = −29.4 (c 1, CHCl3)Source of chirality = 5,5-dimethyl-4-isopropyl oxazolidin-2-one[(4S)-4-Benzyl-2-oxo-5,5-diphenyl-oxazolidin-3-yl]-phosphonic acid diethyl esterC26H28NO5P[α]D = −35.0(c 1, CHCl3)Source of chirality = 5,5-diphenyl-4-benzyl oxazolidin-2-one[(SP,4S)-4-Isopropyl-5,5-dimethyl-2-oxo-oxazolidin-3-yl]-phosphonic acid ethyl methyl esterC11H22NO5P[α]D = −7.0 (c 1, CHCl3)Source of chirality = 5,5-dimethyl-4-isopropyl oxazolidin-2-one[(RP,4S)-4-Isopropyl-5,5-dimethyl-2-oxo-oxazolidin-3-yl]-phosphonic acid ethyl methyl esterC11H22NO5P[α]D = −33.7 (c 1, CHCl3)Source of chirality = 5,5-dimethyl-4-isopropyl oxazolidin-2-one

Organocatalysts for the asymmetric reduction of ketimines are presented that function well at low catalyst loadings providing chiral amines in good yield and enantioselectivity, the latter appearing to be independent of the ketimine substrate geometry.

Structural probes used to help elucidate mechanistic information of the organocatalyzed asymmetric ketimine hydrosilylation have revealed a new catalyst with unprecedented catalytic activity, maintaining adequate performance at 0.01 mol% loading. A new ‘dual activation’ model has been proposed that relies on the presence of both a Lewis basic and Brønsted acidic site within the catalyst architecture.

Kinetic resolution of racemic C-3 substituted pyrrolidine-2,5-diones has been achieved for the first time using highly efficient oxazaborolidine catalysts derived from cis-1-amino-indan-2-ol.

Highly stereoselective Friedel–Crafts reactions have been performed using a chiral anthracene template to control the selectivity of the reaction. In the case of additions to fully substituted N-acyliminium ions, competitive elimination and condensation reactions were observed. Retro-Diels–Alder reaction of one of the reaction products led to a precursor that could be used for the construction of pyroglutamic acids bearing quaternary stereogenic centres.

Several 9-(2-aminoethyl)anthracene derivatives were prepared with different nitrogen substitutents including alkyl, acetamide, trifluoroacaeamide and t-butyl carbamate. The selectivity in Diels–Alder cyclodaddition reaction with N-methyl maleimide was evaluated through single crystal X-ray analysis of the products. Models for the change in selectivity with hydrogen bond acceptor are proposed, supported by DFT level calculations.

A highly active organocatalyst has been shown to affect the asymmetric reductive amination of ketones producing both aromatic and aliphatic amines. At 1 mol% catalyst loading, a series of structurally diverse chiral amines were quickly and economically prepared with good enantioselectivity and generally useful yield. The efficient synthesis of the calcimimetic (+)-NPS R-568 (67%, 89% ee) demonstrated the synthetic applicability of this methodology.

Chiral amines are key components in numerous bioactive molecules. The development of efficient and economical ways to access molecules containing this functional group still remains a challenge at the forefront of synthetic chemistry. Of the methods that do exist, the trichlorosilane mediated organocatalytic reduction of ketimines offers significant potential as an alternative strategy. In this perspective, we wish to highlight the progress made in the past decade in this field and offer a direct quantitative comparison to transition-metal mediated process.