Synthesis of highly enantiomerically enriched amines by the diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl)imines

The reaction of triorganozincates with (R)-N-(tert-butanesulfinyl) imines gives the expected α-branched sulfinamides in good to excellent yields with diastereomeric ratios of up to 98:2. The N-sulfinyl group of the products can be easily removed by acidic treatment, affording the corresponding chiral primary amines in enantiomeric excesses of up to 96%. The reactivity and the selectivity shown by the triorganozincates are different from the ones observed with the corresponding Grignard reagents, which allows, in several cases, the preparation of both enantiomers of an amine from the same imine substrate. When mixed triorganozincates are used, one can take advantage of the slow transfer rate of the methyl group to use it as a non-transferable one. Both aromatic and aliphatic aldimines, as well as activated ketimines, are good substrates for these addition reactions.

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(R)-2-Methyl-N-nonylidenepropane-2-sulfinamideC13H27NOS[α]D20=-207.0 (c 0.4, CHCl3)Source of chirality: (R)-tert-butanesulfinamideAbsolute configuration: (R)

(R)-Methyl 5-[(tert-butylsulfinyl)imino]pentanoateC10H19NO3S[α]D20=-206.4 (c 1.7, CHCl3)Source of chirality: (R)-tert-butanesulfinamideAbsolute configuration: (R)

(R)-Ethyl [(tert-butylsulfinyl)imino](phenyl)acetateC14H19NO3S[α]D20=-95.8 (c 0.9, CHCl3)Source of chirality: (R)-tert-butanesulfinamideAbsolute configuration: (R)

(R)-Isopropyl [(tert-butylsulfinyl)imino](phenyl)acetateC15H21NO3S[α]D20=-115.0 (c 1.0, CHCl3)Source of chirality: (R)-tert-butanesulfinamideAbsolute configuration: (R)

(R)-2-Methyl-1-phenylpropan-1-amineC10H15NEe = 88%[α]D20=+6.4 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Cyclohexyl(phenyl)methanamineC13H19NEe = 86%[α]D20=+9.3 (c 1.0, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-Chlorophenyl)propan-1-amineC9H12NClEe = 96%[α]D20=+15.0 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-Methoxyphenyl)propan-1-amineC10H15NOEe = 92%[α]D20=+15.0 (c 1.0, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Undecan-3-amineC11H25NEe = 40%[α]D20=-2.3 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-1-Phenylpentan-3-amineC11H17NEe = 42%[α]D20=+7.5 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-6-Ethylpiperidin-2-oneC7H13NOEe = 62%[α]D20=-3.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-amino-2-phenylbutanoateC12H17NO2Ee = 82%[α]D20=-11.6 (c 1.0, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Isopropyl 2-amino-2-phenylbutanoateC13H19NO2Ee = 58%[α]D20=-56.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)