Asymmetric synthesis of α- and β-amino acids by diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl)imines

The diastereoselective addition of triorganozincates to (R)-N-(tert-butanesulfinyl)imines has been used as a key step to achieve the synthesis of highly enantiomerically enriched N-protected α- and β-amino acids. Desulfinylation of the addition products followed by benzoylation of the nitrogen atom of the obtained primary amines and oxidation of one of the substituents on the carbon atom connected to the nitrogen complete the sequence. Using the same configuration in the sulfinyl chiral auxiliary, α-amino acids with the (R) or the (S) configuration can be prepared by choosing the proper combination of imine and organozincate. α,α-Disubstituted α-amino esters with high enantiomeric purity can also be prepared when α-imino esters are the starting substrates.

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(R)-1-(4-Chlorophenyl)prop-2-en-1-amineC9H10ClNEe = 92%[α]D20=+6.0 (c 0.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-Methoxyphenyl)prop-2-en-1-amineC10H13NOEe = 88%[α]D20=-16.0 (c 0.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-5-Phenylpent-1-en-3-amineC11H15NEe = 60%[α]D20=+4.0 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Undec-1-en-3-amineC11H23NEe = 60%[α]D20=+9.2 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-1-(2-Furyl)-3-methylbutan-1-amineC9H15NOEe = 96%[α]D20=+46.0 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-(2-Furyl)hexan-1-amineC10H17NOEe = 92%[α]D20=+10.4 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-(2-Furyl)-2-phenylethanamineC12H13NOEe = 94%[α]D20=-10.5 (c 1, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-(2-Furyl)-2-methylpropan-1-amineC8H13NOEe = 95%[α]D20=+6.4 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-1-Phenylbut-3-en-1-amineC10H13NEe = 90%[α]D20=-25.3 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(4-Chlorophenyl)but-3-en-1-amineC10H12ClNEe = 92%[α]D20=-44.7 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(4-Methoxyphenyl)but-3-en-1-amineC11H15NOEe = 94%[α]D20=-37.5 (c 0.55, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-1-Phenylhex-5-en-3-amineC12H17NEe = 70%[α]D20=+6.9 (c 0.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Dodec-1-en-4-amineC12H25NEe = 72%[α]D20=-4.0 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-amino-2,3-diphenylpropanoateC17H19NO2Ee = 80%[α]D20=+7.6 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-amino-3-methyl-2-phenylbutanoateC13H19NO2Ee = 62%[α]D20=-12.1 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-N-[1-(4-Chlorophenyl)allyl]benzamideC16H15ClNOEe = 92%[α]D20=+36.0 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-N-[1-(4-Methoxyphenyl)allyl]benzamideC17H17NOEe = 88%[α]D20=+43.6 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-N-[1-(2-Phenylethyl)prop-2-enyl]benzamideC18H19NOEe = 60%[α]D20=+9.7 (c 0.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Octylprop-2-enyl)benzamideC18H27NOEe = 60%[α]D20=+11.0 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-N-[1-(2-Furyl)-3-methylbutyl]benzamideC16H19NO2Ee = 96%[α]D20=+68.0 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-N-[1-(2-Furyl)hexyl]benzamideC17H21NO2Ee = 92%[α]D20=+35.0 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-N-[1-(2-Furyl)-2-phenylethyl]benzamideC19H17NO2Ee = 94%[α]D20=+1.7 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-N-[1-(4-Chlorophenyl)but-3-enyl)benzamideC15H16ClNOEe = 92%[α]D20=-21.5 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[1-(4-Methoxyphenyl)but-3-enyl]benzamideC18H19NO2Ee = 94%[α]D20=-25.2 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-N-[1-(2-Phenylethyl)but-3-enyl]benzamideC19H21NOEe = 70%[α]D20=-4.5 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-N-(1-Octylbut-3-enyl)benzamideC19H29NOEe = 72%[α]D20=+11.5 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-benzamido-2-phenylbutanoateC19H21NO3Ee = 92%[α]D20=-4.2 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-benzamido-2,3-diphenylpropanoateC24H23NO3Ee = 80%[α]D20=+40.1 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-benzamido-3-methyl-2-phenylbutanoateC20H23NO3Ee = 62%[α]D20=-5.2 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-2-Benzamido-2-phenylacetic acidC15H13NO3Ee = 94%[α]D20=+58.0 (c 0.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Benzamido-2-(4-chlorophenyl)acetic acidC15H12ClNO3Ee = 92%[α]D20=+49.0 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Benzamido-2-(4-methoxyphenyl)acetic acidC16H15NO4Ee = 88%[α]D20=+31.0 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Benzamido-4-phenylbutanoic acidC17H17NO3Ee = 58%[α]D20=+7.2 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Benzamidodecanoic acidC17H25NO3Ee = 60%[α]D20=+6.1 (c 0.4, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-2-Benzamidobutanoic acidC11H13NO3Ee = 92%[α]D20=-14.0 (c 0.3, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-2-Benzamido-4-methylpentanoic acidC13H17NO3Ee = 96%[α]D20=-10.0 (c 0.3, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-2-Benzamidoheptanoic acidC14H19NO3Ee = 92%[α]D20=-5.0 (c 0.5, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-2-Benzamido-3-phenylpropanoic acidC16H15NO3Ee = 92%[α]D20=-17.5 (c 0.5, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-2-Benzamido-3-methylbutanoic acidC12H15NO3Ee = 92%[α]D20=-27.6 (c 0.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-3-Benzamido-3-phenylpropanoic acidC16H15NO3Ee = 88%[α]D20=+73.0 (c 1.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-Benzamido-3-(4-chlorophenyl)propanoic acidC16H14ClNO3Ee = 92%[α]D20=+4.0 (c 0.5, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-3-Benzamido-5-phenylpentanoic acidC18H19NO3Ee = 70%[α]D20=+10.8 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-3-Benzamidoundecanoic acidC18H27NO3Ee = 72%[α]D20=+7.5 (c 0.5, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-N-[1-(4-Methoxyphenyl)-2-formylethyl]benzamideC17H17NO3Ee = 92%[α]D20=+15.0 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)