tert-Butyl esters of peptides as organocatalysts for the asymmetric aldol reaction

Enantioselective aldol reactions between ketones and aldehydes were shown to be catalysed by a variety of tert-butyl esters of peptides. Amongst the peptides tested, Pro-Glu(OtBu)-OtBu proved to be the best, affording the product in good to excellent yields, diastereoselectivities and enantioselectivities.

Up to 100% yield, 98:2 dr, >99% ee.Figure optionsDownload as PowerPoint slide

(S)-tert-Butyl-2-[(S)-2-amino-3-phenylpropanamido]-3-phenylpropanoateC22H28N2O3[α]D25 = −9.8 (c 1.00, CH3OH)Source of chirality: the precursorAbsolute configuration: (S,S)

(S)-tert-Butyl-2-[(S)-2-amino-3-phenylpropanamido]-2-phenylacetateC21H26N2O3[α]D25 = +57.0 (c 0.33, CH3OH)Source of chirality: the precursorAbsolute configuration: (S,S)

(S)-Di-tert-butyl-2-[(S)-2-amino-3-phenylpropanamido]pentanedioateC22H34N2O5[α]D25 = −11.8 (c 0.33, CH3OH)Source of chirality: the precursorAbsolute configuration: (S,S)

(S)-tert-Butyl 2-amino-4-{[(S)-1-(tert-butoxy)-1-oxo-3-phenylpropan-2-yl]amino}-4-oxobutanoateC21H32N2O5[α]D25 = −1.2 (c 0.5, CH3OH)Source of chirality: the precursorAbsolute configuration: (S,S)

(S)-tert-Butyl 2-amino-4-{[2-(tert-butoxy)-2-oxoethyl]amino}-4-oxobutanoateC14H26N2O5[α]D25 = −0.95 (c 1.00, CH3OH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-tert-Butyl 2-amino-4-{[(S)-1-(tert-butoxy)-3-methyl-1oxobutan-2-yl]amino}-4-oxobutanoateC17H32N2O5[α]D25 = +2.8 (c 0.1, CHCl3)Source of chirality: the precursorAbsolute configuration: (S,S)

(2S,2′S)-Tetra-tert-butyl 2,2′-{[(S)-2-aminosuccinyl]bis(azanediyl)}disuccinateC28H49N3O10[α]D25 = −14.0 (c 1.0, CH3OH)Source of chirality: the precursorAbsolute configuration: (S,S,S)

(2S,2′S)-Tetra-tert-butyl 2,2′-{[(S)-2-aminosuccinyl]bis(azanediyl)}dipentanedioateC30H53N3O10[α]D25 = −16.0 (c 0.1, CH3OH)Source of chirality: the precursorAbsolute configuration: (2S,2′S), (S)

(S)-tert-Butyl 2-[(S)-pyrrolidine-2-carboxamido]propanoateC12H22N2O3[α]D25 = −38.8 (c 0.2, CHCl3)Source of chirality: the precursorAbsolute configuration: (S,S)

(S)-Di-tert-butyl 2-[(S)-pyrrolidine-2-carboxamido]pentanedioateC18H32N2O5[α]D25 = −25.8 (c 0.50, CHCl3)Source of chirality: the precursorAbsolute configuration: (S,S)

(S)-2-[(R)-Hydroxy-(4-nitrophenyl)methyl]-cyclohexanoneC13H15NO4[α]D25 = +6.9 (c 1.00, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(3-(nitrophenyl)methyl]-cyclohexanoneC13H15NO4[α]D25 = +26.7 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(2-nitrophenyl)methyl]-cyclohexanoneC13H15NO4[α]D25 = +29.9 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(4-trifluoromethylphenyl)methyl]-cyclohexanoneC14H15F3O2[α]D25 = +12.5 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(R)-3-[Hydroxy-(2-(S)-oxocyclohexyl)methyl]-benzonitrileC14H15NO2[α]D25 = +19.5 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (R,S)

(S)-2-[(R)-Hydroxy-(4-fluorophenyl)methyl]-cyclohexanoneC13H15FO2[α]D25 = +5.6 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(2-fluorophenyl)methyl]-cyclohexanoneC13H15FO2[α]D25 = +7.3 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(4-bromophenyl)methyl]-cyclohexanoneC13H15BrO2[α]D25 = +2.6 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(2-bromophenyl)methyl]-cyclohexanoneC13H15BrO2[α]D25 = +13.6 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(4-chlorophenyl)methyl]-cyclohexanoneC13H15ClO2[α]D25 = +15.3(c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(2-chlorophenyl)methyl]-cyclohexanoneC13H15ClO2[α]D25 = +20.1 (c 0.5, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(phenyl)methyl]-cyclohexanone hydropyrazoleC13H16O2[α]D25 = +6.4 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(pyridine-4-yl)methyl]-cyclohexanoneC12H15NO2[α]D25 = +18.9 (c 0.5, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-2-[(R)-Hydroxy-(thiophen-3-yl)methyl]-cyclohexanoneC11H14O2S[α]D25 = +10.6 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-3-[(R)-Hydroxy-(4-nitrophenyl)methyl]dihydro-2H-pyran-4(3H)-oneC12H13NO5[α]D25 = +9.0 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-3-[(R)-Hydroxy-(4-nitrophenyl)methyl]dihydro-2H-thiopyran-4(3H)-oneC12H13NO4S[α]D25 = +1.7 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(S)-7-[(R)-Hydroxy-(4-nitrophenyl)methyl]-1,4-dioxospiro[4.5]decan-8-oneC15H17NO6[α]D25 = +2.8 (c 0.5, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(2S,4R)-2-[(R)-Hydroxy-(4-nitrophenyl)methyl]-4-methylcyclohexanoneC14H17NO4[α]D25 = −11.4 (c 1.0, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (2S,4R), (R)

(S)-2-[(R)-Hydroxy-(4-nitrophenyl)methyl]-cyclopentanoneC12H13NO4[α]D25 = +91.2 (c 0.5, CH3OH)Source of chirality: asymmetric reactionAbsolute configuration: (S,R)

(R)-4-Hydroxy-4-(4-nitrophenyl)-butan-2-oneC10H11NO4[α]D25 = +37.2 (c 0.5, CHCl3)Source of chirality: asymmetric reactionAbsolute configuration: (R)