Novel cyclic β-aminophosphonate derivatives as efficient organocatalysts for the asymmetric Michael addition reactions of ketones to nitrostyrenes

Three novel catalysts based upon cyclic β-aminophosphonate derivatives 1–3 were designed to catalyze the asymmetric Michael addition reactions of ketones to β-nitrostyrenes. Among the catalysts that have been prepared in this study, cyclic β-aminophosphonic acid monoethylester 3 showed the highest catalytic ability, giving the corresponding Michael adduct in good yields, high enantioselectivities (up to 92% ee), and high diastereoselectivities (syn:anti up to 95:5).

The novel catalyst, cyclic β-aminophosphonic acid monoethyl ester, has been found to catalyze the asymmetric Michael addition reactions of ketones to β-nitrostyrenes in good yields, high enantioselectivities, and high diastereoselectivities.Figure optionsDownload as PowerPoint slide

(S)-Pyirolidm-2-ylmethylphosphomc acidC5H12NO3P[α]D25=+9.3 (c 1.00, H2O)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-Diethyl pyrrolidin-2-ylmethylphosphonateC9H20NO3P[α]D25=+16.7 (c 0.54, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-Pyrrolidin-2-ylmethylphosphonic acid monomethyl esterC7H16NO3P[α]D25=+13.4 (c 2.32, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-Benzyl 2-((diethoxyphosphoryl)methyl)pyrrolidine-1-carboxylateC17H26NO5P[α]D25=-27.6 (c 3.01, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-Benzyl 2-((ethoxy(hydroxy)phosphoryl)methyl)pyrrolidine-1-carboxylateC15H22NO5P[α]D25=-18.1 (c 0.96, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(R)-5-Nitro-4-phenylpentan-2-oneC11H13NO3Ee = 36%[α]D25=-6.8 (c 0.50, CHCl3)Source of chirality: asymmetric conjugate additionAbsolute configuration: (R)

(3R,4S)-3-Methyl-5-nitro-4-phenylpentan-2-oneC12H15NO3Dr (syn:anti) = 91:9Ee = 54% (syn)[α]D25=-2.1 (c 0.48, CHCl3)Source of chirality: asymmetric conjugate additionAbsolute configuration: (3R,4S)

(R)-6-Nitro-5-phenylhexan-3-oneC12H15NO3Ee = 80%[α]D25=+2.8 (c 0.46, CHCl3)Source of chirality: asymmetric conjugate additionAbsolute configuration: (5R)

(4S,5R)-4-Methyl-6-nitro-5-phenylhexan-3-oneC13H17NO3Dr (syn:anti) = 92:8Ee = 88% (syn)[α]D25=+8.6 (c 0.14, MeOH)Source of chirality: asymmetric conjugate additionAbsolute configuration: (4S,5R)

(S)-2-((R)-2-Nitro-1-phenylethyl)cyclohexanoneC14H17NO3Dr (syn:anti) = 95:5Ee = 92% (syn)[α]D25=-14.9 (c 0.18, CHCl3)Source of chirality: asymmetric conjugate additionAbsolute configuration: (2S,1′R) (syn)

(S)-2-((R)-1-(4-Methoxyphenyl)-2-nitroethyl)cyclohexanoneC15H19NO4Dr (syn:anti) = 81:19Ee = 79% (syn)[α]D25=-18.2 (c 1.53, MeOH)Source of chirality: asymmetric conjugate additionAbsolute configuration: (2S,1′R) (syn)

(S)-2-((R)-1-(4-Chlorophenyl)-2-nitroethyl)cyclohexanoneC14H16ClNO3Dr (syn:anti) = 77:23Ee = 82% (syn)[α]D25=-23.7 (c 1.00, CHCl3)Source of chirality: asymmetric conjugate additionAbsolute configuration: (2S,1′R) (syn)

(S)-2-((R)-1-(2-Chlorophenyl)-2-nitroethyl)cyclohexanoneC14H16ClNO3Dr (syn:anti) = 95:5Ee = 87% (syn)[α]D25=-43.7 (c 0.96, CHCl3)Source of chirality: asymmetric conjugate additionAbsolute configuration: (2S,1′R) (syn)