Enantioselective direct aldol reactions promoted by phosphine oxide aziridinyl phosphonate organocatalysts

A series of phosphine oxide based chiral Lewis bases were screened as organocatalysts for silicon tetrachloride mediated direct asymmetric aldol reactions between cyclohexanone and various aromatic aldehydes. One of the phosphine oxide-aziridinyl phosphonate POAP-A Lewis bases formed the aldol products in up to 75% yield and with 65% ee.

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Diethyl ((R)-1-((S)-1-hydroxy-3-phenylpropan-2-yl)aziridin-2-yl)phosphonateC15H24NO4P[α]D33 = +28.0 (c 5.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

Diethyl ((S)-1-((S)-1-hydroxy-3-phenylpropan-2-yl)aziridin-2-yl)phosphonateC15H24NO4P[α]D34 = −57.6 (c 3.4, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(S)-2-((R)-2-(Diethoxyphosphoryl)aziridin-1-yl)-3-phenylpropyl 4-methylbenzenesulfonateC22H30NO6PS[α]D34 = +25.7 (c 6.8, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

(S)-2-((S)-2-(Diethoxyphosphoryl)aziridin-1-yl)-3-phenylpropyl 4-methylbenzenesulfonateC22H30NO6PS[α]D34 = −7.6 (c 10.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

Diethyl ((R)-1-((S)-1-diphenylphosphoryl-3-phenylpropan-2-yl)aziridin-2-yl)phosphonateC27H33NO4P2[α]D34 = +16.6 (c 5.4, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

Diethyl ((S)-1-((S)-1-(diphenylphosphoryl)-3-phenylpropan-2-yl)aziridin-2-yl)phosphonateC27H33NO4P2[α]D35 = +6.0 (c 7.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)