Asymmetric Diels–Alder cycloadditions of d-erythrose 1,3-butadienes to achiral t-butyl 2H-azirine 3-carboxylate

Two d-erythrose 1,3-butadienes were reacted with electrophilic achiral t-butyl 2H-azirine 3-carboxylate giving cycloadducts with good yields and moderate selectivity. The isomers could be separated to give the major (R)-isomers at C-2 in approximately 50% yield in both cases. Alternatively LACASA-DA methodology was applied to one of the reactions leading to homochiral (R)- and (S)-products by changing the chiral nature of an extra chiral BINOL inductor used.

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(2R,6S)-tert-Butyl 2-((2R,4S,5R)-5-hydroxy-2-phenyl-1,3-dioxan-4-yl)-1-azabicyclo[4.1.0]hept-3-ene-6-carboxylateC21H27NO5[α]D20=-14.9 (c 1.5, CH2Cl2)Source of chirality: d-erythrose, (RS)-BINOLAbsolute configuration: (2R,6S) (2R,4S,5R)

(2S,6R)-tert-Butyl 2-((2R,4S,5R)-5-hydroxy-2-phenyl-1,3-dioxan-4-yl)-1-azabicyclo[4.1.0]hept-3-ene-6-carboxylateC21H27NO5[α]D20=-11.2 (c 1.05, CHCl3)Source of chirality: d-erythrose, (RS)-BINOLAbsolute configuration: (2S,6R) (2R,4S,5R)

(2R,6S)-tert-Butyl 4-((tert-butyldimethylsilyl)oxy)-2-((2R,4S,5R)-5-hydroxy-2-phenyl-1,3-dioxan-4-yl)-1-azabicyclo[4.1.0]hept-3-ene-6-carboxylateC27H41NO6Si[α]D20=-40.5 (c 1.05, CHCl3)Source of chirality: d-erythrose, (RS)-BINOLAbsolute configuration: (2R,6S) (2R,4S,5R)

(2S,6R)-tert-Butyl 4-((tert-butyldimethylsilyl)oxy)-2-((2R,4S,5R)-5-hydroxy-2-phenyl-1,3-dioxan-4-yl)-1-azabicyclo[4.1.0]hept-3-ene-6-carboxylateC27H41NO6Si[α]D20=-4.0 (c 1.8, CHCl3)Source of chirality: d-erythrose, (RS)-BINOLAbsolute configuration: (2S,6R) (2R,4S,5R)