An efficient asymmetric desymmetrization of prochiral glutaric anhydrides with SuperQuat chiral oxazolidin-2-ones

The asymmetric desymmetrization of 3-substituted glutaric anhydrides 1 bearing silyl, aryl and alkyl groups with the lithium salt of chiral oxazolidin-2-ones has been studied. The effects of the substituents at the 4- and 5-positions of the oxazolidin-2-ones on the diastereoselectivity of the anhydride opening were studied in detail. A SuperQuat chiral oxazolidin-2-one 2e with 5,5-diaryl substituents showed optimum selectivity.

Figure optionsDownload as PowerPoint slide

(2S)-2-tert-Butyloxycarbonylamino-1,1-di(2-methoxy-5-methylphenyl)-3-methylbutanolC26H37NO5[α]D22=-143.6 (c 1, EtOH)Source of chirality: (S)-valineAbsolute configuration: (2S)

(4S)-5,5-Di(2-methoxy-5-methylphenyl)-4-isopropyloxazolidin-2-oneC22H27NO4[α]D24=-346.6 (c 0.5, CHCl3)Source of chirality: (S)-valineAbsolute configuration: (4S)

(3′R,4S)-5,5-Di(2-methoxy-5-methylphenyl)-3-{3-[dimethyl(phenyl)silyl]-4-methoxycarbonyl-1-oxobutyl}-4-isopropyloxazolidin-2-oneC36H45NO7SiDe = 90%[α]D23=-157 (c 1.68, MeOH)Source of chirality: asymmetric induction and (S)-valineAbsolute configuration: (3′R,4S)

(3′R,4S)-5,5-Di(2-methoxy-5-methylphenyl)-3-[3-(4-fluorophenyl)-4-methoxycarbonyl-1-oxobutyl]-4-isopropyloxazolidin-2-oneC34H38FNO7De = 90%[α]D23=-173.1 (c 0.84, MeOH)Source of chirality: asymmetric induction and (S)-valineAbsolute configuration: (3′R,4S)

(3′R,4S)-3-{4-tert-Butoxyoxycarbonyl-3-[dimethyl(phenyl)silyl]-1-oxobutyl}-5,5-di(2-methoxy-5-methylphenyl)-4-isopropyloxazolidin-2-oneC39H51NO7SiDe = >95%[α]D21=-165.9 (c 0.64, CHCl3)Source of chirality: asymmetric induction and (S)-valineAbsolute configuration: (3′R,4S)

(3′R,4S)-3-{4-tert-Butoxyoxycarbonyl-3-(4-fluorophenyl)-1-oxobutyl}-5,5-di(2-methoxy-5-methylphenyl)-4-isopropyloxazolidin-2-oneC37H44FNO7De = 90%[α]D23=-161.8 (c 0.9, EtOH)Source of chirality: asymmetric induction and (S)-valineAbsolute configuration: (3′R,4S)

(3R)-tert-Butyl methyl 3-(4-fluorophenyl)pentane-1,5-dioateC16H21FO4Ee = 90%[α]D24=-1.2 (c 1.17, MeOH)Source of chirality: asymmetric inductionAbsolute configuration: (3R)

(3′R,4S)-5,5-Di(2-methoxy-5-methylphenyl)-4-isopropyl-3-(4-methoxycarbonyl-1-oxobutyl-3-phenyl)oxazolidin-2-oneC34H39NO7De = 90%[α]D23=-172.8 (c 1, MeOH);Source of chirality: asymmetric induction and (S)-valineAbsolute configuration: (3′R,4S)

(3′R,4S)-5,5-Di(2-methoxy-5-methylphenyl)-3-(3-isopropyl-4-methoxycarbonyl-1-oxobutyl)-4-isopropyloxazolidin-2-oneC31H41NO7De = 80%[α]D24=-188.3 (c 0.44, EtOH)Source of chirality: asymmetric induction and (S)-valineAbsolute configuration: (3′R,4S)

(3′R,4S)-5,5-Di(2-methoxy-5-methylphenyl)-3-(4-methoxycarbonyl-3-methyl-1-oxobutyl)-4-isopropyloxazolidin-2-oneC29H37NO7De = 88%[α]D23=-198.55 (c 0.69, EtOH)Source of chirality: asymmetric induction and (S)-valineAbsolute configuration: (3′R,4S)