Asymmetric synthesis of 3,5-disubstituted indolizidines by intermolecular addition of an allylsilane on an N-acyliminium ion

A diastereoselective synthesis of 3,5-disubstituted indolizidines based on an intermolecular addition of an allylsilane on an acyliminium ion derived from (S)-pyroglutamic acid is described. The synthetic potential of this methodology is demonstrated by the enantioselective synthesis of (−)-indolizidine 195B, (−)-indolizidine 223AB, (+)-monomorine and (−)-3-butyl-5-propyl indolizidine.

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(3R,5R,8aR)-3-Butyl-5-methylindolizidineC13H25N[α]D25=-90.2 (c 0.75, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 3R,5R,8aR

(3R,5S,8aS)-3-Butyl-5-methylindolizidineC13H25N[α]D25=+17.6 (c 0.21, hexane)Source of chirality: asymmetric synthesisAbsolute configuration: 3R,5S,8aS

(3R,5R,8aR)-3-Butyl-5-propylindolizidineC15H29N[α]D25=-98 (c 2.1, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 3R,5R,8aR

(3R,5S,8aS)-3-Butyl-5-propylindolizidineC15H29NEe = 82%[α]D25=-87.5 (c 0.83, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 3R,5S,8aS