Stereoselective synthesis of 2-azetidinylglycine and aminopyrrolidone derivatives from Garner’s aldehyde

A new route to two hitherto unknown 2-azetidinylglycine derivatives and an aminopyrrolidone derivative has been developed which featured a diastereoselective conjugate addition of benzyl amine to an α,β-unsaturated ester derived from Garner’s aldehyde as the key step.

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(R)-tert-Butyl 4-((S)-1-(benzylamino)-3-hydroxypropyl)-2,2-dimethyloxazolidine-3-carboxylateC20H32N2O4[α]D = −24 (c 0.7, CHCl3).Source of chirality: L-SerineAbsolute configuration : (4R,1′S)

(R)-Benzyl 2-(tert-butoxycarbonyl)-2-((S)-1-tosylazetidin-2-yl)acetateC24H30N2O6S[α]D = +9 (c 1.51, MeOH)Source of chirality: L-SerineAbsolute configuration : (2R,2′S)

(R)-Benzyl 2-(tert-butoxycarbonyl)-2-((S)-1-(4-nitrophenylsulfonyl)azetidin-2-yl)acetateC23H27N3O8S[α]D = −13 (c 1.50, CHCl3)Source of chirality: L-SerineAbsolute configuration : (2R,2′S)

(4S,5S)-4-(Benzylamino)-5-((tert-butyldiphenylsilyloxy)methyl)pyrrolidin-2-oneC28H34N2O2Si[α]D = −2 (c 4.25, MeOH)Source of chirality: L-SerineAbsolute configuration : (4S,5S)