Synthesis of Azetidine Derivatives Using 1-Azabicyclo[1.1.0]butane

Abstract

A THF solution of 1-azabicyclo[1.1.0]butane(2), obtained from 2,3dibromopropylamine hydrobromide (1), was treated with HCl-EtOH, 48% HBr, ClCO 2 Et, Ts 2 O, HCO 2 H -2.7N HCl-MeOH, or Ac 2 O -3N HCl to give the corresponding 3-monosubstituted and 1,3-disubstituted azetidine derivatives (3-7) .Similar treatment of 2 with AcSH afforded 1-acetyl-3-acetylthioazetidine (8), which was converted to 1-(1,3-thiazolidin-2-yl)azetidine-3-thiol hydrochloride (10).The compound (2) and various bromides were heated to furnish 3-bromoazetidine derivatives (12b,c,e,f) and/or N,N-disubstituted 2,3-dibromopropylamines (13a,c-f).The reaction of 2 with benzoyl peroxide or N-bromosuccinimide gave each corresponding 1,3-disubustituted azetidine derivative (14 or 15).1-Azabicyclo[1.1.0]butane(2) has proved to be the unique molecule bearing the highly strained bicyclic structure 1 and is synthetically useful for the preparation of 3-monosubstituted or 1,3-disubstituted azetidines. 2,3Recently, we have disclosed an efficient synthetic method of 2 starting from 2,3-dibromopropylamine hydrobromide (1) and its application to the syntheses of some 3-subustituted † Dedicated to Prof. James P. Kutney on the occasion of his 70th birthday.