Synthesis of 3-azabicyclo[3.1.0]hexanes by insertion of cyclopropylmagnesium carbenoids into an intramolecular C-H bond adjacent to a nitrogen atom

A variety of 3-azabicylo[3.1.0]hexanes were synthesized via 1,5-C-H insertion of cyclopropylmagnesium carbenoids as a key step. 1-Chlorocyclopropyl p-tolyl sulfoxides with an N,N-disubstituted aminomethyl group on the cyclopropane ring were prepared from dichloromethyl p-tolyl sulfoxide, alpha,beta-unsaturated carboxylic acid esters, primary amines, and alkyl halides. Treatment of the sulfoxides with i-PrMgCl generated cyclopropylmagnesium carbenoids, which were inserted into an intramolecular C-H bond adjacent to a nitrogen atom to give 3-azabicyclo[3.1.0]hexanes in yields of up to 94%. The reactivity of the C-H bond toward the insertion increased in the order of NCH3, NCH2CH3, NCH2Ph, and NCH(CH3)(2). Optically active 3-azabicyclo[3.1.0]hexane was successfully synthesized using an S-chiral p-tolylsulfinyl group as a chiral auxiliary. (C) 2015 Elsevier Ltd. All rights reserved.