A NEW VERSATILE REAGENT FOR THE SYNTHESIS OF CYCLOPROPYLAMINES INCLUDING 4-AZASPIRO[2.N]ALKANES AND BICYCLO[N.1.0] ALKYLAMINES

The reaction of dialkylcarboxamides 1 with 1 equiv. of methyltriisopro pyloxytitanium together with only 1.1 equiv. of a Grignard reagent giv es cyclopropylamines 3 in better yields than the previously published method with 2 equiv. of Grignard reagent and 1 equiv. of Ti(OiPr)(4). This new protocol can be applied to intramolecular reactions with in s itu generation of the Grignard reagent from omega-bromo-N,N-dimethylhe xanamide and methyl omega-bromohexanoate yielding the expected 1-dimet hylaminocyclo[4.1.0]hexane 15 and the corresponding alcohol 18. Cycloh exylmagnesium bromide or chloride transforms N,N-dibenzylformamide and ethyl acetate to 7-exo-N,N-dibenzylaminonorcarane and 7-exo-hydroxy-7 -methylnorcarane. N-Methyl-epsilon-caprolactam 25b and even the strain ed N-benzylpropiolactam 25a were converted to the spirocyclopropanated heterocycles 26a,b.