A New Versatile Reagent for the Synthesis of Cyclopropylamines Including 4-Azaspiro[2.n]alkanes and Bicyclo[n.1.0]alkylamines

Article abstract of DOI:10.1055/s-1997-17828

The reaction of dialkylcarboxamides 1 with 1 equiv. of methyltriisopropyloxytitanium together with only 1.1 equiv. of a Grignard reagent gives 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 situ generation of the Grignard reagent from ω-bromo-N,N-dimethylhexanamide and methyl ω-bromohexanoate yielding the expected 1-dimethylaminocyclo[4.1.0]hexane 15 and the corresponding alcohol 18. Cyclohexylmagnesium bromide or chloride transforms N,N-dibenzylformamide and ethyl acetate to 7-exo-N,N-dibenzylaminonorcarane and 7-exo-hydroxy-7-methylnorcarane. N-Methyl-ε-caprolactam 25b and even the strained N-benzylpropiolactam 25a were converted to the spirocyclopropanated heterocycles 26a,b.