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

All articles of this category 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(O i Pr) 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-dimetehylaminocyclo[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-ℇ-caprolactam 25b and even the strained N-benzylpropiolactam 25a were converted to the spirocyclopropanated heterocycles 26a,b . cyclopropylamines - substituted - bicyclic - functionalized - cyclopropanation - titanium mediated