Functionalized chloroenamines in aminocyclopropane synthesis - X. amino-azabicyclo[3.1.0]hexane diastereomers from chloroenamines and - organometallic compounds

Abstract

Morpholino-chlorotetrahydro-N-methyl-pyridine 4 reacted with Grignard reagents 5 or diorganyl-magnesium compounds 6 to give a mixture of azabicyclo[3.1.0]hexane diastereomers 10 and 11 besides the monocyclic ketones 12. The latter were obtained as the sole products from chloroenamine 4 and dimethylzinc 7a or lithium dimethylcopper 8a. Organolithium compounds 9a,c or Grignard reagents 5a–c in the presence of TMEDA transferred 4 exclusively to endo-morpholino isomers 10. exo-Amines 11 could be obtained with high stereoselectivity from 4 via the N,O-acetal 13 and by the substitution of the methoxy moiety by a Grignard reagent 5. The stereochemical result of this substitution reaction can be explained by an intermediate complexation of the pyrrolidine N-atom in 13 by the Grignard reagent 5. An N-benzyl chloroenamine 14 instead of the N-methyl compound 4 showed a different reaction behavior with methylmagnesium bromide 5a leading only to endo-amine 15 which could be used as a precursor of the parent bicyclic system 16. The configurations of the bicyclic diamines 10, 11 and 15 were determined via 1H NMR data.