LITHIATION-SUBSTITUTIONS OF N-BOC N-ALKYL CYCLOPROPYLAMINES

A series of lithiation-substitution reactions at the alpha and beta po sitions of N-Boc N-alkyl cyclopropyl amines is reported. The cycloprop ane ring is the preferred position for lithiation in the N-ethyl and N -methyl derivatives 6 and 7, but the N-allyl and N-benzyl derivatives 8 and 9 undergo lithiation at the methylene groups. Lithiations at bet a positions of the cyclopropylamine ring are observed if the alpha-pos ition is blocked or the beta-positions are activated by phenyl substit ution as shown for the reactions of 10, 15 and 21. Both alpha and beta lithiations can be used in lithiation-cyclization reactions to provid e the bicyclic spiro or endo fused N-Boc amines 15, 16 and 25. Lithiat ions of N-Boc-4-tosyloxy piperidine 30 with s-BuLi/(-)-sparteine follo wed by trimethylsilyl chloride give the N-Boc azabicyclo[3.1.0] hexane 32 with enantiomeric excesses which range from 18-55%. Two beta-carbo methoxy substituted N-Boc cyclopropylamines 18 and 26 can participate in a formal [3+2] cycloaddition with tetracyanoethylene to give highly substituted cyclopentanes. Copyright (C) 1996 Elsevier Science Ltd