SYNTHESIS OF 1-AMINO-2,2-DIALKYLCYCLOPROPANECARBOXYLIC ACIDS VIA BASE-INDUCED CYCLIZATION OF GAMMA-CHLORO-ALPHA-IMINO ESTERS

beta-Chloro ketones were oxidatively transformed into alpha-keto carbo xylic esters and condensed with primary amines in the presence of tita nium(IV) chloride. Base-induced cyclization of the resulting gamma-chl oro-alpha-imino esters, incorporating suitable N-substituents, led dir ectly to 1-amino-2,2-dialkyl- cyclopropanecarboxylic ester derivatives via a 1,5-dehydrochlorination process. Syntheses of different N- and/ or carboxyl-protected geminally (gem) dialkylated cyclopropane amino a cids were developed, while access to the free alpha-amino acids is als o given. The methodology used was further extended by reduction of the gamma-chloro-alpha-imino esters to functionalized gamma-chloro-alpha- amino esters,prior to ring closure, affording N-alkyl-gem-dialkyl-1-am inocyclopropanecarboxylic acid derivatives.