Diastereoselective Formation of Substituted Cyclic Non-Proteinogenic α-Amino Acids by Cyclization of Activated Imines

Abstract

The intramolecular cyclization of alkyl (5-methyl-4-hexenylimino)acetates 7 with trimethylsilyl triflate (TMS-OTf) in toluene or tert-butyl methyl ether affords the cis- and trans-3-isopropenyl-2-piperidinecarboxylates 8 and 9 in ratios from 1:15 to 1:33. TMS-OTf is superior to Lewis acids in this reaction. The imines 7 can be obtained by condensation of 5-methyl-4-hexenylamine 5 and alkyl glyoxylates. Saponification of the diastereomerically pure cyclization product 9 affords the non-proteinogenic α-amino acid 10 (3-isopropenyl-2-piperidinecarboxylic acid).