Structural features in the seven-membered vs. fourteen-membered ring cyclization of hydroxyamido ketals derived from beta-amino alcohols

Hydroxyamido ketals 1 and 3-12, prepared from beta -amino alcohols, are obt ained either as a single form with a trans (1 and 3-8) or cis (9) conformat ion in the R = H series or as two cis and trans rotamers in the R not equal H series (10-12). - The cyclization of these compounds was studied under a cidic conditions (PTSA) and over a well defined range of concentrations (e = 0.1-0.2 M). While cis amide 9 and mixtures of cis and trans rotamers 10-1 2 resulted practically exclusively in the formation of seven-membered ring lactams 22-25, trans compounds 1 and 3-8 afforded fourteen-membered ring bi s-lactams 2, 13-18, the formation of which involves a dimerization. Macrocy cles were obtained as three diastereomers in the chiral series 2, 13-16 and as two isomers in the achiral series 17 and 18. Nineteen macrocyclic bisla ctams have thus been synthesized.