Design and diversity-oriented synthesis of benzo- And pyrido-annulated medium-sized N,S-heterocycles via thio-Michael and Friedel-Crafts approaches

Abstract

Efficient and concise protocol for the synthesis of fused tetracyclic N,S-heterocycles in particular benzo- and pyrido-fused 1,4-thiazonines, 1,4-thiazecines and 1,4-thiazacycloundecanes is described. The process involves Lewis or Brønsted acids-promoted Friedel-Crafts cyclizations of heterocyclic esters. The required starting thiazepinones were obtained in moderate yields via intramolecular thio-Michael additions of mercapto-amides under mild conditions. The present study without stereochemical assignments illustrates the first example of straightforward access to promising pharmaceutical scaffolds in high yields. X SO3H S Simple (3-5) reaction steps Friedel-Crafts cycliacylations N NH2 N N n O - Expedient synthesis - High regioselectivity a-f - Wide starting scope a: n = 1, X = CH; b: n = 2, X = - Mild reaction condition CH; c: n = 3, X = CH; d: n = 1, X = N; e: n = 2, X = N; f: n = 3, - Functional group indulgence X = N