Synthesis of Muscothiazoles A and B: Critical Role of Methyl Group Substitution in RCM-Based Syntheses of Macrocycles

[reaction: see text] Muscothiazoles A (2b) and B (2c) have been prepared by two approaches that differ in the order of assembly of the rings. Comparative studies show that substitution of the carbon chains in substrate 5 or 12 (respective precursors to 13-membered and 14-membered rings by RCM), even by a single methyl group, can have a profound effect on increasing the efficiency of the macrocyclization.