Concise Synthesis of the Isothiourea Organocatalysts Homobenzotetramisole and Derivatives

A concise approach to the synthesis of homobenzotetramisole and derivatives is described. Our strategy features a one-pot acylation cyclization of 2-aminobenzothiazole with alpha,beta-unsaturated acid chlorides to afford annulated pyrimidones. Subsequent Grignard addition followed by acid-promoted dehydration and reduction provides good overall yields of the title compounds in three steps and in quantities up to 10 g. The synthesis employs low-cost and readily available starting materials and enables access to both optical antipodes of these increasingly useful nucleophilic catalysts following chiral separation.