Selective conjugate addition to zerumbone and transannular cyclization of its derivatives

Abstract

Some chemical transformations of zerumbone (1) isolated from rhizomes of Zingiber zerumbet Smith have been described. Regioselective addition of benzenethiol and benzeneselenol to the Δ1,2 double bond of 1 occurs in the presence of tetra-n-butylammonium fluoride (TBAF) as a catalyst to give 1-phenylthio and 1-phenylseleno adducts 2a and 2b, respectively, with moderate diastereoselectivity. In the presence of BF3·OEt2 the reaction of 2a and 2b with trimethylsilyl cyanide proceeds in 1,4-addition fashion to give the corresponding 5-cyano silyl enolates 3a and 3b, respectively. Desilylation of 3a and 3b with HF·pyridine provides (8E)-5-cyano-2,6,6,9-tetramethyl-1-phenylthiocycloundec-8-en-3-one (5a) and (8E)-5-cyano-2,6,6,9-tetramethyl-1-phenylselenocycloundec-8-en-3-one (5b) as a single diastereoisomer, respectively. Treatment of 2a and 2b with TiCl4 affords compounds with a bicyclo[5.3.0]decane skeleton, 6a and 6b, respectively, as trans-fused isodaucane derivatives via a transannular reaction between C-4 and C-9 of 2 followed by rearrangement. Palladium-mediated transannular reaction between C-4 and C-9 of 3b yields 7b with a bicyclo[5.4.0]undec-8-ene skeleton. Bronsted acid-catalyzed transannular reactions between C-3 and C-8 of 5a and 5b afford compounds with bicyclo[5.4.0]undecane skeletons 8a and 8b. A lithium enolate of (1Z)-5-cyano-8,9-epoxyzerumbone 10/10′ derived from 5b gives compounds with tricyclic skeletons, 11 and 12, by a transannular reaction between C-4 and C-8. Compounds 11 and 12 involve the carbon skeleton of 5,8-fused bicyclic natural sesquiterpene, asteriscane. Some molecular structures of key intermediates and products have been characterized by X-ray crystallography.