Abstract
An effective general method for the construction of medium-ring ketones from the corresponding ω-bromocarboxylic acids is described. When the diamide disulfide 10 was treated with NaBH4 and NaH in 2-propanol, reductive cleavage of the sulfur-sulfur bond and concomitant intramolecular coupling of the resulting thiolate anion with the terminal bromide took place and the large-ring lactam sulfide 7, which was the key intermediate for the synthesis of medium-ring ketones, was obtained. Although lithium diisopropyl amide (LDA) treatment of 11 followed by reductive desulfurization provided cycloundecanone (13d) in only 19.5 % yield, intramolecular cyclization of the α-methylated analogues 17 with LDA proceeded smoothly and the keto sulfoxides 18 were obtained in quantitative yields. In the case of the lactam sulfones 21, tert-BuOK was effective as a base for the intramolecular cyclization, affording the keto sulfones 22 in quantitative yields. The keto sulfoxides 18 and sulfones 22 were subjected to reductive desulfurization with Al-Hg to yield medium-ring ketones 19 and 13, respectively, in high yields.
