Medium-ring Ketone Synthesis. Synthesis of Eight- to Twelve-membered Cyclic Ketones based on the Intramolecular Cyclization of Large-membered Lactam Sulfoxides or Sulfones

概要

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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 NaBH_4 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.
公益社団法人日本薬学会の論文
1983-02-25