29 理論計算に基づくラジカル環化反応前駆体の分子設計とステロイド骨格合成への応用(口頭発表の部)

抄録

Radical cyclization is one of the most useful methodology for the formation of carbon-carbon bonds and has been used for the syntheses of natural products that have polycyclic system. Although regio- and stereoselectivities of radical cyclizations have been well studied, it is quite difficult to predict quantitatively the stereoselectivity of radical cyclizations. Herein, we describe about the method of stereochemical prediction for radical cyclization based on MM2 transition state models and its applications for the synthesis of steroid compounds. We planned two strategies using radical cyclization for the synthesis of steroid compounds. First approach is the synthesis of vitamin D_3 CD-ring 2 by a "radical cyclization-trapping reaction" of ω-iodoacrylonitrile derivative 5. Second approach is the synthesis of steroid BCD-ring 9, which is known as an important intermediate for the synthesis of progesterone, by a "tandem radical cyclization" of acyclic intermediate 9 or ten-membered ring compounds 12, 21. MM2 transition state model calculations suggested that the initial radical cyclization of all intermediates 5, 12 and 21 should predominantly give cyclopentylradicals 7A, 17 and 22, respectively, which have a desired trans relative stereochemistry between 13-Me and 14-H. Indeed, radical cyclizations of the intermediates 5, 12 and 21 gave the cyclized products in high yield and stereoselective syntheses of steroid intermediates 2 and 9 were accomplished. Now we examined about solid phase approach to the synthesis of steroid intermediate 9 using a tandem radical cyclization. In this session, we will discuss about detail results of calculations and experiments.