One-pot ethynylation and catalytic desilylation in synthesis of mestranol and levonorgestrel

作者：Wong Fung Fuh^*; Chuang Shih Hsien; Yang Sheng chuan; Lin Yu Hsiang; Tseng Wen Che; Lin Shao Kai; Huang Jiann Jyh

来源：Tetrahedron, 2010, 66(23): 4068-4072.

DOI：10.1016/j.tet.2010.04.008

• Ethynylation
• Catalytic desilylation
• Propargyl alcohol
• Trimethylsilylacetylide
• One pot

A one-pot ethylnylation and catalytic desilylation reaction was developed for the synthesis of mestranol and levonorgestrel. Addition of trimethylsilylacetylide to the carbonyl group at C-17 of the steroids yielded the C-17 alpha-trimethylsilylacetylenyl adducts, which were desilylated with a catalytic amount of TBAF (0.050 equiv) in one pot to provide the corresponding mestranol and levonorgestrel both in 90% yields. A plausible mechanism was proposed for the catalytic desilylation through the regeneration of the fluoride ion from the reaction of alkoxide on the steroid with Me(3)SiF. The one-pot ethynylation and catalytic desilylation methodology provided an alternative route and avoided the traditional use of flammable and explosive acetylene gas toward the synthesis of mestranol and levonorgestrel.

• 出版日期2010-6-5
• 单位中国医科大学