アルケニルホスホナートを基盤とする炭素-炭素結合形成反応の開発

概要

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We have been engaged in the development of asymmetric conjugate addition reactions of lithium thiolates, organolithiums and organocopper reagents under the control of external chiral ligands and we have also developed an efficient asymmetric Horner-Wadsworth-Emmons(HWE) reaction using an external chiral Ligand. We attempted to synthesize axial chiral allenes by combination of these conjugate additin reaction and HWE reaction. In the course of this study, we found that Michael-aldol reaction of alkenylphosphonates 1 using LDA and aldehydes results in the direct formation of α, β-unsaturated hydroxyphosphonate 4, which was efficiently converted to allene by treatment with KH or KH-18-crown-6. Furthermore, allenes were synthesized by sequential double HWE reaction in one-flask manner strarting from methylenebisphosphonate 8. The key to success is a metal exchange of intermediate lithium alkoxide 4-Li to potassium alkoxide 4-K by the addition of t-BuOK. As our continuous study of carbon-carbon bond formation based on alkenylphosphonates, a cyclization reaction of bisalkenylphoshonate 6 was developed. Although the treatment of 6 with organolithium reagents afforded a mixture of addition-cyclization product 9 and deprotonation-cyclization product 10, the treatment of 6 with LDA gave 10 selectively. These cyclization methods were applied to the synthesis of efficient chiral phosphine ligands.
公益社団法人日本薬学会の論文
2001-11-01