Development of reactions based on addition of electrophiles to methylenebisphosphonates

点击翻译按钮获取中文摘要

Allenes are recent focus of versatile class of intermediates in a variety of organic synthetic processes. We developed a novel method to synthesize allenes by successive Horner-Wadsworth-Emmons olefination starting from methylene-bisphosphonate and two carbonyl compounds. The key to success is KH or KH-18-crown-6 as a base for second HWE olefination of hydroxyalkenylphosphonates. Asymmetric allene synthesis based on this method is now in progress.As our continuing studies of efficient synthetic application of lithium phosphonates, we have developed cyclization reaction of bis-alkenylphosphonate 1. Although the reaction of 1 with organolithium reagents afforded both tandem Michael cyclization products and α-deprotonation-cyclization products, the latter was selectively formed in high yield by simply treating 1 with LDA. Application of chiral bis-alkenylphosphonate 2 opens a simple synthetic way to chiral phosphine ligand 5. Treatment of 2 with LDA followed by electrophilic trapping of intermediate cyclic lithium phosphonate 3 with benzaldehyde afforded aldol-type adduct 4 in 54%. The alcohol 4 was transformed to 5 by 6 steps in 16% yield.