Synthesis and applications of functionalized phosphonates

Abstract

Phosphonate-involving 2-isoxazolines and isoxazole have been synthesized by 1,3-dipolar cycloaddition reaction of nitrile oxides with several kinds of unsaturated phosphonates including vinyl, propargyl, allylic, and homoallylic phosphonates. These cycloadduct products can serve as precursors to variously functionalized phosphonates by appropriate transformations. 5-Diethylphosphonomethyl-3-methylisoxazole could be prepared by phosphonylation of 3,5-dimethylisoxazole carbanion besides nitrile oxide cycloaddition, and its alkylation with alkyl halides and olefination with aldehydes were carried out. As a consequence, isoxazole has been used as a new a-stabilizing substituent of phosphonates. 4-Oxo-2-alkenylphosphonates have been synthesized from phosphonoalkyl-2-isoxazolines via their eliminative ring opening by treatment with LDA and subsequent hydrolysis with titanium(III) chloride. The overall synthetic procedure presents a new method for regioselective γ-acylation of allylic phosphonates. The potential of 4-oxo-2-alkenylphosphonates as useful building blocks for synthesis of polyethylene-structured natural compounds has been verified by their olefination with aldehyde, affording dienones. Also, 4-oxo-2-alkenylphosphonates have been synthesized via aliphatic Friedel-Crafts acylation of allyl- and vinylsilanes and base-promoted double bond migration in excellent yields. The silylated allylic phosphonates as intermediates were obtained from vinylic phosphonates as well as allylic phosphonates. This synthetic route to 4-oxo-2-alkenylphosphonates has the advantages of short procedure, high yield, and various products over other ones. Dephosphonylation of alpha-carbamoyl phosphonates was performed by treatment of their metal enolate analogues, generated by reaction of phosphonate carbanions with isocyanates, with lithium aluminum hydride followed by acidic quenching to give secondary amides. The first access to a-alkylation of substituted secondary amides has been...