Synthesis and Synthetic Utilization of α-Functionalized Vinylphosphonates Bearing β-Oxy or β-Thio Substituents

Abstract

The beta-hetero-substituted vinylphosphonates 1a-c on treatment with LDA or LTMP were readily lithiated at the alpha-position of the phosphono group, and the resulting alpha-lithiovinylphosphonates were trapped with various electrophiles to afford the corresponding alpha-functionalized vinylphosphonates 2-14 in 55-96% yields. The Friedel-Crafts reaction of alpha-(silyl)- or alpha-(germyl)phosphonoketene dithioacetals 2, 9, or 4 with acid chlorides gave alpha-acylated phosphonoketene dithioacetals 15-19 in 53-91% yields. The palladium-catalyzed cross-coupling reaction of beta-ethoxy-alpha-(tributylstannyl)vinylphosphonate 13 with a variety of organic halides (R = acyl, allyl, aryl, etc.) provided beta-ethoxy-alpha-substituted vinylphosphonates 21-26 in good to moderate yields. The palladium-mediated cross-coupling reaction of alpha-(iodo)vinylphosphonates 7 and 14 with terminal acetylenes afforded alpha-alkynylated vinylphosphonates 41-44 in 69-83% yields. Several alpha-functionalized beta-hetero-substituted vinylphosphonates were applied to the synthesis of pyrazoles and an isoxazole possessing a phosphono function.

Synthesis of diethyl 2-(aryl)vinylphosphonates by the Heck reaction catalysed by well-defined palladium complexes

“…In almost all cases, working at 140°C allows to reduce noticeably the reaction time to few hours (3-6 h). Interestingly heteroaryl halides ( Table 2, entries 10-15), including 3-bromobenzothiophene (Table 2, entries [22][23][24], gave high yields showing the general applicability of the conditions.…”

“…Furthermore, the reagents are not always readily accessible. As alternatives a-lithiation of boxy or b-thio vinylphosphonates [22], NaH catalysed olefination of benzenesulfinylmethylphosphonates [23] and addition of sodium organyl chalcogenolates to 1-alkynylphosphonates were reported [24]. However, in practice these methods led to formation of regioand stereo-isomers mixture.…”

Controlled Reactivity of Phosphonates by Temporary Silicon Connection

“…57 Thus, a-sil- comparative study between silylated 36 and unsilylated 35 phosphonoketenes dithioacetals has demonstrated that the a-trimethylsilyl substituent was essential to increase reaction rate and yields. 57…”

A novel stereoselective synthesis of (E)-2-arylvinylphosphonates in InCl3–NaBH4–MeCN system

“…Vinylphosphonates have been widely used as synthetic intermediates in organic chemistry [1] and investigated as biologically active compounds [2], especially in stereoselective synthesis of trisubstituted olefins [3] and heterocycle compounds [4]. Up to now, the synthesis of vinylphosphonates has been explored extensively.…”