Synthesis of Unsymmetrical Tertiary Phosphine Oxides via Sequential Substitution Reaction of Phosphonic Acid Dithioesters with Grignard Reagents

Abstract

A facile synthetic method for unsymmetrical tertiary phosphine oxides is reported. Sequential treatment of phosphonodithioic acid S,S-di(p-tolyl) esters with two Grignard reagents enabled the stepwise introduction of different carbon substituents on the phosphorus atom. The chemical stability of dithioesters and monosubstituted thioesters has enhanced the utility of this method, rendering a wide range of organophosphorus compounds easily available.

Continuous Flow Organophosphorus Chemistry

“…Yoshida, Hosoya and co-workers employed a continuous flow process for the synthesis of phosphinate analogs of phthalides using a Grignard reagent. [93] Starting from phosphinic acid thioester 99 bearing a p-tolylthio group as a leaving group, the injection of an isopropyl Grignard reagent followed by an aldehyde 100 allowed to generate the intermediate 101. The latter compound was converted into a mixture of phthalide phosphorus diastereoisomers 102a and 102b (4.5:1) in a high Figure 28.…”

“…Continuous flow generation of phosphinate analogs of phthalide through the use of a Grignard reagent. [93] Recently, Sevov and colleagues reported the electrochemical reduction of triphenylphosphine oxide towards triphenylphosphine. [94] Triphenylphosphine oxide is a common by-product of a wide range of reactions based on triphenylphosphine as a reductant, such as the Wittig, Staudinger, Appel and Mitsunobu reactions (see also section 3.1.)…”

Robust synthesis of NIR-emissive P-rhodamine fluorophores

“…Lowering the reactivity of the electrphile and switching to phosphonic dithioesters solved this problem. Phosphonic dithioester 14 13 in combination with equimolar amounts of the aryllithium reagent derived from 2a produced the triarylphosphine oxide 12a as the major product with some recovered 14 (Table 1). Reducing the reactivity of the aryllithium by conversion to a Grignard reagent gave 55% of the mono-substituted product 15.…”

Novel One‐Pot Access to Diastereoisomeric Tertiary Phospholanes Oxides by Using Enantiomerically Pure Phospholane Oxides Under Catalyst‐Free Conditions

“…Considerable attention is continuously devoted to non racemic tertiary phosphine oxides, since their reduction is one of the most useful methods for the preparation of optically active tertiary phosphines . Various approaches were also described to synthesize these precious targets: metal‐free or transition metal‐catalyzed cross‐coupling reactions, Brønsted acid‐catalyzed synthesis and Grignard reagents …”

“…[10] Various approaches were also described to synthesize these precious targets: metal-free [11] or transition metal-catalyzed cross-coupling reactions, [12] Brønsted acid-catalyzed [13] synthesis and Grignard reagents. [14] Recently, secondary diphenylphosphine oxide was used in Kabachnik-Field reaction to form bis (phosphinoylmethyl) amine served as a precursor for an optically active bidentate P-ligand in the synthesis of a chiral platinum complex. [15] Phospholane oxides and their derivatives have been subjected to hydrophosphinylation, [16] and have emerged as effective precatalysts for an expanding new area of organocatalysts.…”