Formation of 1-Hydroxymethylene-1,1-bisphosphinates through the Addition of a Silylated Phosphonite on Various Trivalent Derivatives

Abstract

An easily handled one-pot synthetic procedure was previously developed for the synthesis of bisphosphinates starting from acyl chlorides. Herein, other trivalent derivatives as acid anhydrides and activated esters were tested to form various bisphosphinates. This modulation of the reactivity can be controlled according to the nature of the acid derivative for the use of sensitive and functionalized substrates.

Synthesis of N-Hydroxysuccinimide Esters, N-Acylsaccharins, and Activated Esters from Carboxylic Acids Using I2/PPh3

“…This compound was eluted using 20:80 EtOAc/hexane solvent (white solid, 205 mg, 96%). mp 49–50 °C; R f = 0.60 (20:80 EtOAc/hexanes); the spectroscopic data is identical to that reported in the literature …”

One-Pot Synthesis of Phosphinylphosphonate Derivatives and Their Anti-Tumor Evaluations

“…Then, a methanolysis step followed by a pH adjustment to 7 yielded 6a as disodium salt in an excellent yield of 91% after easy purification by precipitation. For the latter step, the preparation of bis(trimethylsilyl)phosphonite 5 can be smoothly achieved by the silylation of hypophosphorous acid in the presence of N,O-bis(trimethylsilyl)acetamide (BSA) as previously reported [12][13][14]21,24].…”

“…The afore-mentioned molecules will present fewer negative charges, which should imply a lower hydrophilicity and acidity (similar to carboxylic acid). In this context, we have recently reported the efficient synthesis of substituted HMBPi III by developing a convenient one-pot methodology [12][13][14].…”

“…Inspired by our previous works on HMBPs II or HMBPi III, we focused on the synthesis of the hydroxymethylene(phosphinyl)phosphonate scaffold. HMBPs II [21] or HMBPi III [12][13][14] were actually synthesized by the successive double addition of tris(trimethylsilyl)-phosphite (TTSP, R 2 = OTMS) or bis(trimethylsilyl)phosphonite (BTSP, R 2 = H) onto an acyl chloride, via a silylated α-ketophosphonate or α-ketophosphinate intermediate, respectively (Scheme 1). Our novel strategy consists of obtaining hydroxymethylene(phosphinyl)phosphonate derivatives IV in three steps via the similar in situ formation of a silylated α-ketophosphonate (Scheme 1) [21,22].…”

Synthesis of Aminobisphosphinates through a Cascade Reaction between Hypophosphorous Acid and Bis(trimethylsilyl)imidates Mediated by ZnI2

“…Thereafter, this easily handled methodolo was successfully used on other trivalent electrophiles, like anhydrides and activa Moreover, we also performed the successive double nucleophilic addition of BTSP onto trivalent electrophiles as acyl chlorides, which enabled the formation of hydroxymethylenebisphosphinates (HMBPi) via silylated α-ketophosphinates in good to excellent yields and short reaction times [8,9]. Thereafter, this easily handled methodology was successfully used on other trivalent electrophiles, like anhydrides and activated esters, which led to more functionalized HMBPi derivatives in good yields [10].…”