Phosphination of Phenol Derivatives and Applications to Divergent Synthesis of Phosphine Ligands

Abstract

We describe a general and efficient protocol for the synthesis of organophosphine compounds from phenols and phosphines (R2PH) via a metal-free C–O bond cleavage and C–P bond formation process. This approach exhibits broad substrate scope and excellent functional group tolerance. The synthetic utilities of this protocol were demonstrated by the synthesis of chiral ligands via the various transformations of cyano groups and their applications in asymmetric catalysis.

Transition-Metal Free C–C Bond Cross-Coupling of Aryl Ethers with Diarylmethanes

“…When m -methoxybenzonitrile was subjected to the standard reaction conditions, no desired coupling product was obtained. Based on this result and our previous work on S N Ar-type reactions, we proposed a possible reaction mechanism (Scheme ). 9 H -Xanthene 2a is first deprotonated with KHMDS to generate a nucleophilic species.…”

“…Recently, we developed the S N Ar reaction of aromatic ethers that the KO t Bu-mediated etherification and phosphination of aromatic ethers with nucleophiles via C­(sp 2 )–O bond cleavage, and alcohols and phosphines were applied as nucleophiles to form C–O and C–P bonds, respectively . To this end, we envisaged that carbon nucleophiles could be also suitable for the S N Ar reaction of aromatic ethers, offering a general and efficient method for C–C bond cross-coupling reactions.…”

Metal-Free Cyanation of gem-Difluoroalkenes via Azide-Mediated C–C Double Bond Fragmentation

“…It is intriguing to observe that the gram-scale reaction proceeded well to generate 3 in a 75% yield. Importantly, 2-methoxybenzonitrile 4 can be successfully applied for the synthesis of a chiral phosphinooxazoline ligand Ph-PHOX 34 via a nucleophilic phosphination/cyclization two-step reaction (Scheme b) . It should be mentioned that Ph-PHOX ligand 35 can be employed as an effective chiral ligand in palladium-catalyzed asymmetric Tsuji enol-carbonate allylation reactions .…”

“…Product 24 was purified by column chromatography (petroleum ether/ethyl acetate = 10:1), yielding 24 as a white solid (10 mg, 35% yield). Cinnamonitrile (25). Product 25 was purified by column chromatography (dichloromethane/methanol = 20:1), yielding 25 as a colorless oil (20.1 mg, 90% yield).…”

“…Importantly, 2-methoxybenzonitrile 4 can be successfully applied for the synthesis of a chiral phosphinooxazoline ligand Ph-PHOX 34 via a nucleophilic phosphination/cyclization twostep reaction (Scheme 3b). 25 It should be mentioned that Ph-PHOX ligand 35 can be employed as an effective chiral ligand in palladium-catalyzed asymmetric Tsuji enol-carbonate allylation reactions. 26 Moreover, the nucleophilic etherification of 19 with alcohols was also successful for the rapid construction of structurally complex aromatic nitriles.…”