Green, Palladium‐Catalyzed Synthesis of Benzylic H‐Phosphinates from Hypophosphorous Acid and Benzylic Alcohols

Abstract

Benzylic alcohols cross-couple directly with concentrated H3PO2 using Pd/xantphos (1 or 2 mol-%). Depending on the substrate, DMF at 110°C, or t-AmOH at reflux with a Dean-Stark trap, can be used. A broad range of benzylic alcohols reacted successfully in moderate to good yields. The preparation of other organophosphorus compounds (phosphinic and phosphonic acids) is also demonstrated. Asymmetric reaction with (R)-1-(2-naphthyl)ethanol provided the corresponding H-phosphinic acid in 77% ee. The methodology provides a green, PCl3-free, entry into benzylic-H-phosphinic acids.

Direct Nucleophilic SN1‐Type Reactions of Alcohols

“…Direct amination was observed with electron-deficient anilines and thiols, whereas the addition of H 3 PO 2 to benzylic alcohols by using Pd/xantphos in DMF at 110°C or tAmOH at reflux with a Dean-Stark trap were used. [123] Eur. J.…”

Copper(I)-catalyzed hydrophosphination of styrenes

“…Shifting the selectivity from the phosphine 3 to the phosphine oxide 4 would be of interest since phosphine oxides have biological and medicinal properties [21,22]. Although secondary phosphine oxides can add directly to alkenes (hydrophosphorylation) [21,23,24], the corresponding phosphines are usually less expensive.…”

Hypophosphorous Acid

“…Coudray et al tested a broad range of benzylic alcohols and got the desired products in moderate to good yields. 8 Reaction with the chiral (R)-1-(2-naphthyl)ethanol provided the corresponding H-phosphinic acid in 89% yield and with 77% ee. 9 Under an air atmosphere, 1-octene was heated with H 3 PO 2 in the presence of Pd 2 dba 3 and xantphos to form H-phosphinic acid 2, which was then converted into phosphonic acid 3 smoothly by heating in air.…”