Visible-Light-Induced α-C(sp³)–H Phosphinylation of Unactivated Ethers under Photocatalyst- and Additive-Free Conditions

Abstract

A photocatalyst- and additive-free visible-light-induced α-C­(sp3)–H phosphinylation of unactivated ethers involving a C–O bond cleavage with molecular oxygen as the sole oxidant at room temperature has been achieved. This method provides a sustainable access to α-hydroxyphosphine oxides in up to 88% yield with good functional group compatibility under mild and neutral conditions (34 examples). Moreover, the subsequent two-step conversion of the resulting dihydroxy diarylphosphine oxides afforded α-phosphinylated cyclic ethers in good overall yields (10 examples).

Enantioselective C−P Bond Formation through C(sp3)−H Functionalization

“…However, its functionalization to C−P bonds has been considerably less explored, and the scarce examples reported in the literature work through free‐radical activation using mainly transition metal catalysts [3] . Among them, the α‐C( sp 3 )−H activation involved in a phosphonylation reaction of in situ generated iminium species, for the formation of C−P bonds, has received more attention in recent years (Scheme 1, a), [3] than the analogous transformation of C( sp 3 )−H bonds adjacent to an oxygen atom (Scheme 1, b) [4–6] . Among these scarce examples, Tang and co‐workers pioneered a copper‐catalyzed C( sp 3 )−H phosphonylation of alcohols and ethers using CuCl 2 /TBHP ( tert ‐butyl hydroperoxide) as a catalyst and oxidant, with moderate to good yields of final α ‐hydroxy phosphonates [5] .…”

“…Among these scarce examples, Tang and co‐workers pioneered a copper‐catalyzed C( sp 3 )−H phosphonylation of alcohols and ethers using CuCl 2 /TBHP ( tert ‐butyl hydroperoxide) as a catalyst and oxidant, with moderate to good yields of final α ‐hydroxy phosphonates [5] . More recently, Chen, Huo and co‐workers reported a photocatalyzed and additive‐free visible‐light‐induced α ‐C( sp 3 )−H phosphinylation of unactivated ethers with moderate to good yields (Scheme 1, b) [6] . Lately, Yang and coworkers reported the first asymmetric oxidation addition reaction for the synthesis of enantioenriched α‐hydroxy phosphonates using an aluminum‐based catalyst (Scheme 1, c) [7] .…”

“…[3] Among them, the α-C(sp 3 )À H activation involved in a phosphonylation reaction of in situ generated iminium species, for the formation of CÀ P bonds, has received more attention in recent years (Scheme 1, a), [3] than the analogous transformation of C(sp 3 )À H bonds adjacent to an oxygen atom (Scheme 1, b). [4][5][6] Among these scarce examples, Tang and co-workers pioneered a copper-catalyzed C(sp 3 )À H phosphonylation of alcohols and ethers using CuCl 2 / TBHP (tert-butyl hydroperoxide) as a catalyst and oxidant, with moderate to good yields of final αhydroxy phosphonates. [5] More recently, Chen, Huo and co-workers reported a photocatalyzed and additive-free visible-light-induced α-C(sp 3 )À H phosphinylation of unactivated ethers with moderate to good yields (Scheme 1, b).…”

“…[5] More recently, Chen, Huo and co-workers reported a photocatalyzed and additive-free visible-light-induced α-C(sp 3 )À H phosphinylation of unactivated ethers with moderate to good yields (Scheme 1, b). [6] Lately, Yang and coworkers reported the first asymmetric oxidation addition reaction for the synthesis of enantioenriched α-hydroxy phosphonates using an aluminum-based catalyst (Scheme 1, c). [7] More interesting is the fact that none of the latter processes disclosed in Scheme 1 a), b) and c) imply an asymmetric organocatalytic transformation.…”

Transition-Metal- and Photocatalyst-Free Photoinduced Formation of Carbon–Pnictogen (–N, –P) Bonds

“…Scheme 21 Photoinduced -phosphorylation of N-aryl tertiary amines 60 Huo and co-workers proposed a phosphinylation of unactivated ethers 22b facilitated by visible light, involving C-O bond cleavage under photocatalyst-free conditions (Scheme 22). 61 This strategy is applicable to both cyclic and acyclic ethers. The reaction was initiated via single-electron oxidation of ether 22b by molecular oxygen, resulting in an -alkoxyalkyl radical 22i.…”