Transition metal-free visible light photoredox-catalyzed remote C(sp3)−H borylation enabled by 1,5-hydrogen atom transfer

Abstract

The borylation of unreactive carbon-hydrogen bonds is a valuable method for transforming feedstock chemicals into versatile building blocks. Here, we describe a transition metal-free method for the photoredox-catalyzed borylation of unactivated C(sp3)−H bond, initiated by 1,5-hydrogen atom transfer (HAT). The remote borylation was directed by 1,5-HAT of the amidyl radical, which was generated by photocatalytic reduction of hydroxamic acid derivatives. The method accommodates substrates with primary, secondary and tertiary C(sp3)−H bonds, yielding moderate to good product yields (up to 92%) with tolerance for various functional groups. Mechanistic studies, including radical clock experiments and DFT calculations, provided detailed insight into the 1,5-HAT borylation process.

Visible-Light-Induced Transition-Metal-Free Redox-Neutral Carboxylation of Remote Benzylic C(sp3)–H Bonds via 1,5-Hydrogen Atom Transfer

“…By substituting the tert-butyl group with either an isopropyl or cyclohexyl group, the substrates can undergo the desired transformation to form carboxylation products with inferior yields, which may be attributed to the replacement of a tertiary N-connected alkyl group with a secondary one, leading to weakened N−H bond and thermodynamic effects on the 1,5-HAT process (2b−2c). 25 α-Oxiamido acids bearing monosubstituted groups at the para-position of the amido bond, such as electron-rich groups (OMe and Me) or electron-poor groups (F, Cl, and Br) on the benzene ring, have been demonstrated to be suitable starting materials, giving the desired products in good yields (2d−2h). When the monosubstituted groups are positioned at the ortho sites of the amide bond, there is a distinct decrease in the yield of the corresponding carboxylation products (2i and 2j), while the substrates bearing monosubstituted groups at the meta-position of the amide bond give moderate to desired carboxylation products (2k, 2i, and 2m).…”

“…As summarized in Figure , a broad range of benzylic α-oxiamido acids bearing diverse functional groups on the central arene were used as starting materials. By substituting the tert -butyl group with either an isopropyl or cyclohexyl group, the substrates can undergo the desired transformation to form carboxylation products with inferior yields, which may be attributed to the replacement of a tertiary N-connected alkyl group with a secondary one, leading to weakened N–H bond and thermodynamic effects on the 1,5-HAT process ( 2b–2c ) . α-Oxiamido acids bearing monosubstituted groups at the para-position of the amido bond, such as electron-rich groups (OMe and Me) or electron-poor groups (F, Cl, and Br) on the benzene ring, have been demonstrated to be suitable starting materials, giving the desired products in good yields ( 2d–2h ).…”

“…By integrating photocatalysis with the nitrogen-centered radical 1,5-HAT reaction, not only can remote C­(sp 3 )–H bonds be selectively functionalized under mild conditions ,− but also the coupling of C–C and C–Y bonds (Y = O, N, X, Si, B, etc. ) ,− can be facilitated.…”

Metal-free, photoinduced remote C(sp3)–H borylation

“…Subsequently, carbon radicals at the γ site would be formed via 1,5-HAT, chemoselectively affording alkyl boronic esters through B 2 cat 2 capture ( Scheme 1c ). During the preparation of this manuscript, Mo and co-workers disclosed a metal-free borylation of O -benzoyl hydroxamic ester with B 2 cat 2 , 16 however, a photoredox catalyst and amine additive are necessary. An excited [EY 2− ]* intermediate is proposed as a powerful reducing reagent that undergoes single-electron transfer to O -benzoyl hydroxamic ester, leading to the homolytic cleavage of the N–O bond and formation of N-based radicals.…”

“…Interestingly, 61% yield could be achieved when O -benzoyl hydroxamic ester 9 (ref. 16 and 18 ) was used as starting material, without the use of a photocatalyst.…”