Dual Nickel/Photoredox‐Catalyzed Site‐Selective Cross‐Coupling of 1,2‐Bis‐Boronic Esters Enabled by 1,2‐Boron Shifts

Abstract

Site‐selective transition‐metal‐catalyzed mono‐deboronative cross‐couplings of 1,2‐bis‐boronic esters are valuable methods for the synthesis of functionalized organoboron compounds. However, such cross‐couplings are limited to reaction of the sterically less hindered primary boronic ester. Herein, we report a nickel/photoredox‐catalyzed mono‐deboronative arylation of 1,2‐bis‐boronic esters that is selective for coupling of the more sterically hindered secondary/tertiary position. This is achieved by taking advantage of a 1,2‐boron shift of primary β‐boryl radicals to the thermodynamically favored secondary/tertiary radicals, which are subsequently intercepted by the nickel catalyst to enable arylation. The mild conditions are amenable to a broad range of aryl halides to give β‐aryl boronic ester products in good yields and with high regioselectivity. This method also allows stereodivergent coupling of cyclic cis‐1,2‐bis‐boronic esters to give trans‐substituted products.

1,2-Radical Shifts in Photoinduced Synthetic Organic Transformations: A Guide to the Reactivity of Useful Radical Synthons

“…In the same year, the authors also reported the arylation of 1,2-bis-boronate esters with (hetero)­aryl halides via dual nickel/photoredox catalysis, overcoming the limitations of the previous protocol regarding the use of only electron-deficient arylnitriles . The use of anionic diketonate-based ligands proved to be critical for the regioselectivity of the transformation in comparison to bipyridine ligands, and the study revealed the ligand TMHD was optimal, providing the product with >20:1 rr.…”

“…In the same year, the authors also reported the arylation of 1,2-bis-boronate esters with (hetero)aryl halides via dual nickel/photoredox catalysis, overcoming the limitations of the previous protocol regarding the use of only electrondeficient arylnitriles. 62 The use of anionic diketonate-based ligands proved to be critical for the regioselectivity of the transformation in comparison to bipyridine ligands, and the study revealed the ligand TMHD was optimal, providing the product with >20:1 rr. The effects of the ligands on the regioselectivity are in accordance with findings reported in a study by Molander and co-workers, showing a difference regarding the mechanisms for the reductive elimination step, outer-sphere (for the diketonate ligands) and inner-sphere (for the Ni-bipyridyl system).…”

Site-Selective Functionalization of C(sp3) Vicinal Boronic Esters

“…Interestingly, the procedure has been applied to cyclopentane and cyclohexane cis-1,2-bis(boronates), yielding trans-arylation products for both substrates, unlike the Suzuki−Miyaura cross-coupling that renders the cis-arylated diastereoisomers (Scheme 24b). In a later development of this group, 33 the generation of the secondary radical from 1,2-bis(boronates) can be merged with a dual nickel/photoredox-catalyzed cross-coupling, expanding the scope from (hetero)aryl nitriles to (hetero)aryl bromides (Scheme 24c). Remarkably, starting from vicinal bis-(boronates), this methodology allows for arylation of the more substituted boronic ester (secondary or tertiary) and it is complementary to arylation of the less hindered primary boronic ester by means of a Suzuki−Miyaura cross-coupling.…”

Enantioselective Suzuki cross-coupling of 1,2-diboryl cyclopropanes

“…1a). However, despite the elegant strategies developed to selectively functionalize 1,2-bis-boronates, 11,12 the enantioselective desymmetrization of these species is still an unmet challenge (Fig. 1b).…”