Dual catalysis. Single-electron transmetalation in organoboron cross-coupling by photoredox/nickel dual catalysis

Abstract

The routine application of C(sp3)-hybridized nucleophiles in cross-coupling reactions remains an unsolved challenge in organic chemistry. The sluggish transmetalation rates observed for the preferred organoboron reagents in such transformations are a consequence of the two-electron mechanism underlying the standard catalytic approach. We describe a mechanistically distinct single-electron transfer-based strategy for the activation of organoboron reagents toward transmetalation that exhibits complementary reactivity patterns. Application of an iridium photoredox catalyst in tandem with a nickel catalyst effects the cross-coupling of potassium alkoxyalkyl- and benzyltrifluoroborates with an array of aryl bromides under exceptionally mild conditions (visible light, ambient temperature, no strong base). The transformation has been extended to the asymmetric and stereoconvergent cross-coupling of a secondary benzyltrifluoroborate.

Fig. 1. Comparison of transmetalation in the palladium-catalyzed Suzuki-Miyaura cross-coupling and the proposed single-electron transmetalation in photoredox/nickel cross-coupling

Ir = Ir[dFCF₃ppy]₂(bpy)PF₆, R = generic organic subunit, Ar = aryl group.

Fig. 2. Photoredoxcross-coupling of benzylic trifluoroborates and aryl bromides

All yields are percent isolated yield of pure material after chromatography. Reactions were performed on aryl halide (0.5 mmol). Boc = tert-butoxycarbonyl, Me = methyl, Ph = phenyl, Ac = acetyl.

Fig. 3

Photoredox cross-coupling of a secondary (α-alkoxy)alkyltrifluoroborate with 4-bromobenzonitrile.

Fig. 4. Probing chemo- and stereoselectivity

(A) Competition experiment between potassium benzyltrifluoroborate and potassium phenyltrifluoroborate under photoredox cross-coupling conditions. (B) Stereoconvergent cross-coupling of a racemic trifluoroborate 44 and aryl bromide to afford an enantioenriched product. Reactions were performed on aryl bromide (0.5 mmol). *Determined by chiral supercritical fluid chromatography (SFC). †Absolute configuration was assigned as (S) on the basis of data reported in the literature. er = enantiomeric ratio.