Enabling the Cross-Coupling of Tertiary Organoboron Nucleophiles through Radical-Mediated Alkyl Transfer

Abstract

The construction of quaternary centers is a common challenge in the synthesis of complex materials and natural products. Current cross-coupling strategies that can be generalized for setting these centers are sparse and, when known, are typically predicated on the use of reactive organometallic reagents. To address this shortcoming a new, photoredox-Ni dual catalytic strategy for the cross-coupling of tertiary organoboron reagents with aryl halides is reported. In addition to details on the cross-coupling scope and limitations, full screening efforts and mechanistic experiments are communicated.

Figure 1

Plausible catalytic cycle and key mechanistic experiments. (A) Previously developed conditions for alkyltrifluoroborate coupling. (B) Oxidation experiment and cyclic voltammetry analysis of 13. (C) Stoichiometric experiments with Ni(II) oxidative addition complex 15.

Figure 2

Constrained cyclic alkyltrifluoroborates in cross-coupling.

Figure 3

Aryl bromide scope in the cross-coupling of potassium tert-butyltrifluoroborate under the developed conditions. ‡Reactions irradiated with four H150 blue LED Kessil lamps.

Figure 4

Further aryl bromide scope evaluation with enone derived alkyltrifluoroborate 38

Figure 5

(A) Tertiary alkyltrifluoroborate scope with electron poor aryl bromides. (B) Comparison of enone- and enoate-derived trifluoroborate cross-coupling to metal-catalyzed 1,4-addition chemistry.