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. 2022 Apr 13;144(14):6163-6172.
doi: 10.1021/jacs.2c01630. Epub 2022 Apr 4.

Decarboxylative Borylation and Cross-Coupling of (Hetero)aryl Acids Enabled by Copper Charge Transfer Catalysis

Nathan W Dow  1 , P Scott Pedersen  1 , Tiffany Q Chen  1 , David C Blakemore  2 , Anne-Marie Dechert-Schmitt  2 , Thomas Knauber  2 , David W C MacMillan  1
Affiliations

Decarboxylative Borylation and Cross-Coupling of (Hetero)aryl Acids Enabled by Copper Charge Transfer Catalysis

Nathan W Dow et al. J Am Chem Soc. .

Abstract

We report a copper-catalyzed strategy for arylboronic ester synthesis that exploits photoinduced ligand-to-metal charge transfer (LMCT) to convert (hetero)aryl acids into aryl radicals amenable to ambient-temperature borylation. This near-UV process occurs under mild conditions, requires no prefunctionalization of the native acid, and operates broadly across diverse aryl, heteroaryl, and pharmaceutical substrates. We also report a one-pot procedure for decarboxylative cross-coupling that merges catalytic LMCT borylation and palladium-catalyzed Suzuki-Miyaura arylation, vinylation, or alkylation with organobromides to access a range of value-added products. The utility of these protocols is highlighted through the development of a heteroselective double-decarboxylative C(sp2)-C(sp2) coupling sequence, pairing copper-catalyzed LMCT borylation and halogenation processes of two distinct acids (including pharmaceutical substrates) with subsequent Suzuki-Miyaura cross-coupling.

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Conflict of interest statement

The authors declare the following competing financial interest(s): D.W.C.M. declares a competing financial interest with respect to the Integrated Photoreactor.

Figures

Figure 1.
Figure 1.
Decarboxylative borylation and C–C cross-coupling of (hetero)aryl acids via Cu-LMCT catalysis.
Scheme 1.
Scheme 1.
Development of a Catalytic Cu-LMCT Decarboxylative Borylation Reaction: (a) Plausible Mechanism, (b) Key Components of Optimal Reaction Setup, (c) Summary of Optimization Studies, and (d) Control Reactions for Optimized Conditions aYields determined by 19F NMR. 0.1 M MeCN used in all cases. See SI for experimental details. B2Pin2, bis(pinacolato)diboron; NFSI, N-fluorobenzenesulfonimide.
Scheme 2.
Scheme 2.
Cu-LMCT Catalysis Sequence for Double-Decarboxylative Coupling of Two (Hetero)aryl Acidsb aYield determined by 1H NMR. bIsolated yields unless otherwise indicated. See SI for experimental details.
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