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

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.

Ligand‐to‐Metal Charge Transfer (LMCT) Photochemistry at 3d‐Metal Complexes: An Emerging Tool for Sustainable Organic Synthesis

“…This disparity is a consequence of the slower rate of CO 2 extrusion (10 9 M −1 s −1 for alkyl, 10 6 M −1 s −1 for aryl) on the carboxyl radical, [56–59] which results in inefficient generation of aryl radicals that is overpowered by other faster side reactions, such as hydrogen atom transfer (HAT) or back electron transfer from PC ⋅ − generating a deactivated, ground‐state photocatalyst ( PC ). Interestingly, recent works by the Ritter and MacMillan groups have shown how LMCT activation at Cu(II) can overcome this challenge, enabling radical decarboxylative functionalization of benzoic acids [60–63] . The explanation of this distinct behavior has its roots in the reversible nature of the Cu−O homolysis step, providing an efficient stabilization of the benzoyl radical within the solvent cage and allowing an effective subsequent decarboxylation.…”

Visible light-enabled regioselective chlorination of coumarins using CuCl2via LMCT excitation

“…18 More recently, the Macmillan group reported the decent applications of Cu(MeCN) 4 PF 6 -mediated LMCT to direct decarboxylative halogenation and borylation of aromatic carboxylic acids. 19 Inspired by these fascinating findings, we wish to use this photocatalytic LMCT strategy to generate chlorine radicals to chlorinate coumarins under mild conditions, circumventing the use of strong oxidants or highly oxidative photoredox catalysts. Herein, we report a visible light-enabled chlorination of coumarins and other electron-deficient heteroarenes or olefins using CuCl 2 as a simple LMCT reagent and HCl or LiCl as the halogen source in the presence of air as the terminal oxidant (Scheme 1C).…”

Cu-Catalyzed decarboxylative annulation of N-substituted glycines with 3-formylchromones: synthesis of functionalized chromeno[2,3-b]pyrrol-4(1H)-ones

“…In synthetic organic chemistry, one of the most impactful events in recent years is the introduction of transition-metal catalyzed cross-coupling reactions. Among them, the decarboxylative cross-coupling of carboxylic acids is perhaps one of the most efficient methods of forming C–C, 1,2 C–N, 3 C–O, 4 C–S, 5 C–X, 6 and C–B bonds 7 among others 8 because of their well-known reliability, selectivity, and predictability. 1–5 As a result, more and more strategies have been developed to form the target compounds.…”

“…[1][2][3][4][5] As a result, more and more strategies have been developed to form the target compounds. [1][2][3][4][5][6][7][8] Only some examples of the reactions from the decarboxylative cross-coupling of carboxylic acids have been used to construct some kinds of natural-like heterocyclic compounds via the annulation reaction with amines (forming the C-N bonds) 9 and enolizable substrates (forming the C-C bonds). 10 There have been rare studies reported on the annulation of carboxylic acids with the acyl group of aldehydes (i.e., forming the C-C bonds) (Scheme 1).…”

“…Fortunately, when toluene was used as the solvent, this reaction proceeded smoothly and generated the target compound with a good yield (81%) (Table 1, entry 5), demonstrating that toluene was the optimal solvent. Accordingly, different oxidants tert-Butyl hydroperoxide (TBHP), K 2 S 2 O 8 , and air were used, but the reaction did not progress smoothly (Table 1, entries [6][7][8]. This demonstrated that DTBP was the optimal oxidant for this reaction.…”