Directing Group‐Free Formal Suzuki–Miyaura Coupling of Simple Ketones Enabled by Activation of Unstrained C−C Bonds

Abstract

The use of ketones as electrophiles to couple with arylboronic acid derivatives via CÀ C bond activation has become a significant progress in the area of Suzuki-Miyaura coupling (SMC) reaction, in which a permanent or temporary directing group is often required to promote the activation of the unstrained CÀ C bond via oxidative addition. Herein, we disclosed the first example of directing group free formal SMC reaction of simple ketones with arylboronates via Rhcatalyzed unstrained CÀ C bond activation. A wide range of simple ketones, including aryl alkyl ketones, diaryl ketones and aryl perfluoroalkyl ketones, can serve as electrophiles to participate in the SMC reaction with aryl or perfluoroalkyl as the leaving group. The key to the success of this reaction is by means of nucleophilic addition/β-carbon elimination sequence that can activate the unstrained ketone carbonyl CÀ C bond without the assistance of directing group.

Activation of Unstrained Ketone C(O)–C Bond: 1,2-Nucleophilic Addition Followed by β-Carbon Elimination Strategy

“…Based on these results and previous reports, , a plausible catalytic pathway was proposed as shown in Scheme f. The catalytic cycle was initiated by oxidative addition of in situ formed Pd(0) with bromoarene to generate intermediate A , which was followed by ligand exchange to give complex B .…”

“…Prompted by the achievement of C–C activation of unstrained tertiary alcohols and the shuttle arylation between unstrained alcohols and ketones, , we envisioned that a C–C bond activation reaction of unstrained ketone could be realized by a 1,2-addition of a nucleophile to the carbonyl moiety, followed by β-carbon elimination. Recently, Xia’s group reported a rhodium-catalyzed formal Suzuki–Miyaura coupling reaction of unstrained ketones through a β-carbon elimination strategy enabled by nucleophilic addition of an aryl moeity (Scheme c) . Despite the great progress made in C–C activation of unstrained ketones, arylation of a heterocyclic compound, which could act as a useful structural motif frequently encountered in natural products, drugs, and organic materials, was less studied .…”

“…Recently, Xia's group reported a rhodium-catalyzed formal Suzuki−Miyaura coupling reaction of unstrained ketones through a β-carbon elimination strategy enabled by nucleophilic addition of an aryl moeity (Scheme 1c). 7 Despite the great progress made in C−C activation of unstrained ketones, arylation of a heterocyclic compound, which could act as a useful structural motif frequently encountered in natural products, 8 drugs, 9 and organic materials, 10 substrates. After screening a series of reaction parameters, the desired 2-phenylpyridine N-oxide product (3b) could be obtained in 91% yield in the presence of 10 mol % Pd(TFA) 2 as catalyst, 20 mol % DPEphos as ligand, and 2 equiv of Cs 2 CO 3 in THF (2 mL) under air atmosphere (Table 1, entry 1), and benzoic acid was obtained as the CO-containing byproduct.…”

Aldehyde Olefination with Arylboroxines Enabled by Binary Rhodium Catalysis

“…Thus, alternative protocols for the efficient and straightforward construction of olefins from aldehydes are highly desirable. Following our research interests in rhodium catalysis, we herein disclosed a straightforward strategy for aldehyde olefination with arylboroxines enabled by binary rhodium catalysis under neutral and air conditions. A mechanistic study reveals that the in situ generated Rh­(III) species is in charge of an unusual dehydration process in which the alkoxy–metal intermediate undergoes an oxygen-directed C–H activation followed by β-oxygen elimination (Scheme C).…”

De novo construction of chiral 3‑oxindoles via organocatalyzed enantioselective ortho-Friedel-Crafts addition/novel [1,2]-ester migration

“…However, the enantioselective ortho-C-H addition to ketones was mentioned scarcely due to its low reactivity and di culties in enantiocontrol. In addition, β-carbon elimination [33][34][35] of the unstrained tertiary alcohols is usually inclined to be occurred in the presence of transition metal as the catalyst. For ortho-Friedel-Crafts addition with the CPA catalyst, the para-selectivity is usually preferred [36][37][38][39][40] .…”