Stereospecific Acylative Suzuki–Miyaura Cross-Coupling: General Access to Optically Active α-Aryl Carbonyl Compounds

Abstract

A novel strategy for the stereospecific Pd-catalyzed acylative cross-coupling of enantiomerically enriched alkylboron compounds has been developed. The protocol features an extremely high level of enantiospecificity to allow facile access to synthetically challenging and valuable chiral ketones and carboxylic acid derivatives. The use of a sterically encumbered and electronrich phosphine ligand proved to be crucial for the success of the reaction. Furthermore, on the basis of experimental and computational studies, a unique mechanism for the transmetalation, assisted by the noncovalent interactions of the C(sp 3 )-based organoboron reagent, has been identified.

Rapid, Homogenous, B-Alkyl Suzuki–Miyaura Cross-Coupling of Boronic Esters

“…The challenges with this important cross-coupling stem from the slow transmetalation of alkylboronates, and the ability of alkylboronates to undergo β-hydride elimination prior to transmetalation or before reductive elimination. To address these problems, many reports leverage the use of bulky, electron-rich ligands ,, as well as the use of directing groups at proximal and distal positions, such as benzyl groups, ethers, carbonyl groups, geminal 1,1- and 1,2-diboronates, and even hydroxides, to affect a variety of B-alkyl cross-couplings. Often, aqueous conditions are employed by necessity, as both potassium trifluoroborates and MIDA boronates require hydrolysis prior to transmetalation, ,, or for solubilization of an inorganic base.…”

Synthesis of Chiral α-Aryl Ketones by Photoredox/Nickel-Catalyzed Enantioconvergent Acyl Cross-Coupling with Organotrifluoroborate

“…The only example was palladium-catalyzed stereoinversive acylative synthesis of chiral ketone with chiral organotrifluoroborate via the path all involving close-shell intermediates (Scheme 1b). 13 Herein, we developed an effective method of synthesizing an α-chiral ketone from racemic organotrifluoroborate under neutral ambient conditions by merging nickel-catalyzed asymmetric acylative cross-coupling with photoredox catalysis (Scheme 1c).…”

“…Organotrifluoroborate offers an important alternative to boronic acids in the challenging C­(sp 3 ) coupling of secondary alkyl fragments. , Distinct from boronic acids, the cross-coupling with organotrifluoroborate under anhydrous base-free conditions at low temperature took place more rapidly. , Moreover, secondary alkyl radicals are easily provided by oxidizing corresponding alkyltrifluoroborates. , Meanwhile, the utility of organotrifluoroborate in the asymmetric acylative synthesis of α-chiral ketones was underdeveloped. The only example was palladium-catalyzed stereoinversive acylative synthesis of chiral ketone with chiral organotrifluoroborate via the path all involving close-shell intermediates (Scheme b) . Herein, we developed an effective method of synthesizing an α-chiral ketone from racemic organotrifluoroborate under neutral ambient conditions by merging nickel-catalyzed asymmetric acylative cross-coupling with photoredox catalysis (Scheme c).…”

Palladium‐Catalyzed Ring‐Opening Diarylation of Cyclobutanols for the Synthesis of Acylindanes

“…To date, only a few examples for the preparation of acylindanes have been reported. [6] Hu group described a palladiumcatalyzed defluorination of gem-difluoroalkenes with aryl boronic acids and H 2 O for ketone synthesis. [7] Studer and co-worker also developed a benzylic CÀ H acylation by NHC/photoredox dual catalysis, with two indanes as substrate.…”