Copper‐Catalyzed Borocarbonylative Coupling of Internal Alkynes with Unactivated Alkyl Halides: Modular Synthesis of Tetrasubstituted β‐Borylenones

Abstract

Reported is ag eneral procedure to synthesize tetrasubstituted enones,w hich are borylated in the b-position, using acopper-catalyzed four-component coupling reaction of simple chemical feedstocks:i nternal alkynes,a lkylh alides, bis(pinacolato)diboron (B 2 pin 2 ), and CO.Ab road scope of highly functionalized b-borylated enones,al argely unknown class of organic compounds,c an be accessed efficiently using this method. The synthesis of all-carbon tetrasubstituted enones was realized by employing the b-borylated enone unit, without purification, in aS uzuki-Miyaura coupling.T he utility of the method was further demonstrated by various transformations, including halogenation, oxidation, and protodeboration, of the corresponding reduced oxaborole species to provided ensely substituted allylic alcohol and ketone products.

Transforming carbon dioxide and carbon monoxide into value-added products: boracarboxylation and boracarbonylation

“…In 2018, Mankad and co-workers developed borocarbonylative coupling to construct tetrasubstituted β-borylenones using B 2 pin 2 , CO, internal alkynes, and alkyl halides with [(SIMes) CuCl] as a catalyst and KOMe as the base. 88 This synthetic approach simplified the issues associated with using unactivated alkynes as a reagent and the difficulties in handling boron reagents while having the unique significance of generating the nucleophilic character at the β-position, which is contrary to the previous reports where the electrophilic center is generated via a distinctive umpolung of the enone moiety for easy borocarbonylation. 89 The synthetic method also demonstrated additional noteworthy characteristics, such as the first synthetic route for constructing tetrasubstituted enones and a rare instance of a four-component borocarbonylative coupling.…”

“…In due course, a stereodefined strategy for synthesizing cyclopropyl bis(boronates), the biologically active substances capable of modulating the activity and structural rigidity of a novel drug, was developed by Wu et al 95 In this approach, a novel catalyst system was invented for the borocarbonylation of unactivated alkenes, as the extension of Mankad et al 's report. 88 These stereodefined cyclopropyl bis(boronates) were obtained using [( Me IPr)CuCl] (4 mol%)/xanthphos (4 mol%; as the catalyst with B 2 pin 2 , under a CO (10 bar) atmosphere and NaOEt as the base. Under these best possible conditions, a wide range of alkenes with ethers, thioether, esters, amines, silane, and different cyclic substituents along with heterocyclic and natural product moieties were explored to afford the desired products in excellent yields (Scheme 40).…”

(CAAC)Copper Catalysis Enables Regioselective Three-Component Carboboration of Terminal Alkynes

“…[22] Based on this result, we questioned whether it would be possible to employ C(sp 3 )-based electrophiles in lieu of a proton to develop a three-component carboboration, with regioselectivity and product substitution patterns that would complement existing methodology. [23][24][25][26][27][28][29][30][31][32] Of relevance to this proposal, Xiao and Fu disclosed an important study in which the combination of CuCl (10 mol%) as precatalyst, DMAP (24 mol%) as ligand, and B2pai2 (pai = (+)-pinanediolato) as bis-boron reagent leads to branched-selective carboboration, though in this case yields and regioselectivity were variable (30-70% yield, 64:36-95:5 r.r.). The less common and more expensive B2pai2 nucleophile was employed to maximize regioselectivity, and some synthetically useful carbogenic groups were incompatible with this protocol (e.g., allyl electrophiles).…”