“Cationic” Suzuki–Miyaura Coupling with Acutely Base-Sensitive Boronic Acids

Abstract

Fast, base-promoted protodeboronation of polyfluoroaryl and heteroaryl boronic acids complicates their use in Suzuki-Miyaura coupling (SMC) because a base is generally required for catalysis. We report a "cationic" SMC method using a PAd-Pd catalyst that proceeds at rt in the absence of a base or metal mediator. A wide range of sensitive boronic acids, particularly polyfluoroaryl substrates that are poorly compatible with classic SMC conditions, undergo clean coupling. Stoichiometric experiments implicate the intermediacy of organopalladium cations, which supports a long-postulated cationic pathway for transmetalation in SMC.

Orthogonal Nanoparticle Catalysis with Organogermanes

“…[11] TheS uzuki-Miyaura cross-coupling of organoboron reagents with aryl halides is most widely and ubiquitously used among organic,medicinal, and materials chemists in academia and industry, [12] as the established alternatives can be associated with basicity, instability (organomagnesium and -zinc reagents), toxicity (organotin), or lower reactivity.Despite its relative mildness, broad scope,and high reactivity,this popular coupling class is not free of challenges,h owever.T hese include,f or example, the occasional instability of boronic acids,w hich is particularly pronounced in the case of 2-pyridyl-and multifluoroarylboronic acids and further aggravated by the presence of (and need for) base. [13] Ingenious masking strategies [14,15] or elegantly more reactive systems that make use of aryl diazonium salts as acceptors [16] have been developed to balance the relative kinetics of deactivation versus productive cross-coupling in these cases. [17] Some toxicity concerns in conjunction with organoboron compounds and their deriva-tives have recently also been reported, [18] which may create an eed for alternative approaches in certain applications (Figure 1).…”

Orthogonal Nanoparticle Catalysis with Organogermanes

“…We aspired to widen the conceptual coupling repertoire and focused on organogermanium compounds.P romisingly, no toxicity has been associated with this compound class, [19] and our stability tests of ap entafluoroaryl germane (Ar-GeEt 3 ,A r = C 6 F 5 )i ndicated that as opposed to the corresponding boronic acid, which has al ifetime of milliseconds, [13,16] ArGeEt 3 remains completely stable even upon subjection to acid (HCl) or base (NaOH, KF) for 2h at 90 8 8C ( Figure 2). [20] Similarly the 2-pyridyl derivative proved to be fairly stable under basic conditions but was sensitive to acid.…”

“…Thec ase of pentafluorophenylboronic acid has long been ac hallenge because of its propensity to undergo protodeboronation, [13] typically requiring "designer" conditions. [16] To our delight, when we performed the coupling of triethyl(pentafluorophenyl)germane with aryl iodides,w e obtained near-quantitative yields (27,28). Moreover,g ood yields were obtained also for heterocyclic variants,that is,the 2-and 3-germylated thiophene (24)(25)(26)o rf uran (19,20) reagents.E ven the most challenging substrates,2 -pyridyl germanes,p roved to be robust and stable and allowed for efficient cross-couplings (21-23, 39, 40).…”

Visible‐Light‐Induced Selective Defluoroborylation of Polyfluoroarenes, gem‐Difluoroalkenes, and Trifluoromethylalkenes

“…(Perfluorophenyl)boronic acid 9 was produced in high yield by asimple bromination/hydrolysis cascade,w hich has been widely utilized in cross-coupling reactions to deliver valuable polyfluoroarene compounds. [8] Tr eatment of borane 3a with phenyl bromide under palladium-catalyzed cross-coupling conditions led to mono-(10 a)a nd di-arylation (10 b)o ft he NHC part of 3a in 17 %a nd 35 %y ield, respectively.T he mono-defluoroborylation product 3a could undergo further defluoroborylation to achieve 1,4-diborane product 11 in good yield. Thereaction between 3a and Selectfluor afforded borane difluoride 12 in high yield, which could act as aboronic acid equivalent in further diversifications.…”

“…[7] In this context, fluorinated organic boranes can serve as versatile synthetic precursors to obtain distinct organic fluorides through aw ide spectrum of established and reliable derivatization reactions. [8] Them ost straightforward way to access fluorinated organic borane building blocks is selective C À F bond borylation of polyfluorinated organic compounds. However,t his is inherently challenging for several reasons: 1) TheC ÀFb ond is among the most unreactive functional groups.…”