A Lewis Base Catalysis Approach for the Photoredox Activation of Boronic Acids and Esters

Abstract

Abstract:We report herein the use of ad ual catalytic system comprising aL ewis base catalyst such as quinuclidin-3-ol or 4-dimethylaminopyridine and ap hotoredox catalyst to generate carbon radicals from either boronic acids or esters.T his system enabled awide range of alkylboronic esters and aryl or alkylb oronic acids to react with electron-deficient olefins via radical addition to efficiently form C À Cc oupled products in aredox-neutral fashion. The Lewis base catalyst was shown to form ar edox-active complex with either the boronic esters or the trimeric form of the boronic acids (boroxines) in solution.Carbon-centered radicals are as ynthetically powerful class of reactive intermediates.[1] They are particularly attractive in the context of C À Cb ond-forming reactions, [2] overcoming problems often associated with two-electron processes.[3] By enabling visible-light-promoted single electron transfer, photoredox catalysis has become am ethod of choice for the single-electron reduction or oxidation of organic substrates and allows to generate open-shell intermediates in amild and selective fashion.[4] Ar ange of reductive or oxidative carbon radical precursors are now available to generate carbon radicals in the context of ap hotocatalytic cycle.[5] Oxidative carbon radical precursors are often anionic species suffering from poor solubility in common organic solvents.F or example,e xtensively studied organoborates [6] possess an electron-rich B(sp 3 )m oiety that can be subjected to singleelectron oxidation, leading to an eutral carbon radical after CÀBbond cleavage (Scheme 1A).Despite their ubiquity as reagents in organic synthesis [7] and in biologically active molecules, [8] theuse of boronic acid derivatives to generate carbon-centered radicals remains underexplored.[9] Owing to their high oxidation potentials, they have received much less attention in this regard, with few reports making use of strong stoichiometric oxidants or anodic oxidation.[10] We recently demonstrated that benzyl boronic esters can undergo single-electron oxidation under photoredox conditions when their vacant porbital is engaged in ad ative bond with the norbital of as toichiometric Lewis base (LB) additive (Scheme 1B).[11] Lewis base catalysis was introduced as aconcept by Denmark to enhance the reactivity of electrophilic n*, p*, and s*orbitals.[12] Based on this knowledge,w eh ypothesized that the use of ac atalytic amount of an organic Lewis base would be av iable option for the photoredox activation of boronic acids and esters. [13] Herein, we describe adual catalytic method to effectively form alkyl and aryl radicals from aw ide array of boronic esters and acids by direct photoredox single-electron oxidation under mild and safe conditions,without the requirement for stoichiometric activators or oxidants.T hese reactive species were further engaged in intermolecular C À Cb ondforming processes to deliver desirable C(sp 3 )ÀC(sp 3 )a nd C(sp 2 )ÀC(sp 3 )bonds in ar edox-neutral fashion. Thea ddition of electron-rich carbon...

Practical and Modular Construction of C(sp3)-Rich Alkyl Boron Compounds

“…To that end, the stability of a series of alkyl boronic acids were evaluated under Barluenga-Valdés conditions (Figure 1C). Gratifyingly, although the benzylic (3) and allylic (4) boronic acids decomposed rapidly (<10 min) under these conditions, simple primary, secondary, and tertiary alkyl boronic acids (5)(6)(7), demonstrated remarkable stability (>5 h) to the basic and heat conditions. Based on these results, we surmised that direct access to complex alkylboronic acids 2 could be achieved in a simple and modular fashion from the readily available sulfonylhydrazone and alkylboronic acid building blocks via 1 2-metallate rearrangement of the zwitterion intermediate 1.…”

“…Additionally, transition metal-mediated cross-coupling, a "go-to" approach to access diverse chemical space 4 , has more recently enabled the construction of a variety of C(sp 3 )-C(sp 3 ) bonds. However, this process remains a very challenging undertaking 5 owing to the propensity of intermediary metal-alkyl complexes to undergo b-hydride elimination 6,7 . As such, complex hydrocarbons are often assembled in "roundabout" ways, leading to non-modular, linear processes and detracting from overall efficiency.…”

Generation of Alkyl Radicals: From the Tyranny of Tin to the Photon Democracy

“…The resulting cyclobutyl radical was trapped by methyl vinyl ketone to access the substituted ketone 5 – 2 in a good yield. 100 This reaction was later scaled up under flow conditions by using the Photosyn reactor. In such a way, the authors could synthesize gram amounts per hour of the analogues of some drugs belonging to the GABA family.…”

Advances in the Synthesis of Imine‐Containing Azaarene Derivatives via Photoredox Catalysis

“…Subsequently, the groups of Rueping, Ravelli, Ley and so on subsequently reported conjugate additions of diverse radicals to vinylazaarenes by using different photocatalytic methods (Scheme ). Among them, Ravelli exploited a hydrogen‐atom‐transfer (HAT) catalytic strategy to form radical intermediates, but the use of vinylazaarenes as the substrates in these transformations will be discussed herein.…”

“…In the same year, the Ley group described the employment of a dual catalytic system comprising a Lewis base catalyst and a photoredox catalyst to generate carbon radicals from either boronic acids or esters, which were added to various electron‐deficient olefins (Scheme C) . Although most olefins were activated by ketones or esters, they also tested 2‐vinylpyridine ( 12 a ), 4‐vinylpyridine ( 12 b ) and 2‐(1‐phenylvinyl)pyridine 35 a in the reaction with boronic ester 38 using 2.0 mol% Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 as a photoredox catalyst and 20 mol% quinuclidin‐3‐ol as a Lewis base catalyst at 30 °C.…”