Lewis Base–Boryl Radicals Enabled Borylation Reactions and Selective Activation of Carbon–Heteroatom Bonds

Abstract

Metrics & MoreArticle Recommendations CONSPECTUS:The past decades have witnessed tremendous progress on radical reactions. However, in comparison with carbon, nitrogen, oxygen, and other main group element centered radicals, the synthetic chemistry of boron centered radicals was less studied, mainly due to the high electron-deficiency and instability of such 3-center−5-electron species. In the 1980s, Roberts and co-workers found that the coordination of a Lewis base (amines or phosphines) with the boron center could form 4-center−7-electron boryl radicals (Lewis base−boryl radicals, LBRs) that are found to be more stable. However, only limited synthetic applications were developed. In 2008, Curran and co-workers achieved a breakthrough with the discovery of N-heterocyclic carbene (NHC) boryl radicals, which could enable a range of radical reduction and polymerization reactions. Despite these exciting findings, more powerful and valuable synthetic applications of LBRs would be expected, given that the structures and reactivities of LBRs could be easily modulated, which would provide ample opportunities to discover new reactions. In this Account, a summary of our key contributions in LBR-enabled radical borylation reactions and selective activation of inert carbon−heteroatom bonds will be presented. Organoboron compounds have shown versatile applications in chemical society, and their syntheses rely principally on ionic borylation reactions. The development of mechanistically different radical borylation reactions allows synthesizing products that are inaccessible by traditional methods. For this purpose, we progressively developed a series of NHC−boryl radical mediated chemo-, regio-, and stereoselective radical borylation reactions of alkenes and alkynes, by which a wide variety of structurally diverse organoboron molecules were successfully prepared. The synthetic utility of these borylated products was also demonstrated. Furthermore, we disclosed a photoredox protocol for oxidative generation of NHC−boryl radicals, which enabled useful defluoroborylation and arylboration reactions. Selective bond activation is an ideal way to convert simple starting materials to value-added products, while the cleavage of inert chemical bonds, in particular the chemoselectivity control when multiple identical bonds are present in similar chemical environments, remains a long-standing challenge. We envisaged that finely tuning the properties of LBRs might provide a new solution to address this challenge. Recently, we disclosed a 4-dimethylaminopyridine (DMAP)−boryl radical promoted sequential C−F bond functionalization of trifluoroacetic acid derivatives, in which the α-C−F bonds were selectively snipped via a spin-center shift mechanism. This strategy enables facile conversion of abundantly available trifluoroacetic acid to highly valuable mono-and difluorinated molecules. Encouraged by this finding, we further developed a boryl radical enabled three-step sequence to construct all-carbon quaternary centers from a range of trich...

Selective Defluoroalkylation and Hydrodefluorination of Trifluoromethyl Groups Photocatalyzed by Dihydroacridine Derivatives

“…These results suggest that one equivalent of CyS – acts as a reductant to reduce the ACR-4 ·+ , while the other participates in hydrogen atom transfer (HAT), resulting in the formation of CySSCy (the detailed mechanism is given in Supporting Information). B(OAc) 3 ·– was speculated to possess reductive properties similar to BH 4 ·– and BH 3 CN ·– , − and it could potentially be generated in the reaction through HAT between CyS · and BH(OAc) 3 – . In order to investigate the potential of B(OAc) 3 ·– to reduce the trifluoromethyl substrate and generate the gem -difluomethylene radical, cyclohexyl disulfide was employed as an initiator to generate B(OAc) 3 ·– .…”

Boryl radical catalysis enables asymmetric radical cycloisomerization reactions

“…During the course of our study on NHC–boryl radical–triggered cascade cyclization reactions ( 41 ), we hypothesized that if a cascade could generate a β-boryl alkyl radical intermediate, β-elimination would take place to liberate the boryl radical, thereby completing a radical catalytic cycle. Furthermore, our previous work had revealed that the regioselectivity of the boryl radical addition to alkynes was tunable by varying the alkynyl substituents ( 45 , 50 ).…”

“…N -heterocyclic carbene (NHC)–boryl radicals, a class of boron-centered radicals ligated with an NHC component, have shown specific chemical reactivity and have recently found application in chemical synthesis ( 41 , 42 ) since the pioneering work by the groups of Fensterbank, Lacôte, Malacria, and Curran ( 43 ). These radicals can be easily generated from readily available NHC-BH 3 complexes through hydrogen atom abstraction with the aid of a radical initiator ( 43 ).…”

Preparation of Mono and Bis‐Hydrazino‐Substituted N‐Heterocyclic Carbene Boranes

“…N-Heterocyclic carbene (NHC) complexes of boranes have rapidly emerged as outstanding reagents for synthetic chemistry. [1,2] They are for example highly useful as hydrogen atom donors for radical chemistry, [3,4] or for the radical [5][6][7] or other [8][9][10][11] borylation of substrates, including the initiation of radical polymerizations. [12][13][14][15][16] Recent trends involve transient NHC-boron species that can be used catalytically.…”