Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer

Zhang, Zhiqi; Sang, Yueqian; Wang, Chengqiang; Dai, Peng; Xue, Xiao‐Song; Piper, Jared L.; Peng, Zhihui; Ma, Jun‐An; Zhang, Fa‐Guang; Wu, Jie

doi:10.1021/jacs.2c05356

Cited by 86 publications

(38 citation statements)

References 73 publications

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“…boron-centered radicals where the boron atom is coordinated with a Lewis base, are more stable and provide a suitable entry for use in radical chemistry (Figure 1A). 9,10 In particular, N-heterocyclic carbene-based (NHC) boranes are emerging as a convenient source of LBRs: NHC boranes are stable crystalline compounds, and a diverse array of NHCs can be ligated to boranes allowing the LBR properties to be fine-tuned. 11 Notably, these boranes can be uniquely paired with photocatalysis to generate the targeted boron-centered radicals.…”

Section: ■ Introductionmentioning

confidence: 99%

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp³)–C(sp³) Bond Formation

et al. 2022

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Herein, we present a comprehensive study on the use of N-heterocyclic carbene (NHC)-ligated boryl radicals to enable C(sp3)–C(sp3) bond formation under visible-light irradiation via Halogen-Atom Transfer (XAT). The methodology relies on the use of an acridinium dye to generate the boron-centered radicals from the corresponding NHC-ligated boranes via single-electron transfer (SET) and deprotonation. These boryl radicals subsequently engage with alkyl halides in an XAT step, delivering the desired nucleophilic alkyl radicals. The present XAT strategy is very mild and accommodates a broad scope of alkyl halides, including medicinally relevant compounds and biologically active molecules. The key role of NHC-ligated boryl radicals in the operative reaction mechanism has been elucidated through a combination of experimental, spectroscopic, and computational studies. This methodology stands as a significant advancement in the chemistry of NHC-ligated boryl radicals, which had long been restricted to radical reductions, enabling C–C bond formation under visible-light photoredox conditions.

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Section: ■ Introductionmentioning

confidence: 99%

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp³)–C(sp³) Bond Formation

et al. 2022

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“…Meanwhile, Wu, Zhang, and Ma reported a photocatalytic method for hydrodifluoromethylation of unactivated alkenes using ClCF 2 H (Freon-22) as fluorine source, wherein in situ formed Me 3 N–BH 2 • could undergo chlorine atom transfer with ClCF 2 H to give HCF 2 • …”

Section: Lewis Base–boryl Radical Enabled Cabon–heteroatom Bond Activ...mentioning

confidence: 99%

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

2022

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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...

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“…The chemical transformations of boron-containing molecules have attracted tremendous interest in boron chemistry, showing practical synthetic utility and creating versatile new species for medicines and materials . In recent years, the prosperity of radical chemistry has promoted the rapid development of innovative synthetic paradigms of organoboron chemistry, in particular for the ligated boranes for borylations and other state-of-the-art transformations . However, the radical approaches leading to the B–H functionalization of polyhedral boranes are scarcely reported …”

Section: Introductionmentioning

confidence: 99%

Direct B–H Functionalization of Icosahedral Carboranes via Hydrogen Atom Transfer

Ren

Zhang

et al. 2023

J. Am. Chem. Soc.

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The efficient and selective functionalization of icosahedral carboranes (C 2 B 10 H 12 ) at the boron vertexes is a long-standing challenge owing to the presence of 10 inert B−H bonds in a similar chemical environment. Herein, we report a new reaction paradigm for direct B−H functionalization of icosahedral carboranes via B−H homolysis enabled by a nitrogen-centered radical-mediated hydrogen atom transfer (HAT) strategy. Both the HAT process of the carborane B−H bond and the resulting boroncentered carboranyl radical intermediate have been confirmed experimentally. The reaction occurs at the most electron-rich boron vertex with the lowest B−H bond dissociation energy (BDE). Using this strategy, diverse carborane derivatization, including thiolation, selenation, alkynylation, alkenylation, cyanation, and halogenation, have been achieved in satisfactory yields under a photoinitiated condition in a metal-free and redox-neutral fashion. Moreover, the synthetic utility of the current protocol was also demonstrated by both the scale-up reaction and the construction of carborane-based functional molecules. Therefore, this methodology opens a radical pathway to carborane functionalization, which is distinct from the B−H heterolytic mechanism in the traditional strategies.

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Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer

Cited by 86 publications

References 73 publications

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp³)–C(sp³) Bond Formation

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp³)–C(sp³) Bond Formation

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

Direct B–H Functionalization of Icosahedral Carboranes via Hydrogen Atom Transfer

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Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer

Cited by 86 publications

References 73 publications

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp3)–C(sp3) Bond Formation

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp3)–C(sp3) Bond Formation

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

Direct B–H Functionalization of Icosahedral Carboranes via Hydrogen Atom Transfer

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Product

Resources

About

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp³)–C(sp³) Bond Formation

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp³)–C(sp³) Bond Formation