Photoredox catalyzed hydroazolylation of alkenes <i>via</i> phosphoranyl radicals

Zhu, Fan; Qiao, Zhi; He, Na; Nong, Chunxiao; He, Qiping; Xi, Meilan; Song, Xizhong; Lin, Jun; Chen, Jingbo; Jin, Yi

doi:10.1039/d4qo00233d

Cited by 2 publications

(2 citation statements)

References 34 publications

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“…23 However, N-H azoles have not been reported. Recent work by the groups of Zhang 24 and Chen 25 have demonstrated the feasibility of alkene hydroamination via heterocylic NCRs using N-functionalized azoles, such as N-pyridinium salts and hydroxybenzotriazoles, respectively. Thus, identification of a mild and general strategy for N-H bond activation of azoles could prove highly enabling in the development of this and numerous other reactions that deliver medicinally relevant heterocyclic products.…”

Section: Introductionmentioning

confidence: 99%

Cooperative Phosphine-Photoredox Catalysis Enables N–H Activation of Azoles for Intermolecular Olefin Hydroamination

Sedillo,

Fan,

Knowles

et al. 2024

Preprint

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Catalytic intermolecular olefin hydroamination is an enabling synthetic strategy that offers direct and atom-economical access to a variety of nitrogen-containing compounds from abundant feedstocks. However, despite numerous advances in catalyst design and reaction development, hydroamination of N–H azoles with unactivated olefins remains an unsolved problem in synthesis. We report a dual phosphine and photoredox catalytic protocol for the hydroamination of numerous structurally diverse and medicinally relevant N–H azoles with unactivated olefins. Hydroamination proceeds with high anti-Markovnikov regioselectivity and N-site selectivity. The mild conditions and high functional group tolerance of the reaction permit the rapid construction of molecular complexity and late-stage functionalization of bioactive compounds. N–H bond activation is proposed to proceed via polar addition of the N–H heterocycle to a phosphine radical cation, followed by P–N α-scission from a phosphoranyl radical intermediate. Reac-tivity and N-site selectivity are classified by heterocycle N–H BDFE and nitrogen-centered radical (NCR) spin density, respectively, which can serve as a useful predictive aid in extending the reaction to unseen azoles.

show abstract

Section: Introductionmentioning

confidence: 99%

Cooperative Phosphine-Photoredox Catalysis Enables N–H Activation of Azoles for Intermolecular Olefin Hydroamination

Sedillo,

Fan,

Knowles

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…23 However, N−H azoles have not been reported as competent substrates. Recent work by the groups of Zhang 24 and Chen 25 have demonstrated the feasibility of alkene hydroamination via heterocyclic NCRs using N-functionalized azoles, such as Npyridinium salts and hydroxybenzotriazoles, respectively. Thus, identification of a mild and general strategy for N−H bond activation of azoles could prove highly enabling in the development of this and numerous other reactions that deliver medicinally relevant heterocyclic products.…”

Section: ■ Introductionmentioning

confidence: 99%

Cooperative Phosphine-Photoredox Catalysis Enables N–H Activation of Azoles for Intermolecular Olefin Hydroamination

Sedillo,

Fan,

Knowles

et al. 2024

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Catalytic intermolecular olefin hydroamination is an enabling synthetic strategy that offers direct and atom-economical access to a variety of nitrogen-containing compounds from abundant feedstocks. However, despite numerous advances in catalyst design and reaction development, hydroamination of N−H azoles with unactivated olefins remains an unsolved problem in synthesis. We report a dual phosphine and photoredox catalytic protocol for the hydroamination of numerous structurally diverse and medicinally relevant N−H azoles with unactivated olefins. Hydroamination proceeds with high anti-Markovnikov regioselectivity and N-site selectivity. The mild conditions and high functional group tolerance of the reaction permit the rapid construction of molecular complexity and late-stage functionalization of bioactive compounds. N−H bond activation is proposed to proceed via polar addition of the N−H azole to a phosphine radical cation, followed by P−N α-scission from a phosphoranyl radical intermediate. Reactivity and N-site selectivity are classified by azole N−H BDFE and nitrogen-centered radical spin density, respectively, which can serve as a useful predictive aid in extending the reaction to unseen azoles.

show abstract

Photoredox catalyzed hydroazolylation of alkenes via phosphoranyl radicals

Abstract: Herein, a general protocol for the hydroazolylation of alkenes with N-hydroxyl azoles is reported. These reactions proceed via a phosphoranyl radical that is accessed by photoredox catalysis, followed by radical...

Cited by 2 publications

References 34 publications

Cooperative Phosphine-Photoredox Catalysis Enables N–H Activation of Azoles for Intermolecular Olefin Hydroamination

Cooperative Phosphine-Photoredox Catalysis Enables N–H Activation of Azoles for Intermolecular Olefin Hydroamination

Cooperative Phosphine-Photoredox Catalysis Enables N–H Activation of Azoles for Intermolecular Olefin Hydroamination

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