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. 2022 Sep 16;12(18):11216-11225.
doi: 10.1021/acscatal.2c03805. Epub 2022 Sep 1.

The Merger of Benzophenone HAT Photocatalysis and Silyl Radical-Induced XAT Enables Both Nickel-Catalyzed Cross-Electrophile Coupling and 1,2-Dicarbofunctionalization of Olefins

Alberto Luridiana  1 , Daniele Mazzarella  1 , Luca Capaldo  1 , Juan A Rincón  2 , Pablo García-Losada  2 , Carlos Mateos  2 , Michael O Frederick  3 , Manuel Nuño  4 , Wybren Jan Buma  5 , Timothy Noël  1
Affiliations

The Merger of Benzophenone HAT Photocatalysis and Silyl Radical-Induced XAT Enables Both Nickel-Catalyzed Cross-Electrophile Coupling and 1,2-Dicarbofunctionalization of Olefins

Alberto Luridiana et al. ACS Catal. .

Abstract

A strategy for both cross-electrophile coupling and 1,2-dicarbofunctionalization of olefins has been developed. Carbon-centered radicals are generated from alkyl bromides by merging benzophenone hydrogen atom transfer (HAT) photocatalysis and silyl radical-induced halogen atom transfer (XAT) and are subsequently intercepted by a nickel catalyst to forge the targeted C(sp3)-C(sp2) and C(sp3)-C(sp3) bonds. The mild protocol is fast and scalable using flow technology, displays broad functional group tolerance, and is amenable to a wide variety of medicinally relevant moieties. Mechanistic investigations reveal that the ketone catalyst, upon photoexcitation, is responsible for the direct activation of the silicon-based XAT reagent (HAT-mediated XAT) that furnishes the targeted alkyl radical and is ultimately involved in the turnover of the nickel catalytic cycle.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(a) Strategies for generating radicals through metallaphotocatalysis. (b) 1,2-Functionalization reactions enabled by SET and HAT methods. (c) Synergistic use of benzophenone photocatalysis, silane-mediated XAT, and nickel catalysis enables various useful coupling reactions. (H)XAT: HAT-induced XAT, HAT: hydrogen atom transfer, XAT: halogen atom transfer, SET: single electron transfer, RA: redox auxiliaries, PC: photocatalyst.
Figure 2
Figure 2
Survey of the aryl bromide and alkyl bromide reaction partners for the photocatalytic C(sp2)–C(sp3) cross-coupling protocol. Reaction conditions: aryl bromide (0.5 mmol), BP I (20 mol %), Ni II (5 mol %), 2,6-lutidine (1.1 equiv), (TMS)3SiH (1.5 equiv) at room temperature (rt) in Vapourtec UV-150 reactor (λ = 365 nm, 16 W, reactor volume: 10 mL, flow rate: 0.22 mL min–1, τ: 45 min). Yields refer to isolated products. aMeOTs as coupling partner (2.5 equiv) and TBABr as bromide source (2.5 equiv). bReactions performed in batch (16 h) using PhCF3 as solvent (see the Supporting Information). cReactions performed in batch (16 h) using Na2CO3 (1.5 equiv) instead of 2,6-lutidine. Bpin: Pinacol boronic ester, TBABr: tetrabutylammonium bromide.
Figure 3
Figure 3
Survey of the aryl bromides, alkyl bromides, olefins, and acyl chlorides that can participate in the photochemical protocol. Reaction conditions: aryl bromide or acyl chloride (0.5 mmol), BP I (20 mol %), Ni II (5 mol %), 2,6-lutidine (1.1 equiv), (TMS)3SiH (2 equiv) at rt, irradiated at 390 nm for 16 h. Yields refer to isolated product. a,1:1 d.r, b.20:1 d.r.. BP: benzophenone, Cbz: benzyloxycarbonyl, Bpin: pinacol boronic ester.
Figure 4
Figure 4
(a) Photoexcitation of benzophenone entails the hydrogen atom abstraction from the silane. (b) Microsecond triplet–triplet differential absorption spectra recorded at different times after laser excitation of the employed BP I in deoxygenated acetonitrile with a 5 ns laser pulse at 319 nm in the presence of an excess of (TMS)3SiH (8.6 equiv). (c) Comparison of microsecond triplet–triplet differential absorption spectra recorded at 50 μs after 319 nm excitation in the presence of (red dash) (TMS)3SiH (8.6 equiv) and (green dash) tetrahydrofuran (8.6 equiv).
Figure 5
Figure 5
Radical clock experiments. (a) Reaction with (bromomethyl)cyclopropane 55 affords product 56, yield refers to isolated product; (b) reaction with 6-bromo-1-hexene 58 affords a mixture of uncyclized product 59 and cyclized product 60, yields were calculated by gas chromatography–mass spectrometry (GC–MS).
Figure 6
Figure 6
(a) Evaluation of the influence of the nickel loading on the ratio of uncyclized and cyclized products. Reactions performed in the optimized conditions (as in Table 1, entry 1), varying the loading of nickel. (b) Evaluation of the influence of the nature of the aryl bromide on the ratio of uncyclized and cyclized products. Reactions performed in the optimized conditions (as in Table 1, entry 1) with 2.5 mol % of Ni II.
Figure 7
Figure 7
Proposed reaction mechanism for the (H)XAT cross-electrophile coupling.
See this image and copyright information in PMC

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