Catalytic radical generation of π-allylpalladium complexes

Huang, Huan‐Ming; Koy, Maximilian; Serrano, Eloisa; Pflüger, Philipp Miro; Schwarz, J. Luca; Glorius, Frank

doi:10.1038/s41929-020-0434-0

Cited by 156 publications

(92 citation statements)

References 68 publications

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“…1b) 21,22 . Such transformations include desaturation 23 , reduction 24 , addition to (hetero)arenes 25 , carbonylation 26 , and 1,4-difunctionalization of conjugated dienes [27][28][29] . By applying this strategy, the Gevorgyan group reported the first visible light-induced Pd-catalyzed Mizoroki-Heck reaction of alkyl bromides and iodides 30 .…”

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confidence: 99%

Pd-catalyzed formal Mizoroki–Heck coupling of unactivated alkyl chlorides

2021

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The use of alkyl chlorides in Pd-catalyzed Mizoroki–Heck coupling reactions remains an unsolved problem despite their significant potential for synthetic utility and applicability. The combination of the high thermodynamic barrier of alkyl chloride activation and kinetic propensity of alkylpalladium complexes to undergo undesired β-hydride elimination provides significant challenges. Herein, a variety of alkyl chlorides, even tertiary chlorides, are shown to efficiently participate in Mizoroki–Heck cross-coupling reactions with excellent functional group compatibility under mild reaction conditions via photoinduced Pd catalysis. The reaction is applied to late-stage functionalizations of diverse biologically significant scaffolds and iterative double Mizoroki–Heck annulations, affording high molecular complexity in a single step. Notably, studies on the kinetic isotope effects in combination with density functional theory (DFT)-computations completely exclude the involvement of a previously proposed β-hydride elimination in the catalytic cycle, revealing that the chlorine atom transfer process is the key catalytic turnover step. This distinctive single-electron transfer mediated reaction pathway resolves a longstanding challenge in traditional two-electron based Pd-catalyzed Mizoroki–Heck cross-coupling with alkyl electrophiles, wherein the β-hydride elimination is involved in the formation of both the desired product and undesired by-products.

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confidence: 99%

Pd-catalyzed formal Mizoroki–Heck coupling of unactivated alkyl chlorides

2021

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“…Applying the photoinduced Pd catalysis, Gevorgyan and co-workers first succeeded in developing the photoinduced Pd-catalyzed Heck reaction of alkyl halides by utilizing Pd(I)/alkyl radical hybrid species generated by single-electron transfer (SET) activation 37 , 38 . Further elegant achievements have been reported for various synthetically useful reactions, including Heck reaction 28 , 34 , 39 – 41 , desaturation 31 , hydrodehalogenation 42 , C–H alkylation of (hetero)arenes 16 , 19 , carbonylation 36 , and 1,4-difunctionalization of conjugated dienes 32 , 43 , 44 , exploring the Pd catalysis under visible light irradiation.…”

Section: Introductionmentioning

confidence: 99%

Direct C(sp2)–H alkylation of unactivated arenes enabled by photoinduced Pd catalysis

et al. 2020

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Despite the fundamental importance of efficient and selective synthesis of widely useful alkylarenes, the direct catalytic C(sp2)–H alkylation of unactivated arenes with a readily available alkyl halide remains elusive. Here, we report the catalytic C(sp2)–H alkylation reactions of unactivated arenes with alkyl bromides via visible-light induced Pd catalysis. The reaction proceeds smoothly under mild conditions without any skeletal rearrangement of the alkyl groups. The direct syntheses of structurally diverse linear and branched alkylarenes, including the late-stage phenylation of biologically active molecules and an orthogonal one-pot sequential Pd-catalyzed C–C bond-forming reaction, are achieved with exclusive chemoselectivity and exceptional functional group tolerance. Comprehensive mechanistic investigations through a combination of experimental and computational methods reveal a distinguishable Pd(0)/Pd(I) redox catalytic cycle and the origin of the counter-intuitive reactivity differences among alkyl halides.

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“…The paradigm of merging transition metal catalysis with photocatalysis has invoked mechanistic wonders in cross-coupling reactions [14][15][16][17][18][19][20][21][22] . This rede ning of chemistry is forged either by a modulated oxidation state or in situ generation of an excited catalytic species through energy transfer 23 .…”

Section: Main Textmentioning

confidence: 99%

Photoinduced regioselective olefination of arenes at proximal and distal sites

Saha¹,

Guin²,

Ali³

et al. 2020

Preprint

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The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C-H activation protocols. Despite the applicability of the traditional approach in different fields, the associated reactivity and regioselectivity issues had rendered it redundant. The revival of this exemplary reaction requires the development of a mechanistic paradigm that would have simultaneous control on both the reactivity and regioselectivity. Often high thermal energy required to promote olefination leads to multiple site functionalization. To this aim we established a photoredoxcatalytic system constituting a merger of palladium/organo-photocatalyst that forges oxidative olefination in an explicit regioselective fashion of diverse arenes and heteroarenes. Visible light plays a significant role in executing ‘regio-resolved’ Fuijiwara-Moritani reaction without the requirement of silver salts and thermal energy. The catalytic system is also amenable towards proximal and distal olefination aided by respective directing groups (DGs), which entails the versatility of the protocol in engaging the entire spectrum of C(sp2)-H olefination. Furthermore, streamlining the synthesis of natural products, chiral molecules, drugs and diversification through late-stage functionalizations underscore the importance of this sustainable protocol. The photoinduced attainment of this regioselective transformation is mechanistically established through control reactions, kinetic studies and theoretical calculations.

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Catalytic radical generation of π-allylpalladium complexes

Cited by 156 publications

References 68 publications

Pd-catalyzed formal Mizoroki–Heck coupling of unactivated alkyl chlorides

Pd-catalyzed formal Mizoroki–Heck coupling of unactivated alkyl chlorides

Direct C(sp2)–H alkylation of unactivated arenes enabled by photoinduced Pd catalysis

Photoinduced regioselective olefination of arenes at proximal and distal sites

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