Rapid functionalization of multiple C–H bonds in unprotected alicyclic amines

Chen, Weijie; Paul, Anirudra; Abboud, Khalil A.; Seidel, Daniel

doi:10.1038/s41557-020-0438-z

Cited by 87 publications

(44 citation statements)

References 43 publications

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“…Diphenyl and triphenyl C-H positions were also viable substrates that produced excellent yields (9, 10). Aryl-substituted heterocycles were amenable to fluorination at the benzylic position, as both 5-and 6-membered rings were fluorinated in modest yields (11)(12)(13)(14). Excitingly, benzylic sites adjacent to electron-withdrawing groups successfully provided a-fluoro products in one step (14,15).…”

Section: Resultsmentioning

confidence: 99%

“…Aryl-substituted heterocycles were amenable to fluorination at the benzylic position, as both 5-and 6-membered rings were fluorinated in modest yields (11)(12)(13)(14). Excitingly, benzylic sites adjacent to electron-withdrawing groups successfully provided a-fluoro products in one step (14,15). Lastly, isopropylsubstituted heteroarenes, including pyridine, pyrimidine, and pyrazole worked modestly well in the formal hydride abstraction platform (16)(17)(18).…”

Section: Resultsmentioning

confidence: 99%

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A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

Zhang¹,

Fitzpatrick²,

Das³

et al. 2021

Preprint

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While a great number of C–H functionalization methods have been developed in recent years, new mechanistic paradigms to deconstruct such bonds have been comparatively rare. Amongst possible strategies for breaking a Csp3–H bond are deprotonation, oxidative addition with a metal catalyst, direct insertion via a nitrene intermediate, hydrogen atom transfer (HAT) with both organic and metal-based abstractors, and lastly, hydride abstraction. The latter is a relatively unexplored approach due to the unfavorable thermodynamics of such an event, and thus has not been developed as a general way to target both activated and unactivated Csp3–H bonds on hydrocarbon substrates. Herein, we report our successful efforts in establishing a catalytic C–H functionalization manifold for accessing an intermediate carbocation by formally abstracting hydride from unactivated Csp3–H bonds. The novel catalytic design relies on a stepwise strategy driven by visible light photoredox catalysis and is demonstrated in the context of a C–H fluorination employing nucleophilic fluorine sources. Difluorination of methylene groups is also demonstrated, and represents the first C–H difluorination with nucleophilic fluoride. Additionally, the formal hydride abstraction is shown to be amenable to several other classes of nucleophiles, allowing for the construction of C–C or C–heteroatom bonds.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

Zhang¹,

Fitzpatrick²,

Das³

et al. 2021

Preprint

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“…Inspired by natural photosynthesis, artificial photosynthesis utilizes sunlight to produce H 2 and "excited equivalences/molecular catalyst" ratios for efficient water splitting. [19][20][21][22] Recently, Chen and Ardo investigated the mechanistic details and catalytic intermediates in TiO 2 -anchored 3-(3,5-bis((E)-4-(diphenylamino)styryl)phenyl)-2-cyanoacrylic acid catalysts in PEC water splitting cycles when combined with a molecular [Ru(dmb) 2 (dcb)](PF 6 ) 2 chromophore (where dmb is 4,4′dimethyl-2,2′-bipyridine and dcb is 4,4′-dicarboxylic-2,2′-bipyridine). [22] Transient absorption spectral measurements (TAS) showed that largest yield of the twice-oxidized state for the catalyst was observed only at low catalyst coverages, suggesting that large dye/electrocatalyst ratios may be required to achieve the appropriate redox state of the molecular catalyst with a benefit for fast and efficient catalysis.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21][22] Recently, Chen and Ardo investigated the mechanistic details and catalytic intermediates in TiO 2 -anchored 3-(3,5-bis((E)-4-(diphenylamino)styryl)phenyl)-2-cyanoacrylic acid catalysts in PEC water splitting cycles when combined with a molecular [Ru(dmb) 2 (dcb)](PF 6 ) 2 chromophore (where dmb is 4,4′dimethyl-2,2′-bipyridine and dcb is 4,4′-dicarboxylic-2,2′-bipyridine). [22] Transient absorption spectral measurements (TAS) showed that largest yield of the twice-oxidized state for the catalyst was observed only at low catalyst coverages, suggesting that large dye/electrocatalyst ratios may be required to achieve the appropriate redox state of the molecular catalyst with a benefit for fast and efficient catalysis. For semiconductor-molecular catalyst hybrids, the semiconductor can generate a multiple state excited equivalents (i.e., electrons and holes) when irradiated, which can greatly exceed the amount of added molecular catalyst, leading to large intrinsic local "dye/electrocatalyst" ratios.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Photoelectrochemical Water Splitting Systems: From Interface Design to System Assembly

Niu

Wang

et al. 2019

Advanced Energy Materials

189

120

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Photoelectrochemical (PEC) water splitting has attracted increasing attention due to its potential to mitigate energy and environmental issues. Hybrid PEC systems containing semiconductor photosensitizers and molecular catalysts are reported to be highly active and stable for water splitting with great potential for facilitating clean fuels production. In this review, following a showcasing of the fundamental details of hybrid PEC systems for water splitting, semiconductor/molecular catalyst interface designs are highlighted, with a focus on interfacial physicochemical interactions and binding, and interfacial energetics and dynamics for efficient charge transfer. Recent advances in hybrid system assemblies for PEC water splitting are also briefly introduced. Finally, future challenges and directions in the field of hybrid PEC water splitting for solar energy conversion are reviewed. The current review provides state‐of‐the‐art strategies for optimized interface design for creating highly active and stable PEC water splitting assemblies.

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“…iven the ubiquity of cyclic amines in a myriad of natural products and synthetic compounds, a growing emphasis has been placed on how we harness and manipulate such prestigious motifs for the construction of value-added molecules [1][2][3][4] . While significant progress has been made in the development of appending processes for their peripheral variation [5][6][7][8][9][10] , the skeletal diversification by means of ring-opening, -contraction, -expansion or -fusion approaches remains limited (Fig. 1a) 11 .…”

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confidence: 99%

Ring-opening functionalizations of unstrained cyclic amines enabled by difluorocarbene transfer

et al. 2020

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Chemical synthesis based on the skeletal variation has been prolifically utilized as an attractive approach for modification of molecular properties. Given the ubiquity of unstrained cyclic amines, the ability to directly alter such motifs would grant an efficient platform to access unique chemical space. Here, we report a highly efficient and practical strategy that enables the selective ring-opening functionalization of unstrained cyclic amines. The use of difluorocarbene leads to a wide variety of multifaceted acyclic architectures, which can be further diversified to a range of distinctive homologative cyclic scaffolds. The virtue of this deconstructive strategy is demonstrated by successful modification of several natural products and pharmaceutical analogues.

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Rapid functionalization of multiple C–H bonds in unprotected alicyclic amines

Cited by 87 publications

References 43 publications

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

Hybrid Photoelectrochemical Water Splitting Systems: From Interface Design to System Assembly

Ring-opening functionalizations of unstrained cyclic amines enabled by difluorocarbene transfer

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