Practical, metal-free remote heteroarylation of amides <i>via</i> unactivated C(sp<sup>3</sup>)–H bond functionalization

Tang, Nana; Wu, Xinxin; Zhu, Chen

doi:10.1039/c9sc02564b

Cited by 83 publications

(30 citation statements)

References 58 publications

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“…Recently, Zhu et al 37 and Nagib et al 38 independently developed a Cu-catalyzed (hetero)arylation of remote C(sp 3 )–H bonds with boronic acids as the cross-coupling partners. More recently, Zhu et al 39 reported a hypervalent iodine-promoted remote C(sp 3 )–H heteroarylation of amides. Inspired by these reports on remote C(sp 3 )–H (hetero)arylation, here, we report an amidyl radical-triggered, transition metal free and site-selective remote C(sp 3 )–H heteroarylation with non-prefunctionalized heteroarenes under photoredox conditions (Fig.…”

Section: Introductionmentioning

confidence: 99%

Site-selective remote C(sp3)–H heteroarylation of amides via organic photoredox catalysis

Chen¹,

Fan²,

Yuan³

et al. 2019

Nat Commun

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Radical translocation processes triggered by nitrogen-centered radicals (NCRs), such as 1,5-hydrogen atom transfers (1,5-HAT), demonstrated by the well-established Hofmann-Löffler-Freytag (HLF) reaction, provide an attractive approach for the controllable and selective functionalization of remote inert C(sp3)–H bonds. Here we report an amidyl radical-triggered site-selective remote C(sp3)–H heteroarylation of amides under organic photoredox conditions. This approach provides a mild and highly regioselective reaction affording remote C(sp3)–H heteroarylated amides at room temperature under transition-metal free, weakly basic, and redox-neutral conditions. Non-prefunctionalized heteroarenes, such as purines, thiazolopyridines, benzoxazole, benzothiazoles, benzothiophene, benzofuran, thiazoles and quinoxalines, can be alkylated directly. Sequential and orthogonal C–H functionalization of different heteroarenes by taking advantage pH value or polarity of radicals has also been achieved. DFT calculations explain and can predict the site-selectivity and reactivity of this reaction. This strategy expands the scope of the Minisci reaction and serves as its alternative and potential complement.

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Section: Introductionmentioning

confidence: 99%

Site-selective remote C(sp3)–H heteroarylation of amides via organic photoredox catalysis

Chen¹,

Fan²,

Yuan³

et al. 2019

Nat Commun

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“…We also tried this reaction under oxidative conditions. In the presence of N-fluorobenzenesulfonimide (NFSI, 3 equiv) 43,44 or [bis(trifluoroacetoxy)iodo]benzene (PIFA, 3 equiv) 57 , the un-fluoride amide substrate 15 failed to produce the amination product under standard conditions (Equation (4)). In addition, the N-chloroamide could also give the desired product with modest yield (Equation (5)).…”

Section: Scope Of Alkylation Of Tertiary Amine α-C(sp 3 )-H Bondsmentioning

confidence: 99%

Visible-light promoted regioselective amination and alkylation of remote C(sp3)-H bonds

et al. 2020

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The C-N cross coupling reaction has always been a fundamental task in organic synthesis. However, the direct use of N-H group of aryl amines to generate N-centered radicals which would couple with alkyl radicals to construct C-N bonds is still rare. Here we report a visible light-promoted C-N radical cross coupling for regioselective amination of remote C(sp3)-H bonds. Under visible light irradiation, the N-H groups of aryl amines are converted to N-centered radicals, and are then trapped by alkyl radicals, which are generated from Hofmann-Löffler-Freytag (HLF) type 1,5-hydrogen atom transfer (1,5-HAT). With the same strategy, the regioselective C(sp3)-C(sp3) cross coupling is also realized by using alkyl Hantzsch esters (or nitrile) as radical alkylation reagents. Notably, the α-C(sp3)-H of tertiary amines can be directly alkylated to form the C(sp3)-C(sp3) bonds via C(sp3)-H − C(sp3)-H cross coupling through the same photoredox pathway.

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“…Inspired by our findings in photochemical PIFApromoted Minisci-type reaction of free alcohols, we further applied this analogous method in the remote C(sp 3 )-H heteroarylation of aliphatic amides (Scheme 17). 111 In the presence of PIFA and visible light irradiation, many diverse heteroaryls 24 were site-selectively incorporated to the δ-C(sp 3 )-H bond of aliphatic amides including sulfonamides, carboxamides, and phosphoramides.…”

Section: Proposed Mechanismmentioning

confidence: 99%

Radical Functionalization of Remote C(sp ³ )–H Bonds Mediated by Unprotected Alcohols and Amides

Zhu

2020

CCS Chem

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Aliphatic alcohols and amides are highly valued, ubiquitous chemicals in synthetic chemistry. Radical-promoted regioselective functionalization of unactivated C(sp 3 )-H bonds offers an atom and step economic manner for direct transformation of aliphatic alcohols and amides, especially structural elaboration of complex natural products and bioactive molecules without de novo synthesis. Despite the rapid growth of hydrogen atom transfer (HAT) processes mediated by O-or N-centered radicals generated from prefunctionalized precursors of alcohols and amides in the past few years, exploration of remote C(sp 3 )-H functionalization via HAT mediated by unprotected alcohols or amides lags behind, due to the difficult homolysis of O-H and N-H bonds with high bond-dissociation energies (BDEs). In this minireview, the recent advances in regioselective C(sp 3 )-H functionalization mediated by unprotected alcohols and amides are summarized.

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Practical, metal-free remote heteroarylation of amides via unactivated C(sp³)–H bond functionalization

Abstract: A simple and practical approach for the regioselective heteroarylation of amides via unactivated C(sp3)–H bond functionalization is described.

Cited by 83 publications

References 58 publications

Site-selective remote C(sp3)–H heteroarylation of amides via organic photoredox catalysis

Site-selective remote C(sp3)–H heteroarylation of amides via organic photoredox catalysis

Visible-light promoted regioselective amination and alkylation of remote C(sp3)-H bonds

Radical Functionalization of Remote C(sp ³ )–H Bonds Mediated by Unprotected Alcohols and Amides

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Practical, metal-free remote heteroarylation of amides via unactivated C(sp3)–H bond functionalization

Abstract: A simple and practical approach for the regioselective heteroarylation of amides via unactivated C(sp3)–H bond functionalization is described.

Cited by 83 publications

References 58 publications

Site-selective remote C(sp3)–H heteroarylation of amides via organic photoredox catalysis

Site-selective remote C(sp3)–H heteroarylation of amides via organic photoredox catalysis

Visible-light promoted regioselective amination and alkylation of remote C(sp3)-H bonds

Radical Functionalization of Remote C(sp 3 )–H Bonds Mediated by Unprotected Alcohols and Amides

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Practical, metal-free remote heteroarylation of amides via unactivated C(sp³)–H bond functionalization

Radical Functionalization of Remote C(sp ³ )–H Bonds Mediated by Unprotected Alcohols and Amides