C–H Functionalization: A New Strategy for the Synthesis of Biologically Active Natural Products

Rousseaux, Sophie; Liégault, Benoît; Fagnou, Keith

doi:10.1002/9781118342886.ch1

Cited by 19 publications

(11 citation statements)

References 203 publications

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“…Transition‐metal‐mediated couplings of halogenated aromatics have been extensively studied since the 1960s 1. Notwithstanding the success of recent aromatic functionalization strategies such as directed ortho metalation2 and CH functionalization,3–5 Pd‐catalyzed aromatic carbon–halogen bond functionalization remains a central strategy. In this regard, the application of polyhalogenated aromatic compounds in site‐selective transformations is one of the remaining challenges in this field,6 due to overcoupling6h and chemoselectivity issues 7.…”

Section: Methodsmentioning

confidence: 99%

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

2013

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Transition-metal-mediated couplings of halogenated aromatics have been extensively studied since the 1960s. [1] Notwithstanding the success of recent aromatic functionalization strategies such as directed ortho metalation [2] and CÀH functionalization, [3][4][5] Pd-catalyzed aromatic carbon-halogen bond functionalization remains a central strategy. In this regard, the application of polyhalogenated aromatic compounds in site-selective transformations is one of the remaining challenges in this field, [6] due to overcoupling [6h] and chemoselectivity issues. [7] Methods that take advantage of the intrinsic steric and electronic differences between different carbon-halogen bonds have been developed. [6a,i] However, most of these strategies remain limited, requiring difficult substrate prefunctionalization to enforce the desired selectivity. Under traditional catalytic conditions, irreversible oxidative addition to a carbon-halogen bond of A occurs to give B (Scheme 1 a), which lacks a productive reaction pathway. The presence of intermolecular Heck acceptors, or the addition of nucleophiles, is a strategy used to promote a catalytic cycle, as it allows catalytic dead ends to be avoided while increasing product complexity. [6b,f] A more general and attractive solution would be to use catalysts capable of undergoing reversible oxidative addition. [8] Building on the stoichiometric experiments on reductive elimination from ArPd II X complexes conducted by Hartwig et al., [9] and the contributions of Buchwald et al., which afford aromatic C À F [10a] and C À Br bonds; [10b] our group has developed Pd 0 -catalyzed transformations exhibiting reversible oxidative addition as a key to catalysis. [8,11] To this end, the application of our carboiodination method to diiodinated substrates would highlight the unique capabilities of the Pd/QPhos combination: the ability to oxidatively add reversibly to carbon-halogen bonds, and to promote sp 3 carbon-iodine reductive elimination. Herein, we report both the carboiodination, and the sequential intramolecular carboiodination/intermolecular Heck reaction of diiodinated aromatic substrates (Scheme 1 b).We began by optimizing the intramolecular carboiodination of 1 a (Table 1). Although 5 mol % of [Pd(PtBu 3 ) 2 ] in toluene at 100 8C led to full conversion, the desired product (2 a) was obtained in only 30 % isolated yield after 18 h. [12] The yield of 2 a depended on the Pd 0 precatalyst used, as well as the presence of both additional QPhos and base. [13] Based on previous synthetic reports [8,11] and computational evidence, [14a] we believe that the steric bulk of QPhos make it ideal for promoting carbon-iodine reductive elimination. [14b] The optimized conditions were found to be [Pd(QPhos) 2 ] (Pd-1; 5 mol %), additional QPhos (10 mol %), and 1,2,2,6,6-pentamethylpiperidine (PMP; 2 equiv) in toluene at 110 8C. [15] Under these conditions, 2 a was isolated in 74 % yield. With the optimized reaction conditions in hand, we examined a series of diiodinated compounds, 1 b-1 f...

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Section: Methodsmentioning

confidence: 99%

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

2013

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“…This approach has been extensively used to directly install a wide range of new carbon-carbon and carbon-heteroatom bonds. [1][2][3][4] Nonetheless, the selective and predictable transformation of specific C-H bonds into various complicated compounds remains challenging since most organic compounds contain more than one kind of C-H bonds. 3,[5][6][7][8] As a unique hydrocarbon substrate, toluene possesses one benzylic and three different aromatic C-H bonds, and oxidation of the former of which serves as a critical role in yielding industrially important chemicals such as benzyl alcohols, benzaldehydes and benzoic acids.…”

Section: P-nickel Complexmentioning

confidence: 99%

Selective benzylic C_sp3–H bond activations mediated by a phosphorus–nitrogen PN³P-nickel complex

et al. 2022

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“…[1] Notwithstanding the success of recent aromatic functionalization strategies such as directed ortho metalation [2] and CÀH functionalization, [3][4][5] Pd-catalyzed aromatic carbon-halogen bond functionalization remains a central strategy. [1] Notwithstanding the success of recent aromatic functionalization strategies such as directed ortho metalation [2] and CÀH functionalization, [3][4][5] Pd-catalyzed aromatic carbon-halogen bond functionalization remains a central strategy.…”

Section: David a Petrone Matthias Lischka And Mark Lautens*mentioning

confidence: 99%

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

Petrone¹,

Lischka²,

Lautens³

2013

Angew Chem Int Ed

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An I for an I: Conditions for the intramolecular carboiodination and the simultaneous convergent intramolecular carboiodination/intermolecular Heck reaction of various diiodoarenes were developed. The ability of the Pd(0)/QPhos catalyst/ligand combination to undergo reversible oxidative addition allows these reactions to proceed well, thus increasing both the appeal and utility of this class of substrates in site-selective cross-coupling reactions.

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C–H Functionalization: A New Strategy for the Synthesis of Biologically Active Natural Products

Cited by 19 publications

References 203 publications

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

Selective benzylic C_sp3–H bond activations mediated by a phosphorus–nitrogen PN³P-nickel complex

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

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C–H Functionalization: A New Strategy for the Synthesis of Biologically Active Natural Products

Cited by 19 publications

References 203 publications

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

Selective benzylic Csp3–H bond activations mediated by a phosphorus–nitrogen PN3P-nickel complex

Harnessing Reversible Oxidative Addition: Application of Diiodinated Aromatic Compounds in the Carboiodination Process

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Selective benzylic C_sp3–H bond activations mediated by a phosphorus–nitrogen PN³P-nickel complex