Asymmetric synthesis with ynamides: unique reaction control, chemical diversity and applications

Lynch, Ciarán C.; Sripada, Archita; Wolf, Christian

doi:10.1039/d0cs00769b

Cited by 151 publications

(30 citation statements)

References 132 publications

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“…In this section, recently developed strategies for asymmetric synthesis involving enolonium equivalents as the reaction intermediates will be highlighted. Although asymmetric synthesis involving ynamides has been reviewed recently, [64] we will take a perspective of the enolonium synthon, broadly encompassing activated/unactivated alkynes and amides as substrates and also including photocatalytic conditions.…”

Section: Enantioselective Approach Via Enoloniumsmentioning

confidence: 99%

Recent Progress in Enolonium Chemistry under Metal‐Free Conditions

Kumar

Nguyen

et al. 2021

The Chemical Record

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Umpolung approach through inversion of the polarity of conventional enolates, has opened up an unprecedented opportunity in the cross‐coupling via alkylation. The enolonium equivalents can be accessed either by hypervalent iodine reagents, activation/oxidation of amides, or the oxidation of alkynes. Under umpolung conditions, highly basic conditions required for classical enolate chemistry can be avoided, and they can couple with unmodified nucleophiles such as heteroatom donors and electron‐rich arenes.

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Section: Enantioselective Approach Via Enoloniumsmentioning

confidence: 99%

Recent Progress in Enolonium Chemistry under Metal‐Free Conditions

Kumar

Nguyen

et al. 2021

The Chemical Record

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“…In the last 10 years, ynamides, have emerged as very attracting reagents and building blocks for organic synthesis. [1,2] Thanks to their highly polarized triple bond, ynamides have become partners of choice for a myriad of reactions, including cyclizations [3] or asymmetric transformations, [4] through a variety of activation modes. [5][6][7][8][9] In parallel, efficient and robust methods for the synthesis of a broader range of ynamides have been developed.…”

Section: Introductionmentioning

confidence: 99%

N-Metallocenyl Ynamides: Preparation, Oxidative Functionaliza-tion and Synthesis of an ansa[3]-Ferrocenylamide

Mahe

Blacque

Gasser

et al. 2022

Preprint

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The discovery of new organometallic frameworks is of high interest for the field of bioorganometallic chemistry. In this work, to the best of our knowledge, we report the first synthesis of various N-metallocenyl ynamides and some of their reactivity. In particular, the use of hypervalent iodine(III) reagents triggered an unprecedented oxidative cyclization leading to ansa[3]-ferrocenyl compounds while the same reaction conditions with the ruthenocene analogues led to an acyclic acetoxy-adduct. The mechanism of the cyclization has been studied by means of DFT calculations, showing that it proceeds through a Concerted Iodination Deprotonation (CID) step. This study not only expands further the chemistry of ynamides but also opens up new avenues in bioorganometallic chemistry by providing an exclusive access to an original ferrocephane moiety to be employed in this research field.

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“…67 Thus, ynamides display unique reactivities owing to the flexible modulation of EWG and have evolved into versatile synthons and building blocks. [68][69][70][71] We have recently disclosed that ynamides could be used as novel coupling reagents for facilitating amide 72-73 and ester 74-75 bond formation, which were accomplished by taking advantage of the α-addition of carboxylic acid to ynamides (Figure 2a). 71 Furthermore, we have found that the regioselectivity could be reversed by employing basic reaction conditions as exemplified by the regio-and stereoselective hydroamidation 76 and hydrophosphorylation 77 of ynamides.…”

Section: Introductionmentioning

confidence: 99%

Highly Chemo-, Regio- and Stereoselective Cysteine Modification of Peptides and Proteins with Ynamides

Wang

Zhao

Ghadir

et al. 2021

Preprint

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Chemoselective modification of peptides and proteins has wide applications in chemical biology and pharmaceutical development. An efficient cysteine (Cys) precise modification protocol via rationally designed β-addition of ynamides is reported. The strong electron-withdrawing triflyl group on the nitrogen atom of ynamides plays a crucial role for controlling the chemo-, stereo- and regioselectivities of this protocol. Another substituent of the terminal ynamides offers a handle for functionality diversification. This Cys modification with ynamides proceeds efficiently in a slightly basic aqueous media (pH 8) to provide a series of Z-isomer of the corresponding conjugated products with excellent stereoselectivity (> 99%) and superior stability. All the reactive peptide side chain functional groups such as amino, carboxyl, primary amide, and hydroxyl groups, as well as the unprotected imidazole and indole rings are compatible. This method displays a broad substrates scope including linear and cyclic peptides and proteins. The potential application of this method in peptide and protein chemical biology was exemplified by Cys-bioconjugation with ynamides containing different functional molecules, including drug, fluorescent and affinity tags. In addition, this strategy is also compatible with click chemistry (performed in one pot), which remarkably extends the toolbox for further applications. The chemoselective biotinylation of ubiquitin(G47C) variant with a biotinylated ynamide, as well as the regioselective modification of Cys14 and Cys38 in bovine pancreatic trypsin inhibitor (BPTI) were accomplished under the optimized conditions and in high yield, without perturbation of disulfide bonds.

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Asymmetric synthesis with ynamides: unique reaction control, chemical diversity and applications

Abstract: The diversity, utility and mechanistic aspects of asymmetric synthesis with ynamides developed during the last decade is discussed.

Cited by 151 publications

References 132 publications

Recent Progress in Enolonium Chemistry under Metal‐Free Conditions

Recent Progress in Enolonium Chemistry under Metal‐Free Conditions

N-Metallocenyl Ynamides: Preparation, Oxidative Functionaliza-tion and Synthesis of an ansa[3]-Ferrocenylamide

Highly Chemo-, Regio- and Stereoselective Cysteine Modification of Peptides and Proteins with Ynamides

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