Copper(I)-Catalyzed Nucleophilic Addition of Ynamides to Acyl Chlorides and Activated <i>N</i>-Heterocycles

Zhang, Peng; Cook, Andrea M.; Liu, Yang; Wolf, Christian

doi:10.1021/jo500365h

Cited by 24 publications

(14 citation statements)

References 59 publications

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“…Terminal ynamides have been previously shown to be excellent substrates in a variety of Cu-catalyzed C-C bond formations, such as Glaser couplings [18][19][20] and nucleophilic addition to mild electrophiles such as acyl chlorides and chloroformates at room temperature and in high yield. 21 Furthermore, terminal ynamide substrates such as Ntosylynamides have also been employed in CuAAC reactions and tandem variations, 22,23 although terminal Nethynyl imidazolidinone N-ethynyl 1,3-oxazolidinones were shown to decompose under conventional click chemistry conditions. 24 We surmised that the electronic bias present in N-alkynylheteroarenes would strike a balance between enhanced reactivity in CuAAC reactions relative to an aliphatic alkyne.…”

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confidence: 99%

Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine

et al. 2016

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Aromatic ynamines or N-alkynylheteroarenes are highly reactive alkyne components in Cu-catalyzed Huisgen [3 + 2] cycloaddition ("click") reactions. This enhanced reactivity enables the chemoselective formation of 1,4-triazoles using the representative aromatic ynamine N-ethynylbenzimidazole in the presence of a competing aliphatic alkyne substrate. The unique chemoselectivity profile of N-ethynylbenzimidazole is further demonstrated by the sequential click ligation of a series of highly functionalized azides using a heterobifunctional diyne, dispelling the need for alkyne protecting groups.

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confidence: 99%

Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine

et al. 2016

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“…Scheme 9. Asymmetric dearomatization of pyridines with copper acetylides in the presence of (a) a chiral bis-oxazoline or (b) (R)-QUINAP Albeit in a racemic process, different classes of acetylenes, namely ynamides, were also found to be competent substrates for the formation of copper acetylides in situ and the subsequent addition-dearomatization to N-acylpyridinium salts [33]. Both unsubstituted pyridine and C-3 and C-4 substituted pyridines afforded the respective 1,2-dihydropyridines as single regioisomers in high yields.…”

Section: Scheme 2 Dearomatization Of Pyridine With An Organocalcium mentioning

confidence: 99%

Nucleophilic Dearomatization of Activated Pyridines

2018

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Amongst nitrogen heterocycles of different ring sizes and oxidation statuses, dihydropyridines (DHP) occupy a prominent role due to their synthetic versatility and occurrence in medicinally relevant compounds. One of the most straightforward synthetic approaches to polysubstituted DHP derivatives is provided by nucleophilic dearomatization of readily assembled pyridines. In this article, we collect and summarize nucleophilic dearomatization reactions of - pyridines reported in the literature between 2010 and mid-2018, complementing and updating previous reviews published in the early 2010s dedicated to various aspects of pyridine chemistry. Since functionalization of the pyridine nitrogen, rendering a (transient) pyridinium ion, is usually required to render the pyridine nucleus sufficiently electrophilic to suffer the attack of a nucleophile, the material is organized according to the type of N-functionalization. A variety of nucleophilic species (organometallic reagents, enolates, heteroaromatics, umpoled aldehydes) can be productively engaged in pyridine dearomatization reactions, including catalytic asymmetric implementations, providing useful and efficient synthetic platforms to (enantioenriched) DHPs. Conversely, pyridine nitrogen functionalization can also lead to pyridinium ylides. These dipolar species can undergo a variety of dipolar cycloaddition reactions with electron-poor dipolarophiles, affording polycyclic frameworks and embedding a DHP moiety in their structures.

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“…39 The reaction with aromatic acyl chlorides 71 gave a series of 3-aminoynones 72a – f in high yields ranging from 79 to 99% (Scheme 17). Steric hindrance does not seem to affect the reaction and the ynamide addition to pivaloyl chloride gave 72g in 90% yield.…”

Section: Nucleophilic Addition and Substitution Reactionsmentioning

confidence: 99%

Terminal ynamides: synthesis, coupling reactions, and additions to common electrophiles

Cook

Wolf

2015

Tetrahedron Letters

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Ynamides consist of a polarized triple bond that is directly attached to a nitrogen atom carrying a sulfonyl, an alkoxycarbonyl, an acyl or another electron withdrawing group. The triple bond polarization renders ynamides broadly useful building blocks with synthetic opportunities that go far beyond traditional alkyne chemistry. The versatile reactivity of ynamides in cycloadditions, cycloisomerizations, regioselective additions with various nucleophiles or electrophiles, ring-closing metathesis, and many other reactions has been investigated in detail during the past decades. A common feature of these methods is that the triple bond is consumed and either cleaved or transformed to a new functionality. The wealth of reports on these ynamide reactions is in stark contrast to the dearth of carbon-carbon bond formations that leave the triple bond of terminal ynamides intact. The recent introduction of effective synthetic methods for the preparation of terminal ynamides has set the stage to fully explore the synthetic potential of this intriguing class of compounds. This digest letter summarizes the most effective routes to terminal ynamides and the current state of selective nucleophilic addition, substitution and coupling reactions, including the first examples of asymmetric synthesis.

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Copper(I)-Catalyzed Nucleophilic Addition of Ynamides to Acyl Chlorides and Activated N-Heterocycles

Cited by 24 publications

References 59 publications

Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine

Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine

Nucleophilic Dearomatization of Activated Pyridines

Terminal ynamides: synthesis, coupling reactions, and additions to common electrophiles

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