Harnessing the Electrophilicity of Keteniminium Ions: A Simple and Straightforward Entry to Tetrahydropyridines and Piperidines from Ynamides

Abstract

An efficient, modular and straightforwarde ntry to tetrahydropyridines and piperidines is reported. This reaction is based on aformal intramolecular hydroalkylation of readily available,p roperly substituted ynamides which, upon simple activation under acidic conditions,g enerate highly reactive activated keteniminium ions whose reactivity can be finely controlled to induce ar emarkably efficient [1,5]-hydride shift from unactivated CÀHbonds and trigger acationic cyclization which is complete within minutes.

Synthesis of Benzazepinones via Intramolecular Cyclization Involving Ketene Iminium Intermediates

“…Since keteniminium salt intermediates were for the first time described in the late sixties, the field of application of this chemistry was constantly expanded to access new transformations. Among the plethora of accessible scaffolds, cyclobutanones stemming from a [2+2] cycloaddition with an alkene partner are undeniably the most often encountered and can be performed intermolecularly as well as intramolecularly . Besides that, other reactions involving keteniminium intermediates have been described more recently such as 6 π ‐electrocyclizations leading to 3‐aminobenzothiophenes, aminonaphthalenes, and more recently, 3‐aminothiophenes .…”

Cyclization of Ynamide‐Tethered 1,3,8‐Triynes

“…[2] In these reactions, the favorable reactivity of ynamides originates from the electron-rich nitrogen-substituted triple bond, [3] which allows for the formation of ar eactive keteniminium [4] intermediate in the presence of an electrophilics pecies. The recently reported novel ringforming reaction by Evano nicely illustrates this characteristic reactivity of ynamides (Scheme 1), [5] in which initial protonation of ynamide 1 generates ak eteniminiumintermediate that then undergoes a [1,5]-hydrideshift followed by ring-closure to generate final product 2 [Scheme 1, (1)]. I no ur attemptt os ynthesize ynamide-tethered 1,3,6-triyne 3 under the knownc oupling conditions, an unexpectedb icyclic product 4 was obtained instead [ Scheme 1,(2)].…”

One‐Pot Multicomponent Synthesis of β‐Amino Amides

“…For example, ynamides can be protonated in the presence of strong acids to generate an iminium ion, and can be trapped by various building blocks to access numerous heterocycles. [9] In recent years, metal-catalyzed transformation of ynamides has also been explored by Hsung, Liu, Ye, Chang and Zhu. [10] More recently, Zhao and coworkers established that ynamides could be used as racemization-free coupling reagents for amide and peptide synthesis.…”