Silver(I)-Catalyzed Addition-Cyclization of Alkyne-Functionalized Azomethines

Abstract

AgOTf can catalyze an addition-cyclization tandem between alkyne-azomethine and a nucleophile such as ketone, nitroalkane, water, and terminal alkyne to give a polycyclic amide via six-exo-trig selectivity.Alkynes are widely used in synthetic chemistry and it has been well documented that, upon coordination to metals such as Au(I), Au(III), Pt(II), Pd(II), Ag(I) and I(I), alkynes are susceptible to nucleophilic attack, leading to cyclization reactions.1 Such a metal-induced process has played an important role in the synthesis of complex synthetic targets. Compared to the vast majority of gold-catalyzed heterocyclization of alkynes, related Ag(I)-catalyzed reactions are less common, although silver catalysts are generally more cost-effective and can offer complementary reactivity and higher functional group compatibility.1i,j,2 When an ortho alkyne-functionalized aldehyde was applied as a substrate in the presence of an external nucleophile (NuH) such as an alcohol, nucleophilic addition of the aldehyde to alkyne can trigger a further addition of the NuH to the carbonyl group, giving rise to cyclization with additional functionalization. 2f,3 Despite the success, this type of reactivity has been mostly observed for alkyne-tethered carbonyl compounds and in most cases endo cyclization selectivity was followed.2k Thus alkyne-functionalizaed imines have been less explored. 4 In order to further explore and expand the utility of Ag(I) catalysis in cyclization reactions for molecular diversity and complexity, it is necessary to broaden the scope of both the alkyne-imine and the external nucleophile substrates.We recently reported rhodium-catalyzed CÀH activation of azomethine imines derived from arylaldehydes,

Graphene Nanoplatelets: Electrochemical Properties and Applications for Oxidation of Endocrine‐Disrupting Chemicals

“…Li and co‐workers focused on the tandem processes involving nucleophilic addition and intramolecular cyclization 23. The polycyclic amides 49 were formed in 47–90% yields through a silver‐catalyzed alkyne functionalization of azomethine imines 48 , where various nucleophiles including ketones, alkynes, water, and nitromethane were employed.…”

Regiocontrolled and Stereoselective Syntheses of Tetrahydrophthalazine Derivatives using Radical Cyclizations

“…A more direct approach would be a cyclization to form the diazene ring. There are only a few examples of ionic cyclizations, including a Pictet–Spengler‐type cyclization (Scheme B) and a silver‐catalyzed cyclization (Scheme C), and they are limited to electron‐rich arenes (R 1 =electron donating groups), have a narrow substituent scope at R 2 , or can only access specific substitution patterns ( 7 ). As a result of all of these challenges, there are currently no efficient and stereoselective routes to many substituted di‐ and tetrahydrophthalazine analogs.…”

“…Further trials revealed that the reactionw as sufficiently robust to allow for comparable conversionsu sing open-flask conditions with toluene that had not been specially dried (entry 5). Optimization of the equivalents of TTMSS (entries 6, 7), triethyl borane (entries 8,9), and temperature (entry 10) resulted in conditions that could effect near-quantitative cyclization in only 1.5 hours at room temperature (entry 10). To improvet he efficiencyo ft his cyclization process, we next investigated the possibility of achieving mored irect access to the tetrahydrophthalazine directly from the aldehyde.…”

N‐Imide Ylide‐Based Reactions: CH Functionalization, Nucleophilic Addition and Cycloaddition

“…[23] The polycyclic amides 49 were formed in 47-90% yields through a silver-catalyzed alkyne functionalization of azomethine imines 48, where various nucleophiles including ketones, alkynes, water, and nitromethane were employed. A mechanistic study revealed that the cyclization occurred prior to nucleophilic addition in the reaction, producing a silver(I) alkenyl intermediate 50 (Scheme 14).…”