AgOTf/Et₃N Cooperative Catalysis Enabled One‐Pot Access to α‐(Indolizinylethyl)‐Substituted N‐Sulfonyl Ketimines via an Imino‐Alkyne Cyclization

Abstract

The β-Csp 3 À H functionalization of N-sulfonyl ketimines with 2-(2-enynl)pyridines/quinolines via a cooperative Ag(I)-/organobase-catalyzed 5-endo-dig cyclization-addition reaction is reported. This successive CÀ N/CÀ C bond-making reaction provides a simple and atom-economical technique for granting a diverse set of 1,3-disubstituted indolizines/ pyrrolo[1,2-a]quinolines possessing a synthetically resourceful N-sulfonyl ketimine moiety. Moreover, our designed strategy applies to broad substrates and allows various functionalities. Furthermore, this technique has many imperative synthetic points such as mild reaction conditions, low catalyst loading, acceptable chemical yields and highly diastereoselective (up to � 93 : 7 dr). The N-sulfonyl ketimine moiety of indolizine was easily transmuted into the reputed classes of coumarin and benzofuran derivatives.

Ag(I)-Mediated Annulation of 2-(2-Enynyl)pyridines and Propargyl Amines to Access 1-(2H-Pyrrol-3-yl)indolizines

“…Based on the recent reports for the synthesis of indolizines − and the above experimental observations, a plausible mechanism for the preparation of 1-(2 H -pyrrol-3-yl)­indolizine from 2-(2-enynyl)­pyridines 1 and propargyl amines 2 is illustrated in Scheme . First, the pyridine nitrogen could attack the AgX-activated alkyne of 1-(2 H -pyrrol-3-yl)­indolizine, delivering the intermediate A or A′ .…”

“…Single-crystal X-ray diffraction intensity data were collected using a Bruker D8 VENTURE system. The known 2-(2-enynyl)­pyridines 1 were prepared according to the previous literature. − The known propargyl amines 2 were prepared by the Sonogashira coupling reaction …”

“…Among these protocols, the transition-metal-promoted cyclization of 2-(2-enynyl)­pyridines for efficiently synthesizing indolizines has been developed. For instance, the efficient formation of 1,3-substituted indolizines were achieved by the transition-metal-promoted cyclization of 2-(2-enynyl)­pyridines with a single nucleophile . Furthermore, Jia and co-workers reported an interesting protocol toward 1,2,3-trisubstituted indolizines involving the palladium-catalyzed three-component cyclization of 2-(2-enynl)­pyridines, nucleophiles, and allyl chlorides .…”

Silver-catalyzed synthesis of nitrogen heterocycles: recent advancements

“…Samanta and co-workers developed an interesting one-pot protocol for the synthesis of a series of α-(indolizinylethyl)-substituted N -sulfonyl ketimine moieties 44 using the AgOTf 26 /Et 3 N joint catalytic system. 63 This consecutive C–N/C–C bond formation via 5- endo-dig cyclization addition was carried out by reacting 2-(2-enynl)pyridines/quinolines 42 and N -sulfonyl ketimines 43 in the presence of the cooperative catalytic system (0.2 mol%)AgOTf 26 /(20 mol%) Et 3 N in MeCN at room temperature for 12–24 h (Scheme 13). This diastereoselective transformation afforded synthetically potent N -sulfonyl ketimine bearing 1,3-disubstituted indolizines/pyrrolo[1,2- a ]quinolines 44 in moderate to high yields.…”

Metal/catalyst/alkyne/alkene‐free one‐pot synthesis of indolizines from 2‐(pyridin‐2‐yl)acetate, DMF‐DMA and α‐halomethylenes

“…(5) Glorius and coworkers have developed a visible light-mediated synthesis of polycyclic indolizines [24] from brominated pyridines and enol carbamates. To date, the synthesis of indolizines consists of several steps using either acid, or base, or oxidants or catalysts [25]. Majority of the reactions involved, either expensive alkynes or alkene as one of the reaction partners and their synthesis attributes complexity.…”