Indium(iii)-catalyzed tandem synthesis of 2-alkynyl-3,3-dichloropyrrolidines and their conversion to 3-chloropyrroles

Abstract

A convenient route to 2-alkynyl-3,3-dichloropyrrolidines was described by addition of terminal acetylenes to 2,2,4-trichloroaldimines using In(OTf)3 as a catalyst. In the presence of a base these pyrrolidines were transformed into 3-chloropyrroles.

Synthesis of 3,3‐Dichloropiperidines and Further Functionalization via Pd‐Catalyzed Cross‐Coupling Reactions of the Dichloromethylene Moiety

“…Therefore, the reaction of α,α,δ‐trichloroaldimine 7a with phenylacetylene in the presence of a metal catalyst was examined (Tableà). Entry 1 uses the same reaction conditions as obtained for the synthesis of 3,3‐dichloropyrrolidines . Although product 19a was obtained in a decent 59 % yield, another 18 % of propargylamine 18a was still present in the reaction mixture.…”

“…Apart from additions of strong nucleophiles to the azomethine carbon (cyanation, Mannich‐type reactions), where the electrophilicity of the imine is of little importance, there are also examples of catalyzed nucleophilic additions to the azomethine carbon, in which enhanced electrophilicity is required . One‐pot nucleophilic addition to trichlorinated imines and sequential ring closing reactions often leads to interesting substrates, still bearing an electrophilic dichloromethylene group …”

“…Until present, the dichloromethylene group has been used in amine, dihaloalkane, alkyne (AHA) coupling reactions and elimination reactions . Unfortunately, AHA coupling reactions suffer from a small substrate scope, since only dihalomethanes (dichloromethane, dibromomethane and diiodomethane) and benzal halides can be used.…”

Hierarchically Porous Mixed Oxide Sheetlike Copper–Aluminum Nanocatalyzed Synthesis of 2-Alkynyl Pyrrolidines/Piperidines and Their Ideal Green Chemistry Metrics

“…It is well-established that due to the Jahn–Teller effect at the Cu 2+ ion CuAl-hydrotalcites always mix up with other phases such as malachite or gerhardtite. , Nitrogen-containing heterocycles such as pyrrolidines/piperidines are an integral part of a large number of natural products and biologically active compounds that possess a wide range of biological activities such as anticancer, − antihypertensive, , antimicrobial, , anti-inflammatory, , antibacterial, , antitumor, , etc. Although several methodologies for the synthesis of pyrrolidines/piperidines derivatives such as intramolecular hydroamination of aminoalkyl acetylenes followed by alkynylation, coupling of ω-chlorinated ketones with primary amines to aldimines enduring terminal cyclic propargyl amines, Cu­(I)-assisted cyclization of triggered alkynes to yield N-heterocycles, gem-bis-alkylation of tertiary lactams/amides, etc. have been developed, most of these methodologies suffer certain drawbacks such as multistep processes, elongated time, costly catalyst, tedious workup procedure, and costly syntheses. − …”

“…Although several methodologies for the synthesis of pyrrolidines/piperidines derivatives such as intramolecular hydroamination of aminoalkyl acetylenes followed by alkynylation, coupling of ω-chlorinated ketones with primary amines to aldimines enduring terminal cyclic propargyl amines, Cu­(I)-assisted cyclization of triggered alkynes to yield N-heterocycles, gem-bis-alkylation of tertiary lactams/amides, etc. have been developed, most of these methodologies suffer certain drawbacks such as multistep processes, elongated time, costly catalyst, tedious workup procedure, and costly syntheses. − …”