Carbanions of 3-chloropropyl pentachlorophenylsulfone, although they undergo fast cyclization to the corresponding cyclopropyl sulfone, can be trapped with electrondeficient alkenes to produce carbanionic adducts that enter intramolecular substitution to form substituted cyclopentanes.g-Halocarbanions are considered to be short lived intermediates undergoing rapid intramolecular substitution to cyclopropanes. 1 Numerous reported examples of reactions of g-halocarbanions generated via deprotonation of appropriate precursors or by addition of a-halocarbanions to Michael acceptors 2,3 invariably resulted in formation of three-membered rings: cyclopropane derivatives or the Favorski 4 and Ramberg-Bäcklund reactions. 5Recently, we have shown that g-chlorocarbanions generated from g-chlorobutyronitrile, t-butyl g-chlorobutyrate and 3-chloropropyl phenyl sulfone, albeit they undergo very fast intramolecular replacement of the halogen to form substituted cyclopropanes can be efficiently trapped by active electrophilic partners, e.g. aldehydes. The produced aldol type anions undergo rapid cyclization via intramolecular replacement of the halogen to give substituted tetrahydrofurans. 6In this communication we present a new simple method for the construction of substituted cyclopentane ring via reaction of g-chlorocarbanions with electrondeficient alkenes -Michael acceptors. The cyclopentane ring is present in many natural products, pharmaceuticals etc., thus synthetic methods for substituted cyclopentanes are of great interest. 7 There are a few major strategies to achieve this goal: functionalization of an existing cyclopentene or a cyclopentadiene ring, 8 cyclization of an appropriate precursors, 9 or ring contraction. 10In analogy to the synthesis of tetrahydrofurans via addition of g-chlorocarbanions to aldehydes 6 followed by intramolecular substitution, we have expected that addition of the g-chlorocarbanions to electrondeficient alkenes should produce intermediate w-chlorocarbanions, undergoing rapid intramolecular substitution to cyclopentane derivatives. However, treatment of 3-chloropropyl phenyl sulfone and t-butyl acrylate, with t-BuOK or LDA resulted in polymerization of the acrylate and the only isolable product was phenylsulfonyl cyclopropane. The failure of the Michael addition to t-butyl acrylate when the carbanion is generated in the presence of the acceptor could be due to the moderate rate of deprotonation of the carbanion precursor, the base induced polymerization of the acceptor thus becoming the dominating process.Deprotonation of the more acidic 3-chloropropylaryl sulfone should proceed faster whereas its corresponding carbanion should cyclize more slowly, thus its addition to an electrondeficient alkene should be feasible. Indeed the carbanion of 3-chloropropyl pentachlorophenyl sulfone (1, readily prepared from pentachlorothiophenol via its reaction with 1,3-bromochloropropane followed by oxidation) cyclizes much slower than that of 3-chloropropyl phenyl sulfone. Treatment of 1 in THF with t-BuOK...
Dedicated to Professor Rolf Huisgen on the occasion of his 85th birthday g-Chlorocarbanions of proper nucleophilicity, generated from 3-chloropropyl pentachlorophenyl sulfone ( pentachloro[(3-chloropropyl)sulfonyl]benzene; 1; Ar C 6 Cl 5 ), add to electron-deficient formal imines 3a ± l to produce anionic adducts that enter intramolecular substitution leading to substituted pyrrolidines. This new and simple synthesis of pyrrolidines mimics a 1,3-dipolar cycloaddition, although it proceeds in two distinct steps. Substituted pyrrolidine rings are present in numerous alkaloids, pharmaceuticals, plant protecting agents [1], ligands of transition metal catalysts [2], etc., thus, general methods for the synthesis of this ring system are of great interest and demands. There are many routes leading to substituted pyrrolidine rings, based on cationic cyclizations, mainly via iminium ions [3], cyclization proceeding via free radicals [4], dipolar cycloadditions [5], reactions proceeding via carbanions [6], etc.Of particular value and interest is the construction of pyrrolidine and other fivemembered heterocyclic rings via 1,3-dipolar cycloaddition proceeding according to the concept created and pioneered by Huisgen and co-workers [7]. Huisgen also formulated basic structural elements of 1,3-dipoles and general mechanistic features of this process [8]. Addition of readily generated azomethine ylides ( iminium ylides) to alkenes is a general route to pyrrolidines [5].In this paper, we report a simple and efficient protocol of the synthesis of the pyrrolidine ring via reactions of g-halocarbanions with formal imines, that to some extent mimic 1,3-dipolar cycloaddition.Known reactions of g-halocarbanions are limited to intramolecular substitution of the halogen atom leading to three-membered rings. Synthesis of cyclopropanes via alkylation of −methylenic× carbanions with 1,2-dihaloalkanes [9] and via addition of ahalocarbanions to Michael acceptors [10] proceeds via intermediate formation of ghalocarbanions. They are also intermediates in the Ramberg ± B‰cklund [11] and Favorski reactions [12]. Due to the high rate of the intramolecular substitution promoted by the proximity effect, intermolecular reactions of g-halocarbanions are observed only when structural features decelerate [13] or hinder the intramolecular reaction [14].On the other hand, g-halocarbanions containing an electron-deficient C-atom connected to the halogen atom and the nucleophilic carbanion center in a 1,3 relation-
Short lived γ halocarbanions can be trapped by active electrophiles such as aldehydes, imines, and Michael acceptors to give anionic adducts, which undergo intramolecular substi tution to give substituted tetrahydrofurans, pyrrolidines, and cyclopentanes. This has underlain a new method for the synthesis of these valuable ring systems. We have determined the acidity of the γ halocarbanion precursors and have shown that the halogen atoms in the γ position relative to the carbanion center exert a significant stabilizing effect on the carbanion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.