Palladium-Catalyzed Formal (3 + 2) Cycloaddition Reactions of 2-Nitro-1,3-enynes with Vinylaziridines, -epoxides, and -cyclopropanes

Abstract

A two-step Pd-catalyzed (3 + 2) cycloaddition/HNO2 elimination reaction sequence has been developed to give novel cyclic 1,3-dien-5-yne systems from Pd-stabilized zwitterionic 1,3-dipoles and 2-nitro-1,3-enyne substrates. The process is highly atom-efficient and tolerates the reaction of 2-vinyloxirane, 1-tosyl-2-vinylaziridine, and diethyl 2-vinylcyclopropane-1,1-dicarboxylate derived 1,3-dipoles with a variety of 2-nitro-1,3-enyne substrates. The stereochemistry of the intermediate (3 + 2) cycloadducts was determined by single crystal X-ray analysis. Furthermore, a selective kinetic elimination of the cycloadduct with an antiperiplanar relationship between the NO2 group and the participating hydrogen was demonstrated, allowing for efficient isolation of a single diastereoisomer of the cycloadduct.

Diastereoselective Pd‐catalyzed Decarboxylative (4+2) Cycloaddition Reactions of 4‐Vinylbenzoxazinanones and 2‐Nitro‐1,3‐enynes

“…To ascertain the synthetic value of the functionalized tetrahydroquinoline products, the purified major diastereomer 3 a was subjected to Zn/HCl reduction of the 3‐nitro group [16] to give the valuable 3‐aminotetrahydroquinoline product 4 as a single diastereomer in excellent yield (Scheme 4b). Furthermore, base‐promoted elimination of HNO 2 to provide 1,3‐dien‐5‐yne 5 was attempted with DBU [10b] (Scheme 4c), but subsequent oxidation to quinoline 6 was unavoidable under the reaction conditions; complete oxidation was provided by sparging the reaction with air followed by overnight stirring at rt to give quinoline 6 in good yield (Scheme 4c). The 2‐aryl‐quinoline 6 represents a 2,3,4‐trisubstituted quinoline product that contains pendant synthetic handles for further structural manipulation; these molecules represent highly valued medicinal chemistry motifs, as 2‐aryl‐quinolines are commonly found in pharmaceuticals and biologically‐active compounds, [17] e. g., as antimalarials, [18] anti‐cancer agents [19] and neurokinin‐3 receptor antagonists [20] (Scheme 4d).…”

“…Despite the potential for the double bond of the 2‐nitro‐1,3‐enyne moiety to behave as a 2‐carbon synthon in cycloaddition processes leaving the alkyne moiety intact, only two such processes have been reported [10] . One of these, reported by our group, represents the first example of a palladium‐catalyzed cycloaddition [11] with 2‐nitro‐1,3‐enynes (Scheme 1a – A ) [10b] …”

Recent Advances in the Nitration of Olefins

“…Recently, in 2021, Hyland and coworkers reported Pd catalyzed (3 + 2) cycloaddition reaction of 2-nitro-1,3-enynes with vinylaziridines to produce novel cyclic 1,3-dien-5-yne (Scheme 16). [46] The formed cycloadduct had been subjected to many chemical transformations such as Heck reaction, nitration reaction, cross metathesis reaction and cycloaromatization. Here nitration of the cycloadduct was performed using the AgNO 2 /TEMPO protocol.…”

Palladium-catalysed enantio- and regioselective (3 + 2) cycloaddition reactions of sulfamidate imine-derived 1-azadienes towards spirocyclic cyclopentanes

“…A wide range of dipolarophiles have been utilised in conjunction with VCP-derived 1,3-dipoles, 21–43 enabling the synthesis of fused- 23–26,30,43 and spirocyclic cyclopentanes and 5-membered heterocycles via (3 + 2) cycloaddition reactions. 33,37,39,41,42 Among these, benzofuran-derived azadienes (BDAs) are an intriguing potential class of dipolarophiles for Pd-catalysed (3 + 2) reactions for cyclopentane synthesis.…”