Skeletal Reconstruction of 3-Alkylidenepyrrolidines to Azepines Enabled by Pd-Catalyzed C–N Bond Cleavage

Abstract

Herein we report a Pd-catalyzed C–N bond cleavage strategy for the cycloaddition of pyrrolidines with azlactones or butenolides to construct the azepines. Leverage of the readily accessible 3-alkylidenepyrrolidine can serve as an effective precursor for zwitterionic salts. The in situ formation of an allyl-palladium intermediate through the cleavage of inert, cyclic C–N bonds leads to a cascade [5 + 2] cycloaddition, which allows for the diverse synthesis of azepine scaffolds with good functional group tolerance and 100% atom economy.

Rhodium-Catalyzed Synthesis of 2-Methylindoles via C–N Bond Cleavage of N-Allylbenzimidazole

“…The title compound was prepared according to the literature procedure in a 0.1 mmol scale . The crude reaction mixture was purified by column chromatography using silica gel (100–200 mesh size) giving 4 (19 mg) in 80% yield.…”

“…They have also disclosed the branch-selective alkenylation of anilines with the unactivated terminal alkene that is trimethylvinylsilane . In addition to the aforesaid alkenes, allylamine also possesses a terminal unbiased olefinic group, and in classical organic synthesis, allylamines have been utilized for allylation reactions for valuable transformations . However, there are only two reports on ruthenium-catalyzed directed C­(sp 2 )-allylation reaction by Gooßen and Wang (Figure b) .…”

Palladium‐Catalyzed [4 + 4] Cycloaddition of Homo‐TMM All‐Carbon 1,4‐Dipole Precursors for Construction of Benzofuro[3,2‐b]azocines and Furo[3,2‐b]azocines

“…Trimethylenemethane (TMM) is an effective dipole with a wide range of applications that allows for the synthesis of highly functionalized cyclic compounds. [ 9 ] To date, an assortment of TMM dipole precursors has been developed to enable the efficient construction of cyclic compounds (Scheme 1a), encompassing methylene cyclopropanes, [ 10 ] 2‐substituted allyl carbonates (Trost‐TMM), [ 9h,11‐12 ] γ ‐methylidene‐ δ ‐valerolactones, [ 8g,13 ] 2‐methylidenetrimethylene carbonates, [ 14 ] pyrrolidines, [ 15 ] 2‐methylene‐ 1‐indanols. [ 16 ] Among various types of TMM dipole precursors, Trost‐TMM is the most extensively investigated one, which served as an efficient three‐carbon unit in Pd‐catalyzed [3 + n ] cycloadditions.…”

N-Allylbenzimidazole as a strategic surrogate in Rh-catalyzed stereoselective trans-propenylation of aryl C(sp2)–H bond

“…In the presence of the activators (Lewis acid, protic solvent/acids), many pioneering groups have explored the utility of allyl amines for synthetically useful transformations. 7 In the last two decades, transition metal-catalyzed directed C–H bond functionalization has evolved as a powerful tool for step- and atom-economic transformations. However, parallel C–H activation and C–N bond cleavage for C–C bond-forming reactions are still in their infancy.…”