Transformations of 5‐Hydroxy‐1‐pyrrolines in Strong Brønsted Acids: Experimental and Theoretical Study of Intermediate Cationic Species

Abstract

The reaction of 5‐hydroxy‐1‐pyrrolines with arenes in TfOH at room temperature for 1 h afford 5‐aryl‐1‐pyrrolines in 55–98 % yields. 5‐Hydroxy‐1‐pyrrolines in TfOH or H2SO4 at room temperature for 0.5–1 h undergo dehydration with the formation of N‐protonated forms of 3H‐pyrroles, which were characterized by NMR. Upon hydrolysis, the N‐protonated species give quantitatively the corresponding 3H‐pyrroles. The intermediate cationic species derived from the protonation of 5‐hydroxy‐1‐pyrrolines in Brønsted acids have been studied by means of NMR and DFT calculations. Plausible reaction mechanisms are discussed.

Diastereoselective synthesis of tetrahydropyrrolo[1,2-d]oxadiazoles from functionalized Δ1-pyrrolines andin situgenerated nitrile oxides

“…16 Among the latter, the acid-catalyzed reactions of 5-hydroxypyrrolines and 3 H -pyrroles with C-, N-, O- and S-nucleophiles are of particular value as a tool for the construction of rare functionalized pyrrolines. 17 Herein we report our observations on the diastereoselective synthesis of tetrahydropyrrolo[1,2- d ]oxadiazoles from thus-synthesized functionalized Δ 1 -pyrrolines and in situ generated nitrile oxides.…”

Highly Diastereoselective [3 + 2] Cycloaddition of Aziridines with Difluorinated Silyl Enol Ethers: Divergent Synthesis of 4,4-Difluoropyrrolidines and 4-Fluoropyrroles

“…The rapid recrystallization of products demonstrated operational simplicity. Treatment of compound 3a with pyrrolidine in MeCN at 80 °C offered 4-fluoro-3 H -pyrrole 5 in 63% yield (Scheme b) through a deethoxycarboxylation/desulfonation/dehydrofluorination/nucleophilic substitution sequence, and 3 H -pyrroles represented another important family of non-aromatic pyrrole compounds with different kinds of biological activity . In the presence of a strong base, N-functionalization of compound 4a with 3-bromoprop-1-yne and AcCl led to the corresponding products 6 and 7 in 98 and 86% yields, respectively, in which no defluorination process was observed (Scheme c).…”