Regioselective Radical-Relay Sulfonylation/Cyclization Protocol to Sulfonylated Pyrrolidones under Transition-Metal-Free Conditions

Abstract

A simple and low-cost tandem sulfonylation/cyclization of 1,5-diene, aryldiazonium salt, and DABCO•(SO 2 ) 2 is disclosed. This base-promoted multicomponent reaction can provide a "green" and economic synthesis of sulfonylated pyrrolidones under transition-metal-free and moisture/oxygen-insensitive reaction conditions, thus delivering a wide range of sulfonylated pyrrolidones in moderate to high yields with excellent functional group compatibility. A plausible mechanism involving a radical process is proposed, which demonstrates highly chemoselective trapping of the aryl radical with "SO 2 " species, and a regioselective sulfonylation/cyclization protocol in this reaction.

Iron(II)‐Catalyzed Cyanoalkylsulfonylation/Annulation Cascades toward Functionalized Sulfonylated Pyrrolidone Alkylnitriles

“…Later, with an aim to produce a sulfonylated pyrrolidinone scaffold, Wang and co‐workers described a Cu(I)‐catalyzed regioselective sulfonylation/cyclization reaction between vinylamide and arylsulfonyl chloride (Scheme 1b) [11] . Recently, we developed an improved approach with an ease of excluding a transition metal (Scheme 1c) [12] . The in‐situ insertion of a sulfonyl/sulfuryl group to produce aza ‐heterocyclic sulfone derivatives was limited to obtain the aryl‐sulfonylated pyrrolidone products, presumably due to that the alkyl radical intermediate was not reactive as the aryl radical to trap the “SO 2 ” group and the alkyldiazonium salt was not well tolerated.…”

“…[11] Recently, we developed an improved approach with an ease of excluding a transition metal (Scheme 1c). [12] The in-situ insertion of a sulfonyl/sulfuryl group to produce aza-heterocyclic sulfone derivatives was limited to obtain the arylsulfonylated pyrrolidone products, presumably due to that the alkyl radical intermediate was not reactive as the aryl radical to trap the "SO 2 " group and the alkyldiazonium salt was not well tolerated. To this end, we envisioned that a nitrogen radical precursor, such as p-trifluoromethylbenzoyl oxime 2, could be a radical donor to solve the problem under the catalysis of a transition-metal catalyst condition.…”

Transition‐Metal‐Free Synthesis of N‐Heterocyclic Compounds via Multi‐Component Reactions

“…Liu et al reported the synthesis of sulfonylated pyrrolidone derivatives 27 by using 1,5-diene 25, aryldiazonium salt 26 and DABSO in THF at 90 °C using CsF as a base (Scheme 5). [21] The reaction proceeds via formation of free-radical having a highly chemo-and regioselective sulfonylation/cyclization reaction and a series of sulfonylatedpyrrolidones scaffolds were synthesized in moderate to high yields. Initially, aryldiazonium tetrafluoroborate 26 would chemo-selectively react with DABSO through a radical trapping protocol produced arylsulfonyl radical 28 along with a tertiary amine radical cation species 28'.…”

Electrochemical or Photoelectrochemical Alkenylpolyfluoroalkylation of 3-Aza-1,5-dienes: Regioselective Entry to Polyfluoroalkylated 4-Pyrrolin-2-ones

“…Early efforts relied on transition-metal catalyses, and they required the use of a Ru, Ir, Rh, Pd, or Cu complex under elevated temperatures, suffering from a noble/toxic metal catalyst and/or harsh conditions. Recently, 3-aza-1,5-dienes were found to be capable of undergoing a regioselective sulfonylation/cyclization cascade to afford sulfonylated 4-pyrrolin-2-ones . We explored the regioselectivity of the alkylative cyclization of 3-aza-1,5-dienes under photocatalytic conditions, and the electron-rich terminal enaminic double bond was preferentially alkylated .…”