Intramolecular Cyclization of Radicals Generated from α-Halomethylsulfonamides

Abstract

A series of homologous R-sulfonamidyl radicals has been generated by reaction of R-halomethyl precursors with tri-n-butyltin hydride under AIBN catalysis. The intramolecular cyclization capability of these highly reactive intermediates has been evaluated. Where possible, five-membered sultams are formed by 5-exo transition states. The longer C-SO 2 and SO 2 -NR 2 bonds have little demonstrable effect on this pathway. In larger systems, however, the 7-endo option predominates over the 6-exo alternative. A preparatively useful route to sultams has emerged from this investigation.

Synthesis of Spirocyclic β‐ and γ‐Sultams by One‐Pot Reductive Cyclization of Cyanoalkylsulfonyl Fluorides

“…Being inspired by the aforementioned results, we have evaluated the developed approach for the synthesis of analogous spirocyclic β‐sultams. It should be noted that known approaches to β‐sultams (Scheme 5) relied on intermolecular reactions of α‐bromomethyl sulfonamides with α‐halocarbonyl compounds ( A ), [52] [2+2] cycloadditions of sulfonyl chlorides with imines ( B ), [53–55] intramolecular alkylation of sulfonamides bearing a leaving group at the β‐position ( C ), [56, 57] and intramolecular cyclization of β‐amino sulfonyl chlorides ( D ) [44, 58–66] . As in the case of γ‐sultams, the intramolecular reductive cyclization of substituted α‐cyano sulfonyl fluorides has never been reported to date.…”

“…Several approaches to γ‐sultams has been described in recent years (Scheme 2), [12–21] including intramolecular cyclization of 3‐aminopropane‐1‐sulfonyl chlorides ( A ), [22–26] or aryl propane‐1‐sulfonates ( B ), [27, 28] intramolecular N ‐alkylation of propane‐1‐sulfonamides ( C ), [29–37] double alkylation of alkanesulfonamides ( D ), [38, 39] intramolecular C ‐alkylation of N ‐substituted methanesulfonamides ( E ), [40–43] cyclizations of N ‐allyl‐1‐halomethanesulfonamides ( F ), [44] and intramolecular aliphatic C–H sulfonamidations ( G ) [45] …”

Synthesis of heterocycles by radical cyclisation

“…114 The synthesis of 5-and 6-membered ring sultams has been facilitated using cyclisation of α-sulfonamidyl radicals which were generated by reaction between α-halomethyl sulfonamide precursors and Bu 3 SnH. 115 In larger ring cyclisations, 7-endo cyclisation predominates over the 6-exo alternative. 1,3-Dithiol-2-ones can be prepared in a one pot reaction from diisopropyl xanthogen disulfide and alkynes under radical conditions using AIBN as an initiator.…”

The Electrophilic and Radical Behavior of α-Halosulfonyl Systems

“…70 Recently, the intramolecular cyclization of radicals generated from a-halomethylsulfonamides has been scrutinized. 71 Five-membered sultams such as 89 are expectedly formed via 5-exo transition states wherever possible. In larger systems, the longer C-SO 2 and SO 2 -NR 2 bonds contribute to favoring the 7-endo option over the 6-exo alternative.…”