Thiophenol‐Mediated 1,5‐Hydrogen Atom Abstraction: Easy Access to Mono‐ and Bicyclic Compounds

Abstract

A thiophenol-mediated method for cyclization of alkynes is described. The reaction cascade involves the intermolecular addition of a phenylthiyl radical to a terminal triple bond generating an alkenyl radical, followed by a 1,5-hydrogen atom transfer and a 5-exo-trig radical cyclization. This very efficient tinfree procedure allows one to prepare highly functionalized cyclopentane derivatives as well as fused bicyclic and spirocyclic compounds from easily available precursors. During this cyclization process, a phenylthio moiety is incorporated into the final cyclized products. This functionalization is particularly attractive for further transformation of the products.

Recent advances in sulfur- and phosphorous-centered radical reactions for the formation of S–C and P–C bonds

“…For example, the reactions of hexyne derivatives 99 with the phenysulfenyl radical afforded cyclopentane derivatives 100 (Scheme 45). 97,98 In this reaction process, addition of the sulfenyl radical to the alkyne generated the vinyl radical which underwent intramolecular 1,5-H transfer followed by 5-exo-trig cyclization to form the 5-membered ring products 100. This protocol has been employed for the synthesis of fused 1-azabicyclic alkanes 102 using azacyclic ring-substituted …”

Preparation of Five-Membered Rings via the Translocation-Cyclization of Vinyl Radicals

“…38,39 Indeed, when the reaction is run in t-BuOH as a solvent and a stoichiometric amount of 2,2¢-azobis(isobutyronitrile) is slowly added, excellent yields of the translocation-cyclization products are obtained. The modified conditions are applicable to a wide range of substrates.…”

Effect of Brønsted acids on the thiophenol-mediated radical addition–translocation–cyclization process for the preparation of pyrrolidine derivatives

“…Alkenyl radicals can be generated directly from alkenyl halides [9,10] or by radical addition to a terminal alkyne [11][12][13][14][15][16][17][18][19]. The thiophenol-mediated radical addition-translocation-cyclization (RATC) process [20][21][22][23] is preparatively very useful since terminal alkynes are easily accessible [24]. It has been used to prepared simple and fused cyclopentanes as well as spirocyclic compounds such as (-)-erythrodiene [22,23,25].…”

“…The thiophenol-mediated radical addition-translocation-cyclization (RATC) process [20][21][22][23] is preparatively very useful since terminal alkynes are easily accessible [24]. It has been used to prepared simple and fused cyclopentanes as well as spirocyclic compounds such as (-)-erythrodiene [22,23,25]. Starting from homopropargylic amines and amides, it was also possible to prepare the heterocyclic systems related to the indolizidine and pyrrolizidine alkaloid skeleton (Scheme 1) [26].…”

“…This compound was easily prepared by the alkylation of diisobutylamine with propargyl bromide in the presence of potassium carbonate. In order to be compatible with the presence of acid additives, acetonitrile was used as a solvent instead of tert-butanol employed for the thiophenol-mediated RATC processes [23]. For the optimization process, reaction yields were determined by gas chromatography and the results are summarized in Table 1.…”