Self‐Terminating Radical Cyclizations: How Are Thiyl Radicals Performing?

Abstract

AbstractThe performance of thiyl radicals RS· in “self‐terminating radical cyclisations” was explored. Using the medium‐sized cyclodecyne (1) as model system, the reaction of PhS· generated by photolysis of (PhS)2 was used to study the intermolecular S‐radical addition and subsequent intramolecular radical translocations. This reaction resulted in the formation of three stereoisomeric sulfides 17a in very good yield, which all possess the bicyclo[4.4.0]decane framework with either cis and trans ring fusion. The isomeric bicyclo[5.3.0]decane framework was not formed. Product identification was performed using a combination of techniques, e.g. synthesis of authentic samples, X‐ray analysis and computational studies of the potential energy surface, which also revealed valuable insight into the mechanism of this radical cyclisation cascade. The (PhS)2/PhS· system provides an efficient source for in situ generated thiols, which mediate reduction of the α‐thio radical, e.g., 13a → 17a. The radical cascade initiated by the addition of BnS·, tBuS· or AllylS·, respectively, to cycloalkyne 1 was typically terminated also by reduction, even in the absence of an apparent H‐donor, and resulted in formation of various bicyclic and monocyclic thioethers. The desired “self‐termination”, e.g., β‐fragmentation of the S–R bond in radical intermediate 12/13 and release of a stabilized radical R·, was only observed as minor reaction pathway in one particular instance where tBuS· was generated by autoxidation of tBuSH. Computional studies showed that the differentstereochemical outcome of the radical cyclizations involving S‐radicals, compared to O‐ or N‐centred radicals, could be attributed to the reversibility of the initial intermolecular S‐radical addition to the C≡C triple bond in cycloalkyne 1.