Intramolecular Homolytic Substitution of Sulfinates and Sulfinamides

Abstract

A general and efficient method for the synthesis of cyclic sulfinates and sulfinamides based on intramolecular homolytic substitution (S(H)i) at the sulfur atom by aryl or alkyl radicals is described. Both alkyl and benzofused compounds can be accessed directly from easily prepared acyclic precursors. Enantiomerically enriched sulfur-based heterocycles were formed through an S(H)i process with inversion of configuration at the sulfur atom. Cyclization of prochiral radicals proceeded with varying stereochemical outcomes, depending on the size of the incoming radical. 2-Pyridyl and 2-quinolyl radicals led to biaryl compounds, which result from attack onto the ortho position of the arylsulfinate rather than a thiophilic substitution.

Stereochemical aspects and the synthetic scope of the SHi at the sulfur atom. Preparation of enantiopure 3-substituted 2,3-dihydro-1,2-benzoisothiazole 1-oxides and 1,1-dioxides

“…3 One of the most interesting reactions in this field is the cyclization of o-bromoaryl sulfinamide 1 into the corresponding cyclic sulfinamide 2 under radical conditions 4 (Scheme 1a), mainly due to its stereochemical course and the possibility of using 2 as a precursor of chiral sulfonamides. Concerning the first aspect, the inversion of the sulfur configuration at 1 was assumed on the basis of the behavior of sulfoxides 5 and sulfinates, 6 but it was not unambiguously proven (the absolute configuration of 2 was never established). ROBH and HLYP/6-31++G(d,p) calculations suggest this inversion to occur via hypervalent intermediates 7,8 (A in Scheme 1a), susceptible of giving pseudorotation processes prior to its dissociation.…”

7-Selenabicyclo[2.2.1]heptane

“…1e4 While examples can be found of alkyl, aryl, and acyl radicals undergoing this chemistry at the sulfur atom in sulfides, 2e4 sulfoxides, 5e9 sulfinates, 10,11 and sulfinamides, 10,11 to the best of our knowledge there are no examples reported for this chemistry involving sulfones. 7e9 The examples depicted in Scheme 1 illustrate the versatility of this chemistry; radicals derived from acylselenides (e.g., 1), aryl and alkyl bromides (e.g.…”

“…7e9 The examples depicted in Scheme 1 illustrate the versatility of this chemistry; radicals derived from acylselenides (e.g., 1), aryl and alkyl bromides (e.g. 2, 3) afford thiolactones, 12 cyclic sulfoxides, 5 and sultines 10,11 in good yield.…”

“…Recently, we showed that cyclic sulfinates and sulfonamides could be prepared utilizing this chemistry, 10,11 and more recently that computational chemistry provided valuable insight into the intimate mechanistic details of the key bond-forming and bondbreaking steps. 16 With an inherent interest in homolytic substitution reactions involving selenium and their further development, 17 we chose …”

Intramolecular Homolytic Substitutions in Synthesis

“…Examples can be found of alkyl, aryl, and acyl radicals undergoing this chemistry efficiently at the sulfur atom in sulfides, 5 sulfoxides, 12,22,23 sulfinates, [24][25][26] and sulfonamides, [24][25][26] but not at sulfones. 22,27 Scheme 7 illustrates the application of this chemistry to the preparation of the dihydrobenzothiophene-containing tocopherol-like antioxidant (2); α-tocopherol is the main component of vitamin E. In the key step, aryl radical (3), generated under standard conditions, was able to undergo homolytic substitution at sulfur; subsequent deprotection gave 5-hydroxy- (2) in 62% yield over two steps.…”