Oxidative Fragmentations of 2-(Trimethylsilyl)ethyl Sulfoxides − Routes to Alkane-, Arene-, and Highly Substituted 1-Alkenesulfinyl Chlorides

Abstract

The preparation of a collection of alkyl, aryl, and 1-alkenyl 2-(trimethylsilyl)ethyl sulfoxides is outlined, using mostly vinyltrimethylsilane or 2-(trimethylsilyl)ethanesulfenyl chloride (5) as key starting materials. The 2-(trimethylsilyl)ethyl group can be cleaved from many of the sulfoxides under oxidative fragmentation conditions using sulfuryl chloride and the reaction represents a new protocol for sulfinyl chloride synthesis. The method is suitable for most alkane-and arenesulfinyl chlorides (3), but is limited to highly substituted vinylic sulfinyl chlorides. 1-Alkenyl 2-(trimethylsilyl)ethyl sulfoxides with reduced double bond substitution (6, 7, 11) suc-The sulfinyl chloride unit is one of the fundamental building blocks of organosulfur chemistry. [1] It is not only the ultimate starting unit for many sulfinic acid derivatives, [2] but also for a number of sulfonyl-containing functionalities. [3Ϫ6] Sulfinyl chlorides remain one of the key starting points in the preparation of enantioenriched sulfoxides through the intermediacy of chiral sulfinic esters [1,7,8] and amides. [9,10] An extension of that chiral sulfinate chemistry ties to the burgeoning field of asymmetric sulfinimine chemistry and the synthetic diversity that it offers. [11,12] Many preparations of sulfinyl chlorides involve oxidations of a sulfur atom. [1,13] That atom may belong to a thiol, disulfide or thiolacetate and the resulting sulfinyl chloride must be separated from acidic by-products or otherwise treated in the presence of those by-products. A less common protocol entails starting with a sulfoxide and effecting CϪS bond cleavage by way of oxidative fragmentation conditions (Scheme 1). Such a method circumvents the acidic conditions of older procedures and provides a sulfinyl chloride readily available for further functionalization. In this regard, the phthalimidomethyl [14,15] and tert-butyl [16] groups have proved useful for the generation of a number of alScheme 1[a] Guelph-

Thiolsulfinate Allicin from Garlic: Inspiration for a New Antimicrobial Agent

“…Both these synthetic strategies are well documented in the literature. However, since the preparation of alkanesulfinyl chlorides can be nontrivial,26 it was decided to pursue the former approach. Furthermore, the over‐oxidation product of 2 , the thiolsulfonate 3 , was also a desirable target for biological testing.…”

Vinyltrimethylsilane

“…Oxidation to the sulfoxide and reaction with sulfuryl chloride provides 2-chloroethyltrimethylsilane and the sulfonyl chloride in good yield (eq 24). 29 The reaction sequence works well for the preparation of alkyl, aryl, and unsaturated sulfonyl chlorides. …”

“…36 Thus, the reaction under the influence of a Lewis acid results in the formation of the trimethylsilylated cyclic benzothiazine (29) as a mixture of diastereoisomers accompanied by the desilylated analog (30) (eq 28). The silylated (29) can be alkylated and then the double bond introduced through a fluoride-induced, ring-opening elimination of the β-trimethylsilylsulfonamide group to give the 2alkenylsulfonamide, which is converted to the aniline by standard protocol (eq 29). Direct Silylation of Heteroarylcarbonyl Compounds.…”