Stereospecific Grignard reactions of cholesteryl 1-alkenesulfinate esters: Application of the Andersen Protocol to the preparation of non-racemic α,β-unsaturated sulfoxides

Abstract

Enantiomerically enriched α,β-unsaturated sulfinate esters of (–)-cholesterol undergo stereospecific substitutions at sulfur when treated in benzene at 6°C with Grignard reagents. Sulfoxides with ees of 85–99.5% are obtained when enantiopure sulfinates are used. The substitution reactions proceed with inversion of sulfur configuration. Enantiomerically pure cholesteryl (E)-2-carbomethoxyethenesulfinate is not a suitable reactant under the Grignard reaction conditions. It is suggested that the ester group induces unwanted reactions significantly lowering both the yield and sulfur stereogenicity.Key words: sulfinate, sulfoxide, Grignard reagents, stereospecific, unsaturated.

Nucleophilic attack of 2-sulfinyl acrylates: A mild and general approach to sulfenic acid anions

“…As part of our studies regarding the sulfur substitution chemistry of a,b-unsaturated sulfenate esters, we encountered a situation where an alkoxide displaced a sulfenate anion under ostensibly an addition/elimination mechanism (Scheme 1). 17 The reaction resembles an intermolecular version of a Smiles rearrangement 18 on a sulfoxide, but also was similar to chemistry offered from the Furukawa group for the release of sulfenate anions from the 2position of benzothiazoles, or from 2-sulfinyl substituted pyridine-Scheme 1 N-oxides. 9 In keeping with our ongoing studies of unsaturated sulfinyl derivatives, 17, 19 we decided to probe the general usefulness of the acrylate as a sulfenate-releasing group, believing that it may prove more reactive than the aromatic substrates of Furukawa, and may also permit access to a greater breadth of sulfenates.…”

Unexpected reactions of Grignard reagents with selected β-carboalkoxy substituted sulfinate esters

“…The attack occurs in a conjugate fashion in relationship to the carboxylate and releases phenylsulfenate. 43,49 Ethyl 2-methoxycarbonylethanesulfinate (18) was prepared using protocols established for unsaturated sulfinate esters. 50 Its reaction with 3 equiv.…”

“…[32][33][34][35] The sulfinate is particularly appealing for its ability to be readily adapted by reduction, 34,36,37 oxidation, [38][39][40] and transformation to sulfoxide. [41][42][43] Moreover, we have demonstrated that appropriately disposed sulfinate esters can participate in iodosultinization reactions with inversion of sulfinyl configuration. 32 In the current study, we examined the Grignard substitution chemistry of a series of Diels-Alder cycloadducts previously prepared from dienophile 1.…”

Determination of theZ1H NMR chemical shift substituent parameters for the sulfinyl chloride and sulfinate ester functionalities

“…Sulfinyl chloride and sulfinate ester functional groups are part of modern investigations [9,10] and, as such, double bonded compounds bearing these substituents are of interest to us [11][12][13][14][15][16] and to others [17][18][19][20][21][22][23][24][25][26][27]. Unfortunately the alkene additivity rule is unavailable for investigators in this area due to the lack of appropriate substituent constants.…”