M. Mercedes Rodríguez-Fernández

Remote Stereocontrol Mediated by a Sulfinyl Group: Synthesis of Allylic Alcohols via Chemoselective and Diastereoselective Reduction of γ-Methylene δ-Ketosulfoxides

The efficiency of the sulfinyl group as a remote controller of the chemoselectivity and diastereoselectivity of the reduction of alpha, beta-unsaturated alpha-[2-(p-tolylsulfinyl)phenyl] substituted ketones 1 has been demonstrated in reactions carried out under NaBH4 in the presence of Yb(OTf)3 as the chelating agent. The starting unsaturated ketones have been prepared from the corresponding 2-(p-tolylsulfinyl) benzyl alkyl (and aryl) ketones 2 by insertion of the methylidene group under modified Mannich conditions, exploiting ultrasound irradiation to obtain the aminomethylation adducts and silica gel treatment to produce its complete elimination. Desulfinylation of the reduction products yielded the corresponding vinyl carbinols with high enantiomeric purity.

Intermolecular Alkyl Radical Additions to Enantiopure N-tert-Butanesulfinyl Aldimines

The sulfinyl group in (R)-N-tert-butanesulfinyl aldimines provides efficient control of the stereoselectivity in the intermolecular reactions with alkyl radicals. The methodology is applicable to aryl, heteroaryl, benzyl, and alkynyl imines, even those containing CN, CO2Me, COR, and OH groups. The best results are attained with hindered radicals (tertiary and secondary ones) without C═N bond reduction. This reaction complements the well-established organometallic additions to N-sulfinyl aldimines to obtain enantiomerically pure functionalized α-branched primary amines.

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

Intramolecular homolytic substitution (SHi) on the sulfur atom at acyclic N-(o-bromobenzyl)sulfinamides takes place with a complete inversion of the configuration and provides an excellent tool to connect N-tert-butanesulfinylimines with enantiopure 3-substituted benzo-fused sulfinamides (1,2-benzoisothiazoline 1-oxides) and the related pharmacologically relevant sulfonamides.

Remote Asymmetric Induction by Sulfoxides: DIBAL Reduction and Et2AlCN Hydrocyanation of ortho-(p-Tolylsulfinyl)Benzyl Ketones

The efficiency of the sulfinyl group as an element of remote control of the stereoselectivity (1,5-asymmetric induction) in the DIBAL reduction and Et2AlCN hydrocyanation of the carbonyl group in unsubstituted ortho-p-tolylsulfinylbenzyl ketones 1 has been evaluated with and without stoichiometric amounts of Yb(OTf)3 as Lewis acid, as well as its α-methyl derivatives 2a and 2b, with the aim of establishing the influence of an additional stereogenic center on the stereoselectivity. Synthesis of ketosulfoxides 1 has been attained by condensation of (S)-2-(p-tolylsulfinyl)benzyllithium with esters. On the other hand, the α-methyl-substituted compounds 2 have been obtained by two different procedures: a) methylation of 1 with NaH/MeI to afford 2a and 2b as an approximately 1:1 epimeric mixture at the benzylic position and b) by oxidation with PCC of the alcohols (epimeric mixtures at the hydroxylic carbon) obtained from reactions of aldehydes with the lithium carbanion derived from (S)-2-(p-tolylsulfinyl)ethylbenzene.1