Terrohcdron: Asymrry Vol. 3, No. 6, pp. 149-152 1992 09574166/92 S5.Olh.00 Priitcd in Great Britain Pcrgamon Rcss Lid A Useful Synthesis of Chiral Sulfonyl Cyanides: (.S,2S,5R)-2-Isopropyl-5-methylcyclohexanesulfonyl Cyanide Jose M. Blanco, Olga Caamaiio, France Femandez*, Generosa Gdmez and Carmen Ldpez Depatwnento a2 Q&mica Orgdnica. Facultad de Farmacia, Vniversidad de Santiago, 15706santiago de Compostela. Spain. zyxwvutsrqp (Received 29 April 1992) Abstract: A convenient method for the preparation of chiral alkanesulfonyl cyanides, by oxidation of readily available alkyl thiocyanates with m-ClC,&COsH, has been developed. Sulfonyl cyanides are highly reactive nitriles used for the preparation of a variety of aromatic1 and aliphatics heterocycles, for stereospecific synthesis of 2-alkenenitriless and for ar-cyanation of ketone enolates.4 Except in the case of the aromatic target molecules, enantioselectivity can be pursued by the use of chiral sulfonyl cyanides; for example, reaction of (IS)-lo-camphorsulfonyl cyanide with cyclopentadiene leads to the preferential obtention of one of the enantiomers of 2-arabicyclo[2.2.l]heptJ-en-3-one.5 Our desire to use chiral sulfonyl cyanides has led to our developing a very general method for the preparation of chiral sulfinic acids from alcohols,6 the commonest route to sulfonyl cyanides being reaction of cyanogen chloride with the appropiate sodium sulfinate. 7 However, our approach failed to afford (IS,ZS,5R)-2- isopropyl-5methylcyclohexanesulfinic acid from (-)-menthol. We describe here an alternative route from alcohols to chiral sulfonyl cyanides that is satisfactorily simple and efficient and is applicable to substrates prone to structural and/or stereochemical alteration; its key step is the oxidation of readily available alkyl thiocyanates. As a typical example we describe the synthesis of fIS,2S,SR/-2-isopropyl-5 methylcyclohexanesulfonyl cyanide (see Scheme). Neomenthyl thiocyanate (3) was prepared from (-)-menthol (1) via (-)-menthyl tosylate (2), which was obtained from 1 in virtually quantitative yield and subjected to nuceophilic atack by sodium thiocyanate in ethanol; column chromatography of the crude product gave a yield of 56% that compares favourably with those afforded by reaction of the same substrate with other sulfur nucleophiles.* tH n.m.r. spectroscopy confirmed that an S,2 reaction had stereospecifically led to the configuration shown for 3, as well as the high diastereomeric purity of the product: the, aria1 1-H of 2 appears as a triplet of doublets at 6 4.40 ppm with coupling constants of 10.3 Hz (J,,,) and 4.4 Hz (J ar,eq) respectively, whereas the equatorial 1-H of 3 appears at 6 4.02 ppm as an unresolved multiplet with w,,~ cu. 8.1 Hz. H202, NaJO.+ KMn04 and fuming HNO, , with usually oxidize sulfides to sulfones, failed to convert 3 to 4, most of the starting material being recovered zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPON una lte re d . However, m-chloroJreroxybenzoic acid 749