J-Unsaturated Sulfoxides

Although a,/J-unsaturated sulfoxides are easily prepared (see Section D.1.1.1.5.), they arc usually obtained as a mixture of E- and Z-isomers11 both of which may be deprotonated by... 

The Michael addition of nucleophiles to a,/J-unsaturated sulfoxides creates initially a-sulfmyl carbanions by nucleophilic attack on the /J-carbon atom. Russell and Becker157 found that treatment of a mixture of diphenylmethane and anisaldehyde with potassium t-butoxide in DMSO gave at first the condensation product 170, which upon Michael addition afforded the final product 171. 

Asymmetric synthesis using a-suifinyi carbanions and j unsaturated sulfoxides... 

The anions derived from racemic alkyl and benzyl tert-butyl sulfoxides undergo 1,4-addition to a,/J-unsaturated esters to give adducts with high product diastereoselection (>5 1)10,11. Alkyl 4-methylphenyl sulfoxides were found to be less diastereoselective. In the case of 2-methyl-2-(methylsulfinyl)propanc the highly hindered 2,6-di-rer7-butyl-4-methylphenyl ester was required to prevent a competing acylation reaction. 

IV. ADDITION OF NUCLEOPHILES TO P-UNSATURATED SULFOXIDES A. /J-Keto sulfoxides... 

Organocopper reagents RCu (as well as certain R2CuLi) add to a,(J-unsaturated and acetylenic sulfoxides.482... 

Aldol reaction. The reagent (I) adds in a 1,4-fashion to an a,/J-unsaturated ketone lo give an aluminum enolate, which undergoes aldol condensation with an aldehyde. The adduct is converted into an a-substituted-a./l-unsaturated ketone on sulfoxide elimination.1... 

Since early investigations about the asymmetric addition of diethyl sodiomalonate to optically active vinylic sulfoxides,100-101 Posner and his coworkers102-117 have developed a highly useful methodology based on the conjugate addition of carbon nucleophiles to homochiral a-arylsulfinyl-a,(J-unsaturated carbonyl compounds. While acyclic derivatives still lead only to moderate results,103 the strength of this method is for cyclic systems. For example, the 2-sulfinyl-2-cycloalkenones (94) and (95), the 2-sulfinyl-2-alkenolides (96) and (97), as well as their respective enantiomers are excellent substrates. All these compounds are quite readily accessible in enantiomeric purities of >98% and are configurationally stable, at least for several months at 0 C. 

A few examples of additive Pummerer leairangements arc known involving direct conversion of a, -unsaturated sulfoxides into a, -disubstitutBd sulfide. 4 4. 63 Scheme 4 illustrates two gomal pathways for such processes and specific exanqiles of each are known. For example, alk-l-oiyl j oiyl sulfoxiite... 

For the acetylenic sulfoxide, because of its configurationally stable pyramidal stereogenic sulfur atom (a lone electron pair, an oxygen and two different carbon substituents), it can exist in chiral forms. Therefore, in chiral acetylenic sulfoxide, the sulfoxide moiety not only serves as a chemical activator of the acetylene unit, it can also induce stereochemical control at the adjacent carbon centers to achieve enantioselective synthesis. In this article, we shall discuss the preparation of these a, /J-unsaturated synthons and their applications in Diels-Alder reactions, heterocycle and alkaloid syntheses. 

Alonso, 1. and Carretero, J.C. (2001) Highly stereoselective s3mthesis of trisubstituted a, 8-unsaturated sulfoxides by Heck reaction. J. Org. Chem., 66,4453. ... 

Posner, G. H. (1988) Asymmetric synthesis using a-sulfinyl carbanions and p-unsaturated sulfoxides, in Patai, S., Rappoport, X. and Stirling, C. J. M (eds). The Chemistry of Sulphones and Sulphoxides, Chapter 16, pp. 823-848. 

The intramolecular Michael reaction is also a powerful transformation. In the cyclizations reported by Tetsuaki Tanaka of Osaka University (J. Org. Chem. 2004, 69, 6335), the stereochemical outcome is controlled by the chirality of the sulfoxide. Remarkably, subsequent alkylation or aldol condensation leads to one or two additional off-ring stereocenters with high diastereocontrol. Note that the high stereoselectivity in the cyclization is only observed with the (Z)-unsaturated ester. 

S. G. Pyne, Addition of Metalated Allylic Phosphine Oxides, Phosphonates, Sulfones, Sulfoxides and Sulfoximines to a,/3-Unsaturated Carbonyl Compounds , in Stereoselective Synthesis (Houben-Weyl) 4th ed. 1996, (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), 1996, Vol. E21 (Workbench Edition), 4, 2068-2086, Georg Thieme Verlag, Stuttgart. 

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