Sulfones, asymmetric conjugate addition

In contrast to a, -ethylenic ketones or even a, -ethylenic sulfones, a, ) -ethylenic sulfoxides generally are not sufficiently electrophilic to undergo successful nucleophilic j8-addition . a-Carbonyl-a, j8-ethylenic sulfoxides, however, are potent, doubly activated alkenes which undergo rapid and complete -addition of various types of nucleophiles even at — 78 °C. A brief account summarizing this area is available . The stereochemical outcome of such asymmetric conjugate additions to enantiomerically pure 2-sulfmyl 2-cycloalkenones and 2-sulfinyl-2-alkenolides has been rationalized in terms of a metal-chelated intermediate in which a metal ion locks the -carbonyl sulfoxide into a rigid conformation (36 cf. 33). In this fixed conformation, one diastereoface of the cyclic n... 

Other interesting electron-deficient olefin substrates for the asymmetric conjugate addition include cr-acet-amidoacrylic ester SI,101 dimethyl itaconate S2,114 ct,/3-unsaturated sulfones S3,115 and alkenylphosphonate S4116 (Figure 8). 

Asymmetric Conjugate Addition with NitroaLkenes and Sulfones. 157... 

Asymmetric Conjugate Addition with Nitroalkenes and Sulfones... 

Chiral heterocychc amines as organocatalysts for asymmetric conjugate addition to nitroolefins and vinyl sulfones via enamine activation 07CC3123. 

Lately, sulfones have become especially important substrates in organocatalysis [87]. First studies on the asymmetric conjugate addition of aldehydes to vinyl sulfones were carried out by Alexakis and Mossd employing as catalyst bipyrrolidine 30 (25 mol%) for the addition of linear and a-branched aldehydes to l,l-bis(benzenesulfonyl)ethylene [88], Large excess of aldehyde (10 equivalents) was required and moderate levels of enantioselection were obtained for linear aldehydes (53-80% ee), while reactions with a-branched nucleophiles led to racemic or very low selectivities (0-12% ee). With respect to the mechanism, the acyclic synclinal model proposed by Seebach and GoUnski [70] involving a trans enamine intermediate was postulated. 

Scheme 2.67 Asymmetric conjugate addition of nitroalkanes to vinyl sulfones...

The asymmetric conjugate addition of activated methylenes is one of the most studied organocatalytic reactions. A wide variety of Michael acceptors such as enals, enones, a,P-unsaturated nitriles, nitroolefins, a,(i-unsaturated imides, and vinyl sulfones have been successfully employed as elechophiles with high degree of stereocontrol. 

For the same sequence, vinyl sulfones and vinyl selenones have appeared as new partners in organocatalyzed asymmetric conjugate addition, giving access to valuable building blocks. 

Sulzer-Mosse S, AlexaMs A. Chiral amines as organocatalysts for asymmetric conjugate addition to nitroolefins and vinyl sulfones via enamine activation. Chem. Commun. 2007 (30) 3123-3135. 

Bos PH, Macia B, Femandez-lbanez MA, Minnaard AJ, Fer-inga BL. Catalytic asymmetric conjugate addition of dialkyl-zinc reagents to a,p-unsaturated sulfones. Org. Biomol. Chem. 2010 8(1) 47 9. 

S.2.2.3. a, -Unsaturated Sulfones, Malononitriles, and Maleimides as Acceptors, Base on their previous achievements on the asymmetric Michael addition of aldehydes [24], Lu and co-workers [55] developed the first enantiose-lective conjugate addition of cyclic ketones to vinyl sulfone catalyzed by a primary amine 57 (Scheme 5.28). Various cyclic ketones could be applied, affording the corresponding adducts in good yields and with high to excellent enantioselectivities. However, linear ketones were not suitable substrates for this catalytic system. Performing the desulfonylation procedure on a-substituted ketones and in combination... 

An exclusive 1,4-addition has also been observed88 in iodosulfonylation of conjugated dienes with in situ generated tosyl iodide. With symmetrical acyclic dienes the corresponding (5-iodobut-2-enyl sulfones were obtained. In the case of asymmetrical acyclic dienes, with the exception of isoprene, mixtures of regioisomeric products were isolated (equation 62). 

Good results are obtained from reactions of compounds containing chiral auxiliaries. Thus, 1,3-asymmetric induction in the addition of radicals to 30, 1,4-asymmetric induction by the isopropyl group of the dilactim derived from cyclo(Gly-Val) in the addition to conjugated sulfones, and 1,5-asymmetric induction for SAMP/RAMP hydrazones during the addition to alkenylphosphonate esters are adequate. 

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