Vinyl sulfones, Michael reactions aldehydes

A series of aminal-pyrrolidine-derived organcatalysts was synthesised by Alexakis and coworkers. ° Initially, this family of aminal catalysts was evaluated for catalysing the Michael addition of aldehydes to nitro-olefins. When Ik was used, the products obtained had moderate to good stereoselectivities (up to 79% ee) at ambient temperature (Scheme 9.17). The reaction of vinyl-sulfone with linear aldehydes yielded more satisfactory results. Impressive reactivity and good enantioselectivities were obtained when only 10 mol% of Ik was used and representative examples are presented in Scheme 9.17. The stereocontrol exhibited by the catalyst was possibly associated with the strong interaction between the sulfonyl group and the aminal catalyst. 

Also known as Morita-Baylis-Hillman reaction, and occasionally known as Rauhut-Currier reaction. It is a carbon—carbon bond-forming transformation of an electron-poor alkene with a carbon electrophile. Electron-poor alkenes include acrylic esters, acrylonitriles, vinyl ketones, vinyl sulfones, and acroleins. On the other hand, carbon electrophiles may be aldehydes, a-alkoxycarbonyl ketones, aldimines, and Michael acceptors. 

Scheme 2.26 Enantioselective Michael reaction of aldehydes with vinyl(bis)sulfones.

Other Michael acceptors that were used in addition of aldehydes were vinyl sulfones. Zhu and Lu showed that the most efficient catalyst for this reaction was catalyst C2a with 3,5-bis(trifluoromethyl)phenyl groups (Scheme 8.5). It provided the corresponding products in high yields, with good to high diastereomeric and high enantiomeric purities. Palomo and coworkers also came to the same conclusion. They also extended the scope of the addition to E-a-ethoxycarbonyl vinyl sulfones. 

Since vinyl sulfoxides are poorer Michael acceptors than vinyl sulfones, the DABCO-catalyzed MBH reaction of vinyl sulfoxide with aldehydes required more forcing conditions to achieve a satisfactory yield, albeit with low diastereo-selectivity (Scheme 1.40). No reaction was observed at ambient pressure. Phenyl vinyl sulfonate is surprisingly reactive (Scheme 1.41), but only one example of this class of compounds has been reported. 

A wide variety of carbon nucleophiles have been successfully used in the organocatalytic asymmetric inter- and intramolecular Michael addition to different a,p-unsaturated systems. Among them, the addition of aldehydes to diverse Michael acceptors such as, a,p-unsaturated ketones, alkylidene malonates, P-nitrostyrenes, and vinyl sulfones, is one of the most studied reactions. Enamine catalysis is the most frequently employed chiral activation found in the literature. 

SCHEME 5.54. Intramolecular Michael reaction of aldehydes to vinyl sulfones. 

This organocatalyst and the corresponding trifluoromethyl-substituted derivative have been applied by Zhu and Lu to the asymmetric Michael reaction of aldehydes with other Michael acceptors, such as vinyl sulfones, providing the corresponding Michael products with exceptional enantioselectivities and excellent yields (Scheme 1 A) In order to make this methodology more useful, the authors extended its scope to 2-aryl-substituted vinyl sulfones as acceptors, which yielded the corresponding Michael products in excellent yields, good diastereoselectivities and nearly perfect enantioselectivities, as shown in Scheme 1.4. 

On the other hand, Alexakis et al. have developed a sequential reaction exploiting the compatibility between a cationic iridium catalyst and chiral diphenylprolinol trimethylsilyl ether. The role of the iridium complex was proposed to isomerise the starting allylic primary alcohols into the corresponding aldehydes in the presence of H2, while the chiral amine catalyst promoted the a-functionalisation of these aldehydes through reaction with vinyl sulfone to give the corresponding Michael adducts as a mixture of syn-and (Z h -diastereomers obtained in moderate yields, moderate to excellent... 

Because a different stereochemistry for the aza-MBH reaction involving different Michael acceptors was observed, in a continuation of our work, we reinvestigated systematically the reaction of iV-sulfonated imines with various activated olefins, including ethyl vinyl ketone (EVK), acrolein, phenyl acrylate and a-naphthyl acrylate. An interesting inversion of absolute configuration between the adducts derived from MVK or EVK and those from acrolein, methyl acrylate, phenyl acrylate or a-naphthyl acrylate was observed, indicating that the substitution patterns of the olefin may alter or even invert this trend.Similar to the addition to HFIPA, the (3-ICD-mediated addition of methyl, phenyl and naphthyl acrylates 149 to V-sulfonyl imines afforded adducts 150 with an (5) configuration, which is opposite to that observed with aldehydes (Scheme 2.71). ... 

---