Enones sulfa-Michael reactions

Scheme 4.66 Enantioselective sulfa-Michael reaction of arylthiols with enones catalyzed by natural cinchona alkaloids.

The first asymmetric organocatalytic sulfa-Michael reaction of enones was reported by Wynberg in 1977 [113]. In this report cyclohexenone reacts with thiophenyl... 

Organocatalysis Continuing efforts to harness the cooperative activity of bifunctional organocatalysts have led to the examinations of chiral calix[4]arenes containing amino phenol stractures and chiral per-6-amino-P-cyclodextrin in the asymmetric sulfa-Michael reactions to cyclic and acylic enones.The preliminary results indicated that further structural modification would be required to allow more efficient asymmetric catalyst systems. 

Asymmetric chiral (thio)urea-catalyzed sulfa-Michael reactions have been extended to thioacetic acid and nitroal-kenes (Scheme 46.33). In 2006, Wang and co-workers used Takemoto s chiral thiourea 272 in the addition reaction of thioacetic acid 271 to acyclic enones 270 with modest enan-tioselectivities ranging from 20% to 1Q%P The use of... 

In a completely different context, an A-protected version of the amino acid cysteine has been found to be an excellent promoter for the intramolecular Rauhut-Currier reaction (Scheme 6.20)," in which an enolizable enone played the role of the Michael acceptor, adding to another a,p-unsaturated ketone moiety in already present at the substrate structure. The mechanism of the reaction involved the activation of the enone which has to play the role of the donor by the catalyst via sulfa-Michael addition through the mercapto functionality of the A-protected cysteine derivative. The formed enolate... 

Very recently two comprehensive review articles dealing with organocatalytic carbon-sulfur bond-forming reactions and asymmetric sulfa-Michael additions have been published. Historically, the first catalytic enantio-selective sulfenylations of conjugated enones in the presence of Cinchona alkaloids were published in 1977 by Pracejus where acrylamides and... 

Wang et al. [49] obtained enantioenriched thiochromenes through a cascade sulfa-Michael-aldol-dehydration reaction between 2-mercaptobenzaldehydes and a,p-unsaturated aldehydes, catalyzed by 17a (Scheme 14.17a). Cordova and coworkers [50] obtained comparable results despite some minor changes of the reaction conditions. An analogous process with cyclic enones afforded tetrahydrothioxanthe-nones in only moderate enantioselectivities (Scheme 14.17b). In this case, chiral pyrrolidines 18 and 19 gave the best results in terms of enantioselectivities [51]. 

Whereas secondary amines are suitable catalysts for activation of a,(3-unsaturated aldehydes, more difficulties are usually encountered with sterically demanding substrates, such as a,(5-unsaturated ketones. Primary amines can be useful catalysts in such cases. Yoshida et al. [52] reported an amino acid-catalyzed sulfa-Michael addition of arylmethyl mercaptans to cyclic enones. The proposed mechanism invokes the formation of an imine intermediate. However, even with the best screened catalyst, 5-trityl L-cysteine, the reaction proceeded with modest levels of enantioselectivity (8-58% ee). 

In addition, Shimizu et al. have applied novel multifunetional inherently chiral calix[4]arene to the sulfa-Michael addition of thiols to cyclohexenone. The expected Michael adducts were obtained in generally excellent yields (18-99%) but with low enantioselectivities (<25% ee). The reaction system was also applied to other cyclic and acyclic enones, providing the corresponding products with a comparable degree of enantioselectivity to that obtained with cyclohexenone. 

Cinchona-alkaloid-catalysed conjugate cyanation of enones has enabled the synthesis of trifluoromethyl-substituted diarylpyrroles with ee<96%P° Thiochro-manes have been formed by asymmetric domino sulfa-Michael-aldol reactions of 2-mercaptobenzaldehyde with a,/ -unsaturated A-acylpyrazoles. Asymmetric organocatalysed oxy-Michael addition to y-hydroxy a,/ -unsaturated thioesters on reaction with t-BuCHO has been used to form -hydroxy carbonyl compounds HOCH2C H(OH)CH2CO.SAr via cyclic hemiacetal intermediates. 

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