Michael sulfa

For a general review on sulfa-Michael reactions see D. Enders, K. Luttgen and A. A. Narine, Synthesis, 2007, 959. 

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

Scheme 4.67 Enantioselective sulfa-Michael reaction of thioacetic acid with nitroalkenes and application to the synthesis of (R)-sulconazote.

The structural and electronic analogies between the nitro and the imide groups have also been surveyed in this transformation (Scheme 4.69). Takemoto s catalyst has been employed in the reaction of thiophenol to imides derived from benzoic add, furnishing excellent yields of the sulfa-Michael... 

Scheme 4.69 Enantioselective sulfa-Michael reaction of aryl and alkylthiols with a,P-unsaturated imides.

Two examples of hetero-Michael reactions have been reported using these kinds of bis-cinchona alkaloid-based chiral Bronsted bases as catalysts. One of them refers to a sulfa-Michael reaction and the other is a case of an aza-Michael reaction. 

Scheme 6.16 Enantioselective sulfa-Michael reaction catalyzed by 125b.

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... 

One of the first attempts in this field refers to a multicomponent intermolecular sulfa-Michael/amination cascade process in which an a,p-unsatu-rated aldehyde and a thiol were reacted in the presence of a dialkyl azodicarboxylate reagent, giving access to p-amino-y-thioalcohol derivatives with excellent yields and enantioselectivities. Isolation of the final products was accomplished by in situ reduction followed by base-promoted cyclization (Scheme 7.48). 0-Trimethylsilyl diarylprolinol 31c was identified as the best... 

Scheme 7.48 Intermolecular sulfa-Michael/electrophilic amination reaction catalyzed by 31c.

Using this approach, benzothiopyrans have been prepared by means of a sulfa-Michael/aldol/dehydration cascade and access to dihydroquinolines has been achieved by using an aza-Michael/aldol/dehydration approach (Scheme 7.52). In general, all these reactions proceeded with excellent yields and... 

Scheme 7.53 Sulfa-Michael/aldol cascade using ketones as internal electrophiles.

Scheme 7.71 One example of a cascade sulfa-Michael/aldol reaction catalyzed by a chiral thiourea.

Scheme 7.72 Cascade sulfa-Michael/Michael reaction for the asymmetric synthesis of highly substituted thiochromanes.

The construction of polyheterocycHc spirotetrahydrothio derivatives via a sulfa-Michael/aldol cascade reaction appeared in the literature in the year 2014 (14TL6335).The authors were attraaed to tetrahydrothiophenes due to their ability to serve as building blocks in many pharmaceutical agents and natural products. Previously, methods for preparing tetrahydrothiophenes lacked generality and efficiency. These workers were able to prepare titled compounds by the reaction of various chalcones with 1,4-dithane-2,5-diol under mild conditions. A few examples are shown below.The latter reaction showed excellent diasteroselectivity in the presence of a chiral phase transfer catalyst. 

Optically active sulfur containing compounds play a very important role in biochemistry as well as synthetic chemistry. The asymmetric conjugate addition of sulphur nucleophiles, or sulfa-Michael addition [379], provides a direct and versatile approach toward optically active sulfur compounds. This strategy is particularly valuable, since enantioselective nucleophilic additions to a C-S double bond, unlike those to carbonyls and imines, are not synthetically feasible. 

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