Sulfa-Michael reaction

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.

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 sulfa-Michael reaction of a,p-unsaturated ketones catalysed by the salt derived from 9-amino-9-deoxy-epz -dihydroquinine (9-e/ f-DHQA) and n-N-Boc-phenylglycine, the best results (96% ee) were obtained using fert-bulyl-thiol. ° A similar catalyst, 9-amino-9-deo y-epz-cupreidine (9-epf-CPDA) allowed a diastereodivergent reaction, where selectivity towards both product diastereomers was possible using the same catalyst by changing the acidic additive and reaction conditions (Scheme 15.31). 

Tan and coworkers reported an asymmetric sulfa-Michael reaction, in which the enantioselective step is a protonation. Although the optimal solvent reported was Et20 (a highly hazardous solvent, rank 6,... 

Most reports on organocatalytic sulfa-Michael reactions are based on Br0nsted base catalysis, in order to activate pro-nucleophiles containing a S H or a Se—H bond. The early works, appeared in the lates 1970s, featured natural cinchona alkaloids 1-4 as basic catalysts (Figure 14.1). In their seminal works, Wynberg and co-workers employed less than 1 mol% of quinine 1 as chiral catalyst for the conjugated addition of arenethiols to 2-cyclohexen-l-ones. The enantiocontrol was unsatisfactory with benzyhnercaptan [6]. The quasi-enantiomeric catalyst quinidine 2 furnished the... 

The sulfa-Michael reaction to a (3,(3-disubstituted Michael acceptor, affording adducts with a new quaternary stereocenter, is usually challenging, mainly due to the low reactivity and reversibility of the process. Xiao and co-workers [41] reported that thiourea 12 promoted the highly enantioselective conjugate addition of arenethiols and substituted benzyl thiols to a-substituted (3-nitroacrylates. The enantioenriched adducts could be easily transformed into a-thio-(P -amino acids, valuable building blocks for the synthesis of p- or mixed p/a-peptides (Scheme 14.12). 

Scheme 1.69 Sulfa-Michael reactions catalysed by cinchona alkaloid ammonium salt.

Scheme 1.70 Sulfa-Michael reactions of a,P-xmsaturated sulfonates catalysed by cinchona alkaloid.

Scheme 1.71 Sulfa-Michael reactions of tert-butyl 2-phthalimido acrylates catalysed by bicyclic guanidine.

One of the first reported C-S organocatalytic bond formations was reported by Pracejus in 1977. In this pioneering work benzylthiol, a-phthalimidomethacrylate, and catalytic amounts of chiral amines reacted to form several cysteine derivatives. With the advent of organocatalysis and iminium catalysis, several sulfa-Michael reactions have been developed. 

The first organocatalytic sulfa-Michael reaction of enals was reported by j0rgensen in 2005 [68]. In this report aliphatic and aromatic aldehydes reacted with several thiols in good yields and enantioselectivities under catalysis of 28. The products must be reduced immediately due to their fast epimerization at room temperature (Scheme 33.21). In this work, j0rgensen and coworkers also developed several multicomponent cascade reactions with good to excellent results. 

Scheme 33.21 Sulfa-Michael reaction reported by Jorgensen.

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

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