Sulfa-Michael reactions synthesis

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

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

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). 

The one-pot, organocatalytic Hayashi sequential reaction (HSR) of p-nitroacrylate (806), aldehyde (807), toluenethiol (808), and vinylphosphonate (805) allowed the synthesis of highly functionaKsed cyclohexanes (809) with very high enantioselectivity (up to 99 % ee). The one-pot synthesis consisted of the tertiary amine modified diarylprolinol silyl ether (810)-mediated asymmetric Michael reaction, a domino Michael reaction/the Horner-Wadsworth Emmons reaction, and a sulfa-Michael reaction (Scheme 205). ... 

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

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. 

In addition to conventional Diels-Alder reactions, consecutive [4-1-2] reactions have been subjected to extensive investigation through the iminium-enamine catalytic sequence. Wang, Rios, and others simultaneously described enantioselective cascade sulfa-, oxa-, and aza-Michael/aldol/dehydration reactions promoted by chiral secondary amines. An initial strategy for a one-pot synthesis of chiral thiochromenes with good to high enantioselectivities was reported (Schemes 1.46 and 1.47) [71]. 

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