Thiourea derived catalysts chiral, Michael reactions

Thiourea 123 while bearing only one chiral carbon atom is an adequate catalyst. Although much less commonly employed in the present context for calcium salts, one such appears to he able to team up with ent-96K to direct asymmetric Michael reaction involving a glycine derivative. ... 

Li and coworkers have studied the reaction between cyclic ketones 133 and nitroolefins 134 in the presence of the chiral pyrrolidine-thiourea bifunctional catalyst 135 (Scheme 3.41), finding that it allows an enantioselective synthesis of 3-oxa- and 3-azabicyclo[3.3.1]nonan-9-one derivatives 136, probably via a domino process comprising allylic displacement and Michael reactions as the key steps [90],... 

Bis-thiourea catalysts have been developed by several research groups. Nagasawa et al. synthesized chiral bis-thiourea derivatives and demonstrated their catalytic activity in the Michael reaction of pyrrolidone, giving rise to a,p-unsaturated y-lactones with moderate enantioselectivity [80]. trans-l,2-Diaminocyclohexane-derived bis-thiourea (5) promoted the DMAP mediated Baylis-Hillman reaction to give the adducts with high enantioselectivity (Scheme 2.30) [81]. 

Enders et al. developed an asymmetric synthesis of polyfiinctionalized pyrrolidines based on Mannich-Michael cascade strategy (Scheme 2.42). Under the promotion of 10mol% thiourea catalyst 140b, y-malonate-substituted a,P-unsaturated esters 149 and N-protected aryl aldimines 148 underwent Mannich reaction to afford chiral amine intermediates, which then underwent an intramolecular aza-Michael reaction to yield pyrrolidine derivatives 150 with moderate to good enantioselectivities [60]. 

Cyclohexanediamine-derived amine thiourea 70, which provided high enantio-selectivities for the Michael addition [77] and aza-Henry reactions [78], showed poor activity in the MBH reaction. This fact is not surprising when one considers that a chiral urea catalyst functions by fundamentally different stereoinduction mechanisms in the MBH reaction, and in the activation of related imine substrates in Mannich or Streclcer reactions [80]. In contrast, the binaph-thylamine thiourea 71 mediated the addition of dihydrocinnamaldehyde 74 to cyclohexenone 75 in high yield (83%) and enantioselectivity (71% ee) (Table 5.6, entry 2) [79]. The more bulky diethyl analogue 72 displayed similar enantioselectivity (73% ee) while affording a lower yield (56%, entry 3). Catalyst 73 showed only low catalytic activity in the MBH reaction (18%, entry 4). 

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