Quinine thiourea catalyst

The heterogeneous version of this reaction was quite recently reported by Guo and coworkers [75]. Highly interestingly, in the reaction of the indole with the N-Bs (Bs, benzene sulfonyl) phenyl imine 162, enhanced enantioselectivity (99.2% ee at 40 °C) compared with that (92% ee at 50 °C [74], 93.2% ee at 40 °C [75]) obtained with the homogeneous analogue 40 was achieved using the mesoporous silica (SBA-15) supported epi-quinine thiourea catalyst 161. The increased ee value can be ascribed to the confinement effect [76] of the support (Scheme 8.64). 

A closely related methodology was applied by Zhao et al. to the enantio-selective synthesis of tetrasubstituted thiochromanes on the basis of a domino thia-Michael-Knoevenagel reaction between 2-mercaptobenzaldehydes and benzylidenemalonates with the same quinine thiourea catalyst. Steric and electron effects were found to affect profoundly the stereoselectivities of the reaction. Thus, it was shown that the diastereoselectivity of the reaction... 

Wang and coworkers found that the quinine-derived thiourea catalyst 81b (1 mol%) was also highly reactive and enantioselective for the tandem thio-Michael-aldol reaction of various 2-mercaptobenzaldehydes (103) with a,P-unsaturated oxazolidi-nones (104), furnishing benzothiopyranes (105) with three stereogenic centers in... 

In addition to aldehydes, the hydrophosphonylation reaction was also attempted on ketones. Thus, Xu and Wang have studied the reaction of diphenyl phosphite with N-allq lated isatins catalysed by quinine that gave superior results in comparison to thiourea catalysts (Scheme 15.2). 

Michael addition of a-substituted a-nitroallylphosphonates (293) to various nitroolefins (299) have been shown to produce o,y-diaminophos-phonic esters (300) in the presence of a quinine-derived thiourea catalyst (298), with high diastereo- and enantioselectivity (Scheme 100). ... 

The Soos group, in 2005, prepared the first thiourea derivatives from the cinchona alkaloids quinine QN (8S, 9R-121), dihydroquinidine DHQD (8S, 9S-122), C9-epi-QN (8S, 9P-123), and quinidine QD (SR, 9R-124) via an experimentally simple one-step protocol with epimerization at the C9-position of the alkaloid starting material (Figure 6.39) [278]. The catalytic efficiency of these new thiourea derivatives and also of unmodified QN and C9-epi-QN was evaluated in the enan-tioselective Michael addition [149-152] of nitromethane to the simple model chal-cone 1,3-diphenyl-propenone resulting in adduct 1 in Scheme 6.119. After 99h reaction time at 25 °C in toluene and at 10 mol% catalyst loading QN turned out to be a poor catalyst (4% yield/42% ee (S)-adduct) and C9-epi-QN even failed to accelerate the screening reaction. In contrast, the C9-modified cinchona alkaloid... 

C9-epi-122 98% conv. (99% ee) after 30h, respectively (Figure 6.40). This structure-efficiency relationship supported the results already published by the Soos group for quinine- and quinidine-derived thioureas (Figure 6.39) [278]. C9-epimeric catalysts were found to be remarkably more efficient in terms of rate acceleration and stereoinduction than the analogs of natural cinchona alkaloid stereochemistry. This trend was also observed for the corresponding (thio)ureas derived from DHQD as shown by the experimental results in Figure 6.40 [279]. 

Quite recently, we also observed that quinine-based thiourea derivatives showed dramatic concentration and temperature effects on the enantioselectivity in the alcoholytic desymmetrization ofmeso-cyclic anhydrides, which can also be attributed to the self-association of the catalyst [23]. Of course, the possibility that the variation in... 

In addition to chiral PTCs, cinchona-based thioureas have also been proved to serve as catalysts for nitro-Mannich reactions. In 2006, Ricci and coworkers first reported that the quinine-based thiourea 40 (20mol%) can catalyze the aza-Henry reaction between nitromethane and the N-protected imines 93 derived from aromatic aldehydes [40]. N-Boc-, N-Cbz-, and N-Fmoc protected imines gave the best results in terms of the chemical yields and enantioselectivities (up to 94% ee at —40°C) (Scheme 8.30). 

Later on, the same group developed a highly stereoselective Michael-Michael cascade process catalyzed by the quinine-based thiourea 81b [29b]. In the presence of a low catalyst loading (2 mol%), the reaction of trans-3-(2-mercaptophenyl)-2-prope-noic acid ethyl ester (106) with a wide range of nitroalkenes (107) afforded thio-chromanes (108) having three new stereocenters with high stereoselectivity (dr >30 1, up to 99% ee, Scheme 9.36). 

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