Cinchona alkaloid thioureas

Scheme 6.112 Michael addition of thiophenol to an a,p-unsaturated imide catalyzed by cinchonidine-derived thiourea 116 and cinchonine-derived thiourea 117, the first representatives of this class of bifunctional hydrogen-bonding cinchona alkaloid-thioureas.

Figure 6.39 Cinchona alkaloid-thioureas prepared from quinine (121), dihydroquinine (122), C9-epi-quinine (123), and quinidine (124) catalytic efficiency evaluated in the Michael addition of nitromethane to tram-chalcone 1,3-diphenyl-propenone at 10mol% loading and rt.

Benzotriazole was found to be an efficient ligand for the Cu(I) iodide-catalyzed N-arylation of imidazoles with aryl and heteroaryl halides <07TL4207>. The first enantioselective conjugate addition reaction of I //-benzotriazole with a variety of enones catalyzed by a cinchona alkaloid thiourea affords Michael adducts in good yields with moderate to good enantioselectivities has been reported <07S2576>. 

S. Oxindole Derivatives. Most recently, Curti et al. [140] disclosed the first example of a direct, organocatalytic asymmetric vinylogous Michael addition of 3-alkylidene oxindole to nitroalkenes. Bifunctional cinchona alkaloid/thiourea catalyst 69 could effectively promote the reaction, solely aHbrding the 7-substituted 3-alkylidene oxindoles 146 with excellent regio-, diastereo-, and enantioselectivities (Scheme 5.71). Importantly, both aromatic and aliphatic substituted nitroalkenes were applicable for such a reaction. 

Zhu, J.-L. Zhang, Y Liu, C. Zheng, A.-M. Wang, W. Insights into the Dual Activation Mechanism Involving Bifunctional Cinchona Alkaloid Thiourea Organocatalysts An NMR and DPT Study. /. Org. Chem. 2012, 77, 9813-9825. 

In 2013, Zhao et al. described a highly diastereo- and enantioselective synthesis of trisubstituted cyclohexanols based on a one-pot sequential tandem Henry-Michael reaction catalysed by a combination of a chiral cinchona alkaloid thiourea and 1,1,3,3-tetramethyl guanidine. This process occurred between nitromethane and 7-oxo-hept-5-en-l-als, providing the corresponding tandem chiral products as almost single diastereomers... 

Scheme 2.34 Tandem Henry-Michael-retro-Heniy reaction catalysed by a chiral cinchona alkaloid thiourea and 1,1,3,3-tetramethyl guanidine.

By using the cinchona-alkaloid-thiourea-based bifunctional organocatalyst 55, Asano and Matsubara developed an organocatalytic formal [3 -t- 2] cycloaddition reaction, leading to optically active 1,3-dioxolanes 54 (Scheme 2.15). The reaction... 

Two research groups independently reported the enantioselective 1,4-addition of malonate to nitroalkene catalyzed by cinchona alkaloid thiourea catalysts (Scheme 2.50). Connon et al employed (15a) [105] and Dixon et al utilized (16) [106]. 

Cinchona alkaloid thiourea catalyst 17 (Figure 37.2) was later employed by Gong el al. to induce the enantio- and diastereoselective 1,3-dipolar cycloaddition of azomethine ylides generated from Schiffbases and nitroalkenes [31]. This process provided straightforward access to chiral highly substituted pyrrolidines with good yields, moderate enantioselectivities (<63% ee), and excellent diastereoselectivities... 

These products were produced in high yields, and enantioselectivities of up to 96% ee, with a remarkable general diastereoselectivity of >98% de (Scheme 37.10). The process was induced by cinchona alkaloid thiourea 58, which was employed at only 5 mol% catalyst loading. 

Mannich Reaction Carbamate-protected alkyl imines are important building blocks in the synthesis of chiral alkyl amines. However, they are usually unstable, and most of them cannot be prepared in pure form. As the optimal substitutes, a-amido sulfones 142 were first used in the PTC-catalyzed enantioselective aza-Henry reaction in 2005 [57]. Subsequently, Song et al. reported a chiral Cinchona alkaloid thiourea (130b)-catalyzed Mannich reaction with in situ generation of... 

Zhang HL, Syed S, Barbas CFI. Highly enantio- and diaster-eoselective Mannich reactions of glycine Schiff bases with in situ generated A-Boc-imines catalyzed by a cinchona alkaloid thiourea. Org. Lett. 2010 12(4) 708-711. 

Figure 35.2 Representative chiral cinchona alkaloid, thiourea, and phosphoric acid derivatives (hydrogen bond activation).

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