Thiourea cinchona

Some bifunctional 6 -OH Cinchona alkaloid derivatives catalyse the enantioselective hydroxyalkylation of indoles by aldehydes and a-keto esters.44 Indole, for example, can react with ethyl glyoxylate to give mainly (39) in 93% ee. The enan- tioselective reaction of indoles with iV-sulfonyl aldimines [e.g. (40)] is catalysed by the Cu(OTf)2 complex of (S)-benzylbisoxazoline (37b) to form 3-indolylmethanamine derivatives, in up to 96% ee [e.g. (41a)] 45 Some 9-thiourea Cinchona alkaloids have been found to catalyse the formation of 3-indolylmethanamines [e.g. (41b)] from indoles and /V-PhS02-phenyli mines in 90% ee.46 Aryl- and alkyl-imines also give enantioselective reactions. 

In 2007, Jorgensen and coworkers demonstrated that the bifunctional thiourea-cinchona alkaloid catalysts 81b also promoted the enantioselective addition of oximes 153 as oxygen nucleophiles to nitroolefins 124 giving the adduct 154 in good yield with a high level of enantioselectivity (Scheme 9.52) [45]. The obtained adduct 154 can be converted to the optically active aliphatic nitro- or aminoalcohols. It is believed that the... 

However, when the dienophile was replaced with unsaturated nitrile, 1 j (or lk) was proved to be ineffective. Other bifunctional catalysts, 9-thiourea cinchona alkaloids 11 and lm [21], which were prepared from 9-amino-9-deoxyepiquinidine and 9-amino-... 

Organocatalytic asymmetric hydrophosphonylation/Mannich reactions using thiourea, cinchona and Bronsted acid catalysts 12SL1108. Organocatalytic asymmetric transformations of modified Morita—Bayhs— HiUman adducts 12CSR4101. 

The hybrid thiourea-cinchona alkaloid catalyst 14 proved to be effective in a stereoselective Michael addition reaction between a,p-unsaturated y-butyrolactam 11 and chalcone 12 (Scheme 3.22). The following mechanistic study addressed the issue of the origin of sfereoselecfion. 

Scheme 3.22 Michael addition reaction catalyzed by hybrid thiourea-cinchona alkaloid catalyst 14. (Data from Zhu, J.-L. et al, /. Org. Chem., 77, 9813-9825, 2012.)...

Amere, M. Lasne, M. C. Rouden, J. Highly Enantioselective Decarboxylative Protonation of a-Aminomalonates Mediated by Thiourea Cinchona Alkaloid Derivatives Access to Both Enantiomers of Cyclic and Acyclic a-Aminoacids. Org. Lett. 2007, 9, 2621. 

This challenging problem was addressed by Deng and coworkers [51] by the use of 9-thiourea cinchona alkaloids as acid-base bifunctional catalysts. As shown in Scheme 10.30, the enantioselective aza-Friedel-Crafts reaction proceeded through a network of hydrogen bonding interactions between indoles 145 and A-Ts aldimines 149... 

SCHEME 10.30 Enantiodivergent aza-Friedel-Crafts reaction of indoles with imines catalyzed by bifunctional 9-thiourea cinchona alkaloids. 

The concept of bifunctional catalysis as advanced for the natural cinchona alkaloids and cuprei(di)nes has resulted in the design and synthesis of a range of new cinchona derivatives. The major part of these novel organocatalysts are urea and thiourea cinchona derivatives together with cinchona alkaloids modified with, for example, a sulfonamide, squaramide, or guanidine group (Figure 6.8). 

Amere M, Lasne MC, Rouden J. Highly enantioselective decarboxylative protonation of a-aminomalonates mediated by thiourea cinchona alkaloid derivatives access to both enantiomers of cyclic and acyclic a-aminoacids. Org. Lett. 2007 9 2621-2624. 

A further important advance was also achieved by Rouden et al. [17] who developed the use of thiourea cinchona alkaloids 33-34 in the enantioselective decarboxylative protonation of a-aminomalonates (Scheme 3.12). The basic idea in using these bifunctional catalysts was to take advantage of the good hydrogen-bond donor properties of the thiourea moiety to promote further interactions between the chiral proton source and the prochiral enolate intermediate. Bifunctional catalyst 33 in quinidine series turned out to be especially efficient with a large range of substrates... 

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