Thiourea organocatalysts derivatives

Scheme 6.55 Design principle of amine-functionalized bifunctional thiourea organocatalysts derived from privileged monofunctional thiourea 9 cooperating with an amine base additive (A) and basic bifunctional mode of action of chiral amine...

Figure 6.3 Stereoselective, chiral thiourea derivatives of achiral benchmark thiourea organocatalyst N,N -bis [3,5-(trifluoromethyl)phenyl]thiourea 9 stereoselective hydrogen-bonding thiourea organocatalysts incorporating the privileged 3,5-bis(trifluoromethylphenyl)thiourea moiety. The (thio)urea catalyst structure is the leitmotif for the chapter organization.

The proline-derived thiourea organocatalyst (154) (20 mol%) in conjunction with n-butyric acid (10 mol%) exhibited high stereoselectivity (<99 1 syn. anti and <98% ... 

Tang and coworkers" used bifunctional urea and thiourea-derived orga-nocatalysts (4a,b) for the Michael addition of cyclohexanone to nitro-olefins (Scheme 9.29). Using pyrrolidine-thiourea 4b afforded the desired y-nitroalkanes with high diastereo- and enantioselectivity under solvent-free conditions (up to 99 1 dr, 88-98% ee). Subsequently, Xiao and coworkers screened various bifunctional pyrrolidine-thiourea organocatalysts and identified 4c to be efficient at catalysing the Michael addition of various ketones to nitrostyrenes. Comparable results were observed (up to 99 1 dr and 99% ee) when the reactions were performed in both aqueous media and organic solvents. 

In another one-pot reaction, chiral isoxazoline-fused benzazepines 31 were formed from the reaction of P-nitrostyrene derivatives 30 and 1,3-dicarbonyl species such as dimethyl malonate. The first step is a nitro-Michael addition reaction between the nitro olefin and dimethyl malonate catalyzed by a chiral thiourea organocatalyst, followed by addition of DMAP and Boc anhydride with heating to promote nitrile... 

Brpnsted bases have been explored in cooperative catalysis to deprotonate substrates that subsequently add to metal-activated electrophiles. Regarding the use of these organocatalysts in cooperative catalysis, the combination of quinine and quinine-derived thiourea organocatalysts with Cu(II)-PhBox and Cu(OTf) has been employed in aza-Henry [23] and... 

In 2009, Feng et al. reported the asymmetric hydrophosphonylation of a-keto esters catalysed for the first time by cinchona-derived thiourea organocatalysts. Thus, a series of aromatic and heteroaromatic a-keto esters reacted with dimethyl phosphite to afford the corresponding a-hydroxy phosphonates in high yields and enantioselectivities of up to 91% ee (Scheme 2.53). 

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). 

Hydrogen-bonding catalysis of the Diels-Alder reaction of 2-vinylindoles 39 and methylene-indolinones 69 has been accomplished by the Barbas group using a C2-symmetric bis-thiourea organocatalyst [31]. This efficient transformation provided a powerful approach by which to construct carbazole-spirooxindole derivatives 71 extremely rapidly (less than 10 min) with excellent enantiopurity and structure diversity (Scheme 38.20). 

Aromatic thioureas were more active than alkyl (octyl, cyclohexyl) derivatives. Thioureas with trilluoromethyl substituents were even more effective. The same group also showed that these organocatalysts can act as weak Lewis acids and are thus able to alter the stereochemistry of the Diels-Alder reaction between cyclopentadiene and chiral acrylamide derivatives (Scheme 49) [167]. 

Wang and co-workers reported a novel class of organocatalysts for the asymmetric Michael addition of 2,4-pentandiones to nitro-olefms [131]. A screen of catalyst types showed that the binaphthol-derived amine thiourea promoted the enantiose-lective addition in high yield and selectivity, unlike the cyclohexane-diamine catalysts and Cinchona alkaloids (Scheme 77, Table 5). 

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