Thiourea-based organocatalysts addition

On the Bifunctionality of Chiral Thiourea Tertiary-Amine Based Organocatalysts Competing Routes to C-C Bond Formation in a Michael-Addition... 

Initial mechanistic analysis of the Strecker reaction catalyzed by a urea-based organocatalyst (Scheme 3.18) revealed that the catalytic activity is provided by the urea functionality of structurally complex catalyst 1. However, further studies revealed a bifunchonal character of urea and thiourea-based catalysts " as well as the possibility of multiple mechanistic pathways in catalysis of nucleophile-electrophile addition reactions. " Simplified but sufficiently effective (thio)urea catalysts 4a and 4b were used in the hydrocyanation reaction (Scheme 3.19) that was subjected to a combined experimental and computational study. °... 

Various thiourea-based bifunctional organocatalysts (e.g. 289a and 372a,b) have been successfully applied for the Michael addition of nitroalkanes RCH2NO2 to 3-ylidene oxindoles (373). The resulting enolate intermediates (374) were then trapped by electrophiles, such as enones, maleimide, and sulfone CH2=C(S02Ph)2. The products were obtained with <99% ee and >95 5... 

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...

In 2008, Jorgensen and coworkers reported that oxazolones 140 could also smoothly undergo addition to nitroalkenes 124 in the presence of bifunctional cinchona-based thiourea organocatalysts such as 81a and 81a. The reaction with 4-phenyloxazolones (140, R1 = ph) took place at C4 affording the adducts 141 with moderate to good ee values (up to 83% ee). On the other hand, 4-alkyloxazolones (R = Me, i-Bu) were added to the C2-position of 140, furnishing 142 with a moderate to high enantioselectivity (up to 92% ee) (Scheme 9.48). The adducts 141 can be used... 

In 2005, Sons and coworkers introduced a novel bifunctional thiourea organocatalyst based on a Cinchona alkaloid for the asymmetric conjugate addition of nitromethane to tra s-chalcones. Using 10 mol% of thiourea 17, various electron-rich and electron-poor chalcones were well tolerated providing the desired adducts in high yields (80-94%) and very high enan-tioselectivities (95-96%) (Scheme 19.24). It has to be highlighted that... 

Another member of the ep -cinchona-based thiourea organocatalyst family, depicted in Scheme 1.19, was applied by Vakulya et al. to the asymmetric Michael addition of nitroalkanes to chalcones, giving excellent yields and enantioselectivities of up to 98% ee. The extension of this methodology was further explored to encompass a,p-unsaturated A-acylpyrroles, as a chalcone mimic. The corresponding Michael products were obtained in high yields and enantioselectivities of up to 94% ee, as shown in Scheme 1.19. This simple novel approach allowed a concise stereoselective synthesis of (i )-rolipram to be accomplished. 

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