Thiourea organocatalysts, cinchona-base

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. 

This gives chapter an overview of natural cinchona alkaloids and synthetic derivatives together with examples of their use in asymmetric organocatalysis. In recent years, the emphasis has been on the development of cinchona-based bifunctional catalysts, in particular species with a thiourea moiety. The search for new cinchona-based organocatalysts continues and new derivatives are relentlessly being prepared and applied for specific enantioselective reactions. The design of these new... 

Connon SJ. Asymmetric catalysis with bifunctional cinchona alkaloid-based urea and thiourea organocatalysts. Chem. Commun. 2008 22 2499-2510. 

Malonates, malononitrile, and anthranone, can be added to -nitroalkenes RCH=CHN02 (R = alkyl, Ar) in the presence of the original Takemoto s thiourea organocatalyst (421) (5 mol%) in liquid CO2 (100 bar, room temperature) with 67-89% ee The same reaction, with an extended portfolio of substrates, catalysed by 0 the cinchona alkaloid-based squaramides (lmol%) in CH2CI2 at 15 C exhibited <96% ee ... 

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... 

At almost the same time, and based on their earUer studies with cinchona alkaloid organocatalysts bearing both a Br0nsted-base and thiourea residues, Hiemstra and coworkers were able to achieve good enantioselectivities and yields in the Henry reaction between aromatic aldehydes and nitromethane [8]. With unactivated aromatic aldehydes (i.e., R = 4-MeO-Ph) longer reaction times were required (Scheme 29.3). 

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