Organocatalysts bifunctional thiourea

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...

Fig. 3.10 Thiourea-based organocatalysts. a-c Chemical structure of the bifunctional thiourea-tertiary amine catalyst, bis(3,5-trifluoromethyl)phenyl cyclohexylthiourea (thiourea), and N,N-dimethylcyclohexylamine (Moditied from Dove et til. [42]). d Proposed dual activation pathway of lactide ROP [41] (Adapted with permission from Pratt et al. [41]. Copyright 2013 American Chemictil Society)...

Among them, chiral bifunctional thiourea derivative 109 represents one of the most versatile organocatalyst prepared so far for the addition of activated methylenes to enones since affords, although with poor diastereoselectivities, excellent enantioselectivities and high yields in the conjugate addition of a broad spectrum of nucleophilic enol species such as malonate esters, P-ketoesters, 1,3-diketones, nitroesters, and 1,3-dinitriles to enones in xylenes at rt (Scheme 2.81)[217]. 

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... 

Besides the use of bifunctional thioureas containing a chiral cyclohexane-type linker like catalyst 487, the use of Cinchona alkaloid-derived (thio)-ureas has found to be highly popular and fruitful 366, 367, 417-420). In these cases, the easily obtainable well-defined spatial arrangement of the naturally occurring Cinchona alkaloids can be exploited efficiently to build up highly selective and versatile bifunctional organocatalysts. 

In this pivotal example, the authors have demonstrated the ability of bifunctional thiourea organocatalyst 28 to provide the sufficient activation of organoboronic acids in the Petasis reaction using quinolones 26, as a powerful method for the enantio- and regioselective synthesis of 1,2-adducts 29 against the possibility of generation of 1,4-adducts (Table 4.1) [28],... 

The majority of the organocatalysts that are commonly employed are chiral Lewis or Brpnsted bases, and the catalytic potential of base functionalities has been referred to in previous chapters to some extent already. As discussed before, the use of chiral primary or secondary amines for enamine or iminium activation belongs to the most important applications of asymmetric organocatalysts nowadays. In addition, also the interplay between an acidic (thio)urea and a basic amine separated by a chiral linker was shown to enable the simultaneous activation of both the electrophile and nucleophile. In addition to such bifunctional thiourea-containing acid-base catalysts, chiral catalysts containing a (Lewis or... 

Takemoto et al. were the first to report that bifunctional organocatalysts of the thiourea-tert-amine type efficiently promote certain Michael reactions, for example, the addition of 5-dicarbonyl compounds to nitro olefins [29-31]. 

A pyrrolidine-thiourea organocatalyst (69) facilitates Michael addition of cyclohexanone to both aryl and alkyl nitroalkenes with up to 98% de and ee 202 The bifunctional catalyst (69) can doubly hydrogen bond to the nitro group, leaving the chiral heterocycles positioned for cyclohexyl enamine formation over one face of the alkene. 

Cao CL, Ye MC, Sun XL, Tang Y (2006) Pyrrohdine-thiourea as a bifunctional organocatalyst Highly enantioselective michael addition of cyclohexanone to nitroolefins. Org Lett 8 2901... 

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... 

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