Thiourea-based organocatalysts

Organocatalysts As mentioned earlier, organocatalytic ROP was first reported applying pyridines as the nucleophilic catalyst. Subsequently, guanidine, amidine, and thiourea-based organocatalysts were found to be highly active for the ROP of lactones [40-42],... 

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)...

Tsogoeva et al. described the use of the primary amine thiourea-based organocatalyst 73 in an asymmetric Mannich-type reaction of unmodified aldehydes and ketones 7 with readily available and stable a-hydrazonoesters 74 (Scheme 5.35) [46]. Moderate to good yields and excellent enantioselectivities (90-99% ee) were reported. However, the anti-diastereoselectivity appeared generally poor (8-72% de). 

The concept of tunable chiral thiourea based organocatalysts, useful for a wide variety of asymmetric reactions, was invented by Jacobsen in 1999 and has been extensively reviewed over the last few years. They have been... 

Hamza, A. Schubert, G. Soos, T. Papai, I. Theoretical Studies on the Bifunctionality of Chiral Thiourea-Based Organocatalysts Competing Routes to C-C Bond Formation. J. Am. Chem. Soc. 2006,128,13151-13160. 

Hamza A, Schubert G, Soos T, Papai I. Theoretical studies on the bifunctionality of chiral thiourea-based organocatalysts competing routes to C—C bond formation. J. Am. Chem. Soc. 2006 128(40) 13151-13160. 

Bromolactonization of long-chain olefinic acids (4) to produce medium-sized lactones (6) has been attained using A-bromosuccinimide (NBS) and the zwitterionic thiourea-based organocatalyst (5) at 0 °C " ... 

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

On the Bijunctionalit / of Chiral Thiourea-Tert-Amine-Based Organocatalysts 25... 

The first primary amine-thioureas as effective bifunctional organocatalysts were reported in 2006. Tsogoeva and Wei synthesised a thiourea based on (l5,25)-diphenylethylene-l,2-diamine and a chiral arylethyl moiety, for the Michael reaction between aliphatic ketones and aromatic nitro-olefins (Scheme 19.36). Utilising catalyst 29 (15 mol%) and acetone as the Michael donor, the Michael products were obtained in high yields (84-99%) and enantioselectivities (90-91% enantiomeric excess). When cyclohexanone 31 was employed, product 33 was obtained in high yields (82 and 89%, respectively), good diastereoselectivity (up to 83 17 symanti) and excellent enantioselectivity (96 and 98% enantiomeric excess, respectively). 

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... 

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... 

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... 

Like the reactions discussed in Section 28.5.1.2, a highly enantioselective aza-nitroaldol reaction of imines (173) with nitroalkanes (157) is achieved by use of guanidinium-thiourea bifunctional organocatalyst 204 in the presence of external base such as CSCO3 under phase-transfer conditions. Both catalytic activity and enantioselectivity depend upon the substituents on the guanidinium group. The mono-substituted catalyst 190 gives poor results (yield 89%, 9% ee), whereas cyclic amine-substituted catalyst 204 provides excellent enantiomeric excess (Scheme 28.25) [104]. 

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