Thiourea tertiary amine-functionalized

From the first transition state (TSl, Fig. 1), the reaction path leads to the tetrahedral intermediate 1 (INTI). In the latter, the proton transfer from methanol to the tertiary amine function is completed (from 1.183 to 1.059 A), and the negative charge at the former carbonyl oxygen atom reaches its maximum. This charge is compensated by a further shortening of the bifurcated hydrogen bonds to 2.040 A (-0.103 A) and 1.765 A (-0.096 A) (Fig. 1). The thiourea moiety thus forms an oxyanion hole similar to the amide groups of the serine protease backbone [41]. 

Scheme 6.38 Ring-opening polymerization of L-lactide catalyzed by tertiary amine-functionalized thiourea rac-12.

The Takemoto group synthesized a series ofdiaminocyclohexane-based thiourea derivatives (e.g., 12, 40, 57, and 58) for catalysis of the Michael addition [149-152] ofmalonates to trons-j3-nitrostyrenes (Figure 6.18) [129, 207]. In the model, Michael addition of diethyl malonate to trons-]3-nitrostyrene at room temperature and in toluene as the solvent tertiary amine-functionalized thiourea 12 (10mol% loading) was identified to be the most efficient catalyst in terms of catalytic activity (86%... 

Chen et al. identified (R,R)-l,2-diphenylethylenediamine-derived tertiary amine-functionalized thiourea 79 (20mol% loading), an analog of Takemoto s bifunc-... 

Figure 6.26 Multiple hydrogen-bonding tertiary amine-functionalized thioureas screened in the asymmetric Michael reaction between trans-P-nitrostyrene and acetylacetone at 10mol% loading.

Figure 6.49 Binaphthyl-derived tertiary amine-functionalized bifunctional thiourea derivatives screened in the MBH reaction between 2-cyclohexen-l-one and 3-phenylpropionaldehyde at rt in dichloromethane.

In 2008, Tang and co-workers reported the utilization of tertiary amine-functionalized saccharide-thiourea 211 as a bifunctional hydrogen-bonding catalyst for the enantioselective aza-Henry [224] (nitro-Mannich) addition [72] of... 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

Alternatively, Wang and coworkers reported a highly enantioselective domino thia-Michael/aldol sequence using bifunctional thiourea-tertiary amine catalysts to afford spirocyclic compound 76 [43]. ( )-Benzylidene chromanone derivatives 74 reacted with 2-mercaptobenzaldehydes 75 in the presence of a bifunctional tertiary amine-thiourea catalyst XVIII. The thia-Michael addition to the benzylidene was followed by an intramolecular aldol reaction between the resulting enolate and the aldehyde moiety. As shown in Scheme 10.26, the reaction afforded the highly functionalized spirocycles in excellent yields and stereoselectivities. 

Recent developments in organocatalytic pathways for the ROP of lactide and several lactones, without adverse transesterification creating polymers that are metal-free and therefore perfect candidates for biomedical and microelectronic applications, have been developed using N-heterocyclic carbenes, thiourea-tertiary amines, and amidine and guanidine bases. Here, the exquisite control, the absence of metal ions, the ready synthetic availability of the catalysts, and the mild reaction conditions are of major importance for tailor-made polyesters, and also have high potential for functional polycarbonates [91, 92]. 

Acetoiicetyliition Reactions. The best known and commercially most important reaction of diketene is the aceto acetylation of nucleophiles to give derivatives of acetoacetic acid (Fig. 2) (1,5,6). A wide variety of substances with acidic hydrogens can be acetoacetylated. This includes alcohols, amines, phenols, thiols, carboxyHc acids, amides, ureas, thioureas, urethanes, and sulfonamides. Where more than one functional group is present, ring closure often follows aceto acetylation, giving access to a variety of heterocycHc compounds. These reactions often require catalysts in the form of tertiary amines, acids, and mercury salts. Acetoacetate esters and acetoacetamides are the most important industrial intermediates prepared from diketene. 

P-Amino carbonyl compounds containing an a-atkyUdene group are densely functionalized materials, which are widely applied in the synthesis of medicinal reagents and natural products [265]. These products are usually prepared through the classic aza-Morita-Baylis-Hillman reaction [176, 177] of activated imines and electron-deficient alkenes catalyzed by tertiary amines or phosphines. Chen and co-workers, in 2008, identified bis-thiourea 106 as a suitable catalyst for the... 

Catalyst 3 is proposed to function in a manner similar to the cinchona alkaloid catalysts (1 and 2), with the tertiary amine providing activation for the nucleophilic thiol, which is held in close proximity to the thiourea-bound carbonyl substrate. 

The higher activity of primary amines in the reaction involving enones as Michael acceptors has also been extended to the use of different bifunctional catalysts (Scheme 3.19), which usually contain a primary amine functionality connected to a basic site by means of a chiral scaffold, as is the case in the use of 280 and 55. These diamine catalysts have been found to be excellent promoters of the Michael reaction of enones with cyclic 1,3-dicarbonyl compounds and malonates respectively, the tertiary amine basic site present at the catalyst structure being responsible for assisting in the deprotonation of the Michael donor in order to increase the concentration of the nucleophile species. In a different approach, bifunctional thiourea-primary amine catalyst 56a has also... 

In many examples of Brpnsted base catalysis, the combination of a chiral tertiary amine and a hydrogen-bonding donor, such as a urea or thiourea moiety, significantly enhances the selectivity of the formation of carbon-carbon bonds. Catalysts possessing this combination of functional groups have proven useful due to their ability to simultaneously stabilize and activate both electrophilic and nucleophilic components. 

The utility of the alkylidene oxindole-derived vinylogous enolates was demonstrated in the y-selective asymmetric conjugate addition to nitroolefins (Scheme 38) [67, 68]. Dihydroquinine-derived thiourea 10 earned distinctirm as the most effective catalyst in terms of catalytic efficiency and stereocontroUing ability. The tertiary amine and the thiourea functionalities both appeared to be essential for ensuring catalytic activity. It should be noted that not only perfect y-selectivity but also very high /Z-selectivity were observed under the optimal conditions. A wide variety of nitroolefins and substituted alkylidene oxindoles were amenable to this protocol. 

The bifunctional thioureas represent a group of bifunctional catalysts based on an interplay of Br0nsted acid-base activation that have obtained a prominent position over the last few years. Using these, the second functionality of choice is most often a basic nitrogen, such as a tertiary amine, and a simultaneous activation of nucleophile and electrophile can be achieved (409). 

Later, the same group [35] disclosed the synthesis of various potential bioactive chiral functionalized chromanes 222 with high levels of enantio- and diastereoselectivity (up to 76% ee and >20 1 dr) via the rosin-derived tertiary amine-thiourea 221 catalyzed enantioselective FC alkylation/cyclization cascade of 1-naphthol 217 with a variety of p,y-unsaturated a-ketoesters 209 (Scheme 2.32). 

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