Bifunctional thiourea-amine

The best enantioselectivity in the addition of C-nudeophiles to nitroolefins is that achieved by Takemoto et al. using the bifunctional thiourea-amine catalyst 55 (Scheme 4.26) [45]. 

Table 6.2 Bifunctional thiourea-amine-catalyzed 1,4-additions to cyclic enones.

In 2003, Takanoto et al. reported the first highly enantioselective organocatalytic conjugate addition of 1,3-dicarbonyl compounds to nitroolefins catalyzed by bifunctional thiourea-amine catalyst 142 (Fig. 2.15)[238]. After Takemoto s report a wide... 

Scheme 4.6 Mechanism involved in the polymerisation of trimethylene carbonate using bifunctional thiourea—amine catalyst in presence of an alcohol.

Figure 5.45. Diverse applicability of novel N-heterocyclic carbene, bifunctional thiourea amine, and superbase catalysts for the polymerization of strained heterocyclics. Reprint courtesy of International Business Machines Corporation, copyright 2009 International Business Machines Corporation.

Table 29.3 Bifunctional thiourea-amine catalyzed addition of nitromethane to N-Boc imines.

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...

The Tsogoeva group, in 2006, reported the introduction of newly designed bifunctional secondary amine-functionalized proline-based thioureas (95 and 96) and the primary amine-functionalized thioureas (97-99) for catalysis of the asymmetric addition of ketones to trans-P-nitrostyrenes (Figure 6.30) [260, 261]. Using... 

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.

Table 5.7 Bifunctional tertiary amine/thiourea catalyst in MBH reaction of cyclohexenone and selected aldehydes.

Chiral bifunctional primary amine-thiourea/ f-BuNH2.TFA/DCM/25 °C (09MI1) 12/EtOH/rt (09MI2)... 

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)...

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... 

Despite this, bifunctional thiourea-tertiary amine catalysts have also emerged as useful and very convenient compounds for the activation of enones in Michael reactions. The mentioned problems associated to the single position available for H-bonding interactions and to the lower Bronsted basicity of the carbonyl moiety are circumvented by the formation of a double H-bonding network in which both lone pairs at the oxygen atom participate with two... 

Axial-to-central chirality transfer in cyclization processes 13CSR8434. Bifunctional primary amine-thioureas in asymmetric organocatalysis 13OBC7051. 

Xu and Dixon and co-workers also described a trimolecular cascade process, also involving a nitro-olefln. In this case, however, the nucleophile was a 1,3-dicarbonyl compound 183 whose 1,4-addition into the nitro-olefln 185 was facilitated by bifunctional thiourea catalyst 186. However, a secondary amine... 

The utilization of bifunctional thiourea catalyst containing a chiral secondary amine was first reported by Peng and co-workers [45], The prolinol-derived thiourea catalyst 72 has been successfully appUed to the ATift-selective direct asymmetric... 

Scheme 5.34 First bifunctional thiourea catalyst bearing a secondary amine moiety...

In the domino Michael/alkylation reaction applied to the synthesis of 3-(2H)-furanones, the ethyl 4-bromoacetoacetate 203 and nitrostyrene 204 were first trialed with a range of catalysts. In this instance, the so-called modified Feist Binary reaction was completed with an I-threonine bifunctional tertiary amine/thiourea catalyst 205 to produce the furanone 206 in excellent yield and high enantioselec-tivity (Scheme 7.42) [107]. In another report, the furan ring as part of other bicyclic or tricyclic systems was also prepared through an enantioselective Michael addi-tion/nucleophilic substitution reaction (Scheme 7.43) [108]. When diketones and ( )-P,P-bromonitrostyrenes 207 were stirred, again with a bifunctional thiourea... 

A domino Mannich/aza-Michael reaction was applied to the synthesis of 2,5-cis-configured polysubstituted pyrrolidines from y-malonate-substituted a,P-unsaturated esters with N-protected arylaldimines [117]. In this report, bifunctional thioureas were trialed with the Takemoto catalyst, being the most efficient with respect to yield as well as enantiomeric and diastereomeric excess. In a separate approach, the Garcia-Tellado group approached the pyrrole ring system 234, beginning with a tertiary skipped diyne 233 and a primary amine (Scheme 7.50). 

In 2003, Takemoto and coworkers published the enantioselective Michael addition of malonates to nitro-olefins catalysed by the first bifunctional thiourea 15, providing the corresponding products in high yields and enantioselectivities. The proposed mechanism involved a bifunctional transition state, where activation of the nitro-olefin is promoted by the thiourea group, while the activation of the malonate occurred by the tertiary amine (Scheme 19.18). ... 

More recently, Pihko introduced bifunctional tertiary amine-thioureas 26 and 27 for the Mannich reaction of Boc-imines with malonates. ° Dimethylamino-tertiary amine thiourea 26 proved ideal for aliphatic imines, while the Cinchona derivative 27 provided the best results for aromatic substrates. Catalyst loadings as low as 1 mol% could be employed providing the products in high yields and excellent enantioselec-tivities (Scheme 19.34). Notably, both catalysts presented cooperative assistance via intermolecular hydrogen bonding, as first shown by Smith in 2009. ... 

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