Bifunctional catalysis addition

An interesting bifunctional system with a combination of In(OTf)3 and benzoyl-quinine 65 was developed in p-lactam formation reaction from ketenes and an imino ester by Lectka [Eq. (13.40)]. High diastrereo- and enantioselectivity as well as high chemical yield were produced with the bifunctional catalysis. In the absence of the Lewis acid, polymerization of the acid chloride and imino ester occurred, and product yield was moderate. It was proposed that quinine activates ketenes (generated from acyl chloride in the presence of proton sponge) as a nucleophile to generate an enolate, while indium activates the imino ester, which favors the desired addition reaction (66) ... 

Scheme 6.102 Bifunctional catalysis with primary amine thiourea 99 Proposed transition states to explain the onfi-diastereoselectivity (A) and the syn- diastereoselectivity (B) of the Michael addition of both acylic and cyclic ketones to frans-P-nitrostyrene.

In the presence of thiourea catalyst 122, the authors converted various (hetero) aromatic and aliphatic trons-P-nitroalkenes with dimethyl malonate to the desired (S)-configured Michael adducts 1-8. The reaction occurred at low 122-loading (2-5 mol%) in toluene at -20 to 20 °C and furnished very good yields (88-95%) and ee values (75-99%) for the respective products (Scheme 6.120). The dependency of the catalytic efficiency and selectivity on both the presence of the (thio) urea functionality and the relative stereochemistry at the key stereogenic centers C8/C9 suggested bifunctional catalysis, that is, a quinuclidine-moiety-assisted generation of the deprotonated malonate nucleophile and its asymmetric addition to the (thio)urea-bound nitroalkene Michael acceptor [279]. 

According to the available experimental data, it is impossible to distinguish between these mechanisms, but the second mechanism seems to be preferred [Scheme (7)] for, according to this Scheme, the reaction of amine addition proceeding through a cyclic transition state is completed in one step, whereas for the reaction to occur according to Scheme (2) or (6) it is additionally necessary to transfer the proton. Then, it is probable that the different mechanisms [Schemes (3) and (5)] may precede formation of one and the same transition state [Scheme (7)]. Note finally that the mechanism of bifunctional catalysis [Scheme (7)] is extremely popular in different reactions of nucleophilic substitution at the saturated carbon atom and reactions with participation of a carbonyl group32>. 

A more recent paper by Cunningham and Schmir242 on the hydrolysis of 4-hydroxybutyranilide XL in neutral and alkaline solution suggests that intramolecular nucleophilic attack by the neighbouring hydroxyl group is followed by bifunctional catalysis by phosphate or bicarbonate buffers of the conversion of the tetrahedral intermediate to products. A quantitative comparison was made between the effects of buffer on the hydrolysis of 4-hydroxybutyranilide and on the hydrolysis of 2-phenyliminotetrahydrofuran, since both reactions proceed via identical intermediates. The mechanism suggested243 states that the cyclisation of the hydroxyanilide ion yields an addition intermediate whose anionic form may either cleave to products or revert to reactant and whose neutral form invariably gives aniline and butyrolactone, viz. 

This review is concerned with a discussion of the reactions of hydrocarbons over bifunctional catalysts, primarily from the viewpoint of mechanism and kinetics. Some discussion will also be given of the structure and properties of typical bifunctional reforming catalysts, since this is somewhat helpful in understanding how the catalyst functions in promoting the various reactions. In addition, at appropriate places in the article, the practical application of the principles of bifunctional catalysis in commercial reforming processes will be considered. 

The possibilities of additional applications, other than catalytic reforming, of the ideas of bifunctional catalysis would seem to be good. In all likelihood, bifunctional-type catalysts will find many new uses in the future. 

Catalytic, enantioselective addition of silyl ketene acetals to aldehydes has been carried out using a variant of bifunctional catalysis Lewis base activation of Lewis acids.145 The weakly acidic SiCU has been activated with a strongly basic phor-phoramide (the latter chiral), to form a chiral Lewis acid in situ. It has also been extended to vinylogous aldol reactions of silyl dienol ethers derived from esters. 

Nilsson and coworkers42 showed that addition of trifluoroacetic acid to enamines in dry pentane at 0 °C results initially in protonation at the ft carbon and proposed that the proton is transferred to the nitrogen atom by a bifunctional catalysis according to equation 19. They also showed that appropriate exchange resins can be used to favour selective protonation of enamines42c. 

In 2009, Wang and co-workers developed a new Lewis base-Lewis base bifunctional catalysis for the AFC alkylation of indoles with o,p-unsaturated aldehydes with high efficiency and enantioselectivity. In contrast to the reported system utilizing protic acids as co-catalysts, this protocol demonstrated that it was possible to carry out AFC alkylation reaction in the presence of (S)-104 and triethylamine. The addition products 117 were obtained in good to excellent yields (66-95%) with up to 98% ee (Scheme 6.47). 

A bifunctional catalysis involving urea/ketone hydrogen-bond interactions and ion-pair formation between the nucleophile and the quinucUdine nitrogen are postulate to explain the observed enantioselectivity. On the other hand, imininm catalysis is proposed for salt 204, where both the cation and the anion are chiral, which exhibits high reactivity and selectivity for the addition of alkylic nucleophiles to linear enones (Fig. 2.28) [384]. 

In the present study the catalytic site is introduced on the support at the interface between zeolite and support. The diffusion pathway through the framework to the catalytic site on the support must be minimized, while the channels must be oriented in the direction of the support. Advantages offered by these composites are i) combination of a catalytic site which can not be synthesized or stabilized in the zeolite lattice with framework shape selectivity and ii) bifunctional catalysis by addition of framework activity. A schematical drawing of the composite system design is given in Figure 1. 

The availibility of three geometric isomers of our artificial enzyme lets us examine other reactions that can show bifunctional catalysis. Enolization of a ketone— and its addition to an aldehyde group in an aldol condensation—are two cases examined so far in which an isomer of our catalyst is preferred that is not the one that was best in the ribonuclease mimic. The geometric preference indicates something novel about the geometry of enolization reactions. 

Complexes bearing protic NHC ligands are accessible by various synthetic routes such as the deprotonation of azoles followed by reaction with a transition metal complex, the template-controlled cyclization of functionalized isocyanides, and the oxidative addition of different azoles to transition metal complexes. The complexes with simple monodentate NR,NH-NHCs often tend to tautomerize to give the N-bound azoles. This type of tautomerization is prevented in complexes with donor-functionalized NR,NH-NHCs. Recent smdies demonstrate that complexes with protic NHCs obtained from C2-H azoles are formed by an oxidative addition/reductive elimination reaction sequence. The N—H group in complexes with protic NR,NH-NHCs can serve as a hydrogen bond donor and thus as a molecular recognition unit and may enable various types of bifunctional catalysis. Recent smdies indicate that even biomolecules such as caffeine can be C8-metallated. It... 

Highly functionalized 3,4-disubstituted lactones have been prepared in good delee via Michael addition of aryl methyl ketones to 2-furanones, using bifunctional catalysis by a simple chiral diamine and tosic acid ESI-MS suggests that a catalytic monosalt 0 forms. 0... 

A variety of metal-support effects can occur to alter the adsorptive and/or catalytic behavior of a metal surface, and these include 1) Incomplete reduction of the metal 2) Support-induced cluster size 3) Epitaxial growth 4) Particle morphology 5) Contamination by the support 6) Bifunctional catalysis 7) Spillover and porthole phenomena and 8) Charge transfer between a metal and a semiconductor [2]. In addition, one might cite the stabilization of extremely small (1-3 atom) metal clusters on a support [7]. 

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