Bifunctional catalysis alkylation

A highly enantioselective direct Mannich reaction of simple /V-Boc-aryl and alkyl- imines with malonates and /1-kclo esters has been reported.27 Catalysed by cinchona alkaloids with a pendant urea moiety, bifunctional catalysis is achieved, with the urea providing cooperative hydrogen bonding, and the alkaloid giving chiral induction. With yields and ees up to 99% in dichloromethane (DCM) solvent, the mild air- and moisture-tolerant method opens up a convenient route to jV-Boc-amino acids. 

While the rate of cleavage is given by temperature, acidity of the catalyst and concentration of i-alkyl cations, the rate of desorption is assumed to be enhanced by the steady state concentrations of n-alkenes, i. e., a high dehydrogenation activity of the catalyst favors hydroisomerization. This is the concept of competitive chemisorption which in ideal bifunctional catalysis keeps the residence times of the alkylcarbenium ions low. 

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). 

Scheme 6.47 Lewis base-Lewis base bifunctional catalysis for the AFC alkylation of indoles with o,p-unsaturated aldehydes reported by Wang.

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]. 

Aromatic ketimines are reduced enantioselectively to amines (50 atm H2/toluene/65°C/24h), using a cooperative catalysis involving Knolker s iron complex and a BINOL-derived hydrogen phosphate auxiliary, with P-NMR evidence supporting the bifunctional catalysis. A phosphine-free chiral cationic ruthenium complex catalyses enantioselective hydrogenation of IV-alkyl ketimines, including many heretofore problematic substrates. 0... 

Trost s group reported direct catalytic enantioselective aldol reaction of unmodified ketones using dinuclear Zn complex 21 [Eq. (13.10)]. This reaction is noteworthy because products from linear aliphatic aldehydes were also obtained in reasonable chemical yields and enantioselectivity, in addition to secondary and tertiary alkyl-substituted aldehydes. Primary alkyl-substituted aldehydes are normally problematic substrates for direct aldol reaction because self-aldol condensation of the aldehydes complicates the reaction. Bifunctional Zn catalysis 22 was proposed, in which one Zn atom acts as a Lewis acid to activate an aldehyde and the other Zn-alkoxide acts as a Bronsted base to generate a Zn-enolate. The... 

Various kinds of oxide materials, including single oxides, mixed oxides, molybdates, heteropoly-ions, clays, and zeolites, are used in catalysis they can be amorphous or crystalline, acid or basic. Furthermore the oxides can be the actual catalysts or they can act as supports on which the active catalysts have been deposited. Silica and alumina are commonly used to support both metals and other metal oxide species. Amorphous silica/alumina is a solid acid catalyst, it is also used as a support for metals, when bifunctional (acid and metal) catalysis is required, e.g., in the cracking of hydrocarbons. Other acid catalysts are those obtained by the deposition of a soluble acid on an inert support, such as phosphoric acid on silica (SPA, used in the alkylation of benzene to cumene. Section 5.2.3). They show similar properties to those of the soluble parent acids, while allowing easier handling and fixed bed operation in commercial units. 

Ref. 14S), and the greatest dauylation rate at pH 8 (0.009—0.013 sec" ) was found with bifunctional polymer catalysts (Elm -HA, PVP -HA and HlA-VIm-AAm) (Section S—3). The acylation rate can be further increased by catalysis at higher pH s and by using substrates with longer alkyl chains. 

A number of methods employ an imidazole-2-thione or related compound with a bifunctional reagent to build the thiazine ring in one or two steps. Treatment of (682) with acrylyl chloride directly produced (683) (64JOC1720). Substituting acrylic acid under catalysis allows isolation of the S-alkylated intermediate, which cyclized to (683) upon heating (64JOC1715). 

The largest and most functionally diverse structural family of DNA glycosylases is the HhH-GPD superfamily (Nash et al, 1996 Thayer et al, 1995). The family includes both monofunctional and bifunctional DNA glycosylases, and members recognize a variety of lesions arising from oxidative, alkylation, and hydrolytic damage. Some members of both the MutM and HhH-GPD families contain structural metal ions that play no direct role in catalysis. 

Recently, alkyl dimethylsilyl ethers (58) have been found to serve as bifunctional reagents for a similar reductive etherification, in which (58) function as both reducing agents and oxygen nucleophiles under catalysis by Me3SiI (Scheme 9.33)... 

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