Bronsted bases addition

Our analysis of literature data will focus on two closely related questions about the influence of changes in the relative thermodynamic driving force and Marcus intrinsic barrier for the reaction of simple carbocations with Bronsted bases (alkene formation) and Lewis bases (nucleophile addition) on the values of ks/kp determined by experiment. 

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... 

Hosokawa, Murahashi, and coworkers demonstrated the ability of Pd" to catalyze the oxidative conjugate addition of amide and carbamate nucleophiles to electron-deficient alkenes (Eq. 42) [177]. Approximately 10 years later, Stahl and coworkers discovered that Pd-catalyzed oxidative amination of styrene proceeds with either Markovnikov or anti-Markovnikov regioselectivity. The preferred isomer is dictated by the presence or absence of a Bronsted base (e.g., triethylamine or acetate), respectively (Scheme 12) [178,179]. Both of these reaction classes employ O2 as the stoichiometric oxidant, but optimal conditions include a copper cocatalyst. More recently, Stahl and coworkers found that the oxidative amination of unactivated alkyl olefins proceeds most effectively in the absence of a copper cocatalyst (Eq. 43) [180]. In the presence of 5mol% CUCI2, significant alkene amination is observed, but the product consists of a complicated isomeric mixture arising from migration of the double bond into thermodynamically more stable internal positions. 

The Michael reaction is the conjugate addition of a soft enolate, commonly derived from a P-dicarbonyl compound 24, to an acceptor-activated alkene such as enone 41a, resulting in a 1,5-dioxo constituted product 42 (Scheme 8.14) [52]. Traditionally, these reactions are catalyzed by Bronsted bases such as tertiary amines and alkali metal alkoxides and hydroxides. However, the strongly basic conditions are often a limiting factor since they can cause undesirable side- and subsequent reactions, such as aldol cyclizations and retro-Claisen-type decompositions. To address this issue, acid- [53] and metal-catalyzed [54] Michael reactions have been developed in order to carry out the reactions under milder conditions. 

HF transfers a proton to water. Therefore HF is the Bronsted acid and H2O is the Bronsted base. But in the reverse direction, hydronium ions transfer a proton to fluoride ions. H30+ is the conjugate acid of H2O because it has an additional proton, and F is the conjugate base of HF because it lacks a proton. 

In a broad sense, an acid site can be defined as a site on which a base is chemically adsorbed. Conversely, a basic site is a site on which an acid is chemically adsorbed. Specifically, a Bronsted acid site has a propensity to give a proton, and a Bronsted base has the tendency to receive a proton. Additionally, a Lewis acid site is capable of taking an electron pair and a Lewis basic site is capable of providing an electron pair. These processes can be studied by following the color modifications of indicators, and by using infrared (IR) and nuclear magnetic resonance (NMR) spectroscopies, and calorimetry of adsorption of the probe molecules (see Chapter 4). 

As with the other superacids, the basicity of HSO3F is most easily adjusted quantitatively by direct addition of the conjugate base S03F in the form of the alkali metal cation or ammonium salts. Less directly, the basicity is increased by proton acceptors, e.g. H20 and a vast range of Bronsted bases. Such an increase in basicity is frequently an unwanted result of protonation of solutes or of reaction products but must be taken into account in considering the final level of acidity in any reaction mixture. 

The preceding section describes the primary reaction chemistry of superoxide ion (02 -) to be that of (a) a Bronsted base (proton transfer from substrate), (b) a nucleophile (via displacement or addition), (c) a one-electron reductant, and (d) a dehydrogenase of secondary amine groups. The chemistry is characteristic of all oxyanions (H0 (R0 ), HOO (ROO ), and 02 -)> but the relative reactivity for each is determined by its pXa and one-electron oxidation potential, which are strongly affected by the anionic solvation energy of the solvent matrix. The present focus is on the reactivity of hydroxide ion (HO ), but the principles apply to all oxyanions and permit assessments of their relative reactivity. 

Most of the imprinted sorbents used in MISPE were prepared using MAA and ethylene glycol dimethacrylate (EDMA) as monomers. In these cases elution of more weakly bound analytes such as triazines [19,30,32], 7-hydroxy-coumarin (2) [26] or theophylline (12) [28] can be achieved using methanol or water as elution solvent. For more strongly bound analytes such as stronger nitrogen Bronsted bases, efficient elution has been achieved using eluents of the same base solvent but with the addition of small amounts of acids (e.g. acetic acid, trifluoroacetic acid (TEA)) or base (e.g. triethylamine (TEA)) [20-22,25,33]. 

Caffeine and theophylline have pharmaceutically important chemical properties. Both arc weak BrOnsted bases. The reported pK values are 0.8 and 0.6 fur caffeine and 0.7 for theophylline. These values represent the basicity of the imino nitrogen at position 9. As acids, caffeine has a pK., above 14. and theophylline, a pK., of 8.8. In theophylline, a proton can be donated from position 7 (i.e.. it can act as a Bronsted acid). Caffeine cannoi donate a proton from position 7 and does not act as a Bretnsted acid at pH values under 14. Caffeine docs have electrophilic sites at positions I. 3. and 7. In addition to its Bronsted acid site at 7. theophylline has electrophilic sites at I and 3. In condensed terms, both compounds arc electron-pair donors, but only theophylline is a proton donor in most pharmaceutical system.s. 

The C-C couphng of aromahc hahdes usually requires the addition of a base in stoichiometric amounts, and the most common Bronsted bases are water soluble and can be employed conveniently in biphasic aqueous/organic systems. 

Recently, Liu has developed a Bronsted acid activated trifunctional organocatalyst, based on the BINAP scaffold, that was used for the first time to catalyze aza MBH reactions between N tosylimines and MVK with fast reaction rates and good enantioselectivity at room temperature. This trifunctional catalyst containing a Lewis base, a Bronsted base and a Bronsted acid, required add activation to confer its enantioselectivity and rate improvement for both electron rich and electron deficient imine substrates. The role of the amino Lewis base of 27 was investigated and found to be the activity switch in response to an acid additive. The counterion of the acid additive was found to influence not only the excess ratio but also the sense of asymmetric induction (Scheme 13.23) [36]. 

In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were recently developed by Shibasaki et al., are highly efficient catalysts in stereoselective synthesis. This new and innovative type of chiral catalyst contains a Lewis acid as well as a Bronsted base moiety and shows a similar mechanistic effect as observed in enzyme chemistry. A broad variety of asymmetric transformations were carried out using this catalysts, including asymmetric C-C bond formations like the nitroaldol reaction, direct aldol reaction, Michael addition and Diels-Alder reaction, as well as C-0 bond formations (epoxidation of enones). Thereupon, asymmetric C-P bond formation can also be realized as has been successfully shown in case of the asymmetric hydrophosphonylation of aldehydes and imines. It is noteworthy that all above-mentioned reactions proceed with high stereoselectivity, resulting in the formation of the desired optically active products in high to excellent optical purity. 

No formation of DHQ was observed with increasing either the temperature from 373 to 473 K or the H2 pressure from 2.0 to 4.0 MPa. Also the addition of excess CH3COOH did not modify activity and selectivity, while the addition of a small amount of a 3 M NaOH solution completely inhibited the Q conversion [6], Thus, a Bronsted acid media does not affect the adsorption equilibrium of the deactivating intermediate(s) on the active sites of the catalysts, while a Bronsted base interacts with them too strongly. 

General Bransted acid catalysis begins with the addition of a proton whilst general Bronsted base catalysis begins with the removal of a proton ... 

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