Basicity Brpnsted

We saw m Chapter 1 especially m Table 1 7 that alcohols resemble water m respect to their Brpnsted acidity (ability to donate a proton/rom oxygen) They also resemble water m their Brpnsted basicity (ability to accept a proton on oxygen) Just as proton transfer... 

Preliminary mechanistic studies show no polymerization of the unsaturated aldehydes under Cinchona alkaloid catalysis, thereby indicating that the chiral tertiary amine catalyst does not act as a nucleophilic promoter, similar to Baylis-Hilhnan type reactions (Scheme 1). Rather, the quinuclidine nitrogen acts in a Brpnsted basic deprotonation-activation of various cychc and acyclic 1,3-dicarbonyl donors. The conjugate addition of the 1,3-dicarbonyl donors to a,(3-unsaturated aldehydes generated substrates with aU-carbon quaternary centers in excellent yields and stereoselectivities (Scheme 2) Utility of these aU-carbon quaternary adducts was demonstrated in the seven-step synthesis of (H-)-tanikolide 14, an antifungal metabolite. 

Bifunctional catalysts have proven to be very powerful in asymmetric organic transformations [3], It is proposed that these chiral catalysts possess both Brpnsted base and acid character allowing for activation of both electrophile and nucleophile for enantioselective carbon-carbon bond formation [89], Pioneers Jacobsen, Takemoto, Johnston, Li, Wang and Tsogoeva have illustrated the synthetic utility of the bifunctional catalysts in various organic transformations with a class of cyclohexane-diamine derived catalysts (Fig. 6). In general, these catalysts contain a Brpnsted basic tertiary nitrogen, which activates the substrate for asymmetric catalysis, in conjunction with a Brpnsted acid moiety, such as urea or pyridinium proton. 

The authors identify the new paracyclophane derivative as a catalyst lacking a hydrogen bond donor, and propose that addition is catalyzed by the Brpnsted basic imine moiety. Based on X-ray crystal data of the catalyst, it was hypothesized that... 

Quantitatively, the enhanced reactivity of hydroxylamine, as well as oximate and hydroxamate ions and also other a-nucleophiles, is expressed as a positive deviation on a Br0nsted-type rate-basicity (pX a) ploh i-e. log k vs pTsTa - This is illustrated in Figure 1 for oxygen nucleophiles and in Figure 2 for nitrogen nucleophiles. It is important to note that the reactivity of the a-nucleophile is considered relative to a normal nucleophile of the same Brpnsted basicity. ... 

The design for a direct catalytic asymmetric aldol reaction of aldehydes and unmodified ketones with bifunctional catalysts is shown in Figure 36. A Brpnsted basic functionality (OM) in the heterobimetallic asymmetric catalyst (I) could deprotonate the a-proton of a ketone to generate the metal enolate (II), while at the same time a Lewis acidic functionality (LA) could activate an aldehyde to give (III), which would then react with the metal enolate (in a chelation-controlled fashion) in an asymmetric environment to afford a P-keto metal alkoxide (IV). 

The protonation of a thiolate donor, formation of a nonclassical r 2-H2 complex, release of H2 and addition of D2, and the heterolytic cleavage of this D2 by the concerted attack of the Lewis acidic metal center and the Brpnsted basic thiolate donor are essential steps. The acidic thiol deuteron can exchange with EtOH protons. The resulting free protons and the deuteride complex yield HD and the coordinatively unsaturated species that is the actual catalyst. The detailed mechanism comprises a considerably larger number of steps (and equilibria) (143). For example, the occurrence of r 2-D2 and [M(D)(SD)] intermediates that exchange with H+ should give rise to [M(D)(SH)]... 

S.C. PanandB. List s paper spans the whole field of current organocat-alysts discussing Lewis and Brpnsted basic and acidic catalysts. Starting from the development of proline-mediated enamine catalysis— the Hajos-Parrish-Eder-Sauer-Wiechert reaction is an intramolecular transformation involving enamine catalysis—into an intermolecular process with various electrophilic reaction partners as a means to access cY-functionalized aldehydes, they discuss a straightforward classification of organocatalysts and expands on Brpnsted acid-mediated transformations, and describe the development of asymmetric counteranion-directed catalysis (ACDC). 

The growing demand for efficient chemical transformations and catalysts has inspired a few research groups in recent years to develop rare earth metal catalysts for organic synthesis [1, 2]. Triflates of rare earth metals are strong Lewis acids, which are stable in aqueous solution. Rare earth metal alkoxides on the other hand are of interest as Lewis bases, e.g. in the catalysis of carbonyl reactions, because of the low ionization potentials (5.4-6.4 eV) and electronegativities (1.1-1.3) of the 17 rare earth elements. Rare earth metal-alkali metal complexes in contrast show both Brpnsted-basic and Lewis-acidic properties. Impressive applications of such catalysts are presented and discussed here. 

Although the development of a variety of Lewis acids has enabled the reahzation of a wide range of catalytic asymmetric reactions, most of the catalysts have limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activates only one side of the substrate in an intermolecular reaction, whereas the latter not only can activate both sides of the substrate but also can control the orientation of the substrate. If this kind of synergistic cooperation could be realized in synthetic asymmetric catalysis, it would open up a new field in asymmetric synthesis, and a wide range of applications might well ensure. In this section we discuss asymmetric two-center catalysis promoted by chiral lanthanide complexes with Lewis acidity and Brpnsted basicity [44,45]. 

While nonbonded electron pairs in molecules do not enter into covalent bonding in the usual sense, they may exhibit a secondary kind of valency by being transferred into vacant molecular orbitals in suitable acceptor molecules. This results in the transformation of a coordination complex in which the bond formed between the electron-pair donor and the acceptor is said to be a coordinate covalent or dative bond. Brpnsted basicity is the simplest example of coordinate covalent bond formation. A Brpnsted base donates a pair of nonbonded electrons to a vacant Is orbital of a hydrogen ion to form the conjugate acid. The o-bond formed between the base and the hydrogen ion results in the loss of identity of the nonbonded pair previously localized on the base. The formation of coordination complexes has significance in the interpretation of spectra of compounds having nonbonded electron pairs. 

Unequivocal evidence for associative activation within Cr(DMF)63+, A ion pairs in DMF is given in Table 8.1, which shows that azide ion attacks the Cr center some 100 times faster than solvent exchange and 650 times faster than bromide. This is of particular interest in that no comparable result can be obtained for the reaction of N3 with Cr(H20)63+ in water because of the Brpnsted basicity of azide that causes the reaction to proceed via HN3 and Cr(H20)50H2+, but in anhydrous DMF the relative nucleophilic power of anionic reagents toward Cr111 is clearly displayed N3- NCS > Cl > Br > C104, BPh4 . 

At the time of the study by Dessy et al. (7), little was known about the Brpnsted basicity of MLn in a quantitative sense. Therefore, what role, if any, was played by the parameter H in the Edwards equation was unclear. Recently, a number of pKa values were measured for transition metal hydrides, both neutral, HMLn, and cationic, HMLn+. The solvents used were chiefly methanol (12) and acetonitrile (13, J. R. Norton and J. Sullivan, personal communication). 

A very strong correlation between nucleophilic reactivity and Brpnsted basicity occurs. The correlation is not perfect, but it cannot be expected to be, because a variety of types of nucleophiles are represented, and the solvents also vary. Clearly, the dependence on H in equation 5 is as great as the dependence on E°. 

As explained earlier, Figures 1 and 2 will not be greatly changed if data in solution are used. Individual bases will move up or down, parallel to the lines shown. Therefore, under the normal conditions for nucleophilic substitution, ease of oxidation (E0 ) and Brpnsted basicity are not independent parameters for bases where the donor atom is a second-row element. Either parameter may be used as a measure of nucleophilic reactivity. 

An alternative stabilization effect on the protonation to these two bases leading to their highly potential basicity is through bidentate-type hydrogen bond formation as shown in Figure 1.4. Alder also discussed the effects of molecular strain on the Brpnsted basicity of amines [9]. 

Room, E.-I.,Kutt, A., Kaljurand, Let a/. (2007) Brpnsted basicities of diamines in the gas phase, acetonitrile and tetrahydrofuran. Chemistry - A European Journal, 13, 7631-7643. 

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