Basicity Bronsted

This finding is also in agreement with another three-component Michael/aldol addition reaction reported by Shibasaki and coworkers [14]. Here, as a catalyst the chiral AlLibis[(S)-binaphthoxide] complex (ALB) (2-37) was used. Such hetero-bimetallic compounds show both Bronsted basicity and Lewis acidity, and can catalyze aldol [15] and Michael/aldol [14, 16] processes. Reaction of cyclopentenone 2-29b, aldehyde 2-35, and dibenzyl methylmalonate (2-36) at r.t. in the presence of 5 mol% of 2-37 led to 3-hydroxy ketones 2-38 as a mixture of diastereomers in 84% yield. Transformation of 2-38 by a mesylation/elimination sequence afforded 2-39 with 92 % ee recrystallization gave enantiopure 2-39, which was used in the synthesis of ll-deoxy-PGFla (2-40) (Scheme 2.8). The transition states 2-41 and 2-42 illustrate the stereochemical result (Scheme 2.9). The coordination of the enone to the aluminum not only results in its activation, but also fixes its position for the Michael addition, as demonstrated in TS-2-41. It is of importance that the following aldol reaction of 2-42 is faster than a protonation of the enolate moiety. 

Heterobimetallic asymmetric complexes contain both Bronsted basic and Lewis acidic functionalities. These complexes have been developed by Shibasaki and coworkers and have proved to be highly efficient catalysts for many types of asymmetric reactions, including catalytic asymmetric nitro-aldol reaction (see Section 3.3) and Michael reaction. They have reported that the multifunctional catalyst (f )-LPB [LaK3tris(f )-binaphthoxide] controls the Michael addition of nitromethane to chalcones with >95% ee (Eq. 4.140).205... 

The LLB catalyst system needs a rather long reaction time and the presence of excess ketone to get a reasonable yield. Yamada and Shibasaki63 found that another complex, BaBM (91), was a far superior catalyst. Complex 91 also contains a Lewis acidic center to activate and control the orientation of the aldehyde, but it has stronger Bronsted basic properties than LLB. The preparation of BaBM is shown in Scheme 3-35. 

The development of catalytic asymmetric reactions is one of the major areas of research in the field of organic chemistry. So far, a number of chiral catalysts have been reported, and some of them have exhibited a much higher catalytic efficiency than enzymes, which are natural catalysts.111 Most of the synthetic asymmetric catalysts, however, show limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activate only one side of the substrate in an intermolecular reaction, whereas the latter can not only activate both sides of the substrate but can also control the orientation of the substrate. If this kind of synergistic cooperation can be realized in synthetic asymmetric catalysis, the concept will open up a new field in asymmetric synthesis, and a wide range of applications may well ensure. In this review we would like to discuss two types of asymmetric two-center catalysis promoted by complexes showing Lewis acidity and Bronsted basicity and/or Lewis acidity and Lewis basicity.121... 

We can also crudely estimate the basicity of the carbonyl oxygen atom. Since the HOMO is strongly localized to the oxygen atom (the coefficient of 2pQ is close to 1), and the oxygen atom is monocoordinated but uncharged, one should expect the Lowry-Bronsted basicity to be less than that of alkoxides, which are monocoordinated but charged. 

Nucleophilicity. A distinction is usually made between nucleophilicity and Lowry-Bronsted basicity [213]. The latter involves specifically reaction at a proton which is complexed to a Lewis base (usually H2O), while the former refers to reactivity at centers other than H. Linear correlations have been shown for gas-phase basicity (proton affinity) and nucleophilicity of nitrogen bases toward CH3I in solution [214] where the solvent is not strongly involved in charge dispersal. In each case, reaction of the base/nucleophile... 

Studies of catalytic asymmetric Mukaiyama aldol reactions were initiated in the early 1990s. Until recently, however, there have been few reports of direct catalytic asymmetric aldol reactions [1]. Several groups have reported metallic and non-metallic catalysts for direct aldol reactions. In general, a metallic catalysis involves a synergistic function of the Bronsted basic and the Lewis acidic moieties in the catalyst (Scheme 2). The Bronsted basic moiety abstracts an a-pro-ton of the ketone to generate an enolate (6), and the Lewis acidic moiety activates the aldehyde (3). 

Compared with f>,0-acetals, thioacetals are much more stable to acid as a result of the lower Bronsted basicity of sulfur To increase the leaving-group capacity of sulfur, and thus to simplify the cleavage of thioacetaK three different methods can in principle be invoked 13 l One can use metal coordination to take advantage of the high affinity of heavy-metal cations for sulfur A salt of Hg(II), Ag(I). Ag(Il), CutII) or ri(III) would thus be introduced. 

With this method, Bronsted basic conditions are avoided, resulting in excellent chemoselectivities. Because of the quantitative conversions, workup and purification are extraordinary simple separation of the product from the catalyst is achieved by... 

This process relies on rapid base-induced racemization of the azlactone and rate-limiting ring opening by the alcohol nucleophile. In this process the DMAP derivative 79a acts as both Bronsted-basic and as nucleophilic catalyst. With 2-propanol as reagent enantiomeric excesses up to 78% were achieved for the product amino acid esters [87]. 

The mechanisms for metal-catalyzed and organocatalyzed direct aldol addition reactions differ one from another, and resemble the mode of action of the type 11 and type I aldolases, respectively. Some metal-ligand complexes, for example, 1-4 and 9 are considered to have a bifunctional character [22], embodying within the same molecular frame a Lewis acidic site and a Bronsted basic site. Whereas base would be required to form the transient enolate species as an active form of the carbonyl donor, the Lewis acid site would coordinate the acceptor aldehyde carbonyl, increasing its electrophilicity. By this means, both transition state stabilization and substrates preorganization would be provided (see Scheme 5 for a proposal). 

Climent, M. J., Corma, A., Ihorra, S. and Velty, A. Designing the adequate base solid catalyst with Lewis or Bronsted basic sites or with acid-base pairs, J. Mol. Catal., A, 2002, 182-183, 327-342. 

Figure 9.13. The acetaldehyde formation mechanism, where A and B are Lewis acid sites and Bronsted basic sites, respectively. Dehydration requires the combination of an acid and strong base site with an adjacent strong basic site. After Di Cosimo et al. [184].

Lewis and Bronsted basicities of enamino ketones, which present the possibility of O, C or N protonation, have been determined experimentally by Geribaldi and coworkers290 and additional STO-3G calculations for 4-Af,Af-dimethylaminopent-3-en-2-one and its protonated forms have been performed. 

We have already stressed that acetals are far more susceptible to hydrolysis than thioacetals and Scheme 2.62 attests to the assertion.133-135 The high acid stability of 55-acetals compared with 0,0-acetals may be attributed to the lower Bronsted basicity of sulfur compared with oxygen and the barrier to formation of a thionium ion with its bond. The large number of methods that... 

The measure of basicity of phosphine hgands most widely quoted in the hterature is p/fa (aqueous), which is a measure of Bronsted basicity or proton affinity. A selection of pA a values for various phosphines is given in Table 4. AngeUci and coworkers have established a method for determining proton affinities from enthalpies of protonation using the extremely powerful acid CF3SO3H. The enthalpy values (A//hp) and pATa values are related by the empirical equation (3) ... 

Very recently, Ikariya reported chiral amido ruthenium complex-catalyzed asymmetric Michael addition of dimethyl malonate with conjugate enones using Ru[(i ,i )-TsDPEN](>7 -arene) ((R,R)-TsDPEN = (lR,2R)-N-(p-toluenesulfonyl)-l,2-di-phenylethylenediamine) [84], The reaction of cyclopentenone with dimethyl malonate gave the corresponding /3-alkylation product in 99% yield with 97% e.e. (Eq. 9.60). For this mthenium-catalyzed asymmetric Michael addition, the Bronsted basicity of the amido ligand is responsible for the excellent catalytic activity. 

---