Lewis acids enhancement effect

Lewis acid enhancement effect in Si—Si and C—C coupling reactions... 

Enzymatic enantioselectivity in organic solvents can be markedly enhanced by temporarily enlarging the substrate via salt formation (Ke, 1999). In addition to its size, the stereochemistry of the counterion can greatly affect the enantioselectivity enhancement (Shin, 2000). In the Pseudomonas cepacia lipase-catalyzed propanolysis of phenylalanine methyl ester (Phe-OMe) in anhydrous acetonitrile, the E value of 5.8 doubled when the Phe-OMe/(S)-mandelate salt was used as a substrate instead of the free ester, and rose sevenfold with (K)-maridelic acid as a Briansted-Lewis acid. Similar effects were observed with other bulky, but not with petite, counterions. The greatest enhancement was afforded by 10-camphorsulfonic acid the E value increased to 18 2 for a salt with its K-enanliomer and jumped to 53 4 for the S. These effects, also observed in other solvents, were explained by means of structure-based molecular modeling of the lipase-bound transition states of the substrate enantiomers and their diastereomeric salts. 

Reactions of compound 8a with butadiene, 2,3-dimethylbutadiene, and isoprene required more drastic conditions (150°C, autoclave) [24]. In the case of isoprene, a 60 40 regioisomeric mixture was obtained (the major product being the para-adduct). The influence of Lewis acid catalysis on the reaction of cyclopentadiene with different ethynyl aryl sulfoxides [Ar =p-Tolyl, o-nitrophenyl, and l(2-methoxynaphthyl)] has been recently reported [25].Dienophilicities of acetylenic sulfoxides were greatly enhanced by the presence of various Lewis acids (the effect being greater with stronger Lewis acid), but the stereoselectivity was scarcely affected by the catalysis. 

The kinetics of copolymerization and the microstructure of copolymers can be markedly influenced by the addition of Lewis acids. In particular, Lewis acids are effective in enhancing the tendency towards alternation in copolymerization of donor-acceptor monomer pairs and can give dramatic enhancements in the rate of copolymerization and much higher molecular weights than are observed for similar conditions without the Lewis acid. Copolymerizations where the electron deficient monomer is an acrylic monomer e.g. AN, MA, MMA) and the electron rich monomer is S or a diene have been the most widely studied." Strictly alternating copolymers of MMA and S can be prepared in the presence of, for example, dictliylaluminum scsquichloridc. In the absence of Lewis acids, there is only a small tendency for alternation in MAA-S copolymerization terminal model reactivity ratios are ca 0.51 and 0.49 - Section 7.3.1.2.3. Lewis acids used include EtAlCT, Et.AlCL ElALCL, ZnCT, TiCU, BCl- LiC104 and SnCL. 

Studies on solvent effects on the endo-exo selectivity of Diels-Alder reactions have revealed the importance of hydrogen bonding interactions besides the already mentioned solvophobic interactions and polarity effects. Further evidence of the significance of the former interactions comes from computer simulations" and the analogy with Lewis-acid catalysis which is known to enhance dramatically the endo-exo selectivity (Section 1.2.4). 

In contrast to the situation in the absence of catalytically active Lewis acids, micelles of Cu(DS)2 induce rate enhancements up to a factor 1.8710 compared to the uncatalysed reaction in acetonitrile. These enzyme-like accelerations result from a very efficient complexation of the dienophile to the catalytically active copper ions, both species being concentrated at the micellar surface. Moreover, the higher affinity of 5.2 for Cu(DS)2 compared to SDS and CTAB (Psj = 96 versus 61 and 68, respectively) will diminish the inhibitory effect due to spatial separation of 5.1 and 5.2 as observed for SDS and CTAB. 

First of all, given the well recognised promoting effects of Lewis-acids and of aqueous solvents on Diels-Alder reactions, we wanted to know if these two effects could be combined. If this would be possible, dramatic improvements of rate and endo-exo selectivity were envisaged Studies on the Diels-Alder reaction of a dienophile, specifically designed for this purpose are described in Chapter 2. It is demonstrated that Lewis-acid catalysis in an aqueous medium is indeed feasible and, as anticipated, can result in impressive enhancements of both rate and endo-exo selectivity. However, the influences of the Lewis-acid catalyst and the aqueous medium are not fully additive. It seems as if water diminishes the catalytic potential of Lewis acids just as coordination of a Lewis acid diminishes the beneficial effects of water. Still, overall, the rate of the catalysed reaction... 

The rate of the Lewis-acid catalysed Diels-Alder reaction in water has been compared to that in other solvents. The results demonstrate that the expected beneficial effect of water on the Lewis-acid catalysed reaction is indeed present. However, the water-induced acceleration of the Lewis-add catalysed reaction is not as pronounced as the corresponding effect on the uncatalysed reaction. The two effects that underlie the beneficial influence of water on the uncatalysed Diels-Alder reaction, enforced hydrophobic interactions and enhanced hydrogen bonding of water to the carbonyl moiety of 1 in the activated complex, are likely to be diminished in the Lewis-acid catalysed process. Upon coordination of the Lewis-acid catalyst to the carbonyl group of the dienophile, the catalyst takes over from the hydrogen bonds an important part of the activating influence. Also the influence of enforced hydrophobic interactions is expected to be significantly reduced in the Lewis-acid catalysed Diels-Alder reaction. Obviously, the presence of the hydrophilic Lewis-acid diminished the nonpolar character of 1 in the initial state. 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

Good Cram selectivity is observed for Lewis acid induced reactions between allylstannanes and aldehydes with alkyl-substituted a-chiral centers66,87. This enhanced Cram selectivity may be due to the effect of the Lewis acid on the trajectory of nucleophilic attack on the aldehyde66. 

Lewis acids such as zinc chloride, boron trifluoride, tin tetrachloride, aluminum chloride, methylaluminum dichloride, and diethylaluminum chloride catalyze Diels-Alder reactions.22 The catalytic effect is the result of coordination of the Lewis acid with the dienophile. The complexed dienophile is more electrophilic and more reactive toward electron-rich dienes. The mechanism of the addition is believed to be concerted and enhanced regio- and stereoselectivity is often observed.23... 

Several modifications of the Simmons-Smith procedure have been developed in which an electrophile or Lewis acid is included. Inclusion of acetyl chloride accelerates the reaction and permits the use of dibromomethane.174 Titanium tetrachloride has similar effects in the reactions of unfunctionalized alkenes.175 Reactivity can be enhanced by inclusion of a small amount of trimethylsilyl chloride.176 The Simmons-Smith reaction has also been found to be sensitive to the purity of the zinc used. Electrolytically prepared zinc is much more reactive than zinc prepared by metallurgic smelting, and this has been traced to small amounts of lead in the latter material. 

The reactivity of oxime ethers as radical acceptors is enhanced by Lewis acids, BF3 being the most effective.343... 

The effect of water molecules on pericyclic reactions can also be compared with the effects of Lewis acids on these reactions. The enhanced polarization of the transition state in these reactions would lead to stronger hydrogen bonds at the polar groups of the reactants, which will result in a substantial stabilization of the transition states in the same way Lewis acids do. A computer-simulation study on the Diels-Alder reaction of cyclopentadiene by Jorgensen indicated that this effect contributes about a factor of 10 to the rates.7... 

In the synthesis of the tetracyclic intermediates for the synthesis of isoarborinol and its CDE-antipode femenol, the stereochemistry of the Diels-Alder reaction can be varied using various Lewis-acid catalysts in aqueous media (Eq. 12.36).97 Their results show that the hydrophobic effects play an important role in enhancing reaction rates and can control product distribution. Novel 2,4-dialkyl-1-alkylideneamino-3-(methoxycarbonylmethyl)azetidines were obtained from aldazines and... 

These changes are more consistent with an /-effect, rather than an R-effect, on the B—C bond. That such diborylacetylenes have a diminished electron density at boron relative to alkyl- and vinylboranes is evident from their enhanced Lewis acidity bis(diethylboryl)acetylene (40) forms a bis(tetrahydrofuran) complex, as is evident from the1 B NMR spectrum37 (Eq. 11). Alkyl- and vinylboranes exhibit no such shifts in their11B signals in THF solution. 

Mg/Me (Me=Al, Fe) mixed oxides prepared from hydrotalcite precursors were compared in the gas-phase m-cresol methylation in order to find out a relationship between catalytic activity and physico-chemical properties. It was found that the regio-selectivity in the methylation is considerably affected by the surface acid-basic properties of the catalysts. The co-existence of Lewis acid sites and basic sites leads to an enhancement of the selectivity to the product of ortho-C-alkylation with respect to the sole presence of basic sites. This derives from the combination of two effects, (i) The H+-abstraction properties of the basic site lead to the generation of the phenolate anion, (ii) The coordinative properties of Lewis acid sites, through their interaction with the aromatic ring, make the mesomeric effect less efficient, with predominance of the inductive effect of the -O species in directing the regio-selectivity of the C-methylation into the ortho position. 

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