Mixed Lewis acid approach

Shaw and co-workers used a mixed Lewis acid approach to synthesize chiral furanmethanol derivatives from glycals. These compounds are important intermediates in the synthesis of many biologically significant compounds and serve as precursors for furanmethanes and 3-acylfurans. Reaction of a selectively protected 6-azido glycal with zirconium(IV) chloride and zinc(II) iodide gave the desired chiral furan selectively in 74% yield. 

A very interesting technique that has been used widely in the MTO-catalyzed olefin oxidation reaction is the microencapsulation technique. This technique uses poly(4-vinylpyridine) (PVP), either 2% or 25% cross-linked with divinylbenzene (PVP-2% or PVP-25%, Fig. 4), as well as poly(4-vinylpyridine-/V-oxide) (PVPN-2%, Fig. 4). In addition, 2% cross-linked PS (PS-2%, Fig. 4, X = CH2) and a mixture of PS-2% and PVP-2% (5 1, Fig. 4, X = N) have been used as support polymers. This approach is based on the physical envelopment of the Lewis-acidic MTO by the PS polymer, enhanced by interactions of the 7t-electrons of the phenyl rings with MTO. In the case of the pyridine-containing polymers, Lewis acid-Lewis base interactions between the pyridine moiety and MTO obviously play an important role. In the case of the PVP and PVPN polymers, MTO can be incorporated in the support matrix by mixing the polymer and MTO in ethanol to obtain the desired immobilized catalyst. 

The topic of interactions between Lewis acids and bases could benefit from systematic ab initio quantum chemical calculations of gas phase (two molecule) studies, for which there is a substantial body of experimental data available for comparison. Similar computations could be carried out in the presence of a dielectric medium. In addition, assemblages of molecules, for example a test acid in the presence of many solvent molecules, could be carried out with semiempirical quantum mechanics using, for example, a commercial package. This type of neutral molecule interaction study could then be enlarged in scope to determine the effects of ion-molecule interactions by way of quantum mechanical computations in a dielectric medium in solutions of low ionic strength. This approach could bring considerable order and a more convincing picture of Lewis acid base theory than the mixed spectroscopic (molecular) parameters in interactive media and the purely macroscopic (thermodynamic and kinetic) parameters in different and varied media or perturbation theory applied to the semiempirical molecular orbital or valence bond approach [11 and references therein]. 

Later on, Schreiber used consecutively these two reactions in the key step for the synthesis of diterpene (-i-)-epoxydictimene (73), starting from natural (R)-pulegone [116,117]. This approach was built on their preliminary studies on Lewis acid mediated intermolecular Nicholas reactions [118]. They prepared functionalized enyne 70 bearing a mixed acetal. This compound was transformed into its dicobalt-hexacarbonyl complex and, in the presence of a carefully selected Lewis acid, it formed a stabilized carbocation by release of the more accessible ethyl moiety. This cation reacted intramolecularly with the allylsilane giving the central eight membered ring of the natural product... 

As discussed at the beginning of Sect. 4.1, a masked carbonyl, such as acetal, is more suitable for macrocyclization than the carbonyl itself b ause the nucleophilic substitution reaction on the former is irreversible. Overman and coworkers [111] developed a C—C bond-forming cyclization approach to 8-membered ethers by Lewis acid-promoted alkene substitution of mixed acetals. Thus, oxocenes with... 

Diels-Alder (DA) reaction is one of the most powerful synthetic approaches for the construction of six-membered carbocycles [144]. The most attractive feature of this reaction is the simrdtaneous, regioselective formation of two bonds leading to the potential creation of up to four chiral centers at the binding sites with largely predictable relative stereochemistry. Since the discovery of the accelerating effect of Lewis acids on the DA reaction of a,p-unsaturated carbonyl compounds, its broad and fine application imder mild reaction conditions has been amply demonstrated [144]. In addition to the acceleration effect on the reaction, other important role of Lewis acid in the DA reaction is its alteration of chemo-, regio-, and diastereoselectivity. The titanium compounds commonly used in DA reaction are titanium halides, alkoxides, or their mixed salts [145]. A cyclopentadienyl complex such as Cp2Ti(OTf)2 is also documented as a very effective promoter for the DA reaction [146] (Scheme 14.57). 

One of the more novel synthetic approaches to the synthesis of vinylphosphines entailed the addition of alkynes to a functionalized tertiary phosphine (Scheme 4.319) [433]. These compounds are part of a special class of compounds that contain an intramolecnlar frustrated Lewis acid-base pair (FLP). These FLPs have been used to react with small molecules such as hydrogen and carbon dioxide. The P—C bond-forming reaction was operationally trivial and consisted of mixing the aUcyne with the specialized precursor in a hydrocarbon solvent for 1 h. The product precipitated and was separated by simple filtration. Although the substrate scope for this reaction is limited at present, this approach does provide a pathway to an intriguing class of vinylphosphines. 

Hoffmann and coworkers further extended the scope of this reaction to chiral acetals to achieve asymmetric [4-1-3] cycloadditions [30]. Under similar Lewis acid catalysis, the homoacetal derivatives of 105 prepared from 2 equiv of chiral alcohols proceeded to cycloadditions, but this approach suffered from the difficulty of cleaving the chiral auxiliary from the cycloadduct, as well as being wasteful of 1 equiv of the chiral alcohol, which was eliminated. Hoffmann and coworkers then devised the use of mixed chiral acetals such as 117 as chiral oxyallyl cation precursors (Scheme 18.25). They demonstrated that under silyl triflate... 

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