Synthetic Lewis-acid controlled

Unsaturated sugars are useful synthetic intermediates (11). The most commonly used are the so-called glycals (1,5- or 1,4-anhydroalditol-l-enes). In the presence of a Lewis-acid catalyst, 3,4,6-tri-0-acetyl-l,5-anhydro-2-deoxy-D-arabinohex-l-enitol [2873-29-2] commonly called D-glucal triacetate, adds nucleophiles in both kineticaHy controlled and thermodynamically controlled (soft bases predominately at C-3 and hard bases primarily at C-1) reactions (11,13). 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

The introduction of the halogens onto aromatic rings by electrophilic substitution is an important synthetic procedure. Chlorine and bromine are reactive toward aromatic hydrocarbons, but Lewis acid catalysts are normally needed to achieve desirable rates. Elemental fluorine reacts very exothermically and careful control of conditions is required. Molecular iodine can effect substitution only on very reactive aromatics, but a number of more reactive iodination reagents have been developed. 

It is important to select stoichiometric co-reductants or co-oxidants for the reversible cycle of a catalyst. A metallic co-reductant is ultimately converted to the corresponding metal salt in a higher oxidation state, which may work as a Lewis acid. Taking these interactions into account, the requisite catalytic system can be attained through multi-component interactions. Stereoselectivity should also be controlled, from synthetic points of view. The stereoselective and/or stereospecific transformations depend on the intermediary structure. The potential interaction and structural control permit efficient and selective methods in synthetic radical reactions. This chapter describes the construction of the catalytic system for one-electron reduction reactions represented by the pinacol coupling reaction. 

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... 

Synthesis of a key 3,4-dihydropyran 196 during synthetic studies towards reveromycin B is achieved using an asymmetric hDA reaction. No chiral Lewis acid catalysts or auxiliaries are necessary as the stereochemistry at the spirocentre is controlled by the anomeric effect (Equation 93) <1997JOCl 196>. 

Substitution of the hydrogen of many other aromatic compounds is controllable, but the problem of site selectivity still limits the synthetic utility of this reaction (Table 9). In an attempt to improve selectivity the fluorination of chlorobenzene was investigated in the presence of Lewis acids (Table 10). The addition of the Lewis acid is found to increase both conversion and selectivity. The best results are obtained in the presence of 0.9 equivalents of boron trichloride the effect of the boron trichloride is explained by the formation of a complex 7 with the fluorine, which is the fluorinating species. Large amounts of Lewis acid are required due to the formation of a stable complex between the boron trichloride and the fluoride formed as the fluorination progresses which effectively removes the catalyst from the system. ... 

Cycloadditions (Athene Five-Membered Cyclo-adduct) The levels of selectivity found for 1,3-dipolar cycloaddition reactions are not as high as those obtained for Lewis acid-catalyzed Diels-Alder reactions. However, the 10,2-camphorsultam auxiliary can achieve synthetically useful levels of induction in these reactions, and this has been attributed to efficient enoyl conformational control by the sultam moiety leading to preferred C(a)-re face attack even in the absence of metal complexation. ... 

Diels-Alder reaction is one of the premiere reactions in synthetic organic chemistry. The traditional approach to the normal Diels-Alder reaction is to activate the di-enophile by means of a Lewis acid such that the transformation can be carried out under practicable conditions. A variety of Lewis acids catalyze this reaction selectively and among these copper(II) compounds have been very successful in enantioselective transformations. The use of bisoxazolines in combination with copper triflate or copper antimony hexafluoride has afforded high selectivity. Pioneering work in this area by Evans, Jprgensen, Kanemasa, and others has shed light on the different controlling features of the copper Lewis acids. 

Scheme 9 demonstrates the further synthetic application of the thus obtained N,0-acetals. Substitution of the alkoxy or acyloxy group by nucleophiles like enol ethers, enol esters, enamines, other electron-rich olefins, CH-acidic compounds, electron-rich aromatics, isocyanides, trimethylsilyl cyanide, organometallics, vinyl and allyl silanes, hydroxy functions, or trialkylphosphites either catalyzed by Lewis acids or proton acids leads to the product of the amidoalkylation reaction (path a). In the presence of stereocenters as control elements, diasteroselective amidoalkylation reactions can be performed as shown in a large number of examples. On the other side, as Nyberg showed for the first time [196], elimination with formation of enecarbamates [208] and enamides [196,208,209] followed by reaction with electrophiles or nucleophiles (path b) also is possible. 

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