Lewis Acid Mediated System

Although the rates of MBH reactions can be improved significantly with the assistance of TiCl4 with or without additive, the yields are generally only 

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Trost and Ghadiri19 have found a Lewis-acid-mediated intramolecular cyclization of allyl sulfones. When the allyl sulfone 40 is treated with A1C13, polycondensed aromatic system 41 can be obtained in good yield (equation 24). The mechanism probably involves... 

Lewis acid-mediated addition of allylsilanes to carbon nucleophiles. Also known as the Hosomi-Sakurai reaction. The allylsilane will add to the carbonyl compound directly if it is not part of an a,P-unsaturated system (Example 2), giving rise to an alcohol. 

Additional heterocyclic ring systems, such as benzofurans [125], dihydropyrroles and dihydroazepines [41], piperidines and dihydropyrimidines 36 [126], and fused oxazole derivatives [127], have been described (Eq. 7). The formation of epoxides and aziri-dines, formally emanating from ylides, was recently reported by Doyle et al. [77]. Rho-dium(II)-catalyzed isomiinchnone cycioaddition followed by Lewis acid-mediated ring opening has been used as an entry into the protoberberine azapolycyclic ring structure [128]. 

A Lewis-acid-mediated intramolecular cyclization of allenyl stannane 344 furnishes 2,6- //-tetrahydropyran as the major product, the stereochemistry of which can be switched to syn with moderate effect if a propargylstannane 345 is used as a substrate (Equation 147, Table 16) <1996TL3059>. The stereoselectivity observed in an analogous system, the intramolecular cyclization of y-alkoxyallyl stannanes 346 with a tethered aldehyde, can be controlled by changing the geometry of the alkene (Scheme 83) <1997JOC7439>. y-Alkoxyallyl stannanes are also known to cyclize both diastereoselectively and enantioselectivity, by incorporation of both a chiral auxiliary and a chiral catalyst respectively into the reaction <1999JOC4901>. 

Lewis acid-mediated reactions can be classified into two groups (Fig. 4). In the first (type 1) the complex between substrate and Lewis-acid reagent produces the product. Claisen rearrangement promoted by a Lewis-acid catalyst is a typical example of this type. Some complexes formed between Lewis acids and substrates are, however, stable enough to react with a variety of reagents from outside the system to generate the product (type 2). The Diels-Alder reaction between Lewis acid-activated unsaturated carbonyl compounds and dienes is an example of type 2 reactions. 

Other types of heterofunctionalized cyclopropane derivatives used as starting materials in transition metal mediated conversions are acylcyclopropanes and similar systems. These systems, being electrophilic cyclopropanes, are opened by carbanion nucleophiles (e.g. cuprates, see Section l.B.2.1.3.) or nucleophilic transition-metal centers. In combination with siloxy groups, push-pull (capto-dative) substituted cyclopropanes are available as homoenolate precursors via Lewis acid mediated ring opening (see Section 1. B.2.1.4.).. This latter procedure has been used in tetrahydrofuran synthesis. 

In contrast to the mechanism discussed in the previous section, catalytic, enantioselective aldol addition processes have been described which proceed through an intermediate aldolate that undergoes subsequent intermolecular silylation. Denmark has discussed this possibility in a study of the triarylmethyl-cation-catalyzed Mukaiyama aldol reaction (Scheme 10) [73]. The results of exploratory experiments suggested that it would be possible to develop a competent catalytic, enantioselective Lewis-acid mediated process even when strongly Lewis acidic silyl species are generated transiently in the reaction mixture. A system of this type is viable only if the rate of silylation of the metal aldolate is faster than the rate of the competing silyl-catalyzed aldol addition reaction (ksj>> ksi-aidoi Scheme 10). A report by Chen on the enantioselective aldol addition reaction catalyzed by optically active triaryl cations provides support for the mechanistic conclusions of the Denmark study [74]. 

Shortly after the discovery of the Lewis acid-mediated Mukaiyama aldol addition reaction of enol silanes the general mechanistic aspects of the reaction were intensely investigated [30a, 30b, 30c, 30d]. These processes are considered to proceed by electrophilic activation of the aldehyde towards addition by the nucleophilic enol silane. However, aldol addition processes that proceed by alternative mechanistic pathways have been documented and studied. It is worth considering those systems that have been developed for catalytic, enantioselec-tive aldehyde addition reactions through metaiioenoiate intermediates. 

A comparative study has been carried out to assess the importance of the incipient non-six-membered ring in Lewis acid mediated IMDA reactions of enones98. All the reactions were found to be selective for the cry-fused products. The yields decreased markedly for medium-ring systems (n = 5, 6, 7). 

Abstract. Three types of polymer-supported rare earth catalysts, Nafion-based rare earth catalysts, polyacrylonitrile-based rare earth catalysts, and microencapsulated Lewis acids, are discussed. Use of polymer-supported catalysts offers several advantages in preparative procedures such as simplification of product work-up, separation, and isolation, as well as the reuse of the catalyst including flow reaction systems leading to economical automation processes. Although the use of immobilized homogeneous catalysts is of continuing interest, few successful examples are known for polymer-supported Lewis acids. The unique characteristics of rare earth Lewis acids have been utilized, and efficient polymer-supported Lewis acids, which combine the advantages of immobilized catalysis and Lewis acid-mediated reactions, have been developed. 

This reaction has been extended to the reaction between aldehydes and alkenyl complexes of boranes, silanes, and stannes to give allylic alcohols, " where the reaction with alkenyl complexes of silanes is known as the silyl-Prins reaction. In addition, several Lewis acids-mediated or -promoted Prins reactions have recently been developed, including the application of TMSI, hafnium (IV) bis(perfluorooctanesulfonyl)amides (in fluorous biphase system),iron (III) species," and 2,6-di-f rf-butylphenoxy(difluoro)borane. J... 

Whilst the above results demonstrate the clear potential of stilbenoid compounds for the photochemical synthesis of large aromatic systems, the scope has not yet been exhausted. Indeed, the ready synthetic availability of the stilbene precursors, together with the tolerance to a large selection of substituents and mild reaction conditions, make this approach particularly attractive for - and complementary to - other cyclization strategies such as the Lewis acid-mediated SchoU reaction, which is compatible with only a few classes of functional groups (vide supra). 

Compared with chiral nonracemic a-amino carbonyl compounds - which are not suitable substrates for MBH reaction, mainly due to their racemization under normal conditions after prolonged exposure times to catalyst or due to poor diastereoselectivity " a-keto lactams, enantiopure 3-oxo-azetidin-2-ones 168, readily react with various activated vinyl systems promoted by DABCO to afford the corresponding optically pure MBH adducts 169 without detectable epimerization (Scheme 1.69). " However, the Lewis acid-mediated reaction of electron-deficient alkynes with azetidine-2,3-diones 168 as an entry to p-halo MBH adduets was not very sueeessful the coupling product 170 was achieved with concomitant acetonide cleavage as a single ( )-isomer in low yield, in the presence of trimethylsilyl iodide under BF3 OEt2-induced catalysis (Scheme 1.69). 

TiCl4-Lewis Acid Mediated Catalyzed System... 

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