Lewis acid catalysts heterocycles

The Pictet-Spengler reaction has mainly been investigated as a potential source of polycyclic heterocycles for combinatorial apphcations or in natural product synthesis [149]. Tryptophan or differently substituted tryptamines are the preferred substrates in a cyclocondensation that involves also aldehydes or activated ketones in the presence of an acid catalyst. Several versions of microwave-assisted Pictet-Spengler reactions have been reported in the hter-ature. Microwave irradiation allowed the use of mild Lewis acid catalysts such as Sc(OTf)3 in the reaction of tryptophan methyl esters 234 with different substituted aldehydes (aliphatic or aromatic) [150]. Under these conditions the reaction was carried out in a one-pot process without initial formation of the imine (Scheme 86). 

Cycloaddition of furan (5) has again been performed successfully under pressure and solvent-free conditions [12, 44], Usually, however, the cycloaddition of furan and heterocyclic compounds requires a Lewis-acid catalyst to give good yields. 

For the synthesis of heterocycles, an efficient strategy has been introduced utilizing the dual transition metal sequences (Scheme 6).11,lla The key issue is the compatibility of the two catalyst systems. Jeong et al. studied the one-pot preparation of bicyclopentenone 35 from propargylsulfonamide 33 and allylic acetate.11 This transformation includes two reactions the first palladium-catalyzed allylation of 33 generates an enyne 34 and the following Pauson-Khand type reaction (PKR) of 34 yields a bicyclopentenone 35. The success of this transformation reflects the right combination of catalysts which are compatible with each other because the allylic amination can be facilitated by the electron-rich palladium(O) catalyst and the PKR needs a Lewis-acidic catalyst. Trost et al. reported the one-pot enantioselective... 

In acidic media, loss of a proton can give traces of methylene forms of type (609). Alternatively, a Lewis acid catalyst such as acetic anhydride may be used which involves formation of complexes of type (618) from which proton loss is facile. Such methylene bases can also react with electrophiles, gradually causing complete conversion of the heterocycle. 

GATTERMANN ALDEHYDE SYNTHESIS. Preparation of aldehydes of phenols, phenol ethers, or heterocyclic compounds hy treatment of the aromatic substrate with hydrogen cyanide and hydrochloric acid in the presence of Lewis acid catalysts. 

Certain aziridines undergo ring opening to azomethine ylides (e.g., 85 86), a process which can also be facilitated by Lewis acid catalysts . These reactive intermediates can be trapped by a variety of dipolar-ophiles to give new heterocyclic species. For example, methyl vinyl ethers convert aziridines such as 85 into pyrrolidines (i.e., 87) in the presence of a zinc(salen) Lewis acid catalyst 84 <2004JA2294>. Likewise, under the... 

For a study of Diels-Alder reaction on trienic esters in the absence and presence of a Lewis acid catalyst, see M. Toyota, Y. Wada and K. Fukumoto, Heterocycles, 1993, 35, 111. 

A solid-phase Ugi-Reissert reaction on chloroformate resin, has been reported. The product, the ot-carbamoylated isoquinoline 230, is released by oxidative cleavage (Scheme 33a). Interestingly, the enamide moiety in the adduct can be exploited to perform this process in tandem with a Povarov MCR [189, 190]. In this way, by interaction of dihydroisoquinoline 231 with aldehydes, anilines and a suitable Lewis acid catalyst, the polyheterocyclic system 232 was prepared (Scheme 33b). The Zhu group devised an innovative approach for the synthesis of this class of compounds. They employed the heterocyclic amine 233, which was oxidized in situ to the dihydroisoquinoline 234 with IBX, to undergo the classic Ugi reaction. Remarkably, all the components are chemically compatible, allowing the sequence to proceed as a true MCR (Scheme 33c) [191]. 

Asymmetric catalytic hetero Diels-Alder reactions give access to synthetically important substituted heterocycles [45]. Asymmetric oxa Diels-Alder reactions involving aldehydes and ketones and catalyzed by chiral Lewis acid catalysts can be performed with a high degree of chiral induction [46]. The field is much less advanced that of the corresponding catalytic enantioselective aza Diels-Alder reactions. 

Three-component reactions of aldehydes, amines, and allyltributyltin also proceeded smoothly in micellar systems with Sc(OTf)3 as Lewis acid catalyst, to afford the corresponding homoallylic amines in high yields (Eq. 19) [68]. Not only aromatic aldehydes but also aliphatic, unsaturated, and heterocyclic aldehydes worked well. The procedure is very simple—merely mixing an aldehyde, an amine, and allyltributyltin in the presence of Sc(OTf)3 and SDS in water no homoallylic alcohol (an adduct between an aldehyde and allyltributyltin) was produced. It was suggested that imine formation from aldehydes and amines was very fast under these conditions, and that the selective activation of imines rather than aldehydes was achieved. 

The Heck reaction makes a C-C bond and adds a highly functionalised fragment that can be elaborated into many other functional groups. The same is true of the Friedel-Crafts reaction that generally works well with azoles or other heterocycles able to do electrophilic substitution. As usual, it is best to have only one free position so that no regioselectivity problems arise. In the Heck reaction, the site of attack is marked by the iodine atom, but the Friedel-Crafts can occur at any free position. Our example is a pyrazole that acylates cleanly with Lewis acid catalysts to give eventually the herbicide pyrazolate 196. 

Molecular Iodine Mild, Green, and Nontoxic Lewis Acid Catalyst for the Synthesis of Heterocyclic Compounds... 

Abstract The synthetic uses of molecular iodine are described. This chapter discusses the versatile uses of iodine in heterocyclic synthesis. Iodine is a universal oxidizing agent, a mild and nontoxic Lewis acid catalyst, and it catalyzes various organic reactions with high efficiency and selectivity. Also, iodine acts as an electrophile-nucleophile dual activator in the reactions. Further applications are the introduction of protecting groups, deprotection, iodocyclization, C-C bond formation, and formation of heterocycles. It is quite clear from the growing number... 

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