Electrophiles heterocyclic

Electrophilic heterocyclizations onto C—C bonds mediatedby halogen or chalco-gen atoms 970PP33. 

Another very mild procedure involves reaction of the alcohol with the heterocyclic 2-chloro-3-ethylbenzoxazolium cation.28 The alcohol adds to the electrophilic heterocyclic ring, displacing chloride. The alkoxy group is thereby activated toward a nucleophilic substitution that forms a stable product, 3-ethylbenzoxazolinone. 

With even more electrophilic heterocycles, addition of the lithiated species to the starting material can become a problem—for example, LDA will lithiate pyrimidine 181 at — 10°C, but the product, after work up, is the biaryl 182 resulting from ortholithiation and readdition (Scheme 91). By lithiating in the presence of benzaldehyde, a moderate yield of the alcohol 183 is obtainable . Strategies for the lithiation of pyrimidines and other very electrophilic heterocycles are discussed below . 

Electrophilic heterocyclizations of 2-(pent-l-en-5-yl)-l,3-benzoxazin-4-ones (142) and their C-2 epimers afforded diastereomeric mixtures of 9-methyl-5a,6,7,8,9,ll-hexahydropyrido[2,l-h][l,3]benzoxazin-10-ones (143 and 144), and their C-5a epimers, respectively, containing the 9-methyl group in the pseudo-axial orientation (89TL7321 90TL6765). Diastere-omers 143 and 144 interconvert in response to acidic catalysis (89TL7321). 

Several recent reviews have included specific types of electrophilic cyclofunctionalization reactions.1 Important areas covered in these reviews are halolactonization u cyclofunctionalization of unsaturated hydroxy compounds to form tetrahydrofurans and tetrahydropyrans lb cyclofunctionalization of unsaturated amino compounds lc cyclofunctionalization of unsaturated sulfur and phosphorus compounds ld lf electrophilic heterocyclization of unconjugated dienes 1 synthesis of y-butyrolactones 1 h synthesis of functionalized dihydro- and tetrahydro-furans lj cyclofunctionalization using selenium reagents lk lm stereocontrol in synthesis of acyclic systems 1" stereoselectivity in cyclofunctionalizations lP and cyclofunctionalizations in the synthesis of a-methylenelactones.lq Previous reference works have also addressed this topic.2... 

The generation of nitrogen heterocycles by electrophilic heterocyclization has been reviewed recently., c Examples of functional groups used as nitrogen nucleophiles are shown in Figure 2. 

The (3-lactone moiety represents a ubiquitous structural motif present in natural products and its moderately electrophilic heterocyclic ring reacts with nucleophilic residues of many proteins active sites. For example, esterastin is a known pancreatic... 

Lactones, electrophilic heterocyclization of unsaturated carboxylic acids in the synthesis of 88KGS1299. 

Double Michael reaction in synthesis of N-heterocycles 86YGK96. Electrophilic heterocyclization of unsaturated amino compounds into... 

In some instances, perfluorinated olefins can be used for the introduction of perfluoroalkyl group into highly electrophilic heterocycles. For example, reported in patent literature nucleophilic reaction of C2F5 (generated from tetrafluoroethylene... 

The electronic character of the indole ring can be adjusted by introduction of substituents so as to become more reactive as a dienophile in inverse-electron-demand Diels-Alder reactions. For example, 2-ethoxy-1-methylindole reacts with the electrophilic heterocycle (56) (Equation (138)) <87ZN(B)1032>. 

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