Electron-withdrawing groups EWGs

The modification of the Madelung indole synthesis achieved by introduction of an electron withdrawing group (EWG) at the benzylic carbon atom of the N-acylated-o-alkylanilines has been quite successful. Orlemans et al. reported that indoles were isolated in decent yields when the amides were treated with t-BuOK in THF for a period of 10 minutes at room temperature. ... 

The first condensation is conducted selectively on a variety of 3-ketoesters and a-formylesters. The first step works well on most simple anilines even when sterically congested and is mostly affected by basicity. Formation of intermediate 3 is problematic when strong electron-withdrawing groups (EWG) are attached to the aniline (e.g., nitro). The cyclization step is promoted thermally in inert solvents as well as using acidic solvents at elevated temperature. When there exists an opportunity to form isomers on cyclization (e.g., m-substituted anilines) a mixture of the 5- and 7-substituted quinolines usually results. 

Due to the commercial availability of EMME in good purity, there has not been a need to develop new methods to prepare 3-anilino-acrylates therefore, only a few alternatives have been reported. One approach described thermal carbene generation from 37, and rearrangement to form 38. Cyclization in refluxing 1,2-dichlorobenzene (1,2-DCB) provided the 2, 3, 4-trisubstituted quinolines. An electron-withdrawing group (EWG) on the carbene carbon was required for this reaction, and therefore led to the EWG substitution in the 2-position of the quinoline. 

The best known of metal carbene reactions, cydopropanation reactions, have been used since the earliest days of diazo chemistry for addition reactions to the carbon-carbon double bond. Electron-donating groups (EDG) on the carbon-carbon double bond facilitate this catalytic reaction [37], whereas electron-withdrawing groups (EWG) inhibit addition while facilitating noncatalytic dipolar cycloaddition of the diazo compound [39] (Scheme 5). There are several reviews that describe the earlier synthetic approaches [1, 2,4, 5,40-43], and these will not be duplicated here. Focus will be given in this review to control of stereoselectivity. 

A second important reaction type considered in this chapter is conjugate addition, which involves addition of nucleophiles to electrophilic double or triple bonds. A crucial requirement for this reaction is an electron-withdrawing group (EWG) that can stabilize the negative charge on the intermediate. We focus on reactions between enolates and a,(3-unsaturated carbonyl compounds and other electrophilic alkenes such as nitroalkenes. 

Electron donor groups (EDG) on the aromatic ring favour its displacement to the right while electron withdrawing group (EWG) favours its displacement to the left. Selenobenzophenone monomer in solution is isolated as a dimer in the solid state. Dimerization of the stable 12 to the 1,3-ditelluretane was observed in the solid state, in solution the dimer reforms 12.25 26 Contrary to the reaction in the solid state dimerization does not take place in solution. 

Alkylation with Diazo Compounds Diazomethane or diazoethane are commonly used as diazo compounds. The reactions of these alkylating agents proceed smoothly only with AN containing electron-withdrawing groups (EWG) adjacent to the a-C atom (4-6) (Scheme 3.3). 

The last reaction in Scheme 13 becomes possible when the sulfide has a CH2 or CH fragment, adjacent to the sulfur atom whose protons are getting more acid when the molecule is oxidized. Electron-withdrawing groups (EWGs) increase the ease of deprotonation of this site even more. Thus, a-MeO-, a-AcO-, and a-F-sulfides were prepared (Eq. 9) [67-70]. When the nucleophihc attack is sterically hindered or a-protons are absent, products acetoxylated in the phenyl ring are... 

Electron withdrawing group (EWG) stabilises the carbojq late anion and strengthens the acid... 

A third property that characterizes the reactivity of isocyanides is their a-acidity. Introduction of an electron withdrawing group (EWG) at the a-position of isocyanides considerably lowers the pKa-value of the a-hydrogens. Consequently, a-acidic isocyanides have, besides the aheady unusual reactivity of the isocyanide functional group, an additional nucleophilic center upon proton abstraction. This opens different reaction paths towards a range of interesting products, including heterocycles. 

An electron-withdrawing group (EWG) on the indole nitrogen appears to be required for these cycloadditions to occur, since, for example, l-methyl-3-nitroindole fails to react with miinchnone 425d after 24 h at reflux in THF or diglyme at most, <1% of products are formed. 

Nucleophilic Additions to Alkenes. Nucleophilic additions to alkenes (Scheme 3.9) are mechanistically very closely related to an ElcB process. In fact, the addition process simply involves a reversal of the steps in response to an equilibrium constant that favors the addition product over the alkene. A notable example is the Michael addition of an enolate to an alkene bearing a strong electron-withdrawing group (EWG). 

Y/ .v-(3-Lactains have also been obtained by the Staudinger reaction carried out between divinylimine and /V-acylimidazoles possessing an electron-withdrawing group (EWG) in a position [111]. This latter were prepared by treatment of a-EWG substituted carboxylic acids with 1,1-carbonyldiimidazole. 

It is known that two electron-withdrawing groups (EWGs) attached to the same carbon atom in an alkene increase substantially the reactivity of the alkene towards electrophiles. At the same time, ozonides with EWGs become too unstable. A compromise between stability and reactivity is attained with unsaturated... 

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