Electron-withdrawing substituted group

The high nucleophilicity of sulfur atoms is preserved, even if it is bound to electron withdrawing carbonyl groups. Thiocarboxylales, for example, substitute bromine, e.g. of a-bromo ketones. In the presence of bases the or-acylthio ketones deprotonate and rearrange to episulfides. After desulfurization with triphenylphosphine, 1,3-diketones are formed in good yield. Thiolactams react in the same way, and A. Eschenmoser (1970) has used this sequence in his vitamin B]2 synthesis (p. 261). 

A mild procedure which does not involve strong adds, has to be used in the synthesis of pure isomers of unsymmetrically substituted porphyrins from dipyrromethanes. The best procedure having been applied, e.g. in unequivocal syntheses of uroporphyrins II, III, and IV (see p. 251f.), is the condensation of 5,5 -diformyldipyrromethanes with 5,5 -unsubstituted dipyrromethanes in a very dilute solution of hydriodic add in acetic acid (A.H. Jackson, 1973). The electron-withdrawing formyl groups disfavor protonation of the pyrrole and therefore isomerization. The porphodimethene that is formed during short reaction times isomerizes only very slowly, since the pyrrole units are part of a dipyrromethene chromophore (see below). Furthermore, it can be oxidized immediately after its synthesis to give stable porphyrins. 

For electron withdrawing substituted methylenecyclopropanes (R = EWG) the stabilization of the negative charge by the EWG group as in TS-A justifies the high regioselectivity observed. 

A Ni(dppe)Br2-Zn system effectively catalyzes co-cydotrimerization of an allene with a propiolate. The reaction is highly regio- and chemoselective to afford a poly-substituted benzene derivative in good yield. (Scheme 16.82) [92], From the observation that no desired [2 + 2 + 2] product is obtained for the reaction of 1-hexyne and phenylacetylene with w-butylallene under similar conditions, the presence of an electron-withdrawing C02Me group in the alkyne moiety is essential for the success of the present [2 + 2 + 2]-co-cyclotrimerization. 

Diazophenol formation is most competitive when a nitramine substrate contains an electron-withdrawing nitro group ortho to the nitro group being displaced and hence meta to the nitramine functionality, assumedly because that site is then activated towards nucleophilic aromatic substitution. Heating nitramines in inert chlorinated solvents also favours diazophenol formation but this is suppressed by using urea or sulfamic acid as additives. 

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