Mechanistic switchover

The mechanisms of asymmetric synthesis of aziridines from guanidinium ylides and arylaldehydes have been probed by varying para-substituents in the aldehyde.339 Hammett plots show a mechanistic switchover going from electron-donating to electron-withdrawing groups. 

The photocycloaddition of L-ascorbic acid derivatives (e.g., 93) with 4-chlorobenzaldehyde (94) and benzyl methyl ketone led to preferential attack on the less hindered a-face of the enone with approximately 2 1 regioselectivity (33% de for 96) (see Scheme 22) [147]. When the substrate was changed to benzophenone, the regioselectivity was reversed, even though the facial selectivity remained the same (35% de). This was proposed to be the result of a mechanistic switchover, from a 1,4 diradical process for benzophenone to a photoinduced electron transfer process for the other substrates. 

The acid-catalysed hydrolysis of three iV-phenylalkanesulfinamides (49, R = i-Pr, t-Bu, 1-adamantyl) in aqueous mineral acids (HCl, HBr, H2SO4, HCIO4) was found to proceed via a slow spontaneous (uncatalysed) pathway, an A2 acid-catalysis pathway, and an acid-dependent nucleophilic catalysis pathway, the last of which predominates in hydrobromic and hydrochloric acid solutions (Scheme 16a). A mechanistic switchover from A2 to A1 (Scheme 16b) was detected for the isopropyl and t-butyl compounds in concentrated sulfuric acid. Order of catalytic activity, effect of added salts, Arrhenius parameters, kinetic solvent isotope, and solvent effects were all consistent with the proposed mechanisms. ... 

Diastereomeric phosphoramides have been employed to catalyse the asymmetric aldol addition of trichlorosilyl enolates to benzaldehyde. Good anti/syn product ratios were achieved, but these were reversed on employing a more hindered catalyst, and the ratios were also affected by the catalyst concentration. A mechanistic switchover is proposed one transition-state geometry involves a 1 1 complex (cat-alyst enolate) favoured by a hindered catalyst in low concentration, while the other route involves a 2 1 stoichiometry. 

However, the switchover from an A2 to an A1 hydrolysis is a very common mechanistic pathway in strong acid media, probably more common than the pure A2 mechanism. Excess acidity analyses have shown that thioacetic acid, several thiobenzoic acids, and many thiolbenzoate and thionbenzoate esters show this sort of mechanism switch.179 Acylals and thioacylals also show this behavior,116 with thioacylals using two water molecules and acylals one. Many hydroxamic acids react this way,127,216 as do esters of various types,41,217,218 episulfoxides219 and aryloxatriazoles.220 Acylhydrazines can also show a mechanism switch of this sort, although with these substrates the situation is somewhat more complex.221... 

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