Electrophilicities of Benzaldehyde-Derived Iminium Ions: Quantification of the Electrophilic Activation of Aldehydes by Iminium Formation

Abstract

Rate constants for the reactions of benzaldehyde-derived iminium ions with C-nucleophiles (enamines, silylated ketene acetals, and enol ethers) have been determined photometrically in CH3CN solution and used to determine the electrophilicity parameters E of the cations defined by the correlation log k(20°C) = s(N)(E + N) (Mayr, H.; et al. J. Am. Chem. Soc. 2001, 123, 9500-9512). With electrophilicity parameters from E = -10.69 (Ar = p-MeOC6H4) to E = -8.34 (Ar = p-CF3), the iminium ions Ar-CH═NMe2(+) have almost the same reactivities as analogously substituted arylidenemalononitriles Ar-CH═C(CN)2 and are 10 orders of magnitude more reactive than the corresponding aldehydes. The rate constants for the reactions of iminium ions with amines and water in acetonitrile are 10(3)-10(5) times faster than predicted by the quoted correlation, which is explained by the transition states which already experience the anomeric stabilization of the resulting N,N- and O,N-acetals.

Asymmetric Ketone Reduction by Imine Reductases

“…This is in accordance with the work of Mayr and co-workers,w ho described the electrophilicity of benzaldehyde-derived iminium ions and their higherr eactivities compared to substituted imines. [27] Consistent with this trend, IREDs showed higher initial rates in transformations with iminium ions than with the corresponding imines. [10,20] Regarding speculations of the roles of amino acid residues for C=Np rotonation in IREDs, [11,25] there is some supporting evidenceb ased on mutations of putative catalytically important aspartic acid residues displaying reduced catalytic efficiencies over wild-type enzyme.…”

Dimerization and comments on the reactivity of homophthalic anhydride

“…16 The fact that imine 2 under these conditions is apparently much more reactive toward HPA than the C-3 carbonyl group of HPA itself suggests that the reaction does not involve the anion of HPA adding to the imine carbon, but rather, the reaction could feature a protonated iminium electrophile derived from 2 .…”

Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA

“…It will be interesting to explore how spermine and other polyamines in the nucleus modulate the fate of Ap sites in genomic DNA. The polyamine-derived imines 2 and 3 (Scheme 1) are expected to be much more reactive than the parent aldehydes Ap and 1 (89–91). Indeed, the spermine-mediated formation of the nicked cross-links described here is substantially faster than the formation of the full-length dA-Ap cross-link described previously ( 4 , Scheme 2) (55).…”