Quantification of the Electrophilic Reactivities of Aldehydes, Imines, and Enones

Abstract

The rates of the epoxidation reactions of aldehydes, of the aziridination reactions of aldimines, and of the cyclopropanation reactions of α,β-unsaturated ketones with aryl-stabilized dimethylsulfonium ylides have been determined photometrically in dimethyl sulfoxide (DMSO). All of these sulfur ylide-mediated cyclization reactions as well as the addition reactions of stabilized carbanions to N-tosyl-activated aldimines have been shown to follow a second-order rate law, where the rate constants reflect the (initial) CC bond formation between nucleophile and electrophile. The derived second-order rate constants (log k(2)) have been combined with the known nucleophilicity parameters (N, s(N)) of the aryl-stabilized sulfur ylides 4a,b and of the acceptor-substituted carbanions 4c-h to calculate the electrophilicity parameters E of aromatic and aliphatic aldehydes (1a-i), N-acceptor-substituted aromatic aldimines (2a-e), and α,β-unsaturated ketones (3a-f) according to the linear free-energy relationship log k(2) = s(N)(N + E) as defined in J. Am. Chem. Soc.2001, 123, 9500-9512. The data reported in this work provide the first quantitative comparison of the electrophilic reactivities of aldehydes, imines, and simple Michael acceptors in DMSO with carbocations and cationic metal-π complexes within our comprehensive electrophilicity scale.

Kinetic Selectivity and Thermodynamic Features of Competitive Imine Formation in Dynamic Covalent Chemistry

“…[1][2][3][4][5] The formationo fr eversible C=Nc onnections from reactiono fp rimary amines, hydrazide, hydrazinea nd hydroxylamined erivatives with carbonyl compounds [6][7][8][9][10] has been actively investigated to developt he core of DCC in view of their dynamicf eaturesa sw ell as for their use for generating conjugates in chemistry and biology.N ucleophiles such as hydrazine and hydroxylamine where the amino group has an a-substituent bearing al one pair have long been known to act as stronger nucleophiles than normal primary amines [11] and their low basicity allowst he formation of more stable imine products. However,t he kinetics of the condensation reactions are also of basic interesta nd have received increasing attention, [25][26][27][28][29][30][31] as they mayb ee xpected to affectt he compositiono fadynamic C=Nl ibrary as af unction of time in the course of its generation from carbonyl and aminoc omponents. [24] Attention has been mainly paidt ot he thermodynamic features of the constituents of DCLsb ased on the formation of C=Nc onnections.…”

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

“…His) is devoid of significant quenching activity, one may argue that the first imine intermediate acts as an intramolecular catalyzer constraining the imidazole ring to approach the b carbon atom in an arrangement constantly conducive to the Michael addition, which would be further favored due to the slightly more electrophilic character of the imine derivative compared to the free carbonyl as recently analyzed (Appel and Mayr 2011).…”

Comparison of the Electrophilic Reactivities of N‐Acylpyridinium Ions and Other Acylating Agents

“…When the slope is set to unity as required by Equation (2) is, by minimization of Δ 2 = Σ{lg k 2s N (N + E)} 2 using fixed values of N and s N as published previously. The reactivity of 1 is one order of magnitude lower than that of benzaldehyde (E = -19.52), [6] which can be rationalized by ground-state stabilization due to the mesomeric interaction of the oxygen lone pair with the carbonyl group. The reactivity of 1 is one order of magnitude lower than that of benzaldehyde (E = -19.52), [6] which can be rationalized by ground-state stabilization due to the mesomeric interaction of the oxygen lone pair with the carbonyl group.…”

“…There has been much debate concerning whether attack of the nucleophiles at the carbonyl group displaces Xin a concerted manner or whether tetrahedral intermediates are involved. [6] For these investigations, acceptor stabilized carbanions, such as malonate or the highly nucleo- philic phenylacetonitrile anions, could not be used as reference nucleophiles because of the high reversibility of these reactions. [3] lationship lg k 2 (20°C) = s N (N + E), separate correlation lines for different types of nucleophiles were found when (lg k 2 )/ s N was plotted against N for the reactions with acyl derivatives 2-5.…”