Cyano, Amino, and Trifluoromethyl Substituent Effects on the Claisen Rearrangement

Abstract

Ab initio quantum mechanical methods with the B3LYP/6-31G* method were used to model the reactants, transition states, and products of Claisen rearrangements of allyl vinyl ethers substituted at all positions with CN, NH 2 or CF 3 groups. The calculations predict that 1-CN, 1-CF 3 -cis, 5-NH 2 , 6-CN, and 6-CF 3 substituents increase the activation barriers, in agreement with experimental results on substituent effects by CN, CF 3 , and the related 5-OCH 3 example. All other substituents lower activation energies. A Marcus theory type analysis was applied to separate the intrinsic and thermodynamic contributions to the activation energies.

A Dataset of Computational Reaction Barriers for the Claisen Rearrangement: Chemical and Numerical Analysis

“…On the other hand, substituting EDG such as NH 2 and OCH 3 to X1 enhances the stability of the product by delocalizing a lone pair of electrons to the carbonyl π* orbital. In particular, NH 2 forms an amide bond with the carbonyl group and significantly stabilizes the product [34,35] . It is known that reaction barriers often correlate with products’ stability [36,37] .…”

“…It was shown that the interaction between HOMO of the enolate moiety and LUMO of the allyl moiety favors the Claisen rearrangement. [34,35] More specifically, the reactivity is enhanced when HOMO's MO coefficients at C2 and LUMO's MO coefficients at C4 and C5 are high. It was also discussed that substituting EDG to X1 and EWG to X2 increase HOMO's MO coefficients at C2 and that substituting EWG to X3 and EDG to X4 and X5 increase LUMO's MO coefficients at C4 and C5.…”

Rearrangement of N‐Aryl‐2‐Vinylaziridines to Benzoazepines and Dihydropyrroles: A Synthetic and Theoretical Study

“…To achieve a more quantitative estimate of substituent effects on the chemoselectivity of the N-aryl-2-vinylaziridines to benzoazepines rearrangement, we have tried to correlate the activation energies of the rate-determining step, 1 to 1 I, with the corresponding reaction energies. The activation energies of Claisen rearrangements have been shown to be related to the corresponding reaction energies [62] through Marcus theory. [63] Briefly, Marcus theory allows the separation of the energy barrier into intrinsic and thermodynamic contributions [Eq.…”

Cyanovinylation of Aldehydes: Organocatalytic Multicomponent Synthesis of Conjugated Cyanomethyl Vinyl Ethers

“…Cyanomethyl vinyl ethers (CMVEs) 1 constitute densely functionalized linear synthetic platforms which have found use as monomeric units in the construction of alkenyl ether-vinyl ester copolymers [ 1 , 2 , 3 , 4 , 5 ], as building blocks in the construction of multi-substituted 2,3-dihydrofurans [ 6 , 7 ] and 2,3-dihydropyrroles [ 7 ], and as convenient platforms for mechanistic investigations in the Claisen rearrangement of allyl vinyl ethers [ 8 , 9 , 10 ] ( Scheme 1 A). They are usually synthesized in a step-wise manner from the corresponding aldehydes through the formation of the O -formyl cyanohydrin intermediate and carbonyl methylenation [ 9 ] ( Scheme 1 B).…”