Computational Studies on 3-Aza-Cope Rearrangements: Protonation- Induced Switch of Mechanism in the Reaction of Vinylpropargylamine

Abstract

The 3-aza-Cope rearrangements of 3-azoniahexa-l,S-diene (1), 3-azonia hex-l-ene-5-yne (3), and 3-azahex-l-ene-5-yne (5) were investigated up to the coupled-cluster level, CCSD(T), by using a valence triple-s basis set. Activation barriers and geometrical parameters of the transition states are provided. Conforma tional studies were performed for all reactants and products of the reactions. Solvent effects were estimated from self-consistent reaction field calculations. In contrast to the other two species, the Cope rearrangement of 5 was found to proceed by a stepwise mechanism.

Synthesis of 1,2-Dihydro-Substituted Aniline Analogues Involving N-Phenyl-3-aza-Cope Rearrangement Using a Metal-Free Catalytic Approach

“…13 C NMR further confirms the formation of the product, as propargylic peaks at δ 85.9 and δ 73.5 disappeared and new peaks at δ 117.6 and δ 122.1 appeared, representing the formation of double bond. HRMS data further confirmed the formation of the desired product F. We propose a mechanism pathway for the above aza-Cope rearrangement, as shown in Scheme 3, which is quiet similar to the one reported previously [30]. In brief, when compound (a) is heated to 180°C, it undergoes a [3,3]-sigmatropic rearrangement yielding the allene (b).…”

“…Observation of 13 C NMR spectra shows the proximity of all these signals presents very similar chemical deviations. In the case of the proposed structures, it is possible Journal of Chemistry to draw a plane of symmetry passing along the dihydropyridine ring, and that due to the planarity of all the different functional groups, all obtained molecules extend beyond this ring [30].…”

Synthesis of Dihydromotuporamine C via 3‐Azonia‐Cope Rearrangement of 11‐Membered Cyclic α‐Vinylamine

“…From the above observations, we tentatively attributed the ring-enlarging pathway as a cationic chargeaccelerated 3-azonia-Cope rearrangement (Scheme 4). [21,22] Initially, the N-benzylated cyclic amine was added to the triple bond of ethynyl p-tolyl sulfone to produce the zwitter-ionic intermediate 20, in which the vinyl carbanion was stabilized by the tosyl group. From 20, protonation proceeded to afford quaternary ammonium specie 21, which underwent the sigmatropic rearrangement to furnish, via deprotonation of 22, the ring-enlarged product 19.…”

“…From the above observations, we tentatively attributed the ring‐enlarging pathway as a cationic charge‐accelerated 3‐azonia‐Cope rearrangement (Scheme 4). [21,22] …”

Evasive Neutral 2‐Aza‐Cope Rearrangements. Kinetic and Computational Studies with Cyclic Nitrones

“…To explore the energetics of the 2‐aza‐Cope rearrangements studied above, we also performed DFT calculations with both B3LYP28 and M06‐2X29 functionals using the 6‐311+G(d,p)30 basis set. B3LYP calculations have been reported to provide accurate results in the study of Cope rearrangements,31 although in the case of protonated species they lead to an underestimation of the activation energies, indicating insufficient consideration of the electronic correlation effects 32. On the other hand, Thrular's functionals33 have emerged as powerful tools that provide more accurate energy values in several types of reactions 34.…”