On the Mechanism of the Formal [2+2] Cycloaddition – Retro‐electrocyclization (CA‐RE) Reaction

Abstract

The [2+2] cycloaddition ‐ retro‐electrocyclization (CA‐RE) reaction is a “click‐like” protocol for facile synthesis of donor‐acceptor chromophores from an alkyne and tetracyanoethylene. Herein we shed light on the mechanism of this reaction by detailed kinetics studies using 1H NMR spectroscopy. By considering several experiments simultaneously, a variety of mechanistic models was evaluated. Surprisingly, a model in which the final 1,1,4,4‐tetracyanobuta‐1,3‐diene product promoted the first step was the only one that described well the experimental data. This autocatalysis model also involved a non‐concerted, stepwise formation of the cyclobutene cycloaddition adduct. By proper choice of conditions, we were able to generate the transient cyclobutene in sufficient amount to verify it as an intermediate using 13C NMR spectroscopy. For its final retro‐electrocyclization step, simple first‐order kinetics was observed and only minor solvent dependence, which indicates a concerted reaction.

A study of [2 + 2] cycloaddition–retroelectrocyclization in water: observation of substrate-driven transient-nanoreactor-induced new reactivity

“…2a). 26,27 Additionally, the H 2 O addition to the EDG-delocalized CN group on 1a to generate 4-donor-substituted merocyanine dye/5-membered heterocycles 2a was proposed by Bruce and co-workers. 11 It was proposed that amide forms an intermediate upon the addition of water to the TCBD, which then further cyclizes to produce amidofulvene.…”

A Study of [2+2] Cycloaddition–Retroelectrocyclization in Water: Observation of Substrate-driven Transient Nanoreactor Induced New Reactivity

“…A plausible mechanism for the transformation of TCBD 1a to 2a and then 3a: The formation mechanism of TCBD 1a from the reaction of TCNE with alkyne has been quite established by Diederich and co-workers, and also recently by Nielsen and coworkers with cyclobutene intermediate (Figure 2a). 15,16 Whereas, the H2O addition to EDG-delocalized CN group on 1a to generate 4-donor-substituted merocyanine dye/5-membered heterocycles 2a was proposed by Bruce and co-workers. 11 It was proposed that amide forms an intermediate upon water addition to the TCBD which then further cyclizes to produce amidofulvene.…”

[2 + 2] Cycloaddition/Retro-Electrocyclization/Decarboxylation Reaction Sequence: Access to 4-Aminopyridines from Methylideneisoxazolones and Ynamines

“…The structure of diene 4a was confirmed by single-crystal X-ray diffraction analysis (see the Supporting Information). Most probably this product was formed via the [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) reaction which occurs between electron-rich alkynes and electron-deficient alkenes , and used recently for the creation of nonplanar donor–acceptor (D–A) molecular chromophores − and D–A organic polymers . The most used electron-deficient alkenes are tetracyanoethylene (TCNE), 7,7,8,8-tetracyanoquinodimethane, and other gem -dicyanosubstituted alkenes (Scheme ).…”

“…The most used electron-deficient alkenes are tetracyanoethylene (TCNE), 7,7,8,8-tetracyanoquinodimethane, and other gem -dicyanosubstituted alkenes (Scheme ). − Sometimes, when an electron-deficient alkene contains a heterodiene system, in addition to the CA-RE reaction, a HDA reaction can be implemented . Here, we report the synthesis of 4-(1-aminoallylidene)­isoxazol-5-ones by the reaction of 4-methylideneisoxazol-5­(4 H )-ones with ynamines, a DFT study of the reaction mechanism and the preparation of substituted 4-aminopyridines via decarboxylative non-catalytic isomerization of the CA-RE reaction products.…”