Reactions in the conjugated ‘ene–ene–yne’ manifold: five-membered ring fragmentation and ring formation via coarctate/pseudocoarctate mechanisms

Abstract

The fragmentation of a 5-membered heteroaromatic ring to afford a conjugated ene-ene-yne skeleton, and the corresponding reverse process, cyclization of the hetero-ene-ene-yne motif to generate a variety of heterocyclic systems, are the subject of this review. These synthetically useful reactions, which proceed through a coarctate/pseudocoarctate mechanistic pathway, are unique in that they involve the generation of either a carbene or nitrene intermediate, and provide access to hard to obtain heterocyclic or ene-ene-yne structures. While fragmentation of heteroaromatic rings containing a exocyclic carbene or nitrene has been well documented in the literature for over 40 years, the use of hetero-ene-ene-yne precursors to synthesize heterocycles is a relatively new approach that is generating much interest in the literature. This review highlights both the synthetic and mechanistic aspects of these unique reactions.

Synthesis of α-Ketoester- and α-Hydroxyester-Substituted Isoindazoles via the Thermodynamic Coarctate Cyclization of Ester-Terminated Azo-Ene-Yne Systems

“…1 Such heterocyclic compounds have found uses as diverse as incorporation into organic light emitting devices to utilization as pharmacaphores in medicinal applications. 2–4 Our laboratory has been studying a subset of ‘ene-ene-yne’ reactions, namely the coarctate cyclization of azo-ene-yne 5–8 and azo-ene-nitrile 9 systems.…”

Coarctate versus Pericyclic Reactivity in Naphthalene‐Fused Azo–Ene–Ynes: Synthesis of Benzocinnolines and Benzoisoindazoles

“…Purification by column chromatography (1:1 Et 2 O/hexanes) provided 24 (0.86 g, 54 %) as a yellow solid. 1 Alkyne 26: Amine 25 (0.40 g, 1.2 mmol) in dry THF (60 mL) was cooled to À78 8C and then BuLi (1.6 m in hexanes, 4 mL, 6.0 mmol) was added. The reaction mixture was stirred at À78 8C for 30 min, then warmed to 0 8C and stirred for an additional hour.…”

“…Purification by column chromatography (1:1 hexanes/CH 2 Cl 2 ) afforded 26 (95 mg, 50 %) as a tan solid. 1 Computational methods: All computations were performed by using the Gaussian 03 [27] suite of programs at the B3LYP/6-31G* level of theory. [18] All stationary points were confirmed by harmonic frequency analysis and checked for stability for triplet and SCF convergence.…”

“…The crystal structure analysis revealed the new product to be the cis isomer 17 ( Figure 2). Believing that the acidic www.chemeurj.org nature of the CDCl 3 was behind the isomerization, a freshly prepared sample of 16 was dissolved in CD 2 Cl 2 and monitored by 1 H NMR spectroscopy. By keeping the sample in the instrument, no isomerization was detected after 48 h, which indicated that ambient light triggered the isomerization.…”

“…[1] In particular, we have been examining the dual reaction pathways of conjugated azoene-ynes (1, Scheme 1), [2] where under thermal conditions a pericyclic cyclization generates a new benzo-fused six-membered ring (2), or addition of a carbene stabilizer induces a coarctate cyclization [3,4] to form a new benzo-fused fivemembered ring (3). Through these methodologies, a variety of substituted cinnolines and isoindazoles, respectively, are available from simple anilines in high yields and in only a few steps.…”