Biscyclization Reactions in Butadiyne- and Ethyne-Linked Triazenes and Diazenes:  Concerted versus Stepwise Coarctate Cyclizations

Abstract

A series of alkyne-linked bis-2H-indazoles has been prepared by the double cyclization of ethyne- or butadiyne-linked phenyltriazene or phenyldiazene moieties. Even though there are two five-membered ring cyclizations and several triple bond shifts involved, the reactions proceed rapidly under neutral conditions with mild heating, affording the heterocycles in excellent yields. DFT calculations, in agreement with experimental observations, indicate that the reactions: (1) occur via a very short-lived carbene intermediate, (2) are concerted via an asymmetrical transition state, or (3) are even synchronous, with as many as 16 bonds that are made or broken simultaneously. The biscyclizations presented herein strikingly illustrate the concept of coarctate reactions, the stabilization of transition states by coarctate Möbius aromaticity, the ethynologation principle, and the stereochemical rules.

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

“…[2,5,[7][8][9][10][11] This level of theory has proven to give reliable results that are comparable to experimental findings in prior cyclization studies. To reduce the number of conformational degrees of freedom, the NEt 2 substitution on the triazene was replaced with an NMe 2 group.…”

“…[2, 7,8,10] Extension of this methodology to naphthalene derivatives would suggest three potential cycli-zation precursors 5-7, which would originate from the corresponding halonaphthalenamines 8-10 (Scheme 2). Examination of the literature revealed that related structures 9 [14] and 10 [15] are known compounds, whereas linear derivative 8 (X = I, Br) is unknown and therefore an alternate precursor is necessary.…”

Carbenes and Nitrenes

“…18 Experimental data and DFT calculations support carbene (9) as an intermediate in this stepwise, nonsynchronous coarctate reaction. Methoxy(methylthio)carbene (12) has been observed by UV photoelectron spectroscopy after gas-phase decomposition of oxadiazoline (11).…”

Coarctate cyclization reactions: a primer

“…More important, Austin showed that the double cyclization occurred cleanly at 90 1C in ODCB and afforded only the bisisoindazoles; cinnolines were never detected. 50 Monoyne 63 could cyclize to the corresponding bisisoindazole 64, but required higher temperatures and/or carbene stabilisers to induce cyclization (Scheme 23). 50 Interestingly, heating 61 and 63 in excess DMB or protic solvents produced only 62 and 64; as we initially hoped, carbene-trapped products were not observed.…”

“…50 Given the high degree of reactivity of the diynyl bisdiazene, we did not even attempt to prepare the monoyne derivative.…”