Pseudopericyclic 1,5- versus Pericyclic 1,4- and 1,6-Electrocyclization in Electron-Poor 4-Aryl-2-azabuta-1,3-dienes: Indole Synthesis from 2H-Azirines and Diazo Compounds

Abstract

Transformations of 2-azabuta-1,3-dienes, formed in Rh2(OAc)4-catalyzed reactions of diazo carbonyl compounds with 2H-azirines, dramatically depend on the nature of substituents. 4,4-Diphenyl-2-azabuta-1,3-dienes with two electron-acceptor substituents at C(1) undergo thermal 1,5-cyclization to give indoles in good yields. The increase in electron-withdrawing ability of C(1)-substituents facilitates the reaction that proceeds via pseudopericyclic 1,5-electrocyclization of 2-azabutadiene into 7aH-indolium ylide followed by prototropic shift. 3,4-Diphenyl-2-azabuta-1,3-dienes, resulting from reaction of 2,3-diphenyl-2H-azirine and diazo compounds, do not produce indoles via 1,5-cyclization due to the trans-configuration of the 4-Ph-group and the nitrogen, but undergo 1,4-cyclization to 2,3-dihydroazetes. 1,6-Cyclization into 2H-1,4-oxazines with participation of the oxygen of ester or amide group at C(1) of corresponding 2-azabuta-1,3-dienes does not take place due to kinetic and thermodynamic reasons. Instead of this, 1,6-electrocyclization with participation of phenyl substituent at C(4) of the 2-azabuta-1,3-dienes, providing isoquinoline derivatives, can occur at elevated temperatures. The DFT-calculations (mPWB1K/6-31+G(d,p)) confirm the dependence of 2-azabuta-1,3-diene transformation type on the nature of substituents.

Single‐Step Modular Synthesis of Unsaturated Morpholine N‐Oxides and Their Cycloaddition Reactions

“…To the best of our knowledge, 2 H ‐1,4‐oxazine N ‐oxides 6 and 7 have not previously been reported, and discussions of oxazines similar to 10 are rare and limited to their use as latent azadienes ,. Due to the demand for new heterocycles for medicinal and material applications, we decided to explore the reactivity of 6 and 7 to determine how they might be applied in the preparation of new structurally diverse libraries.…”

“…Oxazine 19 similarly underwent a [4+2] cycloaddition with the same dienophile but the initial cycloaddition product rearranged to the corresponding pyridine 21 under the reaction conditions. These transformations are in contrast to the reactivity reported for similar oxazines generated from 2 H ‐azirines and diazoesters, which favor ring opening and rearrangement ,. The preparation of cycloaddition products 20 and 21 also further supports the unique utility of oxazines such as 6 – 8 and 10 for the diversity‐oriented synthesis of new heterocyclic structures.…”

Electrocyclizations of Conjugated Azapolyenes Produced in Reactions of Azaheterocycles with Metal Carbenes

“…In particular, 1,4-cyclization of 3,4-diphenylsubstituted azadiene 13 derived from 2,3-diphenyl-2H-azirine 10 and rhodium carbene 12 gave dihydroazete 14 in good yield under mild conditions (Scheme 2) [26,27]. The analogous reaction of azirine 10 with diazoamidoester 15 in 1,2-dichloroethane (DCE) resulted in the formation of dihydroazete 18 and revealed the stereoselective nature of both the formation of the intermediate azadiene 17 and its cyclization [28]. It is notable that the cyclizations of azadienes 13 and 17 occurred irreversibly in both cases.…”

“…Particularly, the azahexatriene containing an alkoxycarbonyl and cyano group at C1 isomerized smoothly to the corresponding indole, even at room temperature. According to the results of the DFT calculations, the activation barrier of 1,5-electrocyclization of azadiene 141 to indolium ylide 142 turned out to be lower than those of 1,4-electrocyclization to dihydroazete 145 and 1,6-electrocyclization to dihydroisoquinoline 146 (Scheme 28) [28]. Further intramolecular prototropic shift in indolium ylide 142 has an extremely low barrier.…”

“…2-Azadienes 139 (2-azahexa-1,3,5-trienes with the terminal C=C bond as a part of the benzene system) containing two phenyl substituents at the C4 and two electronwithdrawing groups at the C1 undergo unusual 1,5-electrocyclization involving the C=C bond of the aromatic ring to give indole derivatives 140 (Scheme 27). On the basis of this reaction, an efficient method for the synthesis of N-substituted indoles 140 from 2,2-diphenyl-2H-azirines 138 and diazocarbonyl compounds 24 without isolation of the intermediate azahexatrienes 139 was developed [28]. It was found that an increase in the electron-withdrawing ability of substituents at the C1 of 2-azabutadienes facilitates the indole formation.…”