1,3‐Dipolar Cycloadditions of Cyanoheteroarenes with non‐stabilized Azomethine Ylides : C≡N vs Aromatic C=C Reactivity

Abstract

Indoles, benzofurans and benzothiophenes substituted by a cyano group at positions 2 or 3 are shown to behave differently toward azomethine ylide 1,3‐dipole 1, in (3+2) cycloadditions. While the C2=C3 aromatic double bond of 3‐cyanoheteroarene reacts as dipolarophile to generate the corresponding dearomatized cycloadducts, the C≡N bond of 2‐cyanobenzofuran reveals more reactive and imidazoline are obtained in this case. 2‐Cyanoindole substituted by an electron‐withdrawing triflyl group on the nitrogen atom allows the formation of the bis‐cycloadduct where the C=C and C≡N moieties both reacted. The C≡N vs C=C reactivity is nicely supported by DFT computations.

Dithioallyl Cations in Stereoselective Dearomative (3 + 2) Cycloadditions of Benzofurans: Mechanism and Synthetic Applications

“…The dithioallyl cation derived from alcohol 26 is a more sterically hindered carbocation, which indeed may also skew the regioselectivity back toward the somewhat less encumbered indole-C3 position. This result seems to corroborate our analysis that the stereoselectivity of these (3 + 2) cycloadditions is related to the nucleophilicity of the heteroarene substrate . The reversal of regioselectivity observed between benzofurans and indoles seems to hinge on electronic factors, but other factors also should be taken into account.…”

Dichotomic Dearomatizations of Benzene vs Pyridine Rings of Sulfonyloxypyridine via (3 + 2) Cycloaddition

“…- 3,5a,6,7,8,8a,8boctahydropyrrolo[3,isoindol-3a(1H)-yl)sulfonyl)oxy)nicotinate (6a). Method GP2 using 4.0 equiv of dipole, orange solid, (column chromatography), R f = 0.49, eluent (cyclohexane/ethyl acetate 7:3), mp = 99−101 °C, 106 mg (0.3 mmol) scale reaction (in 2 mL of DCM) for 4 h, 65 mg (0.105 mmol) was isolated, 35% yield, 89:11 dr. Major trans diastereomer.…”

“…Lately, there has been an increasing interest in dearomative (3 + 2) processes in particular through the involvement of electron-poor electrophilic indoles, to furnish valuable indolines bearing a tetrasubstituted carbon center at the ring junction . In particular, 1,3-DC involving the electron-rich azomethine ylide dipole has been reported on differently substituted indoles to lead to pyrrolidinoindoles of interest . Involving benzene or pyridine rings in such transformations still remains challenging, however.…”