[4 + 2] Annulation of 3-Nitroindoles with Alkylidene Malononitriles: Entry to Substituted Carbazol-4-amine Derivatives

Abstract

A general and transition-metal-free method for the construction of the carbazol-4-amine motif via a vinylogous Michael addition/cyclization/isomerization/elimination reaction of 3-nitroindoles with alkylidene malononitriles has been developed. This novel methodology allows the facile synthesis of a series of di- and trisubstituted carbazol-4-amine derivatives in moderate to good yields. A gram-scale experiment was successfully performed, highlighting the practicability of this method. Moreover, this strategy is also applicable to 3-nitrobenzothiophene, affording the corresponding dibenzo[ b, d]thiophen-1-amine derivatives in moderate yields.

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…The methodology reported by Yang and co-workers for the construction of substituted carbazol-4-amine derivatives 1011 exploited the vinylogous addition of alkylidene malononitriles 1009 to 3-nitroindoles 1010 , followed by cyclization/isomerization/elimination reactions (Scheme ). This base-activated one-pot procedure provided carbazolamines 1011 in moderate to good yields. The reaction was performed in an achiral environment because the aromatization step leads to the loss of the stereogenic centers.…”

Synthesis of Substituted Phthalimides via Ultrasound-Promoted One-Pot Multicomponent Reaction

“…It should be mentioned that US irradiation is a clean and efficient energy source for organic transformations, especially in the field of multicomponent reactions . The sonochemistry has several benefits such as enhancement of reaction rates, having lower costs, minimizing the side products, having more selectivity, and affording excellent yields that have led to widespread applications in many organic synthesis processes. − Moreover, 2-(4-oxo-2-thioxothiazolidin-5-ylidene)­acetates are unique starting materials for the diversity-oriented synthesis of chemical compounds, and they have been employed as electrophilic C2 synthons in several formal [2 + 3] and [2 + 4] cycloaddition reactions . Indeed, we reasoned that from the formal [4 + 2] annulation of starting materials, a spiro intermediate could be produced, , which after tandem CS 2 cleavage/aromatization/nucleophilic acyl substitution could be transformed to phthalimide derivatives.…”

Reactivity of 3-nitroindoles with electron-rich species

“…reported the (4+2) annulation of 3-nitroindoles 1 with alkylidene malononitriles 82 (Scheme 33). 50 In the presence of triethylamine, carbazol-4-amine derivatives 83 were obtained via a four-steps sequence involving (i) vinylogous Michael addition, (ii) cyclization, (iii) isomerization, (iv) nitrous acid elimination. This reaction was recently extended to different ,dicyanoalkenes 82.…”