Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles via Indole Intermediates

Abstract

The previously unexplored Grignard addition to oxindoles provides a regiospecific approach to 2- and 2,3-disubstituted indole derivatives in high yields via a one-pot aromatization driven dehydration pathway. This method allows a convenient preparation of diallyl indoles that are used as ring-closing metathesis (RCM) precursors for the orthogonal synthesis of pyrido[1,2- a]indoles and carbazoles. The synthetic utility of this method is illustrated by the synthesis of a microtubulin inhibitor and naturally occurring carbazole alkaloids.

Ring Closing Metathesis Approach for the Synthesis of o‐Terphenyl Derivatives

“…Olefin metathesis based approaches have received considerable attention for creating aromatic and heteroaromatic compounds . In continuation of our work on RCM based approaches for the synthesis of biologically significant compounds,, we herein disclose the synthesis of o ‐terphenyl scaffolds using ring closing metathesis (RCM) as the key step. We have synthesized both symmetrical and unsymmetrical o ‐terphenyls using 1,2‐diphenylethane‐1,2‐dione (benzil) derivatives as our synthetic precursors.…”

Domino Relay Olefin Metathesis of Triallyl Oxindole and Indole Precursors to Access Cyclic Indoxyls and Carbazoles

“…Although ring‐closing metathesis (RCM) has emerged as one of the most powerful methods in organic synthesis, only few examples are reported for the construction of spirocyclic or fused 3‐oxindoles using RCM . Recently, we have reported RCM based strategies for the synthesis of fused indole heterocycles, carbazoles and pyridoindoles from isatins . The heteroaromatic carbazole is a privileged structural motif, found in a variety of natural products and bioactive molecules .…”

“…[22] Recently, we have reported RCM based strategies for the synthesis of fused indole heterocycles, carbazoles and pyridoindoles from isatins. [27] The heteroaromatic carbazole is a privileged structural motif, found in a variety of natural products and bioactive molecules. [28] In this work, we have employed isatins for assembling triallyl oxindoles and indoles as RCM precursors for the construction of C2-spirocyclic or fused indoxyls and functionalized carbazoles (Scheme 1).…”

“…[27] The addition of allylmagnesium bromide to 1,3-diallyl oxindoles 3 provided metathesis precursors triallyl indoles 4 in good yields (Scheme 2). [27] We then explored RCM of allyl oxindoles 2 and indoles 4 under standard metathesis conditions. We were intrigued with the outcome of different metathesis catalysts on these RCM precursors.…”

“…Further, N-allyl dihydro-carbazole derivatives 12 a and 12 b underwent DDQ mediated aromatization to obtain N-allyl carbazole derivatives 14 a and 14 b in 95 % and 90 % yields, respectively (Scheme 5). [27] Interestingly, when the triene 4 a was heated with 5 mol % Ru-III or Ru-I in CH 2 Cl 2 at 45°C, dimer 15 a along with the expected dihydro-carbazole 12 a were obtained ( Table 3). The conversion of 12 a to 15 a was monitored with time using 1 H-NMR of the crude reaction mixture (entries 1-4, Table 2).…”