Discovery of an Acid-Promoted [3+2] Cyclodimerization of 3-Vinylindoles and the Development of a General Lewis Acid Catalyzed Process

Abstract

A novel proton-catalyzed [3+2]-type cyclodimerization of 3-vinylindoles is reported leading to fused cyclopenta [b]indoles, contrasting to the normal [4+2]-cycloaddition pathway. The development of a general, high yielding version of the reaction catalyzed by zinc bromide in toluene is described.

Shortcut Approach to Cyclopenta[b]indoles by [3+2] Cyclodimerization of Indole-Derived Cyclopropanes

“…Meanwhile, related [3+2] cyclodimerizations of 3-vinylindoles lead to different stereochemical results. 14,16 Figure 1 Representative HMBC (a) and NOE (b) responses for dimer 2a…”

Highly efficient [3 + 2] reaction of 3-vinylindoles with 3-indolylmethanols by Brønsted-acid catalysis

“…Recently, James McNulty and co-workers described a metal salt catalyzed dimerization of 3-vinylindoles. 8 Inspired by this, and our previous works about using 3-indolylmethanols as alkylation reagents, we rationally designed a [3 + 2] reaction of 3-vinylindoles 9 and 3-indolylmethanols 10 to synthesize the 2,3-BIMs (Scheme 1). According to this rout, the 3-indolylmethanols 1 are dehydrated and produce the active vinylogous imino intermediates I in the promotion of an acid catalyst.…”

Enantioselective Domino Reaction of 3-Vinylindole and p-Quinone Methides Enabled by Chiral Imidodiphosphoric Acids: Asymmetric Synthesis of Multisubstituted 3-Indolyl Cyclopenta[b]indoles

“…In the past decade, several asymmetric methods for enantio-rich 3-indolyl cyclopenta­[ b ]­indoles have been established. − In 2012, Guo’s group reported an asymmetric, three-component cascade reaction of 3-indolylmethanol, α,α-disubstituted aldehydes, and indoles toward 3-indolyl cyclopenta­[ b ]­indoles with excellent enantioselectivities . Subsequently, Shi’s group contributed 3-indolyl cyclopenta­[ b ]­indole architectures with good to high enantioselectivities via chiral phosphoric acid-catalyzed [3+2] cycloadditions of 3-vinylindoles with 3-indolylmethanol .…”

“…Subsequently, Shi’s group contributed 3-indolyl cyclopenta­[ b ]­indole architectures with good to high enantioselectivities via chiral phosphoric acid-catalyzed [3+2] cycloadditions of 3-vinylindoles with 3-indolylmethanol . It is worth mentioning that a [3+2] dimerization of 3-vinylindoles under Lewis acid or TFA catalysis could give the corresponding 3-indolyl cyclopenta­[ b ]­indoles. , In fact, this is the most effective method for synthesizing 3-indolyl cyclopenta­[ b ]­indoles. However, due to the high reaction energy barrier, as well as the difficulty in separating its products via HPLC, an asymmetric version has not yet been reported.…”