Lewis Acid‐Catalyzed (3+2) Cycloaddition of 2‐Indolylmethanols with β,γ‐Unsaturated α‐Ketoesters

Abstract

A Lewis acid-catalyzed (3 + 2) cycloaddition of 2-indolylmethanols with β,γ-unsaturated α-ketoesters was established, which afforded a series of cyclopenta [b]indoles in overall high yields (up to 98 %) with excellent diastereoselectivities (up to > 95 : 5 dr). This reaction not only represents the first C3nucleophilic (3 + 2) cycloaddition of 2-indolylmethanols, but also provides a good example for (2 + n) cycloaddition of β,γunsaturated α-ketoesters, which will add new contents to the chemistry of 2-indolylmethanols. In addition, this approach provides an atom-economic and useful method for the construction of biologically important cyclopenta[b]indole scaffold.

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles

“…Among these protocols, the (3+2) annulation of 2-indolylmethanols and olefins is an atom-economic strategy for the synthesis of these fused indole derivatives [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. In recent years, 2-indolylmethanols have become intriguing reactants because of their unique properties of electrophilicity and nucleophilicity at the C3 position [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Despite these impressive achievements, a more efficient and diversity-oriented approach for cyclopenta[ b ]indoles is still required.…”

Ag2O-Induced Regioselective Huisgen Cycloaddition for the Synthesis of Fully Substituted Pyrazoles as Potential Anticancer Agents

“…Indicated by the type II frontier molecular orbital theory of 1,3-dipolar [3 + 2] cycloaddition, the similarity of lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energies in dipole and dipolarophile contributed to both HOMO dipole –LUMO dipolarophile and HOMO dipolarophile –LUMO dipole interactions, which may be important in determining reactivity and regiochemistry. In recent years, a large number of reactions through [3 + 2] cycloaddition have been reported . Hence, two kinds of pyrazole configuration would be obtained in the cycloaddition of hydrazonyl chloride and δ-acetoxy allenoate.…”

Construction of heterocycle-fused tetrahydrocarbazoles through a formal [3 + 3]-annulation of 2-indolylmethanols with para-quinone methides

“…Since our expertise lies in the area of p -quinone methide ( p -QM) chemistry, 12 we thought of utilizing this chemistry for this purpose. Herein, we describe an acid-mediated direct annulation reaction between 3-indolyl- p -quinone methides and 2-indolylmethanols 13 leading to a wide range of unsymmetrical tetrahydroindolo[2,3- b ]carbazoles. This general protocol was elaborated to the synthesis of other heterocycle-fused tetrahydrothieno carbazoles, which have found a lot of applications in electronic materials.…”