Alkylation of 1,2,5-Trisubstituted Pyrroles with Donor-Acceptor Cyclopropanes
Abhijit Gogoi1, Kriti Yadav1, Bhaskar Kundu1
1Department of Chemical Sciences, Tezpur University, Napaam, Sonitpur, Assam 784028, India.
Abstract:
Despite their inherently high nucleophilicity, pyrroles have rarely been explored in Friedel-Crafts-type alkylation reactions with donor-acceptor cyclopropanes (DACs). Herein, we report the first examples of such reactions of 1,2,5-trisubstituted pyrroles using DACs. Catalyzed by Sc(OTf)3, the reaction provides efficient access to 1,2,3,5-tetrasubstituted pyrroles─an important class of bioactive compounds─in yields up to 93%. As anticipated, the C3 position of the pyrrole consistently outcompetes other potential nucleophilic sites, including tethered electron-rich arenes and indoles. Thus, this work not only expands the synthetic utility of DACs but also offers a powerful new tool to access diverse and complex pyrrole scaffolds.
Related Concept Videos
Cycloaddition Reactions: MO Requirements for Thermal Activation
Cycloaddition Reactions: Overview
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Nucleophilic Aromatic Substitution: Elimination–Addition
Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.

![[DPEPhosbcpCu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59739.jpg&w=3840&q=50)
