C-H Functionalization of Imidazo[1,5- a]pyridines: A Metal-Free Approach for Methylene Insertion to Access C(sp2)-C(sp3)-H-C(sp2) Bond Formation

Shivangani Mahajan; Sanghapal D Sawant

doi:10.1021/acsomega.4c03823

C-H Functionalization of Imidazo[1,5- a]pyridines: A Metal-Free Approach for Methylene Insertion to Access C(sp²)-C(sp³)-H-C(sp²) Bond Formation

ACS Omega. 2024 Dec 5;9(50):49071-49080. doi: 10.1021/acsomega.4c03823. eCollection 2024 Dec 17.

Authors

Shivangani Mahajan^{1

2}, Sanghapal D Sawant^{1

3

2}

Affiliations

¹ Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
² Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
³ Organic Chemistry Division, CSIR-National Chemical Laboratory, Pune 411008, India.

Abstract

Formaldehyde has been used as a solvent and a source of carbon to insert a methylene group for bridging two imidazo[1,5-a]pyridine molecules without using any metal catalysis. This strategy has been extended on other alkyl-, aryl-, and heteroaryl aldehydes as well. This C(sp²)-C(sp³)-H-C(sp²) bond forming reaction proceeds via C(sp²)H functionalization of imidazo[1,5-a]pyridine and was applied on a wide range of substrates offering moderate to good yields of methylene-bridged/inserted bis-imidazo[1,5-a]pyridines. Most importantly, as an application, the bis-heteroarene product has been demonstrated as a ligand. The ligand-like behavior of bis-imidazo[1,5-a]pyridines has been demonstrated as an extension of current methodology. This reaction works well at the gram scale level.