3-Amino-1-methyl-1H-pyridin-2-one as Inbuilt Directing Group for Additive-Free Late-Stage ortho-Amination under Copper Catalysis towards Biologically Relevant Molecules

Priyadarshi Manna; Arunima Chatterjee; Mrinalkanti Kundu; G. Prabhakar Rao; Rusmita Mukherjee; Swarnali Podder; Bandita Datta; Susanta Adhikari

doi:10.1055/s-0040-1720160

Synthesis, Table of Contents

Synthesis 2025; 57(06): 1199-1212
DOI: 10.1055/s-0040-1720160

paper

3-Amino-1-methyl-1H-pyridin-2-one as Inbuilt Directing Group for Additive-Free Late-Stage ortho-Amination under Copper Catalysis towards Biologically Relevant Molecules

Authors

Priyadarshi Manna

^aTCG Lifesciences Pvt. Ltd., BN-7, Sector-V, Salt Lake City, Kolkata 700091, India

^bDepartment of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700009, India
Arunima Chatterjee

^aTCG Lifesciences Pvt. Ltd., BN-7, Sector-V, Salt Lake City, Kolkata 700091, India

^cDepartment of Chemistry, Amity Institute of Applied Sciences, Action Area II, Newtown, Kolkata 700135, India
Mrinalkanti Kundu∗

^aTCG Lifesciences Pvt. Ltd., BN-7, Sector-V, Salt Lake City, Kolkata 700091, India
G. Prabhakar Rao

^aTCG Lifesciences Pvt. Ltd., BN-7, Sector-V, Salt Lake City, Kolkata 700091, India
Rusmita Mukherjee

^aTCG Lifesciences Pvt. Ltd., BN-7, Sector-V, Salt Lake City, Kolkata 700091, India
Swarnali Podder

^aTCG Lifesciences Pvt. Ltd., BN-7, Sector-V, Salt Lake City, Kolkata 700091, India

^cDepartment of Chemistry, Amity Institute of Applied Sciences, Action Area II, Newtown, Kolkata 700135, India
Bandita Datta

^cDepartment of Chemistry, Amity Institute of Applied Sciences, Action Area II, Newtown, Kolkata 700135, India
Susanta Adhikari∗

^bDepartment of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700009, India

Abstract

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Abstract

Arylamines are essential building blocks that are found in biologically important substances, agrochemicals, and natural products. One of the C–N bond formation methods that is conveniently step- and atom-economical is the C–H bond activated amination process. We divulge an operationally simple and general method using 3-amino-1-methyl-1H-pyridin-2-one (AMP) as inbuilt directing group (DG) for additive-free, copper(II)-catalyzed ortho amination of β-C(sp²)–H bonds of arenes and heteroarenes. Notably, this cross dehydrogenative amination reaction exhibits a broad scope regarding amine coupling partners, including heterocyclic amines, secondary aliphatic amines, and cyclic amides, with exclusive site selectivity and excellent functional group tolerance. Moreover, implementing this methodology, we could also synthesize medicinally important compounds to showcase the suitability of this inbuilt DG for late-stage functionalization.

Key words

C(sp²)–H amination - amidation - external-ligand-free - additive-free - Cu(OAc)₂ catalysis - late-stage functionalization

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References

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