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DOI: 10.1055/s-0040-1720160
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
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 functionalizationPublication History
Received: 30 October 2024
Accepted after revision: 11 December 2024
Article published online:
21 January 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
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References
- 1a Boaen NK, Hillmyer MA. Chem. Soc. Rev. 2005; 34: 267
- 1b Hili R, Yudin AK. Nat. Chem. Biol. 2006; 2: 284
- 1c Rappoport Z. The Chemistry of Anilines 2007; 1180
- 1d Ricci A.; Amino Group Chemistry: From Synthesis to the Life Sciences; Wiley-VCH: Weinheim, 2008.
- 1e Manfredi N, Cecconi B, Abbotto A. Eur. J. Org. Chem. 2014; 7069
- 1f Novak M, Zhang Y. Adv. Phys. Org. Chem. 2012; 46: 121
- 2 For a review, see: Corpet M, Gosmini C. Synthesis 2014; 46: 2258
- 3a Lam PY. S, Clark CG, Saubern S, Adams J, Winters MP, Chan DM. T, Combs A. Tetrahedron Lett. 1998; 39: 2941
- 3b Chan DM. T, Monaco KL, Wang RP, Winters MP. Tetrahedron Lett. 1998; 39: 2933
- 3c Paul F, Patt J, Hartwig JF. J. Am. Chem. Soc. 1994; 116: 5969
- 3d Guram AS, Buchwald SL. J. Am. Chem. Soc. 1994; 116: 7901
- 3e Ullmann F. Ber. Dtsch. Chem. Ges. 1903; 36: 2382
- 3f Zaitsev VG, Shabashov D, Daugulis O. J. Am. Chem. Soc. 2005; 127: 13154
- 3g Rouquet G, Chatani N. Angew. Chem. Int. Ed. 2013; 52: 11726
- 4a Evano G, Blanchard N, Toumi M. Chem. Rev. 2008; 108: 3054
- 4b Beletskaya IP, Cheprakov AV. Organometallics 2012; 31: 7753
- 4c Van der Eycken E, Bariwal J. Chem. Soc. Rev. 2013; 42: 9283
- 5a Patel P, Chang S. ACS Catal. 2015; 5: 853
- 5b Park J, Chang S. Angew. Chem. Int. Ed. 2015; 54: 14103
- 5c Shin K, Baek Y, Chang S. Angew. Chem. Int. Ed. 2013; 52: 8031
- 5d Yu S, Wan B, Li X. Org. Lett. 2013; 15: 3706
- 6a John A, Nicholas KM. J. Org. Chem. 2011; 76: 4158
- 6b Uemura T, Imoto S, Chatani N. Chem. Lett. 2006; 35: 842
- 6c Shang M, Sun S.-Z, Dai H.-X, Yu J.-Q. J. Am. Chem. Soc. 2014; 136: 3354
- 6d Yoo EJ, Ma S, Mei T.-S, Chan KS. L, Yu J.-Q. J. Am. Chem. Soc. 2011; 133: 7652
- 7a Tran LD, Roane J, Daugulis O. Angew. Chem. Int. Ed. 2013; 52: 6043 ; Angew. Chem. 2013, 125, 6159
- 7b Roane J, Daugulis O. J. Am. Chem. Soc. 2016; 138: 4601
- 7c Naidu SR, Reddy GM, Sarma MH. ChemistrySelect 2018; 3: 11148
- 7d Singh H, Sen C, Suresh E, Panda AB, Ghosh SC. J. Org. Chem. 2021; 86: 3261
- 7e Kumar M, Verma S, Mishra PK, Verma AK. J. Org. Chem. 2019; 84: 8067
- 7f Zhao H.-Y, Wang H.-Y, Mao S, Xin M, Zhang H, Zhang S.-Q. Org. Biomol. Chem. 2017; 15: 6622
- 7g Kathiravan S, Suriyanarayanan S, Nicholls IA. Org. Lett. 2019; 21: 1968
- 8a Pati TK, Debnath S, Kundu M, Khamrai U, Maiti DK. Org. Lett. 2018; 20: 4062
- 8b Mitra T, Kundu M, Roy B. J. Org. Chem. 2020; 85: 345
- 8c Pati TK, Ajarul Sk, Kundu M, Tyade D, Khamrai U, Maiti DK. J. Org. Chem. 2020; 85: 8563
- 8d Manna P, Kundu M, Roy A, Adhikari S. Org. Biomol. Chem. 2021; 19: 6244
- 8e Hajra AK, Ghosh P, Roy C, Kundu M, Ghosh S, Das S. Org. Biomol. Chem. 2024; 22: 6617
- 8f Mondal B, Ghosh P, Kundu M, Das S. Org. Biomol. Chem. 2021; 19: 1604
- 8g Mondal B, Ghosh P, Kundu M, Das TK, Das S. Org. Biomol. Chem. 2021; 19: 360
- 9a Ma JL, Zhou XM, Guo PH, Cheng HC, Ji HB. Chin. J. Chem. 2022; 40: 1204
- 9b Lee W-CC, Shen Y, Gutierrez DA, Li JJ. Org. Lett. 2016; 18: 2660
- 9c Sarkar W, Mishra A, Bhowmik A, Deb I. Org. Lett. 2021; 23: 4521
- 9d Wang Z, Kuninobu Y, Kanai M. Org. Lett. 2014; 16: 4790
- 10a Semple G, Ashworth DM, Baker GR, Batt AR, Baxter AJ, Benzies DW. M, Elliot LH, Evans MD, Franklin RJ, Hudson P, Jenkins PD, Pitt GR, Rooker DP, Sheppard A, Szelke M, Yamamoto S, Isomura Y. Bioorg. Med. Chem. Lett. 1997; 7: 1337
- 10b Kusakabe K, Tada Y, Iso Y, Sakagami M, Morioka Y, Chomei N, Shinonome S, Kawamoto K, Takenaka H, Yasui K, Hamana H, Hanasaki K. Bioorg. Med. Chem. 2013; 21: 2045
- 11 Caraballo R, Larsson M, Nilsson SK, Ericsson M, Qian W, Nguyen TN. P, Kindahl T, Svensson R, Saar V, Artursson P. Eur. J. Med. Chem. 2015; 103: 191
- 12 Zhao D, Luo H, Chen B, Chen W, Zhang G, Yu Y. J. Org. Chem. 2018; 83: 7860
- 13 Kinetic solubility (in PBS, pH 7.4): >200 μM; liver microsomal stability CLint, app = 20.16, <14.44, and 22.89 μL/min/mg in human, rat, and mouse, respectively.