Copper-Catalyzed Intramolecular Olefinic C(sp2)-H Amidation for the Synthesis of γ-Alkylidene- γ-lactams

Kanako Nozawa-Kumada; Masahito Hayashi; Eunsang Kwon; Masanori Shigeno; Akira Yada; Yoshinori Kondo

doi:10.3390/molecules28186682

Copper-Catalyzed Intramolecular Olefinic C(sp²)-H Amidation for the Synthesis of γ-Alkylidene- γ-lactams

Molecules. 2023 Sep 18;28(18):6682. doi: 10.3390/molecules28186682.

Authors

Kanako Nozawa-Kumada^{1

2}, Masahito Hayashi¹, Eunsang Kwon^{3

4}, Masanori Shigeno^{1

5}, Akira Yada², Yoshinori Kondo¹

Affiliations

¹ Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Miyagi, Japan.
² Interdisciplinary Research Center for Catalytic Chemistry, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba 305-8565, Ibaraki, Japan.
³ Endowed Research Laboratory of Dimensional Integrated Nanomaterials, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Miyagi, Japan.
⁴ Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Miyagi, Japan.
⁵ Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Kawaguchi 332-0012, Saitama, Japan.

Abstract

Herein, we report the copper-catalyzed dehydrogenative C(sp²)-N bond formation of 4-pentenamides via nitrogen-centered radicals. This reaction provides a straightforward and efficient preparation method for γ-alkylidene-γ-lactams. Notably, we could controllably synthesize α,β-unsaturated- or α,β-saturated-γ-alkylidene-γ-lactams depending on the reaction conditions.

Keywords: C(sp2)–H amidation; copper-catalyst; cross-dehydrogenative coupling; nitrogen-centered radical; γ-alkylidene-γ-lactam.

Grants and funding

This work was financially supported by JSPS KAKENHI Grant-in-Aid for Scientific Research (C) (Grant no. 21K06470 to K.N.K.) and Transformative Research Areas (A) Digi-TOS (Grant no. 21H05224 to A.Y.). This work was also supported by Takeda Science Foundation, the Iwatani Naoji Foundation, Astellas Foundation for Research on Metabolic Disorders, SEI Group CSR Foundation, the Uehara Memorial Foundation to K.N.K. and JST, the establishment of university fellowships towards the creation of science technology innovation (Grant no. JPMJFS2102 to M.H.).