Electrophilic Halospirocyclization of N-Benzylacrylamides to Access 4-Halomethyl-2-azaspiro[4.5]decanes

Zhongyi Zhang; Wei Zhang; Zhong-Wei Hou; Pinhua Li; Lei Wang

doi:10.1021/acs.joc.3c01315

Electrophilic Halospirocyclization of N-Benzylacrylamides to Access 4-Halomethyl-2-azaspiro[4.5]decanes

J Org Chem. 2023 Oct 6;88(19):13610-13621. doi: 10.1021/acs.joc.3c01315. Epub 2023 Sep 11.

Authors

Zhongyi Zhang^{1

2}, Wei Zhang¹, Zhong-Wei Hou¹, Pinhua Li^{2

3}, Lei Wang^{1

2

3}

Affiliations

¹ Advanced Research Institute and School of Pharmaceutical Sciences, Taizhou University, Jiaojiang 318000, Zhejiang, P. R. China.
² Department of Chemistry, Huaibei Normal University, Huaibei 235000, Anhui, P. R. China.
³ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032, P. R. China.

PMID: 37694951
DOI: 10.1021/acs.joc.3c01315

Abstract

An electrophilic spirocyclization of N-benzylacrylamides with N-halosuccinimides (NXS) as the halogenating reagents has been developed. This reaction is carried out at room temperature under simple conditions without relying on metal reagents, photochemistry, or electrochemistry, providing a fast and efficient route to synthesize a wide variety of 4-halomethyl-2-azaspiro[4.5]decanes with satisfactory yields. The approach is further highlighted through gram-scale synthesis and diverse transformations of the spiro products.