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Synthesis
DOI: 10.1055/s-0042-1751574
DOI: 10.1055/s-0042-1751574
paper
Transition-Metal-Free Selective Halocyclization of N-Alkoxy Amides: Synthesis of N-Alkoxy Lactams and Oximinolactones
This research has been performed as a part of the Ph.D. work of Sunil Dattatray Chakave, affiliated to the Mangalore University, funded by Syngenta Research & Technology Centre, Goa.
Abstract
A new method for the synthesis of N-alkoxy lactams and oximinolactones, involving the selective N-cyclization and O-cyclization of unsaturated N-alkoxy amides, is presented. This approach features mild reaction conditions and no requirement for transition-metal catalysts. The protocol demonstrates a wide range of applicability in 5-exo-trig and 6-exo-trig cyclization, accommodating chloro, bromo, and iodo electrophiles. The N-cyclization process can be achieved in the presence of strong lithium base such as LiHMDS or n-BuLi, while the O-cyclization occurs spontaneously without the addition of any base. Mechanistic studies reveal the N-cyclization reactions proceed through cyclic lithium intermediates, as confirmed by FT-IR studies and control experiments, which contribute to the N-selectivity. The current methodology was successfully used in synthesis of natural product (E/Z) des-hydroxy triticone A and B.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751574. Included are characterization data of 1a–z, 2a–s, 3a–p; 1H, 13C, and 19F NMR spectra (PDF).
- Supporting Information
Publication History
Received: 24 January 2024
Accepted after revision: 28 February 2024
Article published online:
20 March 2024
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