Cleavage and reassembly of 1,3-dicarbonyls with enaminones to synthesize highly functionalized naphthols

Abstract

The cleavage of carbon-carbon bonds and their subsequent reassembly into highly functionalized and useful molecules in an atom-efficient manner has always been a central focus in the realm of organic synthesis. In this report, we describe the construction of highly functionalized naphthol esters via a tandem reassembly process, driven by Ullmann-type coupling of enaminones and 1,3-dicarbonyl compounds. Mechanistic investigations suggest the involvement of C(sp2)-C(sp3) coupling, cyclization, two acyl migrations, aromatization, and additional transformations within this tandem sequence. This methodology offers several notable advantages, such as the use of inexpensive and easily accessible starting materials, the elimination of the need for expensive transition metal catalysis, simple operation in the atmosphere, exceptional compatibility with a wide range of substrates, and ease of conversion into drug scaffolds.Agency for Science, Technology and Research (A*STAR)Nanyang Technological UniversitySubmitted/Accepted versionWe gratefully acknowledge the financial support from the Natural Science Basic Research Plan of Shaanxi Province (2023-JC-YB-109), the Fundamental Research Funds for the Central Universities (D5000210701), and the Distinguished University Professor grant (Nanyang Technological University) and the Agency for Science, Technology, and Research (A*STAR) under its MTC Individual Research Grant (M21K2c0114) and RIE2025 MTC Programmatic Fund (M22K9b0049) for T.-P. L