Synthesis 2021; 53(21): 4110-4116
DOI: 10.1055/a-1532-8656
paper

Total Synthesis of Methyl 1,5,8-Trimethoxy-1H-isochromene-3-carboxylate and Its Derivatives via Palladium-Catalyzed Annulation of 2-Alkynylbenzaldehydes

Nolan Nardangeli
a   Department of Chemistry and Centre for Biotechnology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario L2S 3A1, Canada
,
Jared Thomson
a   Department of Chemistry and Centre for Biotechnology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario L2S 3A1, Canada
,
b   Laboratory for Biomimetic Chemistry, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, Croatia
,
a   Department of Chemistry and Centre for Biotechnology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario L2S 3A1, Canada
› Author Affiliations
We are grateful to the following agencies for financial support of this work: the Natural Sciences and Engineering Research Council of Canada (NSERC; Idea to Innovation and Discovery Grants), the Canada Research Chair Program, the Canada Foundation for Innovation (CFI), TDC Research, Inc., the TDC Research Foundation, the Ontario Partnership for Innovation and Commercialization (OPIC), and The Advanced Biomanufacturing Centre (Brock University).


Abstract

A 7-step total synthesis of methyl 1,5,8-trimethoxy-1H-isochromene-3-carboxylate and a 5-step synthesis of its C-3 derivatives are reported. Sonogashira coupling of 2-halobenzaldehydes with terminal acetylenes was employed to access 2-alkynylbenzaldehydes, which underwent a Pd-catalyzed annulation to afford the corresponding isochromene-containing products.

Supporting Information



Publication History

Received: 30 April 2021

Accepted after revision: 21 June 2021

Accepted Manuscript online:
21 June 2021

Article published online:
27 July 2021

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