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Synthesis of 2-BMIDA Indoles via Heteroannulation: Applications in Drug Scaffold and Natural Product Synthesis

George E. Bell, James W. B. Fyfe, Eva M. Israel, Alexandra M. Z. Slawin, Matthew Campbell and Allan J. B. Watson*

*EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, United Kingdom, Email: aw260st-andrews.ac.uk

G. E. Bell, J. W. B. Fyfe, E. M. Israel, A. M. Z. Slawin, M. Campbell, A. J. B. Watson, Org. Lett., 2022, 24, 3024-3027.

DOI: 10.1021/acs.orglett.2c00959


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Abstract

A Pd-catalyzed heteroannulation approach provides highly functionalized 2-borylated indole scaffolds with complete control of regioselectivity. The utility of the process is demonstrated in the synthesis of borylated sulfa drugs and in the concise synthesis of the Aspidosperma alkaloid Goniomitine.

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General Procedure

An oven-dried 5 mL microwave vial was charged with Pd(dppf)Cl2 (7.3 mg, 10 Ámol, 5 mol%), propyne boronic acid MIDA ester (39.0 mg, 0.2 mmol, 1.0 equiv.), 2-iodoaniline (52.6 mg, 0.24 mmol, 1.2 equiv.), and NaOAc (41.0 mg, 0.5 mmol, 2.5 equiv.). The vial was capped and purged with N2 before DMSO (2 mL, 0.1 M) was added via syringe. The mixture was then stirred at 80░C for 18 hours. The vial was allowed to cool to room temperature, decapped, and diluted with EtOAc (10 mL). The mixture was then washed with 10% aqueous LiCl solution (2 x 5 mL). The organic extract was dried over Na2SO4, filtered, and concentrated to give a residue that was purified by flash column chromatography (silica gel, 5-20% MeCN in DCM) to give the product as an off-white solid (48 mg, 84%).


Key Words

indoles


ID: J54-Y2022