Palladium-Catalysed Alkynylations of 2-Pyrone (Pyran-2-one) Halides

Abstract

The 2-pyrone sub-unit is found in a large number of natural products possessing broad-spectrum biological activity. As such, efficient synthetic methods are required to enable facile access to substituted 2-pyrone derivatives. Important conditions for the Sonogashira alkynylation of 4-bromo-6-methyl-2-pyrone (3a) have been developed, and compared against Negishi’s methodology. The best conditions for Sonogashira alkynylation was found to be the use of Pd/C with added Ph₃P as the catalyst, in the presence of catalytic CuI, in a mixture of MeCN and Et₃N at reflux. Using Negishi’s standard conditions, terminal alkynylzinc reagents, generated in situ from terminal alkynes with LDA or n-BuLi and subsequent reaction with anhydrous ZnBr₂, were reacted with 3a at room temperature using Pd(PPh₃)₄ as the catalyst in THF.

Key words

palladium - Negishi reaction - Sonogashira reaction - 2-pyrones

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21

We have employed these conditions in Sonogashira reactions of 5-bromo-2-pyrone and 3,5-dibromo-2-pyrone with several terminal alkynes with similar success. The latter reaction is regioselective for the 3-position, previously noted in Ref. [8b]