Palladium-catalysed alkynylations of 2-pyrone (pyran-2-one) halides

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 Cut, 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.