Highly Stereoselective Palladium Catalysed Cross-Coupling Approaches to the Total Synthesis of Phthoxazolin A

The first total synthesis of racemic Phthoxazolin A 4 is described, involving a convergent series of palladium cross-coupling reactions to stereoselectively construct the Z,Z,E-trienyl unit. The most important steps involve using vinylboronate pinacol ester 1 as a vinyl dianion equivalent, by employing a Heck coupling of a vinyl iodide 9 with the vinyl boronate 1, followed by a deboronation–iodination sequence with inversion of alkene stereochemistry to provide a new alkenyl iodide 6. Final Stille coupling of the vinyl iodide 6 with an oxazolyl alkenyl stannane 40 provided Phthoxazolin A 4.