A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15-C16 bond formation

作者：Carrillo Jokin; Gomez Alex; Costa Anna M^*; Fernandez Patricia; Isart Caries; Sidera Mireia; Vilarrasa Jaume

来源：Tetrahedron Letters, 2014, 55(33): 4623-4627.

DOI：10.1016/j.tetlet.2014.06.066

• Negishi cross-coupling reactions
• Screening of phosphine ligands
• Palmerolides
• Melanoma-inhibiting macrolides

The esterification of fragment C1-C8 (2) with fragment C16-C23 (3) to give iodo derivative 4, followed by a Pd-catalysed coupling with a C9-C15 fragment (7 or 8), may provide a common precursor of most palmerolides. Ligands and reaction conditions were exhaustively examined to perform the C15-C16 bond formation via Negishi reaction. With simple models, pre-activated Pd-Xantphos and Pd-DPEphos complexes were the most efficient catalysts at RT. Zincation of the C9-C15 fragment (8) and cross coupling with 4 required 3 equiv of t-BuLi, 10 mol % of Pd-Xantphos and 60 degrees C.

• 出版日期2014-8-13