The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis.
Herein, a research team led by Prof. YANG Weibo at Shanghai Institute of Materia Medica of Chinese Academy of Sciences reported a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.
This work was published online in Journal of the American Chemical Society on May 20. PhD student SONG Bichao at University of Chinese Academy of Sciences (Institute: Shanghai Institute of Materia Medica of Chinese Academy of Sciences) is the first author, Prof. YANG Weibo, Prof. XIA Yuanzhi at Wenzhou University, and Prof. Houk at University of California are the corresponding authors.
