Kinetically controlled stereoselective access to branched 1,3-Dienes by Ru-Catalyzed remote Conjugative Isomerization
Dienes are important structural motif in numerous natural products/biologically active molecules and can serve as building blocks for the synthesis of a broad range of compounds.1 Although a plethora of synthetic processes have been developed their stereoselective synthesis still represents a considerable challenge.2 Surprisingly examples of conjugated branched 1,3-dienes obtained by alkene isomerization are underdeveloped. Following such a mild redox-economic synthetic methodology could offer great flexibility allowing for their selective synthesis.3,4
Herein we describe an operationally simple Ru-catalyzed isomerization reaction that affords stereoselectively branched 1,3-dienes by conjugation of two minimally differentiated remote alkenes.5 These kinetic products can be obtained in high yield, regio- and stereoselectivity. A variety of functional groups and heterocycles showed to be well tolerated and the isomerization can be sustained over several methylene units. Mechanistic investigations support a metal-hydride mechanism consisting of iterative migratory insertion/β-H elimination, which is initiated preferentially at the terminal olefinic site. The potential of the method has been demonstrated by two sequential multimetallic selective catalytic sequences using [Ru/Cu] and [Ru/Rh] couples.
[1] Norman Herrmann, Dennis Vogelsang, Arno Behr, Thomas Seidensticker, ChemCatChem, 2018, 10, 5342–5365.
[2] Raquel Soengas, Humberto Rodríguez–Solla, Molecules, 2021, 26, No. 249.
[3] Heiko Sommer, Francisco Juliá−Hernández, Ruben Martin, Ilan Marek, ACS Cent. Sci., 2018, 4, 153−165.
[4] Nicka Chinkov, Swapan Majumdar, Ilan Marek, J. Am. Chem. Soc., 2002, 124, 10282–10283.
[5] Simone Scaringi, Clément Mazet, ACS Catal., 2021, 11, 7970–7977.