Efficient and scalable asymmetric total synthesis of (−)-Emetine

In the course of a scalable asymmetric total synthesis of (−)-Emetine, cross-metathesis reaction promoted by ruthenium-based second-generation Grubbs catalyst, between ethyl acrylate and olefin intermediate 1, in THF in the presence of copper iodide as co-catalyst afforded, after HCl treatment, the desired adduct 2 in 85.3% yield on more than 800 grams scale (Scheme below). [1]

This additive has a strong effect on the ruthenium catalyst performance by increasing its lifetime and its activity, especially as phosphine scavenger leading to a (tricyclohexylphosphine)copper(I) iodide complex. [2] [3]

[1] M. Yamada, K. Azuma, I. Takizawa, Y. Ejima, M. Yamano, K. Satoh, T. Doi, H. Ueda, H. Tokuyama. Org. Process Res. Dev. 2023, 27, 343-357.

[2] K. Voigtritter, S. Ghorai, B. H. Lipshutz, J. Org. Chem. 2011, 76, 4697-4702.

[3] S. Byun, S. Park, Y. Choi, J. Y. Ryu, J. Lee, J.-H. Choi, S. Hong, ACS Catal. 2020, 10, 10592-10601.