(736g) Probing the Reacting Interface of a Liquid-Liquid Cu-Free Sonogashira Coupling

Hartman, R., New York University
Rizkin, B., NYU
This presentation summarizes our recent discoveries highlighted in Reaction Chemistry & Engineering on the mechanism of a biphasic Cu-free Sonogashira coupling [1]. We report the first ever direct probing of a cross-coupling in a liquid-liquid interface. A microfluidic device with in situ Raman spectroscopy was designed to confine an aqueous-organic interface [2]. The cross-coupling of an aryl alkyne with an aryl halide was accomplished using hydrophilic phosphine ligand. Directly probing the reacting interface yielded interesting information on the Pd/ligand lifecycle. Measurement of the Pd bond states present in organic bulk, interface, and aqueous bulk revealed that the cross-coupling takes place in the thin film. This validated previous kinetic models based on thin film theory [3, 4]. The Pd pre-catalyst salt was also found to dissociate within the reacting interface to form alkyne-PdII complexes. By process of elimination, the intermediates present in the interface support that either cationic or anionic deprotonation mechanisms govern the reaction. The presence of water also likely switches the rate determining step of the catalytic cycle from oxidative addition to the dissociation of the vinyl-PdII complex. Our discoveries could be applied to study other important carbon-carbon bond formations important in fine chemicals, materials, natural products, and pharmaceutical syntheses.

[1] Rizkin, B.A. and Hartman, R.L., React. Chem. Eng. (2018) DOI: 10.1039/C8RE00021B.

[2] Pinho, B. and Hartman, R.L., React. Chem. Eng., 2, 189 (2017).

[3] Sabio, J., Domier, R.C., Moore, J.N., Shaughnessy, K., and Hartman, R.L., Chem. Eng. Technol., 38, 1717-1725 (2015).

[4] Domier, R.C., Moore, J.N., Shaughnessy, K., and Hartman, R.L., Org. Process Res. Dev., 17 (10), 1262-1271 (2013).