Advancing Metal-Free Asymmetric Hydrogenation: From FLP Catalyst Design to Synthetic Innovations

Abstract

Asymmetric hydrogenation (AH) is one of the most important transformations in organic synthesis, enabling efficient access to enantioenriched molecular building blocks used in pharmaceuticals, agrochemicals, and fine chemicals. AH is largely dominated by catalysts based on precious transition-metals. However, concerns over cost, supply, and toxicity have intensified interest in developing metal-free alternatives. Frustrated Lewis pairs (FLPs) – combinations of sterically encumbered Lewis acids and bases – have emerged as a promising metal-free platform for AH, yet they face significant challenges that must be addressed to enable widespread adoption. Our group aims to contribute to this effort by developing new chiral FLP catalysts for AH and exploring FLP-mediated transformations beyond hydrogenation. In this perspective, we summarize the state-of-the-art, outline current challenges, and discuss opportunities to advance the field towards sustainable catalysis.