(621a) Flexible Homogeneous Hydroformylation: On-Demand Tuning of Aldehyde Branching with a Cyclic Fluorophosphite Ligand

Hydroformylation is one of the most widely practiced homogeneous catalyzed reactions in industry. Aldehydes produced by hydroformylation are routinely used in commodity chemicals, fragrances, and pharmaceuticals. The degree of branching of the aldehydes and their derivatives, including alcohols, amines, and acids affect the final product properties and functions. Tuning aldehyde regioselectivity via homogeneous hydroformylation of olefins using the same catalyst system remains a challenge. Here, we present flexible rhodium (Rh)-catalyzed hydroformylation of 1-octene and propylene with a bulky cyclic monofluorophosphite ligand L (Figure 1A.). Hydroformylation of 1-octene with Rh/L catalyst achieves, for the first time, turnover frequencies exceeding 75,000 mol ald.mol Rh^-1.h^-1 (at 30% conversion) in segmented flow, while enabling access to an unmatched tuneable aldehyde branching (0.06<linear/branched<15) with the same ligand L. Our mechanistic studies demonstrate that L provides a viable alternative to traditional bidentate phosphine/phosphite ligands for high activity with the added benefit of tuneable selectivity. The unique high flexibility feature of L over traditional linear- or branched-selective ligands allows for on-demand tuning from 90% linear to 75% branched aldehyde in a continuous flow reactor without the need for ligand/catalyst alteration. (Figure 1B.) The high turnover frequencies obtained with L in flow will enhance the economics of the production of aldehydes and their isotopically labelled analogues by significantly reducing the reaction time, thereby enabling better utilization of the increasingly expensive Rh catalyst and minimizing the need for catalyst/ligand separation and recycle.

Figure 1. A) Linear- and branched-selective hydroformylation of 1-octene with L. B) Continuous, on-demand switching from predominantly linear to branched aldehyde in the flow reactor. P_total=24.13 bar, t_R=15 min, [1-octene]=0.05 M in toluene, and [L]=10 mM.