A Practical Protocol for the Auto‐Tandem Isomerizing Hydroformylation: Systematic Optimization and Transferability Across Different Substrates

ABSTRACT

Rh/BiPhePhos‐catalyzed isomerizing hydroformylation is an efficient strategy for converting internal olefins into valuable linear aldehydes through an auto‐tandem process combining double bond isomerization and hydroformylation. Despite extensive research, previous studies have mainly focused on ligand development or individual reaction parameters, while systematic optimization of interacting reaction conditions remains comparatively rare. In this work, the isomerizing hydroformylation of 2‐octene was systematically investigated using a design of experiments approach to identify key parameter interactions governing catalytic activity and linear selectivity. Two sets of optimized conditions were developed. Set 1: maximizing catalytic efficiency (118°C, 12 bar CO/H ₂ , and 0.47 mol% catalyst), an l / b ‐ratio of 20.9 was obtained with a TOF ₂₀ of 272.7 h ⁻¹ . Set 2: provided particularly high l / b ‐ratios (105°C, 5 bar CO/H ₂ , and 0.1 mol% catalyst) provided even higher l / b ‐ratios of up to 27.4 at a conversion of 85.6%. Additional substrates like, 2‐undecene yielded l / b ‐ratios of up to 30.2, while substrates requiring further isomerization steps, like 3‐hexene, afforded l / b ‐ratios up to 34.3. Even for the challenging renewable substrate methyl oleate, linear aldehyde yields up to 35.8% were achieved, representing the highest value reported for this auto‐tandem catalysis. This study establishes systematically optimized reaction conditions that expand the practical applicability of BiPhePhos‐based isomerizing hydroformylation.