Binuclear Pd(I)–Pd(I) Catalysis Assisted by Iodide Ligands for Selective Hydroformylation of Alkenes and Alkynes

Since
its discovery in 1938, hydroformylation has been thoroughly
investigated and broadly applied in industry (>107 metric
ton yearly). However, the ability to precisely control its regioselectivity
with well-established Rh- or Co-catalysts has thus far proven elusive,
thereby limiting access to many synthetically valuable aldehydes.
Pd-catalysts represent an appealing alternative, yet their use remains
sparse due to undesired side-processes. Here, we report a highly selective
and exceptionally active catalyst system that is driven by a novel
activation strategy and features a unique Pd­(I)–Pd­(I) mechanism,
involving an iodide-assisted binuclear step to release the product.
This method enables β-selective hydroformylation of a large
range of alkenes and alkynes, including sensitive starting materials.
Its utility is demonstrated in the synthesis of antiobesity drug Rimonabant
and anti-HIV agent PNU-32945. In a broader context, the new mechanistic
understanding enables the development of other carbonylation reactions
of high importance to chemical industry.