Despite its great potential for the synthesis of valuable ketone products, the intermolecular hydroacylation of olefins with a broad scope of the alkene component is an unsolved problem. Here we present a method that promotes the hydroacylation of an exceptionally wide range of unactivated, terminal alkenes with salicyladehyde derivatives. Good to excellent yields, as well as high regioselectivities (linear products) were obtained and catalyst loadings as low as 2% [Rh] could be employed. Key for the observed reactivity and selectivities is a bulky, chiral phosphoramidite ligand whose mechanistic role was investigated by in situ 31P NMR spectroscopy and x-ray crystallography. Further mechanistic studies based on 2H-labeling and the 12C/13C kinetic isotope effect led to a detailed mechanistic proposal. The applicability of the catalytic method was demonstrated by the total synthesis of several recently isolated natural products.

Rh-catalyzed intermolecular hydroacylation of unactivated alkenes with salicylaldehydes: Mechanistic studies and application to natural product synthesis

243rd National Meeting (2012)

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