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Catalytic Directing Groups in Hydroformylation

“Synthesis of Quaternary Carbon Centers via Hydroformylation”  Sun, X.; Frimpong, K.; Tan, K. L. J. Am. Chem. Soc. 2010, 132, 11841.  DOI: 10.1021/ja1036226

Just as the advent of protecting groups opened up new chemical space accessible by current synthetic techniques, so too did the advent of the directing group.  Both however come with the downside of often requiring additional synthetic steps for the installation and removal of these groups.  For example, the past decade or so has seen a number of efforts at using directing groups such as phosphines to affect the course of hydroformylation reactions.  I should mention here that people are so interested in the hydroformylation of alkenes in part because it is such an industrially important reaction, with 9 million tons of aldehyde products being produced in this way per year (ref).  The challenges with this reaction are selectivity, one of the foremost issues being that terminal alkenes preferentially give linear products.  Shown below is a 2001 example from the Leighton group where a phosphine directing group on allylic ethers yields the branched hydroformylation product (Markovnikov addition), whereas the linear product (anti-Markovnikov) would be favored in the absence of the directing group:

The Up-Side: this method offers access to substrates not previously available through hydroformylation.   The Down-Side: it is hard to imagine an industrially-relevant product containing that specific phosphine moiety, so it would undoubtedly have to be cleaved, making the overall process highly atom un-economical.  This latter point could be addressed by somehow using the phosphine group in a catalytic, instead of stoichiometric, fashion.  This is exactly what the research group of Kian Tan at Boston College has been up to lately.  They have developed what they term a “scaffolding ligand” that coordinates to the organometallic catalyst as well as rapidly and reversibly (two important things for this type of catalysis) forms covalent bonds with alcohols.  In doing so it brings the substrate (in blue below) and catalyst (in red below) in close proximity and influences the course of the reaction.