Breit, Rein, Demel, Outten and Netscher. ACIEE, 2007, EarlyView. DOI: 10.1002/anie.200703268.
Just a short post to mention a nice little synthesis of this tocopherol by Bernhard Breit’s group at Freiburg. I first came across his work when I saw him present at OMCOS-13 in Geneva, and have been quite a fan since. This synthesis concerns his “Reagent Directing Group” (RGD) approach, which he’s been working on for a few years now (though wasn’t the originator of the idea). The concept is simple – use the substrate as the chiral ligand on which a catalyst operates. In this manner, the substrate is controlling the asymmetry in the catalyst, which inself informs a reagent controlled asymmetric process. Now to see it in action:
In this case, the reaction is a rhodium catalysed hydroformylation, and the directing group is an ortho diphenylphosphine benzoate ester, resulting in a good yield and diastereomeric control. I also liked the synthesis of the vinyl silane… With that half of the molecule complete, it was time to couple to the other fragment. I haven’t covered it’s synthesis – suffice to say that it was short and efficient. The coupling, though, is rather special:
Rather than just bin the RDG, they used it as a leaving group for a copper-mediated allylic displacement, in which the stereochemistry was transferred nicely. Reductive removal of both the olefin and benzyl ether completed this short synthesis rather neatly.
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