Synthesis of Highly Enantioenriched Compounds via Iron Mediated Allylic Substitutions

In this account we describe our efforts over more than a decade to develop a synthetically useful and practical methodology for the synthesis of highly enantioenriched compounds via iron promoted allylic substitutions. After first attempts based on a kinetic resolution of planar chiral tetracarbonyl(η ³-allyl)iron(1+) complexes and an auxiliary controlled diastereoselective formation of the iron complexes, the "chirality transfer" approach turned out to be an efficient solution. Starting from enantiopure easily accessible and cheap acceptor substituted allylic substrates, the corresponding (η ³-allyl)tetracarbonyl iron cation complexes are formed and trapped with a variety of carbon and heteroatom nucleophiles including silyl enol ethers, electronrich arenes and heteroarenes, functionalized organozinc compounds and amines. The iron mediated allylic substitutions proceed with virtually no loss of chirality information from central (C-O) over planar (C-Fe) back to central chirality (C-C or C-X) affording products of high enantiomeric purity with overall retention (double inversion). In addition, complete γ-regioselectivity and conservation of the double bond geometry is achieved. First applications in the synthesis of virtually enantiopure natural products are described.