Olefins as alkylating agents: Zirconium-catalyzed electrophilic olefin alkylations in stereoselective organic synthesis

An efficient and selective method for alkylation of unactivated olefins is disclosed. Using a catalytic amount of a zirconocene complex in the presence of an alkyl Grignard reagent, unactivated olefins are rendered highly nucleophilic such that common and inexpensive electrophiles (e.g. alkyl halides and alkyl tosylates) can be added with high regioselectively and yields. Simple manipulation of the Grignard reagent allows access to functionalized alkylmagnesium halide products. This transformation can also be carried out in an intramolecular fashion when the electrophile is tethered within the substrate olefin, thereby allowing facile access to both carbo- and heterocyclic structures. In addition, when cyclic allylic ethers are used as substrates, Zr-alkoxide elimination occurs after C-C bond formation to effect a net allylic substitution.*; Substantial progress towards the first asymmetric synthesis of the marine diterpene, erogorgiaene, was accomplished through the use of two methodologies developed within our labs. Cu-catalyzed conjugate addition of dimethylzinc to an α,β-unsaturated ketone using a peptide-based chiral Schiff base ligand was used to establish stereochemistry at C7. In the second key step, a Zr-catalyzed diastereoselective intramolecular carbomagnesation was used to set the center at C4 and form erogorgiaene's 1,4-disubstituted tetrahydronaphthalene core.*; *Please refer to dissertation for diagrams.