A method is described for reversing the usual regioselectivity in the hydroformylation of allylic alcohols. Using the hydroxyl group as a handle, a phosphole tether is attached which directs the hydroformylation to give greater than 20:1 selectivity for the branched aldehyde. In the case of α-substituted alcohols, the hydroformylation proceeds in up to 96:4 selectivity favoring the anti diastereomer. In the case of methallyl alcohol, an unprecedented reversal of regioselectivity is achieved, with the quaternary aldehyde favored over the less branched product in a 12:1 ratio.
Additionally, a series of 1,2-aminoalcohol-derived phosphine-sulfonamide ligands are shown to be useful in Cu-catalyzed conjugate addition of dialkylzinc reagents to enones. These ligands are conveniently synthesized and provide optimum selectivity at room temperature, affording greater than 96% enantiomeric excesses for a range of cyclic ketones, as well as the highest enantioselectivities yet observed in the production of isopropyl-substituted ketones. Modification of these ligands has led to new "tripodal" N-P-N compounds which show promise in conjugate addition with acyclic enones. Efforts towards adaptation of this methodology to employ Grignard reagents are also described.
