Multicatalytic Stereoselective Synthesis of Highly Substituted Alkenes by Sequential Isomerization/Cross-Coupling Reactions.

Abstract

Starting from readily available alkenyl methyl ethers, the stereoselective preparation of highly substituted alkenes by two complementary multicatalytic sequential isomerization/cross-coupling sequences is described. Both elementary steps of these sequences are challenging processes when considered independently. A cationic iridium catalyst was identified for the stereoselective isomerization of allyl methyl ethers and was found to be compatible with a nickel catalyst for the subsequent cross-coupling of the in situ generated methyl vinyl ethers with various Grignard reagents. The method is compatible with sensitive functional groups and a multitude of olefinic substitution patterns to deliver products with high control of the newly generated C═C bond. A highly enantioselective variant of this [Ir/Ni] sequence has been established using a chiral iridium precatalyst. A complementary [Pd/Ni] catalytic sequence has been optimized for alkenyl methyl ethers with a remote C═C bond. The final alkenes were isolated with a lower level of stereocontrol. Upon proper choice of the Grignard reagent, we demonstrated that C( sp2)-C( sp2) and C( sp2)-C( sp3) bonds can be constructed with both systems delivering products that would be difficult to access by conventional methods.