Chromenes through Metal-Catalyzed Reactions of Styrenyl Ethers. Mechanism and Utility in Synthesis

An efficient metal-catalyzed process that converts styrenyl ethers to 2-substituted chromenes is described. This class of reactions may be carried out on either terminal or disubstituted styrenyl substrates. Depending on the level of substitution of the olefins, the Ru−carbene catalyst may initiate reaction either by interaction with the styrenyl or the carbocyclic alkene. Metal-catalyzed rearrangements, carried out under an atmosphere of ethylene, afford excellent yields of monomeric products. With disubstituted styrene ethers, the presence of ethylene is also critical to reaction efficiency. Mechanistic data that rationalize these observations are provided. Although Ru complexes (PCy3)2Cl2RuCHCHCPh2 or (PCy3)2Cl2RuCHPh effectively serve as catalysts, with the more functionalized substrates, higher yields are obtained when Mo(CHCMe2Ph)(N(2,6-(i-Pr)2C6H3))(OCMe(CF3)2)2 is used. A variety of starting materials for the metal-catalyzed chromene synthesis (disubstituted styrenes) are available in the optically pure form through the Zr-catalyzed kinetic resolution protocol, allowing several 2-substituted chromenes to be prepared in high enantiomeric purity. However, a number of functionalized substrates cannot be efficiently resolved by the latter method, indicating that more effective methods that address this deficiency are required.