Highly efficient synthesis of Z-macrocycles using stereoretentive, ruthenium-based metathesis catalysts

A method for producing at least one Z-macrocyclic product represented by Formula (VII):

• wherein:
• q is 1, 2, 3, or 4;
• p is 4, 5, 6, or 7;
• and the Z-macrocyclic product of Formula (VII) is a twelve, thirteen, fourteen, fifteen, sixteen, or seventeen-membered ring with a Z selectivity of 95, or 98, or 99;
• comprising:
• subjecting a diene substrate bearing a Z-olefin moiety represented by Formula (IV):
• wherein:
• R″ is methyl, ethyl, or propyl;
• q is 1, 2, 3, or 4;
• p is 4, 5, 6, or 7;
• to a macrocyclic ring-closing metathesis reaction in the presence of a stereoretentive Ru-based catalyst represented by Formula (II):
• wherein:
• R and R0 are independently nil, H, methyl, ethyl, propyl, iso-propyl, butyl, sec-butyl, tert-butyl, or phenyl;
• R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, and R14 are independently H, methyl, ethyl, propyl, iso-propyl, butyl, sec-butyl, tert-butyl, phenyl, fluoro, chloro, bromo, iodo, nitro, dimethylaminosulfonate, diethylaminosulfonate, or cyano;
• R15, R16, R17, and R18 are independently H or methyl;
• Z1 and Z2 are independently cyano or nitro;
• and
• Y is oxygen, sulfur, nitrogen, or iodo.