Cooperative Brønsted Acid Catalysis

Significance

A completely regioselective alcoholysis of styrene oxides 1 has been accomplished utilizing a catalyst system comprised of N,N′-bis[3,5-bis(trifluoromethyl)phenyl]-thiourea (3, 1 mol%) and mandelic acid (4, 1 mol%). Both simple aliphatic and sterically demanding as well as unsaturated or acid-labile alcohols 2 can be used furnishing the corresponding β-alkoxy alcohols 5 in moderate to high yields. Thiourea 3 or mandelic acid (4) alone were both uneffective. The authors invoke an H-bonding-mediated cooperative Brønsted acid catalysis mechanism to rationalize their experimental findings (see scheme). Support is also provided by DFT computations.