Proline Derived Ligands for the Titanium-Catalyzed Enantioselective Synthesis of Propargyl Alcohols in Presence of Diethylzinc

A novel titanium/proline-derived catalyst system is reported for the enantioselective synthesis of propargyl alcohols. The reaction proceeded smoothly under mild conditions with efficient reaction times. A series of proline and proline-based ligands including Lproline, L-prolinol, trans-hydroxy-L-prolinol, and substituted trans hydroxy-L-proline derivatives were used to have a better stereocontrol on the reaction. Initially, lithium acetylide was employed to carry out the nucleophilic addition reaction, however poor reaction profile was achieved with poor enantioselectivities. When diethylzinc was used instead, high product yields (>85%) and moderate to high enantioselectivities were achieved (68-82%). Three different alkynes, aromatic as well as aliphatic, phenylacetylene, n-hexyne and 3,3-diethoxy-prop-1-yne were used to carry out the reaction with a series of different aromatic and heterocyclic aldehydes. Better reaction profiles were achieved with aromatic alkynes than with aliphatic ones.