C2-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Scope and Mechanism of Catalytic Enantioselective Aldol Additions of Enolsilanes to (Benzyloxy)acetaldehyde

摘要: C2-Symmetric bis(oxazolinyl)pyridine (pybox)−Cu(II) complexes have been shown to catalyze enantioselective Mukaiyama aldol reactions between (benzyloxy)acetaldehyde and a variety of silylketene acetals. The products are generated in high yields 92−99% enantiomeric excess using as little 0.5 mol % chiral catalyst [Cu((S,S)-Ph-pybox)](SbF6)2. With substituted acetals, syn reaction diastereoselection ranging from 95:5 97:3 enantioselectivities ≥95% observed. Investigation into the mechanism utilizing doubly labeled acetals indicates that silyl-transfer step is intermolecular. Further mechanistic studies revealed significant positive nonlinear effect, proposed arise selective formation [Cu((S,S)-Ph-pybox)((R,R)-Ph-pybox)](SbF6)2 2:1 ligand:metal complex. A stereochemical model presented which chelation metal center form square pyramidal copper intermediate accounts for obser...