159709-64-5Relevant academic research and scientific papers
C2-symmetric copper(II) complexes as Chiral Lewis acids. Scope and mechanism of catalytic enantioselective aldol additions of enolsilanes to (benzyloxy)acetaldehyde
Evans, David A.,Kozlowski, Marisa C.,Murry, Jerry A.,Burgey, Christopher S.,Campos, Kevin R.,Connell, Brian T.,Staples, Richard J.
, p. 669 - 685 (2007/10/03)
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 aldol products are generated in high yields and in 92-99% enantiomeric excess using as little as 0.5 mol % of chiral catalyst [Cu((S,S)-Ph-pybox)](SbP6)2. With substituted silylketene acetals, syn reaction diastereo-selection ranging from 95:5 to 97:3 and enantioselectivities ≥95% are observed. Investigation into the reaction mechanism utilizing doubly labeled silylketene acetals indicates that the silyl-transfer step is intermolecular. Further mechanistic studies revealed a significant positive nonlinear effect, proposed to arise from the selective formation of the [Cu((S,S)-Ph-pybox)((R,R)-Ph-pybox)](SbF6)2 2:1 ligand:metal complex. A stereochemical model is presented in which chelation of (benzyloxy)acetaldehyde to the metal center to form a square pyramidal copper intermediate accounts for the observed sense of induction. Support for this proposal has been obtained from double stereodifferentiating reactions, EPR spectroscopy, ESI spectrometry, and, ultimately, the X-ray crystal structure of the aldehyde bound to the catalyst. The C2-symmetric bis(oxazolinyl)-Cu(II) complex [Cu((S,S)-tert-Bu-box)](OTf)2 is also an efficient catalyst for the aldol reaction, but the scope with this system is not as broad.
