C2-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Scope and Mechanism of Catalytic Enantioselective Aldol Additions of Enolsilanes to (Benzyloxy)acetaldehyde
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- 作者：David A. Evans ; Marisa C. Kozlowski ; Jerry A. Murry ; Christopher S. Burgey ; Kevin R. Campos ; Brian T. Connell ; and Richard J. Staples
- 刊名：Journal of the American Chemical Society
- 出版年：1999
- 出版时间：February 3, 1999
- 年：1999
- 卷：121
- 期：4
- 页码：669 - 685
- 全文大小：1149K
- 年卷期：v.121,no.4(February 3, 1999)
- ISSN：1520-5126
文摘
C2-Symmetric bis(oxazolinyl)pyridine (pybox)-Cu(II) complexes have been shown to catalyzeenantioselective 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)](SbF6)2. With substituted silylketene acetals, syn reaction diastereoselection ranging from 95:5 to 97:3 and enantioselectivities 
95% are observed. Investigation into the reactionmechanism 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 selectiveformation of the [Cu((S,S)-Ph-pybox)((R,R)-Ph-pybox)](SbF6)2 2:1 ligand:metal complex. A stereochemicalmodel is presented in which chelation of (benzyloxy)acetaldehyde to the metal center to form a square pyramidalcopper intermediate accounts for the observed sense of induction. Support for this proposal has been obtainedfrom double stereodifferentiating reactions, EPR spectroscopy, ESI spectrometry, and, ultimately, the X-raycrystal 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 systemis not as broad.
95% are observed. Investigation into the reactionmechanism 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 selectiveformation of the [Cu((S,S)-Ph-pybox)((R,R)-Ph-pybox)](SbF6)2 2:1 ligand:metal complex. A stereochemicalmodel is presented in which chelation of (benzyloxy)acetaldehyde to the metal center to form a square pyramidalcopper intermediate accounts for the observed sense of induction. Support for this proposal has been obtainedfrom double stereodifferentiating reactions, EPR spectroscopy, ESI spectrometry, and, ultimately, the X-raycrystal 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 systemis not as broad.