- Catalytic Asymmetric Synthesis of Morpholines. Using Mechanistic Insights to Realize the Enantioselective Synthesis of Piperazines
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An efficient and practical catalytic approach for the enantioselective synthesis of 3-substituted morpholines through a tandem sequential one-pot reaction employing both hydroamination and asymmetric transfer hydrogenation reactions is described. Starting from ether-containing aminoalkyne substrates, a commercially available bis(amidate)bis(amido)Ti catalyst is utilized to yield a cyclic imine that is subsequently reduced using the Noyori-Ikariya catalyst, RuCl [(S,S)-Ts-DPEN] (η6-p-cymene), to afford chiral 3-substituted morpholines in good yield and enantiomeric excesses of >95%. A wide range of functional groups is tolerated. Substrate scope investigations suggest that hydrogen-bonding interactions between the oxygen in the backbone of the ether-containing substrate and the [(S,S)-Ts-DPEN] ligand of the Ru catalyst are crucial for obtaining high ee's. This insight led to a mechanistic proposal that predicts the observed absolute stereochemistry. Most importantly, this mechanistic insight allowed for the extension of this strategy to include N as an alternative hydrogen bond acceptor that could be incorporated into the substrate. Thus, the catalytic, enantioselective synthesis of 3-substituted piperazines is also demonstrated.
- Lau, Ying Yin,Zhai, Huimin,Schafer, Laurel L.
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p. 8696 - 8709
(2016/10/14)
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- Catalytic asymmetric synthesis of substituted morpholines and piperazines
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Under two conditions: Hydroamination catalyzed by group 4 metals is featured in the modular and enantioselective synthesis of 3-substituted morpholines and the diastereoselective synthesis of 2,5-substituted piperazines. Copyright
- Zhai, Huimin,Borzenko, Andrey,Lau, Ying Yin,Ahn, Shin Hye,Schafer, Laurel L.
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p. 12219 - 12223
(2013/02/23)
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