(3R,11aR)-3-Phenyl-2,3,11,11a-tetrahydro-[1,3]oxazolo[3,2-b]-[2]benzazepin-5(10H)-one as a chiral building block for the asymmetric synthesis of 3-substituted 2-benzazepines |
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Authors: | Matthias P. Quick Roland Fröhlich Bernhard Wünsch |
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Affiliation: | 1. Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, Hittorfstraße 58-62, D-48149 Münster, Germany;2. Organisch-Chemisches Institut der Westfälischen Wilhelms-Universität Münster, Corrensstr. 40, D-48149 Münster, Germany |
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Abstract: | A five-step synthesis of the chiral building block cis-2 is described. Key steps in the synthesis were a Heck reaction of 1-bromo-2-iodobenzene with allyl alcohol, the introduction of a carboxy group after Br/Li-exchange, and the diastereoselective formation of the tricyclic oxazolidine system cis-2. Activation of cis-2 with TiCl4 led to formation of a carbenium ion, which was attacked by allyltrimethylsilane exclusively from the Re-face leading to the (3S)-configured 2-benzazepinone 8 in 65% yield. The configuration of the new stereogenic center was determined by X-ray crystal structure analysis, which is the basis for the proposed mechanism of this transformation. Enantiomerically pure 3-substituted 2-benzazepines represent interesting drug candidates. |
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