The First Modular Route to Core‐Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)‐Catalyzed Henry Reactions |
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| Authors: | Dagmar Scharnagel Andreas Müller Felix Prause Martin Eck Jessica Goller Dr Wolfgang Milius Prof?Dr Matthias Breuning |
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| Institution: | 1. Organic Chemistry Laboratory, University of Bayreuth, Universit?tsstrasse 30, 95447 Bayreuth (Germany);2. Institute of Organic Chemistry, University of Regensburg, Universit?tsstrasse 31, 93040 Regensburg (Germany);3. Institute of Inorganic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg (Germany);4. Inorganic Chemistry Laboratory, University of Bayreuth, Universit?tsstrasse 30, 95447 Bayreuth (Germany) |
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| Abstract: | The first modular and flexible synthesis of core‐chiral bispidines was achieved by using an “inside‐out” strategy. The key intermediate, a NBoc‐activated bispidine lactam, was constructed in enantiomerically pure form from a chirally modified β‐amino acid and 2‐(acetoxymethyl)acrylonitrile in just five steps and good 48 % yield. A simple addition–reduction protocol permitted a highly endo‐selective introduction of substituents and, thus, a fast and variable access to 2‐endo‐substituted and 2‐endo,N‐fused bi‐ and tricyclic bispidines. The new diamines were evaluated as the chiral ligands in asymmetric Henry reactions. Excellent enantioselectivities of up to 99 % ee and good diastereomeric ratios of up to 86:14 were reached with a copper(II) complex modified by a 2‐endo,N‐(3,3‐dimethylpyrrolidine)‐annelated bispidine. Its performance is superior to that of the well‐known bispidines (?)‐sparteine and the (+)‐sparteine surrogate. |
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| Keywords: | asymmetric synthesis bispidine Henry reaction polycyclic compounds stereoselective catalysis |
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