Enantioselective Three-Step Synthesis of Homo-β-proline: A Donor-Acceptor Cyclopropane as Key Intermediate
Ludwig K A Pilsl1, Thomas Ertl1, Oliver Reiser1
1Institut für Organische Chemie, Universität Regensburg , Universitätsstr. 31, 93053 Regensburg, Germany.
Abstract:
An enantioselective three-step synthesis of the GABA uptake inhibitor (S)-(+)-homo-β-proline was developed. The basis for the synthesis was the enantioselective CuI-catalyzed cyclopropanation of N-Boc-pyrrole, a substrate that persistently has proved to be challenging in such transformations. The cyclopropanation can be performed on a 150 mmol scale, and the two subsequent steps (i.e., hydrogenation and in situ cyclopropane-opening/double-deprotection) toward the target molecule proceed smoothly in quantitative yield without loss of enantiopurity.
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