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Octahydrocyclopenta[c]pyridine Scaffold – Enantioselective Synthesis and Indole Annulation

Wachtendorf, Daniel and Geibel, Irina and Schmidtmann, Marc and Christoffers, Jens (2018) Octahydrocyclopenta[c]pyridine Scaffold – Enantioselective Synthesis and Indole Annulation. European Journal of Organic Chemistry, 2018 (40). pp. 5524-5531. ISSN 1434-193X . http://resolver.caltech.edu/CaltechAUTHORS:20181126-092543544

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Abstract

An optically active hexahydrocyclopenta[c]pyridine derivative with quaternary stereocenter was prepared as a new heterocyclic scaffold. Key reaction was the Pd‐catalyzed asymmetric allylic alkylation of a piperidine‐based β‐oxoester, which proceeded in very good yield with high level of enantioselectivity (90 %, 95 % ee). The α‐allyl moiety was transformed into a 1,4‐diketone by Pd‐catalyzed Wacker oxidation with molecular oxygen (89 %). This intermediate was cyclized in an intramolecular aldol reaction furnishing the cyclopentenone motif (86 %). Hydrogenation of the C–C double bond gave the cis‐annulated octahydrocyclopenta[c]pyridine (86 %), which was submitted to Fischer indolization (85 %). Although two regioisomers could be expected, only the angular constitution was observed. Relative and absolute configurations were established by X‐ray crystallography of a para‐iodo benzamide derivative. The utility of the title compound as scaffold is further highlighted by a number of synthetically useful transformations, for instance formation of carboxamides, sulfonamides, ureas and reductive aminations with aldehydes.


Item Type:Article
Related URLs:
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https://doi.org/10.1002/ejoc.201801102DOIArticle
Additional Information:© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Issue Online: 25 October 2018; Version of Record online: 15 October 2018; Accepted manuscript online: 13 September 2018; Manuscript received: 12 July 2018. Dedicated to Professor Karl-Heinz Dötz on the occasion of his 75th birthday. We are grateful to Evonik Industries, Marl, Germany for a generous donation of MTBE. Thanks to Julia Prips for her contribution during her Bachelor thesis.
Subject Keywords:Piperidines; Scaffolds; Indole derivatives; Asymmetric allylic alkylation; Quaternary stereocenters
Record Number:CaltechAUTHORS:20181126-092543544
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20181126-092543544
Official Citation:Wachtendorf, D. , Geibel, I. , Schmidtmann, M. and Christoffers, J. (2018), Octahydrocyclopenta[c]pyridine Scaffold – Enantioselective Synthesis and Indole Annulation. Eur. J. Org. Chem., 2018: 5524-5531. doi:10.1002/ejoc.201801102
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:91156
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:26 Nov 2018 17:34
Last Modified:26 Nov 2018 17:34

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