Pyrimidine-Derived Prolinamides as Recoverable Bifunctional Organocatalysts for Enantioselective Inter- and Intramolecular Aldol Reactions under Solvent-Free Conditions

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Title: Pyrimidine-Derived Prolinamides as Recoverable Bifunctional Organocatalysts for Enantioselective Inter- and Intramolecular Aldol Reactions under Solvent-Free Conditions
Authors: Vizcaíno-Milla, Pascuala | Sansano, Jose M. | Nájera, Carmen | Fiser, Béla | Gómez Bengoa, Enrique
Research Group/s: Síntesis Asimétrica (SINTAS)
Center, Department or Service: Universidad de Alicante. Departamento de Química Orgánica
Keywords: Organocatalysis | Aldol reactions | Nitrogen heterocycles | Solvent-free process
Knowledge Area: Química Orgánica
Issue Date: Apr-2015
Publisher: Wiley-VCH Verlag GmbH & Co. KGaA
Citation: European Journal of Organic Chemistry. 2015, 12: 2614-2621. doi:10.1002/ejoc.201500007
Abstract: Chiral L-prolinamides 2 containing the (R,R)- and (S,S)-trans-cyclohexane-1,2-diamine scaffold and a 2-pyrimidinyl unit are synthesized and used as general organocatalysts for intermolecular and intramolecular aldol reactions with 1,6-hexanedioic acid as a co-catalyst under solvent-free conditions. The intermolecular reaction between ketone–aldehyde and aldehyde–aldehyde must be performed under wet conditions with catalyst (S,S)-2b at 10 °C, which affords anti-aldols with high regio-, diastereo-, and enantioselectivities. For the Hajos–Parrish–Eder–Sauer–Wiechert reaction, both diastereomers of catalyst 2 give similar results at room temperature in the absence of water to give the corresponding Wieland–Miescher ketone and derivatives. Both types of reactions were scaled up to 1 g, and the organocatalysts were recovered by extractive workup and reused without any appreciable loss in activity. DFT calculations support the stereochemical results of the intermolecular process and the bifunctional role played by the organocatalyst by providing a computational comparison of the H-bonding networks occurring with catalysts 2a and 2b.
Sponsor: The Spanish Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2010-20387 and Consolider Ingenio 2010, CSD2007-00006), the Spanish Ministerio de Economia y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), Fondos Europeos para el Desarrollo Regional (FEDER), Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017), the Basque Government (GV Grant IT-291-07), the European Commission, FP7 Marie Curie Actions through the ITN ECHONET network (MCITN-2012-316379), the University of Alicante, and the University of the Basque Country are gratefully acknowledged for financial support.
URI: http://hdl.handle.net/10045/46655
ISSN: 1434-193X (Print) | 1099-0690 (Online)
DOI: 10.1002/ejoc.201500007
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Peer Review: si
Publisher version: http://dx.doi.org/10.1002/ejoc.201500007
Appears in Collections:Research funded by the EU
INV - SINTAS - Artículos de Revistas

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