Pyrimidine‐Derived Prolinamides as Recoverable Bifunctional Organocatalysts for Enantioselective Inter‐ and Intramolecular Aldol Reactions under Solvent‐Free Conditions1. Issue 12 (6th March 2015)

• Record Type: Journal Article
• Authors: Vizcaíno‐Milla, Pascuala; Sansano, José M.; Nájera, Carmen; Fiser, Béla; Gómez‐Bengoa, Enrique
• Is Part Of: European journal of organic chemistry. Issue 12(2015)
• Page Start: 2614
• Page End: 2621
• Publication Date: 2015-03-06
• Subjects: Organocatalysis -- Aldol reactions -- Nitrogen heterocycles -- Solvent‐free process; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201500007
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: ChiralL ‐prolinamides2 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 catalyst2 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 catalysts2a and2b . Abstract : The intermolecular ketone–aldehyde and aldehyde–aldehyde aldol reactions and the Hajos–Parrish–Eder–Sauer–Wiechert versions with the employment of chiralL ‐prolinamides containing the ( R, R )‐ and ( S, S )‐ trans ‐cyclohexane‐1, 2‐diamine scaffold and a 2‐pyrimidinyl unit are successfully performed under solvent‐free conditions; WMK = Wieland–Miescher ketone.