Diastereomer Interconversion via Enolization: A Case Study. Issue 11 (4th September 2015)

• Record Type: Journal Article
• Authors: Renzetti, Andrea; Di Crescenzo, Antonello; Nie, Feilin; Bond, Andrew D.; Gérard, Stéphane; Sapi, Janos; Fontana, Antonella; Villani, Claudio
• Is Part Of: Chirality. Volume 27:Issue 11(2015)
• Page Start: 779
• Page End: 783
• Publication Date: 2015-09-04
• Subjects: Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22503
• Languages: English
• ISSNs: 0899-0042

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>The three‐component reaction of indole, isobutyraldehyde, and methyl acetoacetate affords methyl 2‐(acetyl)‐3‐(1<italic>H</italic>‐indol‐3‐yl)‐4‐methylpentanoate as a single diastereomer. To investigate the origin of the observed diastereoselectivity, the thermodynamics and kinetics of interconversion of diastereomers <bold>1</bold> and <bold>2</bold> in solution were studied by a combination of <sup>1</sup>H <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">nuclear magnetic resonance</named-content> (NMR) spectroscopy, high‐performance <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">liquid chromatography</named-content> (HPLC), <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">mass spectrometry</named-content>, and <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">deuteration</named-content> experiments. The results indicate that interconversion is both acid‐ and base‐catalyzed, and that the alpha carbon is the only stereolabile center in the molecule. The evidence points to an <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">enolization</named-content> mechanism for the interconversion process. The selective precipitation of <bold>1</bold> in the presence of the equilibrium <bold>1</bold>⇆<bold>2</bold> eventually results in the exclusive formation of <bold>1</bold> (crystallization‐induced asymmetric transformation). <italic>Chirality 27:779–783, 2015</italic>. © 2015 Wiley Periodicals, Inc.</p> </abstract>