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The three-component reaction of indole, isobutyraldehyde, and methyl acetoacetate affords methyl 2-(acetyl)-3-(1 H-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 1 and 2 in solution were studied by a combination of 1H (NMR) spectroscopy, high-performance (HPLC), , and 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 mechanism for the interconversion process. The selective precipitation of 1 in the presence of the equilibrium 1⇆ 2 eventually results in the exclusive formation of 1 (crystallization-induced asymmetric transformation). Chirality 27:779-783, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]