Search

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]

The mechanism of the TiCl4-promoted condensation of methyl acetoacetate, isobutyraldehyde, and indole was studied by a combination of theoretical and experimental techniques. The energy profile of plausible reaction paths was evaluated by DFT calculations, and various reaction intermediates were isolated or observed in solution by NMR spectroscopy. Theoretical and experimental results indicate that the reaction proceeds in three steps, all promoted by titanium: (1) formation of the enolate ion of methyl acetoacetate, (2) Knoevenagel condensation of the enolate ion and aldehyde, and (3) Michael addition of indole to the Knoevenagel adduct. The study sheds light on the role of titanium in the reaction, providing a mechanistic model for analogous reactions. [ABSTRACT FROM AUTHOR]

Phthalides and α,β-butenolides are two related classes of oxygenated heterocycles with a wide range of biological activities. An innovative strategy to prepare these compounds is based on C—H bond functionalization reactions, in which two simple, unfunctionalized molecules are coupled together with cleavage of a C—H bond and formation of a C—X bond (X=C or heteroatom). This paper reviews the methods for the synthesis of phthalides and α,β-butenolides by C—H bond functionalization from non-halogenated starting materials. Over 30 methods are reported, mostly developed during the past ten years. [ABSTRACT FROM AUTHOR]

The products are obtained as single diastereomers or as mixtures of diastereomers. [ABSTRACT FROM AUTHOR]