En Route to 2‑(Cyclobuten-1-yl)-3-(trifluoromethyl)‑1<i>H</i>‑indole

A six-step synthetic route from 4-chloro-2-methylaniline to 5-chloro-2-(cyclobut-1-en-1-yl)-3-(trifluoromethyl)-1<i>H</i>-indole (<b>1</b>) has been reported. Compound <b>1a</b> is a key impurity of reverse transcriptase inhibitor efavirenz, an important anti-HIV/AIDS drug. Synthetic challenges, dead ends, and detours are discussed

Regioselective Hydrolysis and Transesterification of Dimethyl 3‑Benzamidophthalates Assisted by a Neighboring Amide Group

An efficient, highly regioselective hydrolysis and transesterification of dimethyl 3-benzamidophthalates into the corresponding carboxylic acid monoesters and mixed esters (including <i>tert</i>-butyl esters) under basic conditions is presented. The selectivity is governed by the neighboring 3-benzamido moiety’s participation and by the nature of the solvent. In alcohols the reaction occurred exclusively at the <i>ortho</i>-position to the benzamido functionality, in pyridine or acetonitrile at both ester groups. An insight into the mechanistic pathway was obtained from a ¹H NMR study in perdeuteromethanol

A Way to Avoid Using Precious Metals: The Application of High-Surface Activated Carbon for the Synthesis of Isoindoles via the Diels–Alder Reaction of 2<i>H</i>-Pyran-2-ones

The application of activated carbon (Darco KB) for the acceleration and direction of the transformation of various 2<i>H</i>-pyran-2-ones with <i>N</i>-substituted maleimides toward isoindole derivatives through the reaction sequence cycloaddition/elimination/dehydrogenation is described. In this reaction, the catalyst mainly influences the dehydrogenation step, which is essential to avoid the formation of bicyclo[2.2.2]­octenes as the other possible products. We found that the combination of Darco KB, as the metal-free catalyst, and decalin, as the solvent in a closed vessel, represents the most successful conditions. A comparison of the effect of various dehydrogenation catalysts and reaction conditions is also presented. In addition, we have proven that the aromatization occurs via a hydrogen transfer from the cyclohexadiene intermediate to the maleimide derivative (therefore producing succinimides). This transfer is facilitated by the active surface of the heterogeneous carbon-based catalyst