Intra- and Intermolecular Alkylation of <i>N</i>,<i>O</i>‑Acetals and π‑Activated Alcohols Catalyzed by in Situ Generated Acid

Intramolecular and intermolecular alkylations of carbocation precursors of limited ionization ability, principally <i>N</i>,<i>O</i>-acetals, without the use of an exogenous reagent have been developed. The reactions are carried out in 1,1,2,2-tetrachloroethane (TCE) and take advantage of the ability of this solvent to continuously release small amounts of HCl by thermolytic elimination. A study of the reaction led to several improved protocols such as (1) preheated TCE, (2) microwave-assisted reactions, and (3) flow or sealed-tube conditions, which allow significant reaction rate enhancements and made possible some challenging reactions such as the α-amidoalkylation of ketones. Studies using flow chemistry confirmed not only that very low concentrations of HCl generated from the solvent were responsible for the reactivity but also that TCE had additional beneficial properties in comparison to other chlorinated solvents such as dichloroethane. The method can easily be extended to the alkylation using proelectrophiles such as π-activated alcohols, which are normally unreactive toward HCl catalysis. This work represents the first successful use of HCl, the simplest strong Brønsted acid, as an efficient alkylation catalyst

Synthesis of nitrogen-substituted methylenecyclopropanes by strain-driven overman rearrangement of cyclopropenylmethyl trichloroacetimidates

Nitrogen-substituted methylenecyclopropanes have been prepared by a strain-driven Overman rearrangement of cyclopropenylmethyl trichloroacetimidates. The reaction proceeds at room temperature and without the need of a transition-metal catalyst. Furthermore, it has been shown that C-3-substituted cyclopropenylmethyl trichloroacetimidates undergo a hydrolytic ring-opening reaction to form allenylcarbinols

Chroman-4-one- and Chromone-Based Sirtuin 2 Inhibitors with Antiproliferative Properties in Cancer Cells

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