Translated Abstract
Cyclopropanes and cyclobutanes are widely used building blocks for the synthesis of important carbo- and heterocycles of natural product skeletons through rearrangement or cycloaddition reactions. Although the release of ring strain can be a thermodynamic driving force for ring cleavage, their relatively stable kinetics require effective strategies to be employed for ring opening reactions. By designing the structure of cyclopropanes and cyclobutanes and adopting a suitable catalytic strategy, two kinds of novel catalytic ring opening reactions were realized to afford cyanoalkylated oxindoles, tetrahydroquinolinones, and cycloheptenones, respectively.
Part 1: A copper-catalyzed cyclization of activated alkenes with cyclobutanone O-acyl oximes under redox-neutral conditions has been developed. With copper(I) oxide as catalyst, dioxane as solvent, this reaction provides a highly efficient route to cyanoalkylated oxindoles and tetrahydroquinolinones with excellent substrate scope and functional group tolerance. Mechanistically, cyclobutanone O-acyl oximes undergo single electron reduction with copper catalyst to provide an imine radical. By virtue of ring strain of cyclobutane, β-elimination occurs to afford alkyl cyanide with a distal carbon free radical, which adds to a olefin, followed by cyclization, oxidation, and elimination to complete the catalytic cycle. The mechanism was verified by free radical capture experiment.
Part 2: A phosphine-catalyzed ring enlargement reaction of vinylcyclopropylketones was discovered for the first time, which provides an efficient synthesis of cycloheptenones. Under the catalysis of PtBu3 or PnBu3, 23 examples of the reaction were exemplified with good yields and wide substrate scope. The structure of the products was determined by single crystal X-ray analysis, and further transformations of products were demonstrated. The reaction mechanism was studied by means of NMR tracking, deuterium labeling, and intermediate capture experiments, which lead us to proposed a stepwise mechanism consisting of nucleophilic ring opening, water-assisted proton transfer, and final 7-endo-trig SN2＇ ring-closure. This study enriches the phosphine catalysis by extending the scope from traditional electron-deficient olefins to electron-deficient vinylcyclopropanes, and provides an important C5 synthon for annulation reactions. In addition, this work benefits the development of vinylcyclopropane chemistry.
As alkyl cyanide skeletons are widely embedded in pharmaceutical molecules, the copper-catalyzed redox neutral ring-opening reaction of cyclobutanone O-acyl oximes is expected to found wide application for introducing alkyl cyanides into drug molecules. On the other hand, cycloheptenones are important skeletons of many natural products; the phosphine-catalyzed rearrangement of vinylcyclopropylketones provides a simple and efficient strategy toward the synthesis of these medium-sized carbocycles, which is anticipated to found wide use in natural product synthesis.
Translated Keyword
[Copper catalysis, Cyclobutanone o-acyl oximes, Cycloheptenones, Phosphine catalysis, Vinylcyclopropylketones]
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