Diastereoselective synthesis of a novel cyclic derivative based on 2,3-indolinedione

Abstract

Generally, organic synthesis is renowned for its predictability in determining results. Nevertheless, there are situations where instead of the expected products, unexpected compounds with unique structures may arise. This report is a presentation of one such remarkable cyclic compound with four chiral centres prepared by diastereoselective dimerization of Morita-Baylis-Hillman (MBH) adducts of acrylonitrile to 5-chloro-indole-2,3dione. MBH adducts are very popular in organic chemistry. They are synthesized by the addition of an activated alkene and a carbon electrophile in the presence of a nucleophilic catalyst, such as a tertiary amine or phosphine. The product is densely functionalized, joining the alkene at the α-position to a reduced form of the electrophile with a new carbon-carbon bond. In cases where indol-2,3-dione acts as an electrophile in such reactions, literature examples are found only with N-substituted isatins [1-3]. We attempted to carry out this reaction using unsubstituted 5-chloroindol-2,3-dione. As a result, a series of products were isolated, among which several similar compounds of particular interest were observed, with NMR spectra showing a double set of signals. The overall yield of these compounds was insignificant, and their chromatographic separation proved to be very labour-intensive. In order to enhance the stereo-selectivity of the reaction and consequently increase the yield of the desired compound, conditions were optimized in which the corresponding MBH adduct was used as the starting substrate. In the presence of DABCO and acetic ether as catalysts, primarily, a single substance with an unusual cyclic structure was formed (Figure 1).Figure 1. The synthesis of cyclic dimer. NMR spectra were consistent with the proposed structure. To confirm it, X-ray structural analysis was conducted.