Pd(iv)-induced nucleophile delivery in a cascade double Heck reaction

Abstract

A new cascade reaction has been described. Unsaturated 1,2-diiodides participate in a double Heck coupling with an unprecedented nucleophile inclusion into the core of the first alkene fragment. Thus, the complex carcass of the target molecule is coherently constructed from four independent components in one domino procedure. The assumed mechanism of the transformation sequence is presented. As a key step, the Pd(IV) complex is formed by a previously unreported intramolecular oxidative addition of the transitional σ-alkyl Pd(II) species obtained after the first carbopalladation. This Pd(IV) intermediate is capable of successful reductive elimination, which is unfavorable earlier, therefore connecting the attached sp³-carbon and heteroatom of the nucleophile. As a result, three new important bonds – C(sp²)–C(sp²), C(sp²)–C(sp³), and C(sp³)–O/N – are built in the process. Water, phenols, secondary amines, and anilines were employed as a nucleophile source in basic aqueous media. General synthetic protocols have been devised for styrenes as the employed alkene, although one example of methyl acrylate usage is also revealed. 1,2-Diiodocyclopentene serves as an example of a non-activated olefinic substrate, while multiple examples of 1,2-diiodoarene and 2,3-diiodo-1,4-naphthoquinone usage are reported. The prospects of further development of the discovered reaction include different fields in organic chemistry and catalysis.