High pressure promoted dearomatization of nitroarenes by [4+2] cycloadditions with silyloxydienes.

Simple nitroarenes such as nitronaphthalenes and nitroquinolines smoothly undergo dearomatizing [4+2] cycloadditions with silyloxydienes under 16 kbar. Highly functionalized 3-dimensional polycyclic adducts bearing a tetrasubstituted carbon centre at the ring junction are obtained in one step from simple raw materials. This unprecedented dearomative Diels-Alder process is performed at room temperature without any chemical promoter, illustrating the exceptional role of high pressure as a physical promoter.

How electrophilic are 3-nitroindoles? Mechanistic investigations and application to a reagentless (4+2) cycloaddition.

The electrophilicity of 4 different 3-nitroindole derivatives has been evaluated by Mayr's linear free energy relationship (log (20 °C) = ( + )) and reveals unexpected values for aromatic compounds, in the nitrostyrene range. 3-Nitroindoles are sufficiently electrophilic to interact with a common diene namely the Danishefsky's diene at room temperature, in the absence of any activator, to furnish smoothly the dearomatized (4+2) cycloadducts in good yields.

Reactivity of 3-nitroindoles with electron-rich species.

The indol(in)e building block is one of the "privileged-structures" for the pharmaceutical industry since this fragment plays a central role in drug discovery. While the electron-rich character of the indole motif has been investigated for decades, exploiting the electrophilic reactivity of 3-nitroindole derivatives has recently been put at the heart of a wide range of new, albeit challenging, chemical reactions. In particular, dearomatization processes have considerably enriched the scope of C2[double bond, length as m-dash]C3 functionalizations of these scaffolds.

Dearomatization of 3-cyanoindoles by (3 + 2) cycloaddition: from batch to flow chemistry.

1,3-Dipolar dearomatizing cycloadditions between a non-stabilized azomethine ylide and 3-cyanoindoles or benzofuran afford the corresponding 3D-heterocycles bearing a quaternary carbon centre at the ring junction. While 6 equivalents of ylide precursor 1 are required for full conversion in a classical flask, working under flow conditions limits the excess (3 equiv., tR = 1 min) and leads to a cleaner process, affording cycloadducts that are easier to isolate.