Alkene Thianthrenation Unlocks Diverse Cation Synthons: Recent Progress and New Opportunities.

Oxidative alkene functionalization reactions are a fundamental class of complexity-building organic transformations. However, the majority of established approaches rely on electrophilic reagents that limit the diversity of groups that can be installed. Recent advances have established a new approach that instead relies on the transformation of alkenes into thianthrene-derived cationic electrophiles. These linchpin intermediates can be generated selectively and undergo a diverse array of mechanistically distinct reactions with abundant nucleophiles. Taken together, this unlocks a suite of net oxidative alkene transformations that have been elusive using conventional strategies. This Minireview describes these advances and is organized around the three distinct synthons formally accessible from alkenes via thianthrenation: 1) alkenyl cations; 2) vicinal dications; 3) allyl cations. Throughout the Minireview, we illustrate how thianthrenium salts address key limitations endemic to classic alkene-derived electrophiles and highlight the mechanistic origins of these distinctions wherever possible.

Regiospecific Alkene Aminofunctionalization via an Electrogenerated Dielectrophile.

Modular strategies to rapidly increase molecular complexity have proven immensely synthetically valuable. In principle, transformation of an alkene into a dielectrophile presents an opportunity to deliver two unique nucleophiles across an alkene. Unfortunately, the selectivity profiles of known dielectrophiles have largely precluded this deceptively simple synthetic approach. Herein, we demonstrate that dicationic adducts generated through electrolysis of alkenes and thianthrene possess a unique selectivity profile relative to more conventional dielectrophiles. Specifically, these species undergo a single and perfectly regioselective substitution reaction with phthalimide salts. This observation unlocks an appealing new platform for aminofunctionalization reactions. As an illustrative example, we implement this new reactivity paradigm to address a longstanding synthetic challenge: alkene diamination with two distinct nitrogen nucleophiles. Studies into the mechanism of this process reveal a key alkenyl thianthrenium salt intermediate that controls the exquisite regioselectivity of the process and highlight the importance of proton sources in controlling the reactivity of alkenyl sulfonium salt electrophiles.

Aziridine synthesis by coupling amines and alkenes via an electrogenerated dication.

Aziridines-three-membered nitrogen-containing cyclic molecules-are important synthetic targets. Their substantial ring strain and resultant proclivity towards ring-opening reactions makes them versatile precursors of diverse amine products1-3, and, in some cases, the aziridine functional group itself imbues important biological (for example, anti-tumour) activity4-6. Transformation of ubiquitous alkenes into aziridines is an attractive synthetic strategy, but is typically accomplished using electrophilic nitrogen sources rather than widely available amine nucleophiles. Here we show that unactivated alkenes can be electrochemically transformed into a metastable, dicationic intermediate that undergoes aziridination with primary amines under basic conditions. This new approach expands the scope of readily accessible N-alkyl aziridine products relative to those obtained through existing state-of-the-art methods. A key strategic advantage of this approach is that oxidative alkene activation is decoupled from the aziridination step, enabling a wide range of commercially available but oxidatively sensitive7 amines to act as coupling partners for this strain-inducing transformation. More broadly, our work lays the foundations for a diverse array of difunctionalization reactions using this dication pool approach.