A general alkene aminoarylation enabled by N-centered radical reactivity of sulfinamides

Abstract

We disclose an intermolecular 1,2-aminoarylation of alkenes using aryl sulfinamide reagents as bifunctional amine and arene donors. This reaction features excellent regio- and diastereoselectivity on a variety of activated and unactivated substrates. Using a weakly oxidizing photoredox catalyst, a sulfinamidyl radical is generated under mild conditions and adds to an alkene to form a new C–N bond. A desulfinylative Smiles-Truce rearrangement follows to form a new C–C bond. In this manner, biologically active arylethylamines and valuable building blocks can be rapidly assembled from abundant alkene feedstocks. Additionally, we demonstrate that chiral information from the sulfinamide can be transferred via rearrangement to a new carbon stereocenter in the product, thus advancing development of traceless asymmetric alkene difunctionalization methodologies.

Chiral arylsulfinylamides: all-in-one reagents for visible light-mediated asymmetric alkene aminoarylations

“…An elegant light-mediated intermolecular aminoarylation of alkenes using arylsulfonylacetamides as bifunctional reagents has been demonstrated [40][41][42][43] . The reaction, only applicable to electron-rich styrenes, furnished the corresponding β,β-diarylethylamines in racemic form 40 .…”

A modular photoredox route towards sulfoximines

“…In our previous work, we designed a general methodology for the aminoarylation reaction of unactivated alkenes using sulfinamides as precursors for nitrogen-centered radicals (NCRs) (Scheme 2a). [13] In that work, the NCR was trapped by the unactivated alkene, leading to the Smiles-Truce rearrangements. We had hypothesized divergent reactivity can be achieved when alternative radical acceptors are employed (Scheme 2b).…”

“…[15] The details of the mechanism are still under investigation, however, work conducted thus far has led us to believe we can develop conditions to favor and capture this postulated sulfur-centered radical (SCR) for identification and subsequent reactivity. Results and discussion: Inspired by our prior research on the aminoarylation reaction involving unactivated alkenes and the use of sulfinamides as precursors for NCRs (Scheme 2a), [13] we envisioned synthesizing enamines by employing alkenes bearing leaving groups (Scheme 2c). We hypothesized the generation of a NCR that would perform an addition reaction with a vinyl halide followed by a rapid elimination to the enamine.…”