Synthesis of α‐Aryl Acrylamides via Lewis‐Base‐Mediated Aryl/Hydrogen Exchange

Abstract

Herein we report a method for the synthesis of α-aryl acrylamides leveraging polar S-to-C aryl migrations induced by a Lewis basic organocatalyst. In contrast to previously reported radical aryl migrations of sulfonyl acrylimides, this polar process enables subsequent elimination, ultimately leading to a formal aryl/ hydrogen exchange including SO 2 extrusion. This reaction is selective for electron-deficient aromatic groups, while tolerating a variety of substituents on nitrogen and in the β-position, and it delivers useful building blocks for further transformations, including cycloaddition and cyclisation reactions. The mechanism was investigated in detail using quantum chemical calculations, which unexpectedly revealed the Lewis base to be involved in several decisive steps.

Lewis Base‐assisted Arylation of Unsaturated Carbonyls

“…This selectivity stands out even more when compared to a similar process developed shortly after and utilizing I(III) (18) instead of S(IV) in combination with vinylic oxazoles 19 (Scheme 5B). [13] Therein, electrophilic activation is achieved using TMSOTf and a rearrangement (20) conceptually similar to that shown in Scheme 5A leads to o-iodo vinyl arenes 21, exclusively with E-configuration again attributed to a selective E1cB elimination step, as supported by quantum chemical computations.…”

“…[19] While these methods usually rely on radical sequences, Maulide et al have recently approached these Smiles cascades from a different, polar, point of view-ultimately exchanging arene and hydrogen under loss of SO 2 (Scheme 7). [20] Using the Lewis base DABCO, an aryl migration on α,β-unsaturated N-arylsulfonyl carboximides 29 is induced to afford a range of α-aryl acrylamides 30. It is worthy of note that the ionic nature of this process, proceeding through a spirocyclic (Meisenheimer-)transition state (31), requires the aromatic group to carry electron-withdrawing substituents.…”

Radical-Mediated α-tert-Alkylation of Aldehydes by Consecutive 1,4- and 1,3-(Benzo)thiazolyl Migrations

“…Simultaneously, Int-III undergoes 1,4-heteroaryl migration and generates the alkyl radical Int-V after SO 2 extrusion. It is found that the extruded SO 2 could be captured by pyrrolidine and thus consumes pyrrolidine, evidenced by HRMS analysis . The densely substituted intermediate Int-V undergoes unusual 1,3-heteroaryl migration via four-membered cyclic transition state driven by the Thorpe–Ingold effect, leading to a stable α-amino radical Int-VII .…”