Iron(III)-Mediated Oxysulfonylation of Enamides with Sodium and Lithium Sulfinates

Abstract

An iron-mediated vicinal difunctionalization of enamides and enecarbamates with sulfinic acid salts and alcohols is described. This reaction proceeds under mild conditions and furnishes the oxysulfonylated products in moderate to excellent yields. Moreover, the direct incorporation of sulfur dioxide into the sulfonylated products via organolithium chemistry has been achieved. The formed NO -acetals are competent acylimine precursors. Their utilization as building block for the synthesis of biologically relevant β-amidosulfones is described as well. Introduction: Molecules bearing sulfonyl-derived functional groups, such as sulfones or sulfonamides, play an important role in organic chemistry and are widely used in various fields. 1,2 Among the different classes of sulfonyl-derived functional groups, sulfones are of particular interest. They display intriguing chemical and physical properties as well as interesting biological activities. Sulfones, which are often considered as chemical chameleons 3 , are versatile building blocks in organic synthesis. The sulfone motif can be found in various molecules with different applications ranging from agrochemcials and functional materials to active pharmaceutical ingredients. 2-4 Traditional approaches for the construction of sulfones include Friedel-Crafts type reactions of arenes with sulfonyl chlorides 5 , the oxidation of sulfides and sulfoxides 6 , addition reactions of sulfonyl radicals to alkenes and alkynes 7 or the electrophilic trapping of sulfinic acid salts 8,9. In the last ten years novel approaches based on the direct incorporation of sulfur dioxide 10, 11 or the functionalization of C-H bonds 12,13 have emerged as attractive and more sustainable alternatives.

Photocatalytic Umpolung ofN- andO-substituted alkenes for the synthesis of 1,2-amino alcohols and diols

“…17 Due to their innate nucleophilicity, they are excellent traps for electrophilic radicals, leading to the formation of a nucleophilic aamino radical I (Scheme 1A, a). The latter can then react with a radical trap, 18 undergo oxidation to the a-amino cation, [19][20][21] reduction to the a-amino anion, 22 or addition to an organometallic species followed by reductive elimination. 23 Despite the efficiency associated to such transformations, all enamide difunctionalizations reported so far are based on the initial addition of a highly reactive electrophilic radical, limiting functional group tolerance and the structural diversity of the obtained products.…”

“…It is important to stress that such an approach would completely change the type of transformations accessible, as the rst step would involve reaction with a nucleophile, in opposition to the electrophilic radical already intensively investigated. [17][18][19][20][21][22][23] Although this strategy appears highly attractive to answer current limitations in enamide functionalization, only one example of ene-carbamate hydroacetoxylation has been reported by Nicewicz and co-workers. 29 When considering the importance of nitrogen-containing compounds, a difunctionalization of enamides via photocatalytic Umpolung would be highly desirable.…”

Oxidative Sulfonylation of Multiple Carbon‐Carbon bonds with Sulfonyl Hydrazides, Sulfinic Acids and their Salts

“…Similar difunctionalization reaction was conducted between enamides and sodium or lithium sulfinates using FeCl 3 as the oxidant. [103] Electrochemical 1,2-aminosulfonylation of alkenes with sodium sulfinates and amines was also reported. [104] Scheme 74.…”

Recent Progress in Sulfonylation via Radical Reaction with Sodium Sulfinates, Sulfinic Acids, Sulfonyl Chlorides or Sulfonyl Hydrazides

“…Then sulfonyl radical addition, oxidation reaction and deprotonation occurred in sequence to afford the final product (Scheme 16). Next year, the same group reported iron(III)‐mediated oxysulfonylation of enamides with sodium and lithium sulfinates [25] . The oxysulfonylated products in moderate to excellent yields were obtained.…”