A bioinspired and biocompatible ortho-sulfiliminyl phenol synthesis

Abstract

Synthetic methods inspired by Nature often offer unique advantages including mild conditions and biocompatibility with aqueous media. Inspired by an ergothioneine biosynthesis protein EgtB, a mononuclear non-haem iron enzyme capable of catalysing the C–S bond formation and sulfoxidation, herein, we discovered a mild and metal-free C–H sulfenylation/intramolecular rearrangement cascade reaction employing an internally oxidizing O–N bond as a directing group. Our strategy accommodates a variety of oxyamines with good site selectivity and intrinsic oxidative properties. Combining an O–N bond with an X–S bond generates a C–S bond and an S=N bond rapidly. The newly discovered cascade reaction showed excellent chemoselectivity and a wide substrate scope for both oxyamines and sulfenylation reagents. We demonstrated the biocompatibility of the C–S bond coupling reaction by applying a coumarin-based fluorogenic probe in bacterial lysates. Finally, the C–S bond coupling reaction enabled the first fluorogenic formation of phospholipids, which self-assembled to fluorescent vesicles in situ.

Cu(II)-Catalyzed ortho-Selective Aminomethylation of Phenols

“…In the past decade, many indirect methods have been developed to affect ortho -C–H functionalization of phenols via installation of directing groups on the hydroxyl substituent, such as silanes/silanols, esters, carbamates, ethers, and traceless phosphites (Figure a). The use of the free hydroxyl group as a directing substituent to functionalize phenols, though underdeveloped, is a straightforward, atom-economic, and step-saving strategy to prepare highly substituted phenols.…”

Synthesis of Sulfilimines Enabled by Copper-Catalyzed S-Arylation of Sulfenamides

“…Inspired by sulfur transferases, the Zhao group reported an elegant [2,3]-sigmatropic rearrangement of oxyacetamide derivatives to afford orthosul liminyl phenols (Scheme 1b). 11,12 This strategy again forms the sulfur-nitrogen double bond. To date, this novel strategy has not been expanded beyond the synthesis of ortho-hydroxylaryl sul limines.…”

[2,3]-Sigmatropic Rearrangement of Arylhydroxylamines: Rapid Access to ortho-Sulfonylated Anilines

“…Compared with the [1, 3]-σ rearrangement, the [3, 3]-σ rearrangement of arylhydroxylamine is more common, and has more reaction possibilities, which can even introduce other heteroatom functional groups besides oxygen atom. Tomkinson's group 5 Recently, Zhao, 6 Ren 7 and their co-workers reported the Nsulfonation/[2, 3]-σ rearrangement cascade reaction of aryloxyamines with various thiolating reagents with high regioselectivity and wide substrate range, which were the only two reported examples in the field of [2, 3]-σ rearrangement reaction through N-O bond cleavage (Scheme 2a). Since the arylhydroxylamines have the similar weak N-O bonds that were relatively easy to break, we envisioned that the [2, 3]-σ rearrangement reaction of arylhydroxylamines may also be realized in the presence of suitable reagent, providing structurally diverse ortho-functionalized aniline products (Scheme 2b).…”