A Metal‐Free Direct Arene C−H Amination

Wang, Tao; Hoffmann, Marvin; Dreuw, Andreas; Hasagić, Edina; Hu, Chao; Stein, Philipp M.; Witzel, Sina; Shi, Hongwei; Yang, Yangyang; Rudolph, Matthias; Stuck, Fabian; Röminger, Frank; Kerscher, Martin; Comba, Peter; Hashmi, A. Stephen K.

doi:10.1002/adsc.202100236

Cited by 33 publications

(14 citation statements)

References 61 publications

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“…Hydroxylamines and their derivatives are powerful aminating reagents, which are often used for arene C–H and X-H aminations (X = O, N, S, P) 40 – 45 as well as Schmidt-type reaction 46 , serving as alternative ways to introduce amino groups on various chemical skeletons. Recently, our group 47 published a metal-free arene C–H amination using ArSO 2 ONHR in HFIP. All this prompted us to investigate the possibility of harnessing hydroxylamine derivatives for direct arene dealkylative aminations.…”

Section: Resultsmentioning

confidence: 99%

Hydroxylamine-mediated C–C amination via an aza-hock rearrangement

et al. 2021

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Despite the widespread use of anilines, synthetic challenges to these targets still exist. Selectivity is often an issue, when using the traditional nitration-reduction sequence or more modern approaches, including arene C–H aminations catalyzed by transition metals, photosensitizers, or electrodes. Accordingly, there is still a need for general methods to rapidly, directly access specific isomers of substituted anilines. Here, we report a simple route towards the synthesis of such motifs starting from benzyl alcohols, which are converted to anilines by the use of arylsulfonyl hydroxylamines, via an aza-Hock rearrangement. Good to excellent yields are observed. The method is applicable to various benzyl alcohol surrogates (such as ethers, esters, and halides) as well as simple alkylarenes. Functionalizations of pharmaceutically relevant structures are feasible under the reaction conditions. Over ten amination reagents can be used, which facilitates the rapid assembly of a vast set of compounds.

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Section: Resultsmentioning

confidence: 99%

Hydroxylamine-mediated C–C amination via an aza-hock rearrangement

et al. 2021

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“…Based on precedent we envisage that the reaction proceeds via a radical mechanism [4d–f, 5g, 9b] and tentatively propose that the most likely form of this is a radical chain process, [13] initiated by cleavage of the weak N−O bond that intermediate II possesses once the Boc group is removed (Scheme 3C) [5c–e] . Thermal homolytic cleavage under relatively mild conditions has been shown to be viable for related O ‐methanesulfonyl hydroxylamines [4f] .…”

Section: Figurementioning

confidence: 99%

An Aminative Rearrangement of O‐(Arenesulfonyl)hydroxylamines: Facile Access to ortho‐Sulfonyl Anilines

2022

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Ortho-sulfonyl anilines are important building blocks for a range of applications. We report the discovery of an aromatic rearrangement reaction of O-(arenesulfonyl)hydroxylamines which leads directly to ortho-sulfonyl anilines through formation of a new CÀ N bond with excellent levels of regiocontrol for the ortho position(s) over all others. We establish that the rearrangement is proceeding through an intermolecular mechanism and propose that the regiocontrol observed is the result of attractive non-covalent interactions occurring during the CÀ N bond-forming step. Importantly, this method is complementary to classical aniline sulfonation in terms of the variously substituted regioisomers that can be obtained and it is also applicable to O-(benzylsulfonyl) hydroxylamines.

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“…In continuation of our ongoing work on O ‐substituted hydroxylamine derivatives to develop efficient and simple methodologies, [7a–c] we were next interested to develop an efficient, one‐pot, mild, and transition‐metal‐free method using bench stable N ‐Boc‐ O ‐tosylhydroxylamine (TsONHBoc) as a nitrogen donor for conversion of aryl boronic acids/derivatives to primary aromatic amines. Recently, Hashmi and the group used this reagent for a metal‐free arene C−H amination [7d] . This N ‐Boc protected aminating agent (TsONHBoc) is stable at ambient temperature, easy to handle and generates a non‐interfering, water‐soluble by‐product (TsOH).…”

Section: Introductionmentioning

confidence: 99%

Metal‐Free Direct Transformation of Aryl Boronic Acid to Primary Amines

et al. 2022

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In this work, we report a transition-metal free approach for the construction of primary aromatic amines from aryl boronic acids and esters with N-Boc-O-tosylhydroxylamine as an amine surrogate. Bench stable TsONHBoc is easy to use and it produces a non-interfering water-soluble by-product. The protocol is operative for both electron-rich and electron-deficient aryl boronic acids under acidic conditions, where the former arenes affords a better yield of the desired product. Even, sterically hindered and halogenated substrates are easily amenable under this reaction condition. The current protocol can be scaled up to produce gram-scale primary aromatic amines.

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A Metal‐Free Direct Arene C−H Amination

Cited by 33 publications

References 61 publications

Hydroxylamine-mediated C–C amination via an aza-hock rearrangement

Hydroxylamine-mediated C–C amination via an aza-hock rearrangement

An Aminative Rearrangement of O‐(Arenesulfonyl)hydroxylamines: Facile Access to ortho‐Sulfonyl Anilines

Metal‐Free Direct Transformation of Aryl Boronic Acid to Primary Amines

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