A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

Sundalam, Sunil K.; Nilova, Aleksandra; Seidl, Thomas L.; Stuart, David R.

doi:10.1002/anie.201603222

Cited by 103 publications

(42 citation statements)

References 31 publications

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“…[7] However, despite innovative tactics,c urrent methods have not coupled an aryl fragment with an N,N-dialkylamine partner,which are common molecular scaffolds in active pharmaceutical ingredients (API) of "blockbuster drugs" and prolific in drug discovery and design. [8] Based on our previous efforts in this area, we focused our approach on the discovery of mild reaction conditions that would avoid an aryne intermediate [9] and yield as ingle regioisomer from ipso-substitution. [8] Based on our previous efforts in this area, we focused our approach on the discovery of mild reaction conditions that would avoid an aryne intermediate [9] and yield as ingle regioisomer from ipso-substitution.…”

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confidence: 99%

Metal‐free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

2016

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A mild and metal-free approach to C-N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso-substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal-free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal-free C-N coupling reactions.

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confidence: 99%

Metal‐free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

2016

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“…Stuart and co‐workers have developed an efficient method for generating benzyne species from various diaryliodonium salts using amide base . Different aryne species can be generated by ortho ‐C−H deprotonation of diaryliodonium salts 33 with amide base.…”

Section: Application Of Diaryliodonium Salts As Benzyne Precursorsmentioning

confidence: 99%

“…The cyclic hypervalent iodine compound, phenylbenziodoxole 1 a (also known as diphenyliodonium‐2‐carboxylate) generates benzyne via decarboxylation at high temperatures . Diaryliodonium salts 1 b can be deprotonated by strong bases at the ortho position followed by elimination of ArI and formation of benzyne . Diaryliodonium salts with a silyl substituent in ortho position such as phenyl[2‐(trimethylsilyl)phenyl]iodonium triflate (Kitamura's reagent) 1 c can produce benzyne species via desilylation by fluoride source .…”

Section: Introductionmentioning

confidence: 99%

Iodonium Salts as Benzyne Precursors

Yoshimura

Saitô

Zhdankin

2018

Chemistry A European J

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Reactions involving benzyne and aryne intermediates have found widespread application in organic synthesis. Various benzyne precursors and benzyne generating procedures are known. Recently, methods of benzyne generation from diaryliodonium salts and related hypervalent iodine compounds have received considerable attention. These methods are characterized by mild reaction conditions and applicability in a broad range of chemical transformations. The present minireview is focused on the preparation and reactivity of hypervalent iodine based benzyne precursors. Furthermore, recent developments in their synthetic application are discussed.

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“…Spectral data matches literature. 17 Mesityl(2,4,6-trimethoxyphenyl)iodonium Tosylate (3a). Synthesized according to general procedure using using I 2 (511 mg, 2.0 mmol), mesitylene (0.56 mL, 4.0 mmol), tosic acid (766 mg, 4.0 mmol), and TMP-H (677 mg, 4.0 mmol) in CH 2 Cl 2 (40 mL).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

One-Pot Synthesis of Unsymmetric Diaryliodonium Salts from Iodine and Arenes

2017

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The first synthesis of unsymmetric diaryliodonium salts directly from iodine and arenes is presented. The methodology provides diaryliodonium salts with the trimethoxyphenyl (TMP) moiety as dummy group. The protocol avoids the customary use of iodoarenes, which can be both expensive and toxic. Excess reagents are not required, and the reactions are performed under mild conditions. O-Arylations with these TMP salts were demonstrated to be highly chemoselective. D iaryliodonium salts (diaryl-λ 3 -iodanes) have become exceedingly popular electrophilic arylating reagents for a wide range of nucleophiles under both metal-free and metalcatalyzed conditions in the past decade.1 The interest in applications with these hypervalent iodine reagents was accelerated by the development of novel synthetic routes to diaryliodonium salts, making these easily available at low cost. Our first contribution to this field was the development of a general one-pot route to diaryliodonium salts from iodoarenes using the reagent system mCPBA/triflic acid (TfOH) in dichloromethane, which delivered diaryliodonium triflates in high yields within short reaction times.2 The reaction was extended to the direct synthesis of symmetric diaryliodonium salts from arenes and iodine, a cascade reaction involving iodination, oxidation, and electrophilic aromatic substitution between the arene and the formed iodine(III) intermediate. 2The triflic acid system proved to be too reactive for the synthesis of iodonium salts with both aryl moieties substituted with electron-donating groups. Such diaryliodonium salts have previously been synthesized from [hydroxy(tosyloxy)iodo]-benzene (HTIB, Koser's reagent) derivatives.3 HTIB can be synthesized from the corresponding iodoarene using mCPBA/ tosic acid, 4 and we recently improved the synthesis of HTIB derivatives 1 by two interconnected routes. They can either be obtained by mCPBA-oxidation of iodoarenes (Scheme 1a) or from iodine and arenes by initial oxidative iodination, followed by oxidation to yield 1 (Scheme 1b). 5 The iodination was found to be the most difficult step in this sequence, limiting the substrate scope to arenes with electron-donating (EDG) substituents, and trifluoroethanol (TFE) 6 was employed as cosolvent to increase the reaction rates.To overcome the scope limitations in our mCPBA/triflic acid system, we developed a one-pot synthesis of electron-rich diaryliodonium salts 2 from iodoarenes, which likely proceeds via in situ formation of iodine(III) compounds 1 (Scheme 2a).That transformation could also be extended to the use of iodine and arenes as starting materials (Scheme 2b). 7 The latter route tolerated only arenes with EDG substituents, and the synthesis of unsymmetric diaryliodonium salts (R 1 ≠ R 2 ) was unsuccessful due to product mixtures, further limiting the scope. 8Stuart and co-workers later modified our mCPBA/TsOH conditions into a sequential one-pot reaction with iodoarenes and trimethoxybenzene (TMP-H) to obtain unsymmetric

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A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

Cited by 103 publications

References 31 publications

Metal‐free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

Metal‐free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

Iodonium Salts as Benzyne Precursors

One-Pot Synthesis of Unsymmetric Diaryliodonium Salts from Iodine and Arenes

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