Efficient O‐Functionalization of Carbohydrates with Electrophilic Reagents

Tolnai, Gergely L.; Nilsson, Ulf J.; Olofsson, Berit

doi:10.1002/anie.201605999

Cited by 83 publications

(34 citation statements)

References 76 publications

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“…[7] Our research group has gained considerable experience in metal-free arylations with these reagents using O-, N-and Ccentered nucleophiles. [8] While most of these have been efficiently arylatedb yt he ligand couplingp athway,s everal intriguing indications on alternative reactionp athways have been observed, for example, by formation of regioisomeric products and oxidized byproducts. Mechanistic insights to these fascinating observations would aid further developments with diaryliodonium salts and other iodine(III) reagents, and we thus initiated an investigation on competing pathways in O-arylations using both experimental techniques and DFT calculations.…”

Section: Introductionmentioning

confidence: 99%

Competing Pathways in O‐Arylations with Diaryliodonium Salts: Mechanistic Insights

Stridfeldt

Lindstedt

Reitti

et al. 2017

Chemistry A European J

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A mechanistic study of arylations of aliphatic alcohols and hydroxide with diaryliodonium salts, to give alkyl aryl ethers and diaryl ethers, has been performed using experimental techniques and DFT calculations. Aryne intermediates have been trapped, and additives to avoid by‐product formation originating from arynes have been found. An alcohol oxidation pathway was observed in parallel to arylation; this is suggested to proceed by an intramolecular mechanism. Product formation pathways via ligand coupling and arynes have been compared, and 4‐coordinated transition states were found to be favored in reactions with alcohols. Furthermore, a novel, direct nucleophilic substitution pathway has been identified in reactions with electron‐deficient diaryliodonium salts.

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Section: Introductionmentioning

confidence: 99%

Competing Pathways in O‐Arylations with Diaryliodonium Salts: Mechanistic Insights

Stridfeldt

Lindstedt

Reitti

et al. 2017

Chemistry A European J

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“…Recently,b reakthroughs in the direct O-arylation of free hydroxy groups in carbohydrates by the use of electrophilic arylating agents have been reported. [11] In these reactions, however, strong bases are used, and extensive protection of all other hydroxy groups seems to be necessary to avoid overarylation.…”

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confidence: 99%

Site‐Selective O‐Arylation of Glycosides

et al. 2017

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Direct and site-selective O-arylation of carbohydrates has been a challenge in synthesis. Herein we report a method based on copper-catalyzed O-arylation to address this challenge. Proper choice of the ancillary ligand on copper is critical for the efficiency and site selectivity of this transformation. This method features mild conditions, tolerates various functional groups, and demonstrates broad substrate scope.

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“…After initial optimization (see Table S1), it was found that the target di‐ p ‐tolyliodonium triflate ( 4 a ) could be obtained, after only a two‐seconds residence time, in excellent yield (89 %) after crystallization (Table ). Notably, our flow protocol was highly reproducible and the yields were typically higher than those obtained with conventional batch labware (52–67 %) . The procedure can be readily scaled and, as an example, we obtained 2.04 grams of 4 a (5 mmol scale, 89 %).…”

Section: Methodsmentioning

confidence: 82%

A Modular Flow Design for the meta‐Selective C−H Arylation of Anilines

et al. 2017

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Described herein is an effective and practical modular flow design for the meta-selective CÀHa rylation of anilines.T he design consists of four continuous-flowm odules (i.e., diaryliodonium salt synthesis,m eta-selective CÀHa rylation, inline copper extraction, and aniline deprotection) which can be operated either individually or consecutively to provide direct access to meta-arylated anilines.W ith at otal residence time of 1hour,t he desired product could be obtained in high yield and excellent purity without the need for column chromatography,a nd the residual copper content meets the standards for parenterally administered pharmaceutical substances.Site-selective C À Hb ond functionalization strategies are of paramount importance in modern organic synthesis.[1] However,b ecause of the ubiquitous presence of CÀHb onds in organic molecules,the regioselective assembly of substituted arenes remains am ajor challenge.T raditionally,t he ortho and, to some extent, the para substitution of arenes have been thoroughly explored with the use of Friedel-Crafts chemistry. More recently,m uch work has been carried out on the transition metal catalyzed ortho-functionalization of arenes, and it proceeds by ac yclometalation strategy.[2] In contrast, the development of meta-selective transformations has required much more scientific investigation. Besides traditional approaches which rely on tuning steric and electronic properties of aromatic substrates,n ovel robust catalytic strategies have emerged.[3] Fore xample,t he incorporation of directing-group templates [4] or the use of transient ligand mediators [5] (e.g.,P d/norbornene) have been exploited to carefully navigate transition metals to the meta-position.Among the reported meta-selective C À Hf unctionalization strategies,the meta-arylation of electron-rich arenes is of high interest to access novel biaryl motifs,w hich represent ac ommon moiety within medicines,a grochemicals,a nd functional materials.[6] In particular, Gaunt and co-workers first reported the meta-selective C À Ha rylation of protected anilines. [7] This transformation was believed to proceed via ah ighly electrophilic Cu III

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Efficient O‐Functionalization of Carbohydrates with Electrophilic Reagents

Cited by 83 publications

References 76 publications

Competing Pathways in O‐Arylations with Diaryliodonium Salts: Mechanistic Insights

Competing Pathways in O‐Arylations with Diaryliodonium Salts: Mechanistic Insights

Site‐Selective O‐Arylation of Glycosides

A Modular Flow Design for the meta‐Selective C−H Arylation of Anilines

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