A Gold‐Catalyzed Acid‐Assisted Regioselective Cyclization for the Synthesis of Polysubstituted Oxazoles

Wang, Qian; Hoffmann, Stephanie; Schießl, Jasmin; Rudolph, Matthias; Röminger, Frank; Hashmi, A. Stephen K.

doi:10.1002/ejoc.201900699

Cited by 16 publications

(7 citation statements)

References 74 publications

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“…These disclosed transformations with corresponding oxidatively generated carbene intermediates feature an alkyne dual-functionalization process . However, the reactions developed to date have mainly focused on the intramolecular versions using functionalized alkynes. , So far, the few precedents of intermolecular reactions of these in situ formed carbene intermediates from readily available alkynes were limited to X–H insertion, formal [3+2]-cycloaddition, rearrangement of allylic sulfur ylides, halogenation, and carbonylation with excess oxidant . Beyond these advances, an effective and practical protocol for the direct alkyne multi-functionalization is still very rare, especially the catalytic asymmetric version with commercially available alkynes.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Oxidative Multi-Functionalization of Terminal Alkynes with Nitrones and Alcohols for Expeditious Assembly of Chiral α-Alkoxy-β-amino-ketones

Zhou

Liu

et al. 2021

J. Am. Chem. Soc.

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Catalytic oxidative functionalization of alkynes has emerged as an effective method in synthetic chemistry in recent decades. However, enantioselective transformations via metal carbene intermediates are quite rare due to the lack of robust chiral catalysts, especially in the intermolecular versions. Herein, we report the first asymmetric three-component reaction of commercially available alkynes with nitrones and alcohols, which affords α-alkoxy-β-amino-ketones in good yields with high to excellent enantioselectivity using combined catalysis by an achiral gold complex and a chiral spiro phosphoric acid (CPA). Mechanistically, this atom-economic reaction involves a catalytic alkyne oxidation/ylide formation/Mannich-type addition sequence that uses nitrone as the oxidant and the leaving fragment imine as the electrophile, providing a novel method for multi-functionalization of commercially available terminal alkynes.

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Section: Introductionmentioning

confidence: 99%

Enantioselective Oxidative Multi-Functionalization of Terminal Alkynes with Nitrones and Alcohols for Expeditious Assembly of Chiral α-Alkoxy-β-amino-ketones

Zhou

Liu

et al. 2021

J. Am. Chem. Soc.

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“…The reaction provides access to a range of fully substituted oxazole-4-carboxylates 33 . Hashmi demonstrated in 2020 that alkynylamides are also suitable alkynes in this chemistry …”

Section: Reactions Without Metal Oxidation State Changementioning

confidence: 99%

“…Hashmi demonstrated in 2020 that alkynylamides are also suitable alkynes in this chemistry. 61 In 2014, R.-S. Liu reported an intramolecular variant of carbene trapping by nitriles that allows rapid access to N-(pyridine-2-yl)-ε-lactams (Scheme 18). 62 The proposed mechanism entails the formation of seven-membered nitrilium intermediate AJ upon trapping and subsequent nucleophilic addition at its nitrilium carbon by another molecule of pyridine N-oxide to form intermediate AK, which then undergoes cyclization to generate tricyclic dihydropyridine intermediate AL.…”

Section: Reactions Without Metal Oxidation State Change 21 Activated ...mentioning

confidence: 99%

Homogeneous Gold-Catalyzed Oxidation Reactions

et al. 2021

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Homogeneous gold catalysis has experienced extraordinary development since the dawn of this millennium. Oxidative gold catalysis is a vibrant and fertile subfield and has over the years delivered a diverse array of versatile synthetic methods of exceptional value to synthetic practices. This review aims to cover this topic in a comprehensive manner. The discussions are organized by the mechanistic aspects of the metal oxidation states and further by the types of oxidants or oxidizing functional groups. Synthetic applications of oxidative gold catalysis are also discussed. CONTENTS 4.5. Oxidation of Sulfides and Other Functional Groups 9029 5. Conclusion and Outlook 9030 Author Information 9030 Corresponding Author 9030 Authors 9030 Author Contributions 9030 Notes 9030 Biographies 9030 Acknowledgments 9031 References 9031

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“…For example, intramolecular tandem alkoxylation followed by Claisen rearrangement could be triggered by Au(I) catalyst, engendering both C–O and C–C bonds in a single step . Moreover, use of polarized alkynes, such as propiolates, promoted intermolecular addition of allyl ethers to propiolates and sulfonyl acetylenes . However, our initial efforts to develop an enantioselective version of the intermolecular alkoxyallylation were thwarted by the poor reactivity of allyl ethers, which necessitated wasteful use of excess propiolates (>10 equiv) or elaborate allyl ethers (Scheme b). , Furthermore, the oxonium intermediate I generated side products resulting from apparent [1,3]-rearrangement ( 4 ) and cleavage of allyl moiety ( 5 ) .…”

Section: Introductionmentioning

confidence: 99%

Gold-Catalyzed Asymmetric Thioallylation of Propiolates via Charge-Induced Thio-Claisen Rearrangement

2020

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A gold(I)-catalyzed enantioselective thioallylation of propiolates with allyl sulfides is described. The key mechanistic element is a sulfonium-induced Claisen rearrangement which helps minimize the allyl dissociation and render higher enantioselectivity. This protocol features remarkable scope of the allyl moiety, allowing enantiocontrolled synthesis of all-carbon quaternary centers, and exhibits exceptional functional group compatibility with many Lewis bases and π-bonds. This intermolecular variant of Claisen rearrangement forges both C–S and C–C bonds concomitantly, providing efficient access to interesting optically active organosulfur compounds which can be transformed further through the vinyl sulfide as a functional handle. The rate of the reaction was zeroth order with respect to allyl sulfides, which suggested a reversible inhibition, providing a resting state for the catalyst. The Hammett plot displayed a correlation with σp values, suggesting a turnover-limiting sigmatropic rearrangement where decreased electron-density on sulfur accelerated the rearrangement.

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A Gold‐Catalyzed Acid‐Assisted Regioselective Cyclization for the Synthesis of Polysubstituted Oxazoles

Abstract: Polysubstituted oxazole derivatives are obtained through a regioselective gold-catalyzed reaction of α-alkynylamides and alkynoates in the presence of nitriles. The intermediary obtained gold carbenes are generated by alkyne oxidation [a]

Cited by 16 publications

References 74 publications

Enantioselective Oxidative Multi-Functionalization of Terminal Alkynes with Nitrones and Alcohols for Expeditious Assembly of Chiral α-Alkoxy-β-amino-ketones

Enantioselective Oxidative Multi-Functionalization of Terminal Alkynes with Nitrones and Alcohols for Expeditious Assembly of Chiral α-Alkoxy-β-amino-ketones

Homogeneous Gold-Catalyzed Oxidation Reactions

Gold-Catalyzed Asymmetric Thioallylation of Propiolates via Charge-Induced Thio-Claisen Rearrangement

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