scholarly journals Intermolecular 3+3 Ring Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Aziridinium Ylides

2019 ◽  
Author(s):  
Jennifer Schomaker ◽  
Josephine Eshon ◽  
Kate A. Nicastri ◽  
Steven C. Schmid ◽  
William T. Raskopf ◽  
...  
Keyword(s):  
Natural Product ◽  
Functional Group ◽  
Ring Expansion ◽  
Sigmatropic Rearrangement ◽  
Reactive Intermediate ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Complex Molecules ◽  
Form Complex ◽  
Reaction Proceeds

Bicyclic aziridines undergo formal [3+3] ring expansion reactions when exposed to rhodium-bound vinyl carbenes to form complex dehydropiperidines in a highly stereocontrolled rearrangement. Mechanistic studies and DFT computations indicate the reaction proceeds through the formation of a vinyl aziridinium ylide; this reactive intermediate undergoes a concerted, asynchronous, pseudo-[1,4]- sigmatropic rearrangement to directly furnish the heterocyclic products with net retention at the new C-C bond. In combination with an asymmetric silver-catalyzed aziridination developed in our group, this method quickly delivers enantioenriched scaffolds with up to three contiguous stereocenters. The mild reaction conditions, functional group tolerance, and high stereochemical retention of this method are especially well-suited for appending piperidine motifs to natural product and complex molecules. Ultimately, our work establishes the value of underutilized aziridinium ylides as key intermediates in strategies to convert small, strained rings to larger N-heterocycles.

scholarly journals Intermolecular 3+3 Ring Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Aziridinium Ylides

2019 ◽  
Author(s):  
Jennifer Schomaker ◽  
Josephine Eshon ◽  
Kate A. Nicastri ◽  
Steven C. Schmid ◽  
William T. Raskopf ◽  
...  
Keyword(s):  
Natural Product ◽  
Functional Group ◽  
Ring Expansion ◽  
Sigmatropic Rearrangement ◽  
Reactive Intermediate ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Complex Molecules ◽  
Form Complex ◽  
Reaction Proceeds

Bicyclic aziridines undergo formal [3+3] ring expansion reactions when exposed to rhodium-bound vinyl carbenes to form complex dehydropiperidines in a highly stereocontrolled rearrangement. Mechanistic studies and DFT computations indicate the reaction proceeds through the formation of a vinyl aziridinium ylide; this reactive intermediate undergoes a concerted, asynchronous, pseudo-[1,4]- sigmatropic rearrangement to directly furnish the heterocyclic products with net retention at the new C-C bond. In combination with an asymmetric silver-catalyzed aziridination developed in our group, this method quickly delivers enantioenriched scaffolds with up to three contiguous stereocenters. The mild reaction conditions, functional group tolerance, and high stereochemical retention of this method are especially well-suited for appending piperidine motifs to natural product and complex molecules. Ultimately, our work establishes the value of underutilized aziridinium ylides as key intermediates in strategies to convert small, strained rings to larger N-heterocycles.

scholarly journals Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

2017 ◽  
Vol 13 ◽  
pp. 2610-2616 ◽  
Author(s):  
Tao Fan ◽  
Wei-Dong Meng ◽  
Xingang Zhang
Keyword(s):  
Alkyl Radical ◽  
Functional Group ◽  
High Efficiency ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Type Reaction ◽  
Alkyl Bromides ◽  
Reaction Proceeds ◽  
Palladium Catalyzed ◽  
Hydroxy Groups

An efficient palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides has been developed. The reaction proceeds under mild reaction conditions with high efficiency and excellent functional group tolerance, even towards formyl and hydroxy groups. Preliminary mechanistic studies reveal that a secondary trifluoromethylated alkyl radical is involved in the reaction.

scholarly journals Cu/Pd-catalyzed borocarbonylative trifunctionalization of alkynes and allenes: synthesis of β-geminal-diboryl ketones

2021 ◽  
Author(s):  
Yang Yuan ◽  
Fu-Peng Wu ◽  
Anke Spannenberg ◽  
Xiao-Feng Wu
Keyword(s):  
Organic Synthesis ◽  
Functional Group ◽  
Building Blocks ◽  
Mechanistic Studies ◽  
Efficient Strategy ◽  
New Class ◽  
Reaction Proceeds

AbstractFunctionalized bisboryl compounds have recently emerged as a new class of synthetically useful building blocks in organic synthesis. Herein, we report an efficient strategy to synthesize β-geminal-diboryl ketones enabled by a Cu/Pd-catalyzed borocarbonylative trifunctionalization of readily available alkynes and allenes. This reaction promises to be a useful method for the synthesis of functionalized β-geminal-diboryl ketones with broad functional group tolerance. Mechanistic studies suggest that the reaction proceeds through borocarbonylation/hydroboration cascade of both alkynes and allenes.

scholarly journals 3-Bromotetrazine: A Versatile Precursor for the Synthesis of 3-Monosubstituted s-Tetrazines and the Labelling of Macromolecules

2019 ◽  
Author(s):  
Simon Schnell ◽  
Lukas Hoff ◽  
Advaita Panchagnula ◽  
Simon Sieber ◽  
Anthony Linden ◽  
...  
Keyword(s):  
Natural Product ◽  
Mammalian Cells ◽  
Functional Group ◽  
Aqueous Media ◽  
Diels Alder ◽  
The Novel ◽  
Chemical Probe ◽  
Complex Molecules ◽  
Inverse Electron Demand ◽  
Electron Demand

<div><div><div><p>We report the synthesis of the novel precursor 3-bromotetrazine and its successful use in the synthesis of various families of 3-monosubstituted s-tetrazines. A remarkable functional group selectivity is utilized to site-selectively functionalize different complex molecules. The unexpected stability of 3- bromotetrazine in aqueous media facilitated the development of a protocol for protein functionalization in- stalling a tetrazine unit as a bio-orthogonal handle for inverse electron demand Diels-Alder reactions. Addi- tionally, a novel tetrazine-based chemical probe was developed and its application in the context of thiol- targeted natural product isolation and labelling of mammalian cells is demonstrated.</p></div></div></div>

Molecular Iodine-Catalyzed Carbonyl-Olefin Metathesis

2018 ◽  
Author(s):  
Thanh Vinh Nguyen ◽  
Uyen P. N. Tran ◽  
Giulia Oss ◽  
Martin Breugst ◽  
Eric Detmar ◽  
...  
Keyword(s):  
Chemical Transformation ◽  
Olefin Metathesis ◽  
Functional Group ◽  
Molecular Iodine ◽  
Mechanistic Studies ◽  
Metathesis Reaction ◽  
Reaction Conditions ◽  
Elemental Iodine

The carbonyl-olefin metathesis reaction is a synthetically valuable transformation that could facilitate rapid functional group interconversion and construction of new organic structures. Herein we demonstrate that elemental iodine, a very simple and mild catalyst, can efficiently promote this chemical transformation under mild reaction conditions with excellent outcomes. Our mechanistic studies revealed intriguing aspects of iodine activation mode that could change the previously established perception of catalyst and substrate design for the carbonyl-olefin metathesis reaction.

Acetic Acid-Promoted Rhodium(III)-Catalyzed Hydroarylation of Terminal Alkynes

Synlett ◽  
2019 ◽  
Vol 30 (08) ◽  
pp. 932-938 ◽  
Author(s):  
Chang-Lin Duan ◽  
Xing-Yu Liu ◽  
Yun-Xuan Tan ◽  
Rui Ding ◽  
Shiping Yang ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Functional Group ◽  
Bond Activation ◽  
Side Reactions ◽  
Terminal Alkynes ◽  
Terminal Alkyne ◽  
Mechanistic Studies ◽  
Mild Conditions ◽  
Reaction Proceeds

Rhodium(III)-catalyzed hydroarylation of terminal alkynes has not previously been achieved because of the inevitable oligomerization and other side reactions. Here, we report a novel Cp*Rh(III)-catalyzed hydroarylation of terminal alkynes in acetic acid as solvent to facilitate the C–H bond activation and subsequent transformations. This reaction proceeds under mild conditions, providing an effective approach to the synthesis of alkenylated heterocycles in high to excellent yields (31–99%) with a broad substrate scope (37 examples) and good functional-group compatibility. In this transformation, the loading of the alkyne can be reduced to 1.2 equivalents, which indicates the significant role of HOAc in lowering the reaction temperature and suppressing the oligomerization of the terminal alkyne. Preliminary mechanistic studies are also presented.

scholarly journals Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aijie Cai ◽  
Wenhao Yan ◽  
Xiaojun Zeng ◽  
Samson B. Zacate ◽  
Tzu-Hsuan Chao ◽  
...  
Keyword(s):  
Late Stage ◽  
Density Functional ◽  
Organic Molecules ◽  
Functional Group ◽  
Density Functional Theory Calculations ◽  
Bioactive Molecules ◽  
Mechanistic Studies ◽  
Ligand Effect ◽  
Functional Theory ◽  
Complex Molecules

AbstractOrganic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis in a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This approach simultaneously introduces CF2H groups along with complex alkyl or aryl groups into alkenes with regioselectivity opposite to traditional CF2H radical addition. We demonstrate a broad substrate scope and a wide functional group compatibility. This scalable protocol is applied to the late-stage functionalization of complex molecules and the synthesis of CF2H analogues of bioactive molecules. Mechanistic studies and density functional theory calculations suggest a unique ligand effect on the reactivity of the Cu-CF2H species.

scholarly journals Visible-Light, Iodine-Promoted Formation of N-Sulfonyl Imines and N-Alkylsulfonamides from Aldehydes and Hypervalent Iodine Reagents

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1838 ◽  
Author(s):  
Megan Hopkins ◽  
Zachary Brandeburg ◽  
Andrew Hanson ◽  
Angus Lamar
Keyword(s):  
Drug Discovery ◽  
Visible Light ◽  
Initial Step ◽  
Hypervalent Iodine ◽  
Mechanistic Studies ◽  
Synthetic Methodology ◽  
Reaction Conditions ◽  
Drug Discovery And Development ◽  
Radical Initiator ◽  
Reaction Proceeds

Alternative synthetic methodology for the direct installation of sulfonamide functionality is a highly desirable goal within the domain of drug discovery and development. The formation of synthetically valuable N-sulfonyl imines from a range of aldehydes, sulfonamides, and PhI(OAc)2 under practical and mild reaction conditions has been developed. According to mechanistic studies described within, the reaction proceeds through an initial step involving a radical initiator (generated either by visible-light or heat) to activate the reacting substrates. The reaction provides a synthetically useful and operationally simple, relatively mild alternative to the traditional formation of N-sulfonyl imines that utilizes stable, widely available reagents.

Sunlight-promoted cyclization versus decarboxylation in the reaction of alkynoates with N-iodosuccinimide: easy access to 3-iodocoumarins

2016 ◽  
Vol 18 (14) ◽  
pp. 3935-3939 ◽  
Author(s):  
Shengyang Ni ◽  
Jia Cao ◽  
Haibo Mei ◽  
Jianlin Han ◽  
Shuhua Li ◽  
...  
Keyword(s):  
Ring Expansion ◽  
Easy Access ◽  
Mechanistic Studies ◽  
Reaction Proceeds ◽  
Radical Conversion

We report the green, sunlight-initiated radical conversion of aryl alkynoates to 3-iodocoumarins using NIS without the use of a catalyst or additive. Mechanistic studies indicate that the reaction proceeds through iodination, spirocyclization and ring expansion to form the kinetic product.

scholarly journals 3-Bromotetrazine: A Versatile Precursor for the Synthesis of 3-Monosubstituted s-Tetrazines and the Labelling of Macromolecules

2019 ◽  
Author(s):  
Simon Schnell ◽  
Lukas Hoff ◽  
Advaita Panchagnula ◽  
Simon Sieber ◽  
Anthony Linden ◽  
...  
Keyword(s):  
Natural Product ◽  
Mammalian Cells ◽  
Functional Group ◽  
Aqueous Media ◽  
Diels Alder ◽  
The Novel ◽  
Chemical Probe ◽  
Complex Molecules ◽  
Inverse Electron Demand ◽  
Electron Demand

<div><div><div><p>We report the synthesis of the novel precursor 3-bromotetrazine and its successful use in the synthesis of various families of 3-monosubstituted s-tetrazines. A remarkable functional group selectivity is utilized to site-selectively functionalize different complex molecules. The unexpected stability of 3- bromotetrazine in aqueous media facilitated the development of a protocol for protein functionalization in- stalling a tetrazine unit as a bio-orthogonal handle for inverse electron demand Diels-Alder reactions. Addi- tionally, a novel tetrazine-based chemical probe was developed and its application in the context of thiol- targeted natural product isolation and labelling of mammalian cells is demonstrated.</p></div></div></div>

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