Synthesis of All-carbon Disubstituted Bicyclo[1.1.1]pentanes by Iron-Catalyzed Kumada CrossCoupling

1,3-Disubstituted bicyclo[1.1.1]pentanes (BCPs) are important motifs in drug design as surrogates for p-substituted arenes and alkynes. Access to all-carbon disubstituted BCPs via cross coupling has to date been limited to use of the BCP as the organometallic component, which restricts scope due to the harsh conditions typically required for the synthesis of metallated BCPs. Here we report a general method to access 1,3-C-disubstituted BCPs from 1-iodo-bicyclo[1.1.1]pentanes (iodo-BCPs) by direct iron-catalyzed crosscoupling with aryl and heteroaryl Grignard reagents. This chemistry represents the first general use of iodoBCPs as electrophiles in cross-coupling, and of Kumada coupling of tertiary iodides in general. Benefiting from short reaction times, mild conditions, and broad scope of the coupling partners, it enables the synthesis of a wide range of 1,3-C-disubstituted BCPs including various drug analogues.

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Metal- and Acid-Free Methyl Triflate Catalyzed Meyer–Schuster Rearrangement

Synthesis ◽

10.1055/s-0036-1588800 ◽

2017 ◽

Vol 49 (14) ◽

pp. 3149-3156 ◽

Cited By ~ 7

Author(s):

Qingle Zeng ◽

Lu Yang

Keyword(s):

Carbonyl Compounds ◽

Reaction Times ◽

Mild Conditions ◽

Broad Scope ◽

Rearrangement Process ◽

Methyl Triflate ◽

Propargyl Alcohols

A novel metal- and acid-free preparation of synthetically useful α,β-unsaturated carbonyl compounds from propargyl alcohols has been realized. This Meyer–Schuster rearrangement process is effectively catalyzed by methyl triflate (20 mol%) to prepare a broad scope of conjugated E-enals and E-enones generally in good to excellent yields (up to 90%). This reaction procedure operates under mild conditions (70 °C), in air, with short reaction times (1 h). Moreover, a carbocation intermediate trapped by the solvent 2,2,2-trifluoroethanol was isolated during this transformation.

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Palladium-Catalyzed Cross-Coupling of Gem-Bromofluoroalkenes with Alkylboronic Acids for the Synthesis of Alkylated Monofluoroalkenes

Molecules ◽

10.3390/molecules25235532 ◽

2020 ◽

Vol 25 (23) ◽

pp. 5532

Author(s):

Laëtitia Chausset-Boissarie ◽

Nicolas Cheval ◽

Christian Rolando

Keyword(s):

Organic Synthesis ◽

Functional Group ◽

Materials Science ◽

Cross Coupling ◽

High Yield ◽

Efficient Synthesis ◽

Mild Conditions ◽

Wide Range ◽

Palladium Catalyzed ◽

Novel Strategy

Monofluoroalkenes are versatile fluorinated synthons in organic synthesis, medicinal chemistry and materials science. In light of the importance of alkyl-substituted monofluoroalkenes efficient synthesis of these moieties still represents a synthetic challenge. Herein, we described a mild and efficient methodology to obtain monofluoroalkenes through a stereospecific palladium-catalyzed alkylation of gem-bromofluoroalkenes with primary and strained secondary alkylboronic acids under mild conditions. This novel strategy gives access to a wide range of functionalized tri- and tetrasubstituted monofluoroalkenes in high yield, with good functional group tolerance, independently from the gem-bromofluoroalkenes geometry.

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Integrating Allyl Electrophiles into Nickel-Catalyzed Conjunctive Cross-Coupling

10.26434/chemrxiv.9722348 ◽

2019 ◽

Author(s):

Van Tran ◽

Zi-Qi Li ◽

Timothy Gallagher ◽

Joseph Derosa ◽

Peng Liu ◽

...

Keyword(s):

Organic Synthesis ◽

Cross Coupling ◽

Building Blocks ◽

Reductive Elimination ◽

Mechanistic Studies ◽

Mild Conditions ◽

Wide Range ◽

Directing Group ◽

Weakly Coordinating ◽

Analogous Method

Allylation and conjunctive cross-coupling represent two useful, yet largely distinct, reactivity paradigms in catalysis. The union of these two processes would offer exciting possibilities in organic synthesis but remains largely unknown. Herein, we report the use of allyl electrophiles in nickel-catalyzed conjunctive cross-coupling with a non-conjugated alkene and dimethylzinc. The transformation is enabled by weakly coordinating, monodentate azaheterocycle directing groups, that useful building blocks in synthesis, including saccharin, pyridones, pyrazoles, and triazoles. The reaction occurs under mild conditions and is compatible with a wide range of allyl electrophiles. High chemoselectivity through substrate directivity is demonstrated in the facile reactivity of the β-γ alkene of the starting material, while the ε-ζ alkene of the product is preserved. The generality of this approach is further illustrated through the development of analogous method with alkyne substrates. Mechanistic studies reveal the importance of the weakly coordinating directing group in dissociating to allow binding of the allyl moiety to facilitate C(sp3)–C(sp3) reductive elimination.

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Integrating Allyl Electrophiles into Nickel-Catalyzed Conjunctive Cross-Coupling

10.26434/chemrxiv.9722348.v1 ◽

2019 ◽

Author(s):

Van Tran ◽

Zi-Qi Li ◽

Timothy Gallagher ◽

Joseph Derosa ◽

Peng Liu ◽

...

Keyword(s):

Organic Synthesis ◽

Cross Coupling ◽

Building Blocks ◽

Reductive Elimination ◽

Mechanistic Studies ◽

Mild Conditions ◽

Wide Range ◽

Directing Group ◽

Weakly Coordinating ◽

Analogous Method

Allylation and conjunctive cross-coupling represent two useful, yet largely distinct, reactivity paradigms in catalysis. The union of these two processes would offer exciting possibilities in organic synthesis but remains largely unknown. Herein, we report the use of allyl electrophiles in nickel-catalyzed conjunctive cross-coupling with a non-conjugated alkene and dimethylzinc. The transformation is enabled by weakly coordinating, monodentate azaheterocycle directing groups, that useful building blocks in synthesis, including saccharin, pyridones, pyrazoles, and triazoles. The reaction occurs under mild conditions and is compatible with a wide range of allyl electrophiles. High chemoselectivity through substrate directivity is demonstrated in the facile reactivity of the β-γ alkene of the starting material, while the ε-ζ alkene of the product is preserved. The generality of this approach is further illustrated through the development of analogous method with alkyne substrates. Mechanistic studies reveal the importance of the weakly coordinating directing group in dissociating to allow binding of the allyl moiety to facilitate C(sp3)–C(sp3) reductive elimination.

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A Mesoporous Zirconium-Isophthalate Multifunctional Platform

10.26434/chemrxiv.12661310 ◽

2020 ◽

Author(s):

Sujing Wang ◽

Liyu Chen ◽

Mohammad Wahiduzzaman ◽

Antoine Tissot ◽

Lin Zhou ◽

...

Keyword(s):

Mesoporous Materials ◽

Hydrolytic Stability ◽

Isophthalic Acid ◽

Chemical Diversity ◽

Mild Conditions ◽

Wide Range ◽

Potential Applications ◽

Single Structure ◽

Harsh Conditions ◽

Multifunctional Platform

Mesoporous materials suffer from limitations including poor crystallinity and hydrolytic stability, lack of chemical diversity, insufficient pore accessibility, complex synthesis and toxicity issues. Here the association of non-toxic Zr-oxo clusters and feedstock isophthalic acid (IPA) via a Homometallic-Multicluster-Dot strategy results in a robust crystalline mesoporous MOF, denoted as MIP-206, that overcomes the aforementioned limitations. MIP-206, built up from an unprecedented combination of Zr6 and Zr12 oxo-cluster inorganic building units into a single structure, exhibits accessible meso-channels of ca. 2.6 nm and displays excellent chemical stability under different hydrolytic and harsh conditions. Owing to the abundant variety of functionalized IPA linkers, the chemical environment of MIP-206 can be easily tuned without hampering pore accessibility due to its large pore windows. As a result, MIP-206 loaded with palladium nanoparticles acts as an efficient and durable catalyst for the dehydrogenation of formic acid under mild conditions, outperforming benchmark mesoporous materials. This paves the way towards the utilization of MIP-206 as a robust mesoporous platform for a wide range of potential applications.

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Nickel-Catalyzed System for the Cross-Coupling of Alkenyl Methyl Ethers with Grignard Reagents under Mild Conditions

Organic Letters ◽

10.1021/acs.orglett.8b00313 ◽

2018 ◽

Vol 20 (7) ◽

pp. 1815-1818 ◽

Cited By ~ 10

Author(s):

Thomas Hostier ◽

Zeina Neouchy ◽

Vincent Ferey ◽

Domingo Gomez Pardo ◽

Janine Cossy

Keyword(s):

Cross Coupling ◽

Grignard Reagents ◽

Mild Conditions ◽

The Cross

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A Mesoporous Zirconium-Isophthalate Multifunctional Platform

10.26434/chemrxiv.12661310.v1 ◽

2020 ◽

Author(s):

Sujing Wang ◽

Liyu Chen ◽

Mohammad Wahiduzzaman ◽

Antoine Tissot ◽

Lin Zhou ◽

...

Keyword(s):

Mesoporous Materials ◽

Hydrolytic Stability ◽

Isophthalic Acid ◽

Chemical Diversity ◽

Mild Conditions ◽

Wide Range ◽

Potential Applications ◽

Single Structure ◽

Harsh Conditions ◽

Multifunctional Platform

Mesoporous materials suffer from limitations including poor crystallinity and hydrolytic stability, lack of chemical diversity, insufficient pore accessibility, complex synthesis and toxicity issues. Here the association of non-toxic Zr-oxo clusters and feedstock isophthalic acid (IPA) via a Homometallic-Multicluster-Dot strategy results in a robust crystalline mesoporous MOF, denoted as MIP-206, that overcomes the aforementioned limitations. MIP-206, built up from an unprecedented combination of Zr6 and Zr12 oxo-cluster inorganic building units into a single structure, exhibits accessible meso-channels of ca. 2.6 nm and displays excellent chemical stability under different hydrolytic and harsh conditions. Owing to the abundant variety of functionalized IPA linkers, the chemical environment of MIP-206 can be easily tuned without hampering pore accessibility due to its large pore windows. As a result, MIP-206 loaded with palladium nanoparticles acts as an efficient and durable catalyst for the dehydrogenation of formic acid under mild conditions, outperforming benchmark mesoporous materials. This paves the way towards the utilization of MIP-206 as a robust mesoporous platform for a wide range of potential applications.

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Pt-Pd Nanoalloy for the Unprecedented Activation of Carbon-Fluorine Bond at Low Temperature

10.26434/chemrxiv.11145098 ◽

2019 ◽

Author(s):

Raghu Nath Dhital ◽

keigo nomura ◽

Yoshinori Sato ◽

Setsiri Haesuwannakij ◽

Masahiro Ehara ◽

...

Keyword(s):

Activation Energy ◽

Low Temperature ◽

Dft Calculations ◽

Bond Activation ◽

Mild Conditions ◽

Selective Transformation ◽

Rate Determining Step ◽

Highly Active ◽

Harsh Conditions ◽

Reaction Profile

Carbon-Fluorine (C-F) bonds are considered the most inert organic functionality and their selective transformation under mild conditions remains challenging. Herein, we report a highly active Pt-Pd nanoalloy as a robust catalyst for the transformation of C-F bonds into C-H bonds at low temperature, a reaction that often required harsh conditions. The alloying of Pt with Pd is crucial to activate C-F bond. The reaction profile kinetics revealed that the major source of hydrogen in the defluorinated product is the alcoholic proton of 2-propanol, and the rate-determining step is the reduction of the metal upon transfer of the beta-H from 2-propanol. DFT calculations elucidated that the key step is the selective oxidative addition of the O-H bond of 2-propanol to a Pd center prior to C-F bond activation at a Pt site, which crucially reduces the activation energy of the C-F bond. Therefore, both Pt and Pd work independently but synergistically to promote the overall reaction

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Reversing Reactivity: Stereoselective Desulfurative β-O-Glycosylation of Anomeric Thiosugars with Carboxylic Acids Under Copper or Cobalt Catalysis

10.26434/chemrxiv.11421576.v1 ◽

2019 ◽

Author(s):

Samir Messaoudi ◽

Nedjwa Bennai ◽

Amelie Chabrier ◽

Maha Fatthalla ◽

Expédite Yen-Pon ◽

...

Keyword(s):

Carboxylic Acids ◽

Late Stage ◽

Catalytic Amount ◽

Broad Scope ◽

Wide Range ◽

Glycosylation Reaction

We have discovered a new mode of reactivity of 1-thiosugars in the presence of Cu(II) or Co(II) for a stereoselective O-glycosylation reaction. The process involves the use of a catalytic amount of Cu(acac)2 or Co(acac)2 and Ag2CO3 as an oxidant in α,α,α-trifluorotoluene (TFT). Moreover, this protocol turned out to have a broad scope, allowing to prepare a wide range of com-plex substituted O-glycoside esters in good to excellent yields with an exclusive β-selectivity. The late-stage modification of phar-maceuticals by this method was also demonstrated.

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