Enolate and Other Carbon Nucleophile Alkylation Reactions Using 1,2-Cyclic Sulfates as Terminal Epoxide Equivalents

Thomas R. Hoye; Khushrav B. Crawford

doi:10.1021/jo00082a005

ChemInform Abstract: Enolate and Other Carbon Nucleophile Alkylation Reactions Using 1,2- Cyclic Sulfates as Terminal Epoxide Equivalents.

ChemInform ◽

10.1002/chin.199426080 ◽

2010 ◽

Vol 25 (26) ◽

pp. no-no

Author(s):

T. R. HOYE ◽

K. B. CRAWFORD

Keyword(s):

Cyclic Sulfates ◽

Alkylation Reactions

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Copper Catalyzed sp3 C-H α-Acetylation

10.26434/chemrxiv.11407116.v1 ◽

2019 ◽

Author(s):

Otome Okoromoba ◽

Eun Sil Jang ◽

Claire McMullin ◽

Thomas Cundari ◽

Timothy H. Warren

Keyword(s):

Natural Products ◽

Dft Studies ◽

Alkyl Radicals ◽

Important Chemical ◽

Alkyl Electrophiles ◽

Synthetic Intermediates ◽

Alkylation Reactions

α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in in natural products and pharmaceuticals. We report the sp3 C-H α-acetylation of sp3 C-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CH2R at RT with tBuOOtBu as oxidant via copper(I) β-diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [CuII](CH2C(O)Ar) that capture alkyl radicals R• to give R-CH2C(O)Ar under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH2CH2C(O)Ar.

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Copper Catalyzed sp3 C-H α-Acetylation

10.26434/chemrxiv.11407116 ◽

2019 ◽

Author(s):

Otome Okoromoba ◽

Eun Sil Jang ◽

Claire McMullin ◽

Thomas Cundari ◽

Timothy H. Warren

Keyword(s):

Natural Products ◽

Dft Studies ◽

Alkyl Radicals ◽

Important Chemical ◽

Alkyl Electrophiles ◽

Synthetic Intermediates ◽

Alkylation Reactions

α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in in natural products and pharmaceuticals. We report the sp3 C-H α-acetylation of sp3 C-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CH2R at RT with tBuOOtBu as oxidant via copper(I) β-diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [CuII](CH2C(O)Ar) that capture alkyl radicals R• to give R-CH2C(O)Ar under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH2CH2C(O)Ar.

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An Anthrone-Based Kv7.2/7.3 Channel Blocker with Improved Properties for the Investigation of Psychiatric and Neurodegenerative Disorders

10.26434/chemrxiv.8246417 ◽

2019 ◽

Author(s):

Jacob Porter ◽

Oscar Vivas-Rodriguez ◽

C. David Weaver ◽

Eamonn Dickson ◽

Abdulmohsen Alsafran ◽

...

Keyword(s):

Patch Clamp ◽

Neurodegenerative Disorders ◽

Channel Blocker ◽

Optimal Combination ◽

Channel Blockers ◽

Enolate Alkylation ◽

Cyp Inhibition ◽

Alkylation Reactions ◽

Metabolic Instability

A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (JDP-107) with an optimal combination of potency (IC50= 0.16 𝜇M in a Kv7.2 thallium flux assay), efficacy in a Kv7.2/7.3 patch clamp assay, and drug-like properties.

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Novel Chiral Ligands for Palladium-catalyzed Asymmetric Allylic Alkylation/ Asymmetric Tsuji-Trost Reaction: A Review

Current Organic Chemistry ◽

10.2174/1385272823666190624145039 ◽

2019 ◽

Vol 23 (11) ◽

pp. 1168-1213 ◽

Cited By ~ 4

Author(s):

Samar Noreen ◽

Ameer Fawad Zahoor ◽

Sajjad Ahmad ◽

Irum Shahzadi ◽

Ali Irfan ◽

...

Keyword(s):

Asymmetric Catalysis ◽

Enantioselective Synthesis ◽

Chiral Ligands ◽

Allylic Alkylation ◽

Research Groups ◽

Asymmetric Allylic Alkylation ◽

Catalytic Potential ◽

Long Time ◽

Palladium Catalyzed ◽

Alkylation Reactions

Background: Asymmetric catalysis holds a prestigious role in organic syntheses since a long time and chiral inductors such as ligands have been used to achieve the utmost desired results at this pitch. The asymmetric version of Tsuji-Trost allylation has played a crucial role in enantioselective synthesis. Various chiral ligands have been known for Pdcatalyzed Asymmetric Allylic Alkylation (AAA) reactions and exhibited excellent catalytic potential. The use of chiral ligands as asymmetric inductors has widened the scope of Tsuji-Trost allylic alkylation reactions. Conclusion: Therefore, in this review article, a variety of chiral inductors or ligands have been focused for palladium catalyzed asymmetric allylic alkylation (Tsuji-Trost allylation) and in this regard, recently reported literature (2013-2017) has been described. The use of ligands causes the induction of enantiodiscrimination to the allylated products, therefore, the syntheses of various kinds of ligands have been targeted by many research groups to employ in Pd-catalyzed AAA reactions.

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A Synthetic Route to Quaternary Pyridinium Salt-Functionalized Silsesquioxanes

International Journal of Polymer Science ◽

10.1155/2012/586594 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Nataliya Kostenko ◽

Jochen Gottfriedsen ◽

Liane Hilfert ◽

Frank T. Edelmann

Keyword(s):

Pyridinium Salt ◽

High Yield ◽

Synthetic Route ◽

Alkylation Reactions ◽

Partial Success

A synthetic route to potentially biocidal silsesquioxanes functionalized by quaternary pyridinium functionalities has been developed.N-Alkylation reactions of the precursor compounds 4-(2-(trimethoxysilyl)ethyl)-pyridine (5) and 4-(2-trichloro-silylethyl)pyridine (6) with iodomethane,n-hexylbromide, andn-hexadecylbromide cleanly afforded the correspondingN-alkylpyridinium salts (7–10). The synthesis of a 4-(2-ethyl)pyridine POSS derivative (2) was achieved by capping of the silsesquioxane trisilanol Cy7Si7O9(OH)3(1) via two different preparative routes. Attempts to use compound2as precursor for quaternary pyridinium salt-functionalized POSS derivatives were met with only partial success. Only the reaction with iodomethane cleanly afforded the newN-methylpyridinium salt12in high yield, whereasn-hexylbromide andn-hexadecylbromide failed to react with2even under forcing conditions.

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