Synthesis and stereochemistry of telomers of vinylene carbonate as synthetic intermediates for carbohydrates

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.

Download Full-text

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.

Download Full-text

Synthesis of Nitrile-Bearing Quaternary Centers via an Equilibrium-Driven Transnitrilation and Anion-Relay Strategy

10.26434/chemrxiv.7834940 ◽

2019 ◽

Author(s):

Sebastien Alazet ◽

Michael West ◽

Purvish Patel ◽

Sophie Rousseaux

Keyword(s):

Building Blocks ◽

One Pot ◽

Quaternary Centers ◽

Synthetic Intermediates

The efficient preparation of nitrile-containing building blocks is of interest due to their utility as synthetic intermediates and their prevalence in pharmaceuticals. As a result, significant efforts have been made to develop methods to access these motifs which rely on safer and non-toxic sources of CN. Herein, we report that 2-methyl-2-phenylpropanenitrile is an efficient, non-toxic, electrophilic CN source for the synthesis of nitrile-bearing quaternary centers via a thermodynamic transnitrilation and anion-relay strategy. This one-pot process leads to nitrile products resulting from the gem-difunctionalization of alkyl lithium reagents.

Download Full-text