Regio- and stereoselective 1,3-dipolar cycloaddition reactions between arylideneacetones and stabilized azomethine ylides obtained from ninhydrin and indenoquinoxalinones

A new iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3+2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using catalytic Vaska’s complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent, regio- and diastereoselective, inter- and intramolecular, dipolar cycloaddition reactions with variously substituted electron-poor alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures which ultimately control the unusual selectivities observed in certain cases.

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A General Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides & Lactams

10.26434/chemrxiv.13587995.v1 ◽

2021 ◽

Author(s):

Ken Yamazaki ◽

Pablo Gabriel ◽

Graziano Di Carmine ◽

Julia Pedroni ◽

Mirxan Farizyan ◽

...

Keyword(s):

Density Functional ◽

Azomethine Ylides ◽

Azomethine Ylide ◽

Dipolar Cycloaddition ◽

Cycloaddition Reactions ◽

Reaction Conditions ◽

Functional Theory ◽

Efficient Access ◽

Stabilized Azomethine Ylides ◽

Tertiary Amides

A new iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3+2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using catalytic Vaska’s complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent, regio- and diastereoselective, inter- and intramolecular, dipolar cycloaddition reactions with variously substituted electron-poor alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures which ultimately control the unusual selectivities observed in certain cases.

Download Full-text

A General Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides & Lactams

10.26434/chemrxiv.13587995 ◽

2021 ◽

Author(s):

Ken Yamazaki ◽

Pablo Gabriel ◽

Graziano Di Carmine ◽

Julia Pedroni ◽

Mirxan Farizyan ◽

...

Keyword(s):

Density Functional ◽

Azomethine Ylides ◽

Azomethine Ylide ◽

Dipolar Cycloaddition ◽

Cycloaddition Reactions ◽

Reaction Conditions ◽

Functional Theory ◽

Efficient Access ◽

Stabilized Azomethine Ylides ◽

Tertiary Amides

A new iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3+2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using catalytic Vaska’s complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent, regio- and diastereoselective, inter- and intramolecular, dipolar cycloaddition reactions with variously substituted electron-poor alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures which ultimately control the unusual selectivities observed in certain cases.

Download Full-text