Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study

Casarin, M.; Kukushkin, V.; Kuznetsov, M.

Risultato della ricerca: Article

Abstract

The mechanism of the addition of indazole (Ind)-a bifunctional aromatic N,NH-nucleophile-to cyclohexyl isocyanide coordinated to the palladium(II) center in the model complex cis-[PdCl₂(CNMe)(CNCy)] (1) to give the corresponding aminocarbene ligand was investigated in detail by theoretical (DFT) methods. The most plausible mechanism of this reaction is that of the associative type involving nucleophilic attack of Ind by its unprotonated N atom at the isocyanide carbon atom followed by the stepwise proton transfer from the nucleophile molecule to the isocyanide N atom via deprotonation/protonation steps. Two reaction channels based on two tautomeric forms of indazole were found. The channel leading to the experimentally isolated aminocarbene product is based on the less stable tautomeric form. Another channel based on the more stable tautomer of Ind is slightly kinetically more favorable but it is endergonic. Thus, the regioselectivity of this reaction is thermodynamically rather than kinetically driven. The bonding situation in key species was analyzed.
Lingua originaleEnglish
pagine (da-a)2942-
Numero di pagine20
RivistaMolecules
Volume23
Stato di pubblicazionePublished - 2018

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Molecular Medicine
  • Chemistry (miscellaneous)

Cita questo

Casarin, M.; Kukushkin, V.; Kuznetsov, M. (2018). Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study. Molecules, 23, 2942-.

Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study. / Casarin, M.; Kukushkin, V.; Kuznetsov, M.

In: Molecules, Vol. 23, 2018, pag. 2942-.

Risultato della ricerca: Article

Casarin, M.; Kukushkin, V.; Kuznetsov, M. 2018, 'Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study', Molecules, vol. 23, pagg. 2942-.
Casarin, M.; Kukushkin, V.; Kuznetsov, M. / Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study. In: Molecules. 2018 ; Vol. 23. pagg. 2942-.
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abstract = "The mechanism of the addition of indazole (Ind)-a bifunctional aromatic N,NH-nucleophile-to cyclohexyl isocyanide coordinated to the palladium(II) center in the model complex cis-[PdCl₂(CNMe)(CNCy)] (1) to give the corresponding aminocarbene ligand was investigated in detail by theoretical (DFT) methods. The most plausible mechanism of this reaction is that of the associative type involving nucleophilic attack of Ind by its unprotonated N atom at the isocyanide carbon atom followed by the stepwise proton transfer from the nucleophile molecule to the isocyanide N atom via deprotonation/protonation steps. Two reaction channels based on two tautomeric forms of indazole were found. The channel leading to the experimentally isolated aminocarbene product is based on the less stable tautomeric form. Another channel based on the more stable tautomer of Ind is slightly kinetically more favorable but it is endergonic. Thus, the regioselectivity of this reaction is thermodynamically rather than kinetically driven. The bonding situation in key species was analyzed.",
keywords = "DFT calculations; activation of small molecules; isocyanides; nitriles; nucleophilic addition; reaction mechanism",
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T1 - Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study

AU - Casarin, M.; Kukushkin, V.; Kuznetsov, M.

AU - Casella, Girolamo

PY - 2018

Y1 - 2018

N2 - The mechanism of the addition of indazole (Ind)-a bifunctional aromatic N,NH-nucleophile-to cyclohexyl isocyanide coordinated to the palladium(II) center in the model complex cis-[PdCl₂(CNMe)(CNCy)] (1) to give the corresponding aminocarbene ligand was investigated in detail by theoretical (DFT) methods. The most plausible mechanism of this reaction is that of the associative type involving nucleophilic attack of Ind by its unprotonated N atom at the isocyanide carbon atom followed by the stepwise proton transfer from the nucleophile molecule to the isocyanide N atom via deprotonation/protonation steps. Two reaction channels based on two tautomeric forms of indazole were found. The channel leading to the experimentally isolated aminocarbene product is based on the less stable tautomeric form. Another channel based on the more stable tautomer of Ind is slightly kinetically more favorable but it is endergonic. Thus, the regioselectivity of this reaction is thermodynamically rather than kinetically driven. The bonding situation in key species was analyzed.

AB - The mechanism of the addition of indazole (Ind)-a bifunctional aromatic N,NH-nucleophile-to cyclohexyl isocyanide coordinated to the palladium(II) center in the model complex cis-[PdCl₂(CNMe)(CNCy)] (1) to give the corresponding aminocarbene ligand was investigated in detail by theoretical (DFT) methods. The most plausible mechanism of this reaction is that of the associative type involving nucleophilic attack of Ind by its unprotonated N atom at the isocyanide carbon atom followed by the stepwise proton transfer from the nucleophile molecule to the isocyanide N atom via deprotonation/protonation steps. Two reaction channels based on two tautomeric forms of indazole were found. The channel leading to the experimentally isolated aminocarbene product is based on the less stable tautomeric form. Another channel based on the more stable tautomer of Ind is slightly kinetically more favorable but it is endergonic. Thus, the regioselectivity of this reaction is thermodynamically rather than kinetically driven. The bonding situation in key species was analyzed.

KW - DFT calculations; activation of small molecules; isocyanides; nitriles; nucleophilic addition; reaction mechanism

UR - http://hdl.handle.net/10447/314152

M3 - Article

VL - 23

SP - 2942-

JO - Molecules

JF - Molecules

SN - 1420-3049

ER -