Ruthenium-catalyzed azide-alkyne cycloaddition: scope and mechanism.
The catalytic activity of a series of ruthenium(II) complexes in azide-alkyne cycloadditions has been evaluated. The [Cp*RuCl] complexes, such as Cp*RuCl(PPh 3) 2, Cp*RuCl(COD), and Cp*RuCl(NBD), were among the most effective catalysts. In the presence of catalytic Cp*RuCl(PPh 3) 2 or Cp*RuCl(COD), primary and secondary azides react with a broad range of terminal alkynes containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-triazoles; tertiary azides were significantly less reactive. Both complexes also promote the cycloaddition reactions of organic azides with internal alkynes, providing access to fully-substituted 1,2,3-triazoles. The ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) appears to proceed via oxidative coupling of the azide and alkyne reactants to give a six-membered ruthenacycle intermediate, in which the first new carbon-nitrogen bond is formed between the more electronegative carbon of the alkyne and the terminal, electrophilic nitrogen of the azide. This step is followed by reductive elimination, which forms the triazole product. DFT calculations support this mechanistic proposal and indicate that the reductive elimination step is rate-determining.
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Brant C
BC
Boren
Sridhar
S
Narayan
Lars K
LK
Rasmussen
Li
L
Zhang
Haitao
H
Zhao
Zhenyang
Z
Lin
Guochen
G
Jia
Valery V
VV
Fokin
D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D009942:Organometallic Compounds / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis
D000480:Alkynes; D001386:Azides; D009942:Organometallic Compounds; D014230:Triazoles; D012428:Ruthenium