Huisgen Cycloaddition

Schematic representation of the Huisgen Cycloaddition.
Mechanism of the Huisgen Cycloaddition
Mechanism of the Huisgen Cycloaddition
Original publication
Angew. Chem. Int. Ed.. 1963, 2, 565. Tetrahedron Lett.. 1960, 1, 9. Tetrahedron Lett.. 1960, 1, 5. Tetrahedron Lett.. 1960, 1, 1. J. Org. Chem.. 1984, 49, 276.
Reviews
Angew. Chem. Int. Ed.. 1963, 2, 565. Angew. Chem. Int. Ed.. 1976, 15, 123. Chem. Rev.. 1998, 98, 863. Chem. Rev.. 2005, 105, 2765. Chem. Rev.. 2008, 108, 2887. Org. React.. 1988, 36, 1. Org. React.. 2002, 61, 1. Tetrahedron. 2007, 63, 3235.
Sample reactions
info
intermediate structure intermediate structure
MeCN
RT, 5 h, 65%
"The product was cristallized to optical purity."
intermediate structure
info
intermediate structure
N-Benzylglycine
Dean-Stark
PhMe
Reflux, 15 h, 57%
"Also isolated was the C2-epimer (3 % yield)."
intermediate structure
info
intermediate structure
(CH2O)n
Sealed tube
PhMe
115 °C, 14 h, 70%
intermediate structure
info
intermediate structure
Sealed tube
THF
180 °C, 16 h, 20%
"Also isolated was 70 % of a regioisomer which could be thermally equilibrated to the desired product."
intermediate structure
info
intermediate structure
NaOEt, MeNHOH.HCl
EtOH, PhMe
Reflux, 24-36 h, 75%
intermediate structure
info
intermediate structure intermediate structure
HgO
PhMe
Reflux, 15 h, 96%
intermediate structure
info
intermediate structure
Xylene(s)
Reflux, 3 h
intermediate structure
info
intermediate structure
K2CO3
PhMe
130 °C, 10 h, 68% (2 steps)
intermediate structure