3 Cycloaddition with Azides, Alkynes, Alkenes and Allenes
3.1 Azide–Alkyne Cycloaddition
The copper-catalysed azide–alkyne cycloaddition reaction is a reliable and robust
synthetic method for covalently linking a diverse range of molecular building
blocks [41, 42], bioconjugation [43] and organic synthesis [44–48]. The reaction
proceeds in a highly selective single step, under mild reaction conditions, and is
successful in the presence of a wide range of other functional groups. It has only
recently been established that this reaction proceeds through the mechanism shown
in Scheme 9, whereby η
2 -coordination of a second Cu centre to the Cu–acetylide
complex forms intermediate 20 [49]. Nucleophilic attack at N-3 of the azide by the
Ru
*Cp
Cp*
Cl
SR
Ru
RS
Ru
*Cp
Cp*
Cl
SR
C
Ru
RS
BF 4
C
H HC
Ru
*Cp
Cp*
Cl
SR
C
Ru
RS
BF 4
C
HC C CHR'OH
H 2 O
OH
R'
C
H
R'
Ru
*Cp
Cp*
Cl
SR
C
Ru
RS
BF 4
C
H
H
C
19
OEt
R'
EtOH
HC C CHR'OEt
Ru
*Cp
Cp*
Cl
SR
Cl
Ru
RS
7 (R= alkyl)
HC
C H
C OEt
R'
NH 4 BF 4 +
HC C CHR'OH
R
OH
R
OEt
EtOH
+ 7 (cat.)
R
NH
R
O
R
O
Ar
etc.
a)
b)
ArNH 2
O
O
Scheme 8 (a) Catalysed nucleophilic substitution of propargylic alcohols with a range of
nucleophiles, and (b) Proposed catalytic cycle for the nucleophilic substitution of propargylic
alcohols using the bimetallic Ru thiolate complex (7)
Alkyne Activation Using Bimetallic Catalysts
113