3.1 1,3-Dipolar Cycloaddition
51
Et 3 N, PhMe
100
o C,16 h
84 %
Cl
N
NH
MeO
Boc
N
Cl
N
N
OMe
N
Boc
Cl
Et 3 N, PhMe
rt, 1.5 h
64 %
81:19 A:B
F 3 C
Br
N
NH
CO 2 Me
F 3 C
N
N
CO 2 Me
F 3 C
N
N
CO 2 Me
+
Et 3 N, CHCl 3
rt, 48 h
99 %
Cl
N
NH
Ph
Ph
N N
Ph
Ph
CaC 2 , H 2 O
A
B
Scheme 3.17 Further examples of the cycloaddition of acetylenes with NIs
Benzynes have also been shown by Moses to be a competent dipolarophile,
providing facile access to a range of indazoles (Scheme 3.18) [79]. Due to the
extremely reactive nature of this highly strained intermediate, conditions required for
this transformation appear to be capricious, and difficult to optimise [80]. Precedent
indicates that the use of a hydrazonyl halide as the NI source is required, enabling
an appropriate base to form both the NI and the benzyne species from the relevant
precursors at similar rates.
The reaction of terminal alkynes with NIs is also open to an alternative mode
of reactivity not shared by other dipolarophiles. The enhanced acidity of the alkyne
Cl
N
NH
Ph
OTf
TMS
MeO
CsF, 18-crown-6
MeCN, rt, 5 min
60 %
N
N Ph
MeO
Scheme 3.18 The cycloaddition of NIs and benzynes