100
4 Applications of Nitrile Imine Derivatives
4.1.1 Biomolecules and Natural Products
One of the most common examples of the use of NIs in NP chemistry is in the diversification of pre-existing NPs or NP constituents. Some examples of this are in the
preparation of derivatives of pyrazoles and pyrazolines based on the chromone, oxybicyclo and levoglucosenone skeletons (Scheme 4.1) [4–6]. The biomolecule derivatives may either be used directly as a dipolarophile, or as in the case of chromones,
modified to include a hydrazonyl halide moiety.
Steroids may also be applied within NI cycloaddition chemistry, typically through
the introduction of unsaturation into the D-ring to generate a dipolarophile [7, 8]. Both
endocyclic and exocyclic alkenes can be utilised, however regioselectivity issues
may be encountered when using an endocyclic olefin (Scheme 4.2). Stereoinduction
O
O
H
H
Ph
N
Cl
NH
Ph
Et 3 N, PhMe
110
o C, 1.5 h
55 %
O
O
H
H
N
N
Ph
Ph
N
Br
NH
Ph
O
O
Me
N N
Ph
O
O
Me
Et 3 N, PhH
rt, 1.5 h
60 %
O
O
O
O
chromone
levoglucosenone
Scheme 4.1 Reactions of chromone derivatives and levoglucosenone with NIs
MeO
O
MeO
O
N N
H
H CO 2 Et
Me
EtO 2 C
Cl
N
NH
Me
MeO
O
N
N
H
H
EtO 2 C
Me
AgOAc
rt, 24 h
66 %
44:22 A:B
A
B
+
Scheme 4.2 Regiochemical issues can be encountered when attempting NI cycloaddition with a
steroidal scaffold