Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

46 NITRILE OXIDES
O
(Me 2CHO) 2P
N O
NR
Ph
129 (R @
Ph, C6H4Br-4, Bu)
1,3-Dipolar cycloaddition of nitrile oxide at the C=N bond of indole imino
esters 130, followed by elimination of the alcohol moity gives oxadiazole derivatives
131 (Scheme 1.26) (298). Reaction of N-arylbenzamidines with arenenitrile
N-oxides (generated in situ from oximoyl chlorides) produce unstable 5-amino-
4,5-dihydro-1,2,4-oxadiazoles which, on aqueous acidic treatment hydrolyze to
open-chain N-benzoyloxy-N ′ -arylareneamidines (299).
Poly(ethylene glycol) supported liquid-phase syntheses by both the reaction
of (polyethylene glycol (PEG))-supported imines with nitrile oxides, generated
in situ from aldoximes, (300) and 1,3-dipolar cycloadditions of nitrile oxide,
generated in situ on soluble polymers with a variety of imines (301, 302) have
been described. The solid-phase synthesis of 1,2,4-oxadiazolines via cycloaddition
of nitrile oxide generated in situ on solid support with imines has also
been elaborated (303). These syntheses of 1,2,4-oxadiazolines provide a library
of 1,2,4-oxadiazolines in good yields and purity.
Cycloaddition reactions of ketimines have interesting features, especially with
N-substituted imines. Results of 1,3-dipolar cycloaddition reactions of 1,1diphenyl-2-aza-1,3-butadiene
derivatives 132 with nitrile oxides depend on the
type and on the stereochemistry of the β-substituents (304, 305). With the unsubstituted
compounds 132 (R = R 1 = H, R 2 = Me, Et) the reaction occurs at the
C=C double bond, providing a good method for the synthesis of 4,5-dihydroisoxazole
derivatives 133 (R 2 = Me, Et, R 3 = Ph; R 2 = Me, R 3 = CMe3). The
β-substituted compounds 132 undergo reactions at the N=C double bond, thus
giving, with R 3 CNO (R 3 = Ph, 4-ClC6H4), the 4,5-dihydro-1,2,4-oxadiazole
derivatives 134 (Scheme 1.27). All the reactions occur with high site- and regioselectivity.
The crystal structure of 134 (R = Me, R 1 = H, R 3 = 4-ClC6H4) has been
determined (304).
(CH2)nC=NH
OEt
ArCNO
(CH2)n
O N
N
R
N
R
130
131
R = H, n = 0, 1; R = Me, n = 0. Ar = Ph, 4-O2NC6H4, 4-ClC6H4, 3-MeC6H4, 5-nitro-2-furyl
Scheme 1.26
N
Ar