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

66 NITRILE OXIDES
223 with 2-iodonitrobenzene, followed by reductive cyclization give 3acetylindole
(380). 1,3-Dipolar cycloaddition reactions between nitrile oxides and
stannylalkynes proceed in a regiospeciÞc manner to afford 4-stannylisoxazoles in
good yields. No reaction has been observed with vinyl- or allylstannanes (381).
Me 3Sn
221
O N
R
Me 3Sn
R 1
R
O
222
N
R = Me, Ph, CO 2Et; R 1 = Bu or Ph, Me 3Si, Me 3Sn
Bu 3Sn
O
223
N
Exciting results have been obtained by using copper(I)-catalyzed 1,3-cycloaddition
reactions with 1-alkynes (382). The process is apparently mediated
by species like R-C≡C-Cu, formed in situ by reduction of copper(II) sulfate
with sodium ascorbate, and proceeds at room temperature to give products, in
high yield and with high regioselectivity (Scheme 1.35). For example, thermal
cycloaddition of 4-methoxybenzonitrile oxide to phenylacetylene results, after
8h at 60 ◦ C, in a 4:1 mixture of 3,5- and 4,5-isomers in 62% yield, whereas
only a single regioisomer has been obtained in 92% yield after 1h at ambient
temperature, using Cu(I) as a catalyst. Different alkynes have been employed
in the Cu(I)-catalyzed cycloadditions. In particular, a steroidal isoxazole has been
obtained from 17-ethynylestradiol and 4-methoxybenzonitrile oxide in
98% yield.
A number of publications have appeared concerning polymer-supported syntheses
of isoxazoles via 1,3-dipolar cycloadditions. In particular, soluble polymersupported
alkynes react with nitrile oxides, generated in situ, to give isoxazoles in
good yield (383). A library of isoxazoles and 5-isoxazol-4-yl-[1,2,4]oxadiazoles
has been prepared by combined solution- and solid-phase syntheses (384).
Acetylenic sulfones attached to solid supports by means of ester linkers [polymersupported
4-(alkynylsulfonyl)benzenemethanol benzoate derivatives] have been
employed in cycloaddition reactions with mesitonitrile oxide, followed by cleavage
of the products from the resin by ester hydrolysis or reductive desulfonylation
(385). Solid-phase synthesis of 3-hydroxymethylisoxazoles, by cycloaddition of
alkynes to resin-bound nitrile oxides, give the products in moderate yields and
fair to good purity, depending on the alkyne substituents (386).
OH
N
+
R′ Cl
R H
CuSO 4 .5H 2 O, 2 mol.%
Na ascorbate, 10 mol. %
KHCO 3 , 3 equiv.
H 2 O/t-BuOH, 1:1, r.t., 1-4 h.
Scheme 1.35
N
R′
O
Me
R