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

R 1
Ph
O N
R
217 218
REACTIONS OF NITRILE OXIDES 65
Fe
CO
Ph
2-Alkynyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolanes participate in 1,3-dipolar
cycloaddition reactions with mesito-, benzonitrile oxide or tert-butylformonitrile
oxide to provide isoxazoleboronic esters in good yield and with excellent levels
of regiocontrol. In addition, these potentially valuable synthetic intermediates
have been shown to participate efÞciently in Suzuki coupling reactions (375). The
[3 + 2] cycloaddition reaction of nitrile oxides and alkynylboronates provide direct
access to a wide variety of isoxazole boronic esters with high levels of regiocontrol.
For example, mesitonitrile oxide reacts with 2-(1-hexynyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,
in reßuxing diethyl ether, giving 5-butyl-4-(4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(2,4,6-trimethylphenyl)isoxazole
in 73%
yield. The application of this methodology in the synthesis of non-steroidal antiinßammatory
agents has also been described (376).
3-Substituted 5-(tributylstannyl)isoxazoles have been synthesized in good
yields by the 1,3-dipolar cycloaddition reaction of ethynyltributylstannane with
nitrile oxides, generated in situ. Bu3SnC≡CH and RCNO (R = Me, Ph, CO2Et)
give isoxazoles 219 in 85% to 100% yield. 3-Methyl-5-(tributylstannyl)isoxazole
is easily converted to the corresponding 5-benzoyl- and 5-arylisoxazoles by a
Pd-catalyzed reaction (377). Ynamines, such as, PhNMeC≡CH, react with nitrile
oxides to give the 5-aminoisoxazoles 220 (R = Me3C, Ph, substituted Ph). The
stannyl-substituted ynamine PhNMeC≡CSnBu3 also furnishes the compounds,
220 on reaction with hydroximoyl chlorides (378).
Bu3Sn
O N
R
R
N
O
219 220
CO
Z
N
Ph
N
Me
1,3-Dipolar cycloaddition reaction of trimethylstannylacetylene with nitrile
oxides yielded 3-substituted 5-(trimethylstannyl)isoxazoles 221. Similar reactions
of (trimethylstannyl)phenylacetylene, 1-(trimethylstannyl)-1-hexyne, and bis
(trimethylsilyl)acetylene give the corresponding 3,5-disubstituted 4-(trimethylstannyl)isoxazoles
222, almost regioselectively (379). The 1,3-dipolar cycloaddition
reaction of bis(tributylstannyl)acetylene with acetonitrile oxide, followed by
treatment with aqueous ammonia in ethanol in a sealed tube, gives 3-methyl-4-
(tributylstannyl)isoxazole 223. The palladium catalyzed cross coupling reaction of
R