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

REACTIONS OF NITRILE OXIDES 67
Different aspects of 1,3-dipolar cycloaddition reactions of nitrile oxides at the
C≡C bond have been studied using quantum chemical methods. Quantitative predictions
of substituent and solvent effects on the regioselectivities of nitrile oxide
cycloadditions to electron-deÞcient alkynes have been made, using hybrid DFT
calculations, with the B3LYP/6–31G* method, to calculate the activation barriers
of nitrile oxide cycloadditions to the unsymmetrical alkynes, cyanoacetylene
and Me propiolate. Both, inherent electronic effects and solvent polarity have
been shown to inßuence regioselectivity (387). 1,3-Dipolar cycloaddition reactions
of substituted nitrile oxides RCNO, (R = F, NO2, OMe, OH, CO2Me, CHO,
CONH2, H, Me) with propyne were studied, using the DFT at the 6–311 + + G ∗∗
level. The reaction rates have been calculated at different temperatures from 200
to 400 K. The conclusions are that formation of 5-methyl-substituted isoxazoles is
dominant at low temperatures, while 4-methyl-substituted isoxazoles are favored
at relatively high temperatures (388).
The mechanism for the 1,3-dipolar cycloaddition of benzonitrile oxide to
ethynyl- and propynylboronate has been studied by DFT at the B3LYP/6–31G*
level. These reactions are concerted [3 + 2] processes. The presence of the two
oxygens on the boronic ester precludes the participation of the B atom in the
[3 + 3] processes. The two pathways leading to the formation of the regioisomeric
isoxazoles, bearing the boronic ester unit on the 4- or 5- positions, have been
characterized. The activation parameters are in acceptable agreement with experiments,
allowing the explanation of the factors controlling these regioselective
cycloadditions (389).
It is of interest to mention that DFT study performed, prior to experimental
observations, revealed for Cu(I)-catalyzed cycloaddition of nitrile oxides to
1-alkynes, a stepwise mechanism involving unprecedented metalacycle intermediates,
which appear to be common for a variety of dipoles (382).
1.3.4.3.2. Cycloaddition at C≡N and C≡P Bonds Important information concerning
cycloadditions of nitrile oxides to C≡N and C≡P bonds is collected in
review (289). Here, recent data and those concerning individual unconventional
types of nitriles and phosphaacetylenes are presented.
Reactions of hydroximinoyl chlorides, RCCl:NOH, with cyanogen and diazocyanides,
4-R 1 C6H4N = NCN gave bi[1,2,4]oxadiazoles 224 or arylazooxadiazoles
225 (390). The reaction of dialkylcyanamides with EtO2CCl:NOH gave
(dialkylamino)oxadiazolecarboxylates 226; the reaction of arylcarbohydroximinoyl,
chloridesRCCl:NOH, with N-cyanomorpholine gave 3-aryl-5-morpholino-
1,2,4-oxadiazoles 226 (366).
The carbon-nitrogen triple bond of aryl thiocyanates acts as a dipolarophile in
1,3-dipolar cycloadditions. Reactions with nitrile oxides yield 5-arylthio-1,2,4oxadiazoles
227 (X = O; Y = S). Aryl selenocyanates behave similarly forming
5-arylseleno-1,2,4-oxadiazoles 227 (X = O; Y = Se). Reactions of 5-aryl-
1,2,4-oxadiazoles with secondary amines, such as piperidine, yield 5-piperidino-
1,2,4-oxadiazoles 227 (X = O; YR 1 = piperidino) (391).