1,3‐Dipolare Cycloadditionen, 70. Additionen des Benzonitriloxids an olefinische und acetylenische Dipolarophile

Abstract

Benzonitriloxid (2) bildet mit monosubstituierten Athylenen und Acetylenen 2-~soxazoline (3--10) und Isoxazole (29, 42), bei denen der Rest in der 5-Position erscheint. Ein Cemisch der beiden moglichen Orientierungsisomeren (17/18, 19/20) geht aus den Additionen an p-substituierte Styrole hervor. Abweichend verhielt sich p-Pyrrolidinostyrol, aus dem mit Benzonitriloxid nur 3,4-Diphenyl-S-pyrrolidin0-2-isoxazolin (22) cntsteht. Auch bci andcreii Enaminen diktiert die A m i d unktion ungeachtet sterischer Effekte diese Additionsrichtung. Die Stereospezifitiit der Cycloaddition wurdc an den cis-trans-isomeren 2-Butcncn uiid Stilbenen dargetan (13-16). Neben Cyclopcnten wurdc auch das reaktionstragere Cyclohcxen zur Reaktion gebracht (36, 37). Uas labile bicyclische Primaraddukt des Cyclooctatetraens (38) erleidet eincn clcktrocyclischeii RingschluB zum tricyclischen Produkt 39. 1,3-Dipolar Cycloadditions, 70 1) Additions of Benzonitrile Oxide to Olefinic and Acetylenic DipolarophilesBenzonitrile oxide (2) forms with monosubstituted ethylenes and acetylenes 2-isoxazolines (3 -10) and isoxazolcs (29, 42) substituted in the 5-position. P-Substituted styrenes yield a niixturc of two possiblc oricntation isomers (17/18, 19/20), except P-pyrrolidinostyrene, which produccs only 3,4-diphcnyl-S-pyrrolidino-2-isoxazoline (22). In other enamines, too, thc amino function dictates this dircction of addition notwithstanding steric effects. The stercospecificity of the cycloaddition has been shown by the reactions of the cis-trans-isomeric 2-butcncs and stilbencs (13 -16). Besides cyclopentene the less reactive cyclohexene could be combined with benzonitrile oxide (36, 37). The labile bicyclic primary adduct of cyclooctatetraene (38) undergoes electrocyclic ring closurc to form the tricyclic product 39.Weygund und Buuer6) erhiclten 1927 bei der Umsetzung von Benzohydroximoylchlorid (1) mit Natrium-arylacetyliden 5-Aryl-3-phcnylisoxazole. 1937 gelangten Quilico und Fuirsco 7) zu Tsoxazolen, als sie 1 mit Natriumsalzen von P-Dicarbonyl-Verbindungen und anderen CH-aciden Verbindungen zur Reaktion brachtcn. DaB bei dieser Isoxazol-Synthese Benzonitriloxid (2) als Zwischenstufe auftritt, wurde 1946 von der italienischen Schule8.9) erkannt. uber die zahlreichen und hedeutsameii Publikationen zur Anlagerung der Nitriloxide an CC-1) 69. Mitteil. :

Regioselectivity in cycloaddition reactions on solid phases

“…Treatment of 21 and 22 with benzonitrile oxide, generated in situ from a-chlorobenzaldoxime, at 0°C in THF yielded the polymer-bound benzyl isoxazoles (23) and (24) respectively. Base cleavage of 23 and 24 as before, followed by esterification with CH2N2, gave solely methyl 3-phenylisoxazole-5-carboxylate (25) and only methyl 3,5-diphenylisoxazole-4-carboxylate (26) respectively in reasonable yield (Scheme 2). Although Huisgen et al (26,27) have shown that methyl propiolate and methyl phenylpropio'late reacted in a 1,3-dipolar addition addition reaction to give a 72:28 mixture of 25 and methyl 3-phenyl21n this paper we were particularly interested in the possible change in regioselecfiuity of adducts in going to solid phase Deils-Alder reactions from their solution analogs and were less interested in changes in enantioselectivity.…”

“…Base cleavage of 23 and 24 as before, followed by esterification with CH2N2, gave solely methyl 3-phenylisoxazole-5-carboxylate (25) and only methyl 3,5-diphenylisoxazole-4-carboxylate (26) respectively in reasonable yield (Scheme 2). Although Huisgen et al (26,27) have shown that methyl propiolate and methyl phenylpropio'late reacted in a 1,3-dipolar addition addition reaction to give a 72:28 mixture of 25 and methyl 3-phenyl21n this paper we were particularly interested in the possible change in regioselecfiuity of adducts in going to solid phase Deils-Alder reactions from their solution analogs and were less interested in changes in enantioselectivity. In addition, our base cleavage method is likely to cause cis-trans isomerization of the cycloadducts (22) and hence the original ratio of cis to trans isomers obtained in the solid phase reactions could not be accurately determined.…”

NMR Studies on [2 + 3] Cycloaddition of Nitrile Oxides to Polyunsaturated Medium Size Rings

“…A variety of synthetic methods has been elaborated for preparation of 2-isoxazolines, of which the most convenient and attractive route is the [2 + 3] dipolar cycloaddition of nitrile oxides to alkenes. 1 2-Isoxazolines can be easily reduced to several synthetically important compounds such as b-hydroxy ketones, b-hydroxy esters, a,b-unsaturated carbonyl compounds or iminoketones. 2 The nitrile oxides can be formed either by Huisgen method from aldoximes by chlorination and base-induced dehydrochlorination 1 or by dehydration of primary nitro compounds by phenyl isocyanates (Mukayama method) 3 or ethyl chloroformate (Shimizu method).…”

“…1 2-Isoxazolines can be easily reduced to several synthetically important compounds such as b-hydroxy ketones, b-hydroxy esters, a,b-unsaturated carbonyl compounds or iminoketones. 2 The nitrile oxides can be formed either by Huisgen method from aldoximes by chlorination and base-induced dehydrochlorination 1 or by dehydration of primary nitro compounds by phenyl isocyanates (Mukayama method) 3 or ethyl chloroformate (Shimizu method). 4 A key feature of the cycloaddition is the cis-stereospecificity -from E-alkenes 4,5-anti isomers are produced and from Z-alkenes 4,5-syn products are obtained.…”

Photochemical and thermal reactions of some heterocycles containing C=N-O or N=C-O group

“…When irradiition of (30) in cyclohexane with light of 268-272nm is followed by uv spectroscopy, a-set of isosbestic points is recorded (see Fig. 4); curve a is the uv spectrum of (30) and b that of o-(3-phenyl-2H-azirinyl)-benzalaehyde (31). Although th~photocönversion of (30) to (31) is clean, the preparative scale photoreaction results in the complex proaucts from which (31) is obtained in 26% yield.…”