Allenyl nitrone

The intramolecular dipolar cycloaddition of a nitrone with an unactivated allene was also studied [76], Treatment of 5,6-heptadien-2-one with N-methylhydroxyl-amine in refluxing ethanol yielded allenyl nitrone 78, which cyclized with the terminal allenic C=C bond to give an unsaturated bicyclic isoxazolidine. On the other hand, the site selectivity decreased with an allenic ketone having a trimethylene tether. 

Nakamura and coworkers have successfully developed an efficient and regioselective approach to multisubstituted pyridine N-oxide derivatives from ( )-0-propargylic a,/l-unsaturated oximes via [2,3]-rearrangement to the AT-allenyl nitrones followed by 6.rr-3-azatriene electrocyclization under CuBr(PPh3)g/PPh3 system (Scheme 8.82). Since pyridine N-oxides have recently received much attention in catalytic C-H functionalization, the present methodology is useful to synthesize these substrates [152]. 

As a result of Ag (I) catalyzed cyclization of allenic oximes (124) and (125), stable five- (126) and six-membered (127) cyclic nitrones were obtained (Scheme 2.46) (298a). Recently, a novel method of pyrroline-type nitrone formation via P-allenyl-oxime cyclization has been described (298b). 

Like the nitrone-olefin [3 + 2]-cycloaddition, the nitrone-allene [3 + 21-cycloaddition also takes place regioselectively to furnish methylene-substituted isoxazoli-dine derivatives. The substituents of the 3- and 4-positions of the cycloadducts 72a and 72b are disposed cis in contrast, the reaction of 70 with allenyl sulfone 71c gives rise to the trans-cycloadduct 72c exclusively (Table 12.4). On treatment with base or heating, methyleneisoxazolidines 72 readily rearrange to isoxazo-lines via a 1,3-hydrogen shift. 

A dipolar route of heterocyclization of a monocyclic enallenyl nitrone (from precursor 126 by base-catalyzed propargyl-allenyl isomerization) leads to lactam 127 (05EJO2715) that is an analog of astrocasine (8). 

In constrast with intermolecular nitrone cycloadditions to alkynes and allenes, very little work has been done on the corresponding intramolecular cycloadditions. The bicyclic isoxazolidines (65a-b) were reported as products from reaction of an alkynone with methylhydroxylamine in ethanol.26b Presumably the initial strained bridgehead C—C double bond of the AMsoxazoline added ethanol under the reaction conditions. Cyclization of an allenyl ketone with methylhydroxylamine in ethanol solution also led to isoxazolidines (65a-b) as the major products and isoxazolidine (66) as a minor product.266 Thus, preferential cyclization to the internal C—-C double bond of the allene occurred followed by addition of ethanol to the exocyclic C—C double bond of the methyleneisoxazolidine intermediate. 

In general, synthesis of 4-isoxazolines is accomplished via three routes 1,3-dipolar cycloaddition of nitrones to alkynes or by the oximation of a,i -ethylenic ketones, a-alkynic ketones and aldehydes or from the selective reduction of isoxazolium salts. The nitrone (262) underwent tandem cyclo-addition-[2,3]sigmatropic rearrangement with allenyl sulfoxide (263). And it resulted in 4-isoxazoline (264) (Equation (46)) <89TL663>. 

The copper-catalysed 3 + 2-cycloaddition reactions of nitrones with alkynes leading to / -lactams have been extensively reviewed. The 3+2-cycloaddition reactions of dialkyl-substituted 2-benzylidenecyclopropane-l,l-dicarboxylates (54) and C-carbamoyl nitrones (53) produced simple isomeric spiro[cyclopropane-l,4-isoxazolidine] cycloadducts (55), which are readily transformed into isoxazolidine-fused / -lactams (56) in high yields (Scheme 15). BINOL-derived chiral phosphorami-date Au(l) catalysts have been used to catalyse the 3+2-cycloaddition of A(-allenyl amides with nitrones to produce chiral 4-alkylidenyl isoxazolidines in high yields and excellent enantioselectivity (up to 99% cc). The 3+2-cycloaddition of a-phenylnitroethene and (Z)-CA -diphenylnitrone in polar media (nitromethane and water) yielded 3,4-fra 5 -2,3,5-triphenyl-4-nitroisoxazolidine via a zwitterionic, two-step mechanism. ... 

Dipolar compounds (1,3-dipoles), first designated by Huisgen [1], are a class of 4tt-electron species that can be represented by zwitterionic (or ylide) forms with a separation of charge over three atoms. Basically, 1,3-dipoles are categorized into two subclasses, including the allyl type (carbonyl ylides, carbonyl imines, azomethine ylides, azomethine imines, and nitrones) and the propargyl/allenyl type (azides, diazoalkanes, nitrile ylides, nitrile imines, and nitrile oxides), as shown in Scheme 16.1. 

An intermediate l-methoxyfiilvene is believed to form through a cyclization-cycloaddition cascade on reaction of allenyl acetals with nitrones catalysed by a gold complex and a silver salt (Scheme 1). ... 

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