Isoxazolidines fused

Reaction of porphyrins with nitrones has also been studied and the results obtained showed that this is a versatile approach leading to the synthesis of isoxazolidine fused-chlorins (Scheme 26). For instance, chlorin 74 was successfully prepared from the reaction of the jV-methylnitrone, generated in situ from JV-methyl hydroxylamine and paraformaldehyde, with porphyrin Id . It is important to note that bis-addition also took place, yielding exclusively bacteriochlorin type derivatives 76 and 77 (Figure 6). This result contrasts with those obtained in 1,3-DC reactions with azomethinic ylides where isobacteriochlorins were obtained preferentially. 

Glycoconjugated isoxazolidine-fused chlorins and bacteriochlorins were also elegantly synthesised using a 1,3-DC approach (Scheme 26). For instance, the galactosylnitrone reacted with porphyrin Id in a small volume of toluene, at 60 °C, to yield chlorin 75, accompanied by a small amount of two related bacteriochlorins <02TL603>. 

The 1,3-dipolar cycloaddition of allenes with 3,4-dihydroisoquinoline A -oxides yields the isoxazolidine-fused 1,2,3,4-tetrahydroisoquinoline <97JCS(P1)2973, 97T9575,... 

Isoxazoles and isoxazolidines fused with sugar systems are found to show biological activity. In a continuation of our studies on the utilization of a variety of protocols on the sugar-derived chirons we embarked onto the 1,3-dipolar cycloaddition reactions. Accordingly, intramolecular oxime olefin cyclo-addition (lOOC) reactions on the chiron (91 X=NOH) gave an isoxazolidine-fused saccharide (92) (Scheme 22.21). 

Isoxazolidine-fused P-lactams 85 were synthesized through a base-promoted cyclization-cyclopropane ring opening of 4-spirocyclopro-paneisoxazolidines 84 prepared in turn by 1,3-DC of N-aryl C-carbamoylnitrones and 2-arylmethylidenecyclopropanedicarboxylates (13T5173). 

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. ... 

The isoxazolidine-condensed enediynes 3.800 and 3.802 were synthesized by intramolecular [3- -2] cycloaddition of a nitrile oxide to the additional double bond in enediyne 3.799. The structures of the stereoisomeric bicyclic isoxazolidine-fused enediynes 3.800 and 3.801 were fully confirmed by NMR spectroscopy with NOESY... 

Oxidation of fused isoxazolidine (173) with one equivalent of m-chloroperbenzoic acid produced an oxazine. The mechanism of transformation involves formation of an A/-oxide... 

We are the first group to succeed with the highly enantioselective 1,3-dipolar cycloadditions of nitronates [75]. Thus, the reaction of 5,6-dihydro-4H-l,2-oxazine N-oxide as a cyclic nitronate to 3-acryloyl-2-oxazilidinone, at -40 °C in dichloro-methane in the presence of MS 4 A and l ,J -DBFOX/Ph-Ni(II) complexes, gave a diastereomeric mixture of perhydroisoxazolo[2,3-fe][l,2]oxazines as the ring-fused isoxazolidines in high yields. The J ,J -DBFOX/Ph aqua complex prepared from... 

Formation of cyclohexane fused isoxazolidine 237 from oxime 236 was less selective, providing a mixture of isomers in 51% yield (Eq. 26). On the other hand, citronellal oxime 238 led stereospecifically and in 80% yield to the fused cyclohexane 239 when heated at 190 °C for 5 h. 

It is clear from the foregoing that ring closure to five-membered rings fused to the isoxazolidine, regardless whether part of a pyrrolizidine or of an indolizidine system, led mainly to the cis-anti isomers (see 243 a, b and 246 a, b)... 

The ketal hydrochloride 322 has been used for X-ray crystallographic analysis to establish the stmcture and stereochemistry of the pyrrolizidine alkaloid l,7a-diepialexine <1990P111>, and the fused isoxazolidine 323 is an intermediate in a model synthetic approach to alkaloids such as laccarin, 324 <2002SL1344>. 

These studies were carried out for hve-membered monocyclic TV-alkoxy-(406-408) and /V-siloxyisoxazolidines (178) (A), for iV-siloxytetrahydro-4// -oxazines (274), and bicyclic fused derivatives containing the isoxazolidine ring (B) (99, 157, 337). 

There have been simultaneous reports of the intramolecular cycloaddition of alkenyl nitrones bearing alkenylsulfide (202,203) or alkenylsulfone substitutents (Scheme 1.40) (203). In both cases, the isolated products were the corresponding fused bicyclic isoxazolidine adducts 178 and 179, respectively. 

Saito et al. (351a) reported the previously unprecedented formation of a 4,5-fused bicyclic isoxazolidine by an intramolecular cycloaddition reaction (Scheme 1.68). 

The intramolecular cycloaddition of a silyl nitronate bearing a dipolarophilic appendage provides easy access to fused, bicyclic isoxazolidines (22). This process, in general, is very facile, and has allowed the use of unfunctionalized alkenes as dipolarophiles (Table 2.39) (106,124). Thus, a silyl nitronate bearing an allyl group will undergo the [3 + 2] cycloaddition at room temperature over 15 h to provide the corresponding isoxazoline upon acidic workup in moderate yield. 

Tamura et al. (170-172) discovered that, when reactions of ester-substituted nitrones with allylic alcohols are performed in the presence of an equimolar amount of titanium tetraisopropoxide under heating or at room temperature, transesterification takes place to form new nitrones bearing an inner alkene dipolarophile. The resulting nitrone substrates undergo regio- and stereoselective intramolecular cycloaddition reactions to give the ring-fused isoxazolidines (Scheme 11.52). This tandem transesterification/[3 + 2]-cycloaddition method leads to the selective... 

These cyclic nitrones 91 react with electron-rich olefins in 1,3-cycloaddition reactions to afford fused isoxazolidines 92-94 from which several unusual amino acids 95-97 have been obtained (Scheme 7.22). ... 

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