Nitrone-olefin 1,3-dipolar cycloaddition

Using this methodology, the first total synthesis of the natural product (-)-(19R)-ibogamin-19-ol was reported [106]. The crucial ISQ core containing the entire configurational stereochemistry of the final target compound was prepared in 15 steps. The two key steps involved chirality transfer in an Ireland-Claisen rearrangement and an intramolecular nitrone-olefin 1,3-dipolar cycloaddition described earlier. 

Chiral Cyclopentane Synthesis From Sugars Transformation of monosaccharides into enantiomerically pure penta- substituted cyclopentanes via fragmentation and nitrone-olefin dipolar cycloaddition. 

Dipolar cycloadditkm reactions of nitrones to olefins, 46, 1,3-Dipolar cycloadditions with 3-phenylsydnone, 45, 98 Dispiro[5 1 5 l]tetradecane-7,14-dione, photolysis to cyclohexylidene-cyclohexane, 47, 34 preparation from cyclohexanecarbonyl chlonde and triethylamine, 47,34 Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37... 

The class of 1,3-dipolar cycloadditions embraces a variety of reactions that can accomplish the synthesis of a diverse array of polyfunctional and stereochemically complex five-membered rings.3 The first report of a 1,3-dipolar cycloaddition of a nitrone (a 1,3-dipole) to phenyl isocyanate (a dipolarophile) came from Beckmann s laboratory in 1890,4 and a full 70 years elapsed before several investigators simultaneously reported examples of nitrone-olefin [3+2] cycloadditions.5 The pioneering and brilliant investigations of Huisgen and his coworkers6 have deepened our under-... 

Scheme 60). 1,3-Dipolar cycloaddition reactions of nitrones with olefins are catalyzed by a chiral Ni11 or Pd11 catalyst.283,284... 

The formation of enantiopure tricyclic compounds takes place by intramolecular 1,3-dipolar cycloadditions of acyclic nitrones to cyclic olefinic fragments (Scheme 2.214a,b) (706, 707a), or of cyclic nitrones to acyclic olefins (Scheme 2.214c) (116). Recently (707),b intramolecular nitrone cycloaddition reactions (according to Scheme 2.211a) have been applied in the synthesis of... 

Intermolecular Reactions Intermolecular 1,3-dipolar cycloaddition reactions of nitrones to olefins seem to be the most studied. They are widely used for the synthesis of different enantiomerically pure compounds, including biologically active ones. For example, two new glycosidase inhibitors have been obtained by the nitrone cycloaddition strategy (Fig. 2.32) (733). 

Dipolarophiles Dll. In the 1,3-dipolar cycloadditions of electron-rich olefins, such as vinyl ethers, with nitrone (585), common palladium (II) catalysts were used (Fig. 2.45). Reactions proceeded smoothly under mild conditions and in good yield, affording isoxazolidines (646) (Scheme 2.283) (799). 

Attempts to Catalyze [3 + 2]-Cycloaddition of Nitronates to Olefins In Section 3.2.1.2.2.2, it was noted that [4+ 2]-cycloaddition reactions of nitro-alkenes and alkenes proceed much faster in the presence of LA. At the same time, in the presence of LA, nitronates can rapidly decompose (49) or undergo rearrangements (see Section 3.4.2.5.6 ). Hence, it is not surprising that catalysis of 1,3-dipolar cycloaddition reactions of nitronates with alkenes by LA has attracted little attention until very recent times. An exception is the study by the Japanese... 

Main Aspects of Chemistry and Stereochemistry of Cyclic Nitroso Acetals Chemistry of cyclic nitroso acetals or nitrosals (the term was introduced by Prof. Seebach) has attracted interest only after the discovery of the 1,3-dipolar cycloaddition reaction of nitronates with olefins in 1962 by the research group of Prof. Tartakovsky. (Principal data on nitroso acetals up to 1990 were summarized in the review by Rudchenko (395).)... 

Mukai et al.85 reported an asymmetric 1,3-dipolar cycloaddition of chromium(0)-complexed benzaldehyde derivatives. As shown in Scheme 5 52, heating chiral nitrone 171a, derived from Cr(CO)3-complexed benzaldehyde, with electron-rich olefins such as styrene (173a) or ethyl vinyl ether (173b) generates the corresponding chiral a.v-3,5-disubstitutcd isoxazolidine adduct 174 or... 

The synthesis of these important compounds is very well explored. They can be now prepared almost routinely by a number of methods including the RCM cyclization of the properly activated sugar diolefins, 1,3-dipolar cycloaddition of nitrones and olefins (recent review ref. 6) or other types of cyclizations. 

The 1,3-dipolar cycloaddition between the sugar nitrone and sugar olefins was proposed54 and an example is shown in Fig. 39.54e... 

To use 1,3 dipolar cycloadditions in a retrosynthetic sense, it is necessary to know what 1,3 dipoles are available. The list on pages 319-320 is representative of die more common and useful examples, although many others have been reported. Azides, diazo compounds, and nitrones are normally isolable compounds which can be added to a solution of an olefin. Other 1,3 dipolar species such as nitrile oxides and azomethine ylides are not stable molecules they must be generated in the reaction mixture in the presence of the olefin. As might be expected, many different ways to generate 1,3 dipoles have been developed. 

Dipolar cycloadditions. Nitrones such as 1 combine with alkenes to form isoxazolidines. Tufariello has employed these 1,3-dipolar cycloadditionS as key steps in the synthesis of several alkaloids. Monosubstituted olefins react with nitrones regioselectively to afford 5-substituted iSoxazolidines thus addition of 2 to 1-pyrroline-l-oxide produces the cycioadduct 3, which serves as an intermediate in a total synthesis of elaeocarpine (4). ... 

Dipolar cycloaddition of nitrones to olefins is also catalyzed by chiral cationic palladium complexes [66]. When nitrone 119 is treated with 3-(( )-2-butenoyl)-l,3-oxazoli-din-2-one (120) under the influence of (5)-BINAP PdCla (10 mol %) and AgBF4 (20 mol %), isoxazolidine 121 is obtained in 61 % yield as a 45 55 mixture of endo and exo forms. The endo isomer is obtained in 91 % ee (Sch. 32). The chemical yield and endo selectivity are improved by employing (5 )-p-Tol-BINAP as chiral ligand. 

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