Oxindoles, Diels-Alder reaction

The total synthesis of d/-21-oxo-gelsemine reported by Hart and collaborators (107) features two free radical cyclizations (C-5-C-16 bond formation in gelsemine) to construct both a tricyclic substructure 314 in the terpene part of gelsemine and the spiro-oxindole moiety. The synthesis was initiated with the Diels-Alder reaction between A-methylmaleimide and the diene 302, followed by treatment of the crude cycloadduct with 2,2-dimethyl-l,3-propanediol and a catalytic amount of p-toluenesulfonic acid, to give the perhydro-isoindole 304 in 43% yield. By application of the Grieco dehydra-... 

Other Dienes. Naphtho-fused oxindole derivatives 23 have been accessed by an aiyne Diels-Alder reaction using methyleneindolines as dienes. The proposed mechanism involves a [4+2] cycloaddition followed by isomerization and further dehydrogenation. These results represent the... 

In the last decade, several excellent results were also published in the area of enantioselective nickel-catalysed Diels-Alder cycloadditions. Among them, the reactions of cyclopentadiene with 3-alkenoyloxazolidin-2-ones induced by (i )-BINIM-2QN provided cycloadducts in up to >99% yield, >98% de, and 96% ee. Another excellent result was achieved by using a chiral iV,iV -oxide-derived nickel catalyst in Diels-Alder cycloadditions of 3-vinylindoles with methyleneindolinones for the construction of chiral spiro[carbazole-oxindoles] in up to 97% yield, >98% de, and 98% ee. Moreover, the use of the chiral DBFOX-Ph ligand has allowed an inverse-electron-demand Diels-Alder reaction of a range of Af-sulfonyl-l-azadienes with vinyl ethers to be achieved, providing highly functionalised piperidines in up to 75% yield, 96% de, and 92% ee. 

The synthesis commences with alkylation of oxindole 120 with spiroaziri-dinium triflate 109, providing the 3,3-disubstituted 121 in 53% yield (cf. Scheme 2.17). Treatment of 121 with boron trifluoride etherate at 100°C in toluene initiates the tandem retro Diels-Alder/intramolecular aza Diels-Alder process, leading to spiro-tetracyclic oxindoles 122 and 123 (1.5/1) in 61% yield. Addition of 2-lithio-l,l-diethoxy-2-propene to oxindole 122 provides carbinolamine 124 (95%). Exposure of 124 to p-toluenesulfonic acid in acetone-water followed by treatment with excess triethylamine in acetonitrile at 80°C effects the biomimetic transformation to adduct 126, which possesses the pentacyclic carbon framework of pseudotabersonine. This unique two-step one-pot transformation generates the inherently unstable dihydropyridine portion of dehydrosecodine 125, which participates in an intramolecular reverse electron-demand Diels-Alder reaction, providing 126 in 50% yield. The total synthesis is completed by transformation of the formyl group into the requisite carbomethoxy unit followed by N-benzyl deprotection (Scheme 2.19). 

Recently, Chen, Jorgensen, and coworkers discovered a novel activation mode by the condensation of chiral amines with polyenals 37 to generate reactive trien-amine intermediates J that can participate in asymmetric Diels-Alder reactions with different classes of dienophiles (Scheme 38.12) to afford cycloadducts 38 [20]. With the use of chiral diarylprolinol silyl ether 40 as organocatalysts, various spi-rocyclic oxindoles 41 and multifunctional cyclohexenes 43 can be obtained in high... 

The asymmetric domino three-component Knoevenagel/Diels-Alder addition reaction promoted by the primary amine catalyst 9-amino-9-deoxy-epi-quinine was also reported. Various pharmacological multisubstituted spiro[5,5]undecane-1,5,9-triones were obtained in moderate to good yields (up to 81%) with excellent diastereo-(>99 1 dr) and enantioselectivities (up to 97% ee) [19]. The enamine-mediated Diels-Alder reactions of a,P-unsaturated ketones were also extended to nitroalkenes [20] and 3-olefmic oxindoles [21]. 

SCHEME 1.29 Organocatalyzed Diels-Alder reactions with 3-olefinic oxindoles involving trienamine catalysis. 

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