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Category IbCyclizations-3

DOI: 10.1016/b978-012676945-6/50023-5


Publisher Summary A variation of the Madelung cyclization involves installing a functional group at the o-methyl group, which can facilitate cyclization. For example, a triphenylphosphonio substituent converts the reaction into an intramolecular Wittig condensation. The required phosphonium salts can be prepared by starting with o-nitrobenzyl chloride or bromide. Retrosynthetic path has recently been realized as an effective synthesis of 2, 3-disubstituted indoles using low-valent titanium reagents to affect the reductive cyclization. Several aryl- and methyl-substituted compounds were prepared by using Ti-graphite prepared from K-graphite and TCl3. An improved methodology which avoids the preparation of K graphite was subsequently developed. This procedure uses zinc powder to effect in situ reduction of TiCl3. A stirred solution of o-methylpivalanilide (50 mmol) in dry THF (100 ml) was maintained at 15OC under a nitrogen atmosphere. A 1.5 M solution of n-butyllithium in hexane (3 equiv.) was added dropwise. The solution was then maintained at room temperature for 16 h. The solution was cooled in an ice-bath and treated with 2 N HCI (60ml). The organic layer was separated and the aqueous layer was further extracted with benzene. The combined layers were dried (MgSO4). The product was obtained in 87% yield and recrystallized from ether-cyclohexane.

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