Oxindoles lithium aluminum hydride

The lithium aluminum hydride reduction of l-acetyloxy-2-oxindole (287) gave a polymer, but that of the 1-methoxy analogue (288) yielded [78JCS(P1)1117] 1-methoxyindole. Application of this method (83H1797) led to a valuable synthesis of lespedamine 291. Alkylation of 288 by 1,2-dibromoethane and sodium hydride gave a 3,3-spiro derivative, which dimethylamine converted to 289. Reduction with lithium aluminum hydride now gave 290, as a mixture of isomers, which was dehydrated instantly by acid to 291 (see Section 1II,E). 

J-Oisubstitated SH-indoks. 3,3-Disubstituted 311-indoles (3) can be prepared readily by lithium aluminum hydride [or sodium bis-(2-mcthoxyethoxy)aluminum hydride, 3, 260-261 this volume] reduction of 3,3-disubstituted oxindoles (1), followed by oxidation of the indoline (2) with activated manganese dioxide or potassium permanganate in acetone. 

Vincatine (mp 111-112°) gave a molecular ion at m/e 370, in agreement with a molecular formula of C22H30N2O3. The IR spectrum showed carbonyl absorptions at 1705 and 1735 cm-1 and the UV spectrum indicated the presence of a 2-oxindole. Four aromatic protons were observed in the PMR spectrum together with JV-methyl (3.20 ppm) and carbomethoxyl (3.62 ppm) groups. Lithium aluminum hydride reduction gave a diol 164 but acetylation of this compound gave only a monoacetyl derivative. The structure of vincatine (163) was deduced on the basis of a rationalization of the mass spectra of the parent compound and its various derivatives, particularly the ions at m/e 297, 211, 182, and 124 in the parent compound (Scheme 3) and the base peak at m/e 184 (165) in the mass spectrum of the diol. 

Reduction of oxindoles with limited amount of lithium aluminum hydride, followed by acid treatment has been used in the preparation of indoles 49a). 

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