STUDIES DIRECTED TOWARD THE ENANTIOSPECIFIC SYNTHESIS OF GARDNERIA, VOACANGA, AND ALSTONIA OXINDOLE ALKALOIDS

A method has been developed to convert N-a-methylmacroline-related indoles into their corresponding oxindoles with a high degree of diastereoselectivity. Prudent choice of the osmium reagent led to the stereoselective conversion of (-)-5-methyl-9-oxo-12-benzyl-6,7,8,9,11-hexahydro-6,10-imino-5H-cyclooct[b]indole (14a) into either diastereomeric N-b-benzyltetracyclic oxindole 21a or 24a. Treatment of racemic or (-)-N-b-benzyl ketone 14a with osmium tetraoxide in the absence of amino ligands led to the oxindole 21a with the same configuration about the spiro juncture at C(7) as the Alstonia oxindole alstonisine (1) with 10:1 diastereoselectivity, whereas the oxindole 24a with the opposite configuration was obtained diastereoselectively in greater than 91% yield when ketone 14a was treated with osmium tetraoxide in the presence of quinuclidine ligands. This conversion was found to be almost completely diastereoselective (94% de) to give oxindole 24a when dihydroquinine 4-chlorobenzoate (DHQ-CLB) was employed as the ligand. Tranformation of the N-b-methyltetracyclic ketone 14b produced the oxindole 24b which also possessed the configuration opposite to that of alstonisine (1) at the spirocyclic carbon [C(7)] under all reaction conditions investigated to date. Oxindoles 24a and 24b can be employed for the enantiospecific preparation of Gardneria and Voacanga oxindole bases. In addition, oxindole 21a is now available for the enantiospecific synthesis of Alstonia oxindole alkaloids.