Convergent Routes to the [1,3]Dioxolo[4,5-j]phenanthridin-6(5H)-one and 2,3,4,4a-Tetrahydro[1,3]dioxolo[4,5-j]phenanthridin-6(5H)-one Nuclei. Application to Syntheses of the Amaryllidaceae Alkaloids Crinasiadine, N-Methylcrinasiadine and Trisphaeridine

Abstract

Convergent routes to the title nuclei, (1) and (6), have been developed. Thus, Suzuki coupling of boronic acid (8) with aryl bromide (9) gave the biarylylcarbamate (7) which, on treatment with phosphorus oxychloride (POCl3), underwent Bischler-Napieralski cyclization to give, after acid hydrolysis, the Amaryllidaceae alkaloid crinasiadine (1). The cyclization reaction proceeds via an intermediate chlorophenanthridine (11) which can be isolated and N- methylated. Hydrolysis of the resulting iminium species (17) then afforded N- methylcrinasiadine (2). On the other hand, hydrogenolytic dechlorination of compound (II) affords trisphaeridine (14). Related chemistry has been employed in the preparation of 2,3,4,4a-tetrahydro[1,3] dioxolo [4,5-j]phenanthridin-6(5H)-one (6), the tetracyclic skeleton associated with the narcissus alkaloids lycoricidine (3) and narciclasine (4). Thus, treatment of the gem- dibromocyclopropane (20) with silver cyanate resulted in ring opening thereby affording the allylic isocyanate (25) which could be intercepted with added methanol to give carbamate (24). Suzuki coupling of this last compound with boronic acid (8) gave product (18) which was subjected to treatment with and resulted in the formation of (�)-(6). This latter sequence could be adapted to the preparation of both (R)-(6) and (S)-(6).