Novel synthetic approaches to the 5,10b-ethano-phenanthridine nucleus of the crinine-type amaryllidaceae alkaloids from isoquinoline

Abstract

In an effort to develop an efficient synthetic route to the crinane skeleton from isoquinoline, an unprecedented conversion, several novel reactions have been discovered and explored. N-Benzyl-4,4dialkyldihydroisoquinolmium salts, which can be readily prepared from isoquinoline by utilizing boron-activated enamine alkylation chemistry, undergo facile oxidation with m-chloroperoxybenzoic, acid to afford 3-hydroxy-1-isoquinolones and the corresponding homophthalimides; regioselective sodium borohydride reduction of the latter affords the former. Treatment of 3-hydroxy-1-isoquinolones with sulfinic acid results in the formation of isocarbostyrils by dealkylation or acid-catalyzed dehydrative alkyl migration. In the caw of the 4-spirobutyl system, this reaction sequence represents an efficient entry to the relatively inaccessible 1,2,3,4-tetrahydrophenanthridine nucleus of the crinine, narciclasine, and lycorine type alkaloids.