PART I: THE STEREOSPECIFIC TOTAL SYNTHESIS OF THE EUDESMANE SESQUITERPENE (+)-BETA-SELINENE. PART II: A CONVENIENT SYNTHESIS OF THE MORPHINANS: STUDIES DIRECTED TOWARD THE TOTAL SYNTHESIS OF ESTRONE

LIONEL DEWILDER MOORE, Purdue University

Abstract

Part I. (-)-(beta)-Pinene undergoes an ene reaction with acryloyl chloride at 70(DEGREES)C to afford 6,6-dimethylbicyclo{3.1.1}hept-2-en-2-butanoyl chloride (1), in better than 80% yield. Cyclization of 1 to 10,10-dimethyltricyclo{7.1.1.0('2,7)}undec-2(7)-ene-6-one (2) by way of an intramolecular ene reaction involving a ketene intermediate occurs on heating with tributylamine at 150(DEGREES)C. Unsaturated ketone 2 undergoes a clear retroene reaction to yield (+)-7-isopropylidene-9,10-decal-1-one (3) on brief heating at 265(DEGREES)C. Lithium dimethyl cuprate addition to 3 yields a mixture of four isomeric 7-isopropylidene-10-methyl-1-decalones (4-6) where the isomers having the desired cis relationship between the angular methyl and the isopropylidene groups comprise 75% of the product. Treatment of the ketone mixture with methylenetriphenylphosphorane completes the synthesis of (+)-(beta)-selinene. Part II. Using the acylation-cycloalkylation strategy developed in this laboratory for the synthesis of ferruginol and (beta)-selinene, hydrophenanthrones suitable for conversion to morphine derivatives were prepared. Thus, p-methoxyphenylacetyl chloride (1) reacts with 2' chloroethyl-1-cyclohexene (2) at room temperature in the presence of two equivalents of aluminum chloride to yield phenanthrone 3 in good yield. This phenanthrone was converted to its oxime-acetate 4 which was in turn reduced with diborane to give 3-methoxymorphinan (5). Lithium aluminum hydride reduction of the urethane derivative of 5 gives 3-methoxy-N-methylmorphinan. A similar reaction sequence was used to prepare N-methylmorphinan (6) and 2,3-dimethoxy-N-methylmorphinan (7). By allowing p-methoxyphenylacetyl chloride and 2'-chloroethyl-1-cyclohexene to react in the presence of one equivalent aluminum chloride at 0(DEGREES)C (beta),(gamma)-unsaturated ketone 8 was obtained as the major product. A route to homo-D-estrone using this material as a key intermediate was investigated.

Degree

Ph.D.

Subject Area

Organic chemistry

COinS