The Total Synthesis of (-)-Prezizaene, (-)-Prezizanol, and Other Perzizanoid Sesquiterpenes
Roach, Paula Marianne
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https://hdl.handle.net/2142/67281
Description
Title
The Total Synthesis of (-)-Prezizaene, (-)-Prezizanol, and Other Perzizanoid Sesquiterpenes
Author(s)
Roach, Paula Marianne
Issue Date
1981
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2014-12-13T20:11:20Z
Keyword(s)
Chemistry, Organic
Language
eng
Abstract
The synthesis of four related sesquiterpenes was accomplished by elaboration of the chiral precursor pulegone. The ring system of (-)-prezizaene and (-)-prezizonal was constructed by intramolecular ring expansion of a diazo ethyl hydrindanone. (-)-Georgeone and (-)-georgeol containing a C-6 methyl group were formed by pinacolic rearrangement of a 3a,6-ethanoindene-diol. Favorskii rearrangement of (+)-pulegone and ozonolysis furnished ethyl 5-methyl-2-oxo-cyclopentane carboxylate which was annelated with methyl vinyl ketone to give a mixture of diastereomeric hydrindenones. Hydrogenation to ethyl 3-methyl-6-oxo-cis-hexahydroindane-3a-carboxylate was stereospecific. Ketone protection, reduction of the ester and sulphonylation gave 7a-hydroxymethyl-1-methyl-cis-hexahydroindane-5-one ethylene ketal as a single isomer after crystallization. An X-ray structure determination confirmed the all cis stereochemistry at the three chiral centers. Reduction and hydrolysis afforded a dimethyl ketone which was identical with a sample prepared independently.
Cyanide displacement under solid-liquid phase transfer conditions and reduction of the resulting nitrile provided a ketal amine. Benzoylation, hydrolysis, and nitrosation gave an N-nitroso amide. Treatment with potassium t-butoxide in t-amyl alcohol formed the diazo group which, after intramolecular addition to the ketone and rearrangement, afforded a ca. 1:1 mixture of two tricyclic ketones. These were identified as a 3-methyl-2,3,5,6,8,8a-hexahydro-1H-3a,6-methanoazulene-7(4H)-one and 3-methyl-octahydro-6H-3a,7-methanoazulene-6-one by selenation of the latter and oxidation and elimination to an (alpha),(beta)-unsaturated ketone. Alkylation, methyl lithium addition, and dehydration gave (-)-prezizanol and (-)-prezizaene which were completely identical with the natural products.
Oxidation of the ketal amine followed by hydrolysis afforded a nitro ketone which underwent aldol condensation to a tricyclic nitro alcohol containing the 3a,6-ethanohydrindane skeleton. Ozonolysis of the nitronate salt to 6-hydroxy-3-methyl-octahydro-3a,6-ethano-3aH-inden-5-one and methyl lithium addition provided a mixture of diasteromeric diols which under acidic conditions, underwent pinacolic rearrangement to a single 3a,6-methanoperhydroazulene-7-one. Methylation gave (-)-georgeone (3,6,8,8-tetramethyl-2,3,5,6,8,8a-hexahydro-1H-3a,6-methanoazulene-7(4H)-one, and hydride reduction furnished (-)-georgeol. The spectral properities of both compounds were comparable to those of the natural products.
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