Date of Award
Summer 2013
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Donaldson, William A.
Second Advisor
Steinmetz, Mark G.
Third Advisor
Yi, Chae S.
Abstract
ABSTRACT
PREPARATION OF CYCLOHEXENONES FROM ACYCLIC (PENTADIENYL)IRON(1+) CATIONS: SYNTHESIS OF CARVONE METABOLITES AND SYNTHETIC STUDIES DIRECTED TOWARD DIHYDROTACHYSTEROLS
Charles Felix Manful, BSc.
Marquette University, 2013
Six-membered carbocycles are abundant in natural products. This structural feature is present in terpenes, secosteroids, antibiotics, and even imbedded in the polycyclic framework of complex alkaloids. A wide variety of methodologies have been utilized for the preparation of six-membered carbocycles including Robinson annulation, Diels-Alder cycloaddition, Dieckmann condensation, ring closing metathesis, photochemical carbonylation of alkenylcyclopropanes, addition of soft nucleophiles to acyclic (ç5-pentadienyl)iron cations, etc.
Acyclic (ç5-pentadienyl)iron(+1) cations were first prepared about 50 years ago. The reactivity of these complexes is of continuing interest, particularly for the synthesis of conjugated polyenes and 2-cyclohexenones. These types of cationic complexes are powerful electrophiles and the site of nucleophilic attack is dependent on substituents on the pentadienyl ligand, the nature of the nucleophile, counter ion and "spectator" ligands on the complex. Tricarbonyl(ç5-1-methylpentadienyl)iron(+1), tricarbonyl(ç5-1-phenylpentadienyl)iron(+1), tricarbonyl(ç5-3-methylpentadienyl)iron(+1), and tricarbonyl(ç5-1,5-dimethylpentadienyl)iron(+1) cations were prepared following literature procedures.
The reactivity of these substituted acyclic (pentadienyl)iron cations with malonate, nitroacetate, sulfonate and phosphonoacetate nucleophiles were examined as potential routes to synthesis of natural product possessing six-membered carbocycles. Addition of stabilized/soft carbon nucleophiles occurs preferentially at the internal positions to afford cyclohexenones via (pentenediyl)iron intermediates. Nucleophilic addition at the terminal positions affords (2,4-dienoate)iron complexes mostly as minor products. This observed regioselectivity was explained mainly on the basis of FMO vs charge control.
In order to synthesize the oxygenated terpene (±)-10-Hydroxycarvone a ketoester was synthesized in five steps starting from commercially available 2,4-hexadienal. Deprotonation of the keteoester followed by DIBAL-reduction gave (±)-10-Hydroxycarvone. Alternatively, saponification of the ketoester afforded (±)-carvonic acid.
Furthermore to synthesize the dihydrotachysterol A-ring fragment, a cyclohexenone was synthesized in five steps from commercially available ethyl 3-methyl-4-oxocrotonate. Luche and catalytic reductions of the cyclohexenone gave
diastereomeric mixture of cyclohexanols. Protection followed by desulfonylation of the diastereomeric mixture gave a single diastereomer. á-Selenylation of this diastereomer followed by NaIO4 oxidation gave a racemic mixture dihydrotachysterol A-ring fragments.