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Thesis (Ph. D.)--University of Wisconsin, 1950. / Typescript (carbon copy). eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 39-41).

In biological systems, most of the active organic molecules are chiral. Some of the main constituents of living organisms are amino acids and sugars. They exist predominantly in only one enantiomerically pure form. For example, our proteins are built-up by L-amino acids and as a consequence they are enatiomerically pure and will interact in different ways with enantiomers of chiral molecules. Indeed, different enantiomers or diastereomers of a molecule could often have a drastically different biological activity. It is of paramount importance in organic synthesis to develop new routes to control and direct the stereochemical outcome of reactions. The aim of this thesis is to investigate new protocols for the synthesis of complex chiral molecules using simple, environmentally friendly proline-based organocatalysts. We have investigated, the aziridination of linear and branched enals, the stereoselective synthesis of β-amino acids with a carbene co-catalyst, the synthesis of pyrazolidines, the combination of heterogeneous transition metal catalysis and amine catalysis to deliver cyclopentenes bearing an all-carbon quaternary stereocenter and a new heterogeneous dual catalyst system for the carbocyclization of enals. The reactions presented in this thesis afforded the corresponding products with high levels of chemo-, diastero- and enantioselectivity. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 5: Submitted. </p>

Since 2000 the organocatalytic synthesis has developed massively in a third pillar of asymmetric synthesis standing next to catalysis with metal complexes and enzymatic catalysis. Organocatalysts, due to their various activation modes which could be combined in domino reactions, offer a way for a synthesis of complex molecules from a simple starting material. This thesis deals with investigation of usage of chiral secondary amines as catalysts for asymmetric synthesis of cyclic compounds. The main part of research was devoted to development of organocatalytic method leading to synthesis of enantiomerically pure cyclopentanecarbaldehydes and nitrocyclopentanecarbaldehydes. We focused also on the organocatalytic preparation of cyclohexanecarbaldehydes. During this work we developed an asymmetric domino Michael addition/α- substitution reaction of 2-(2-bromoethyl)malonates resp. 1-bromo-3-nitropropane with various enals catalyzed by chiral secondary amine. In the first case cyclopentanecarbaldehydes were formed where two chiral centres were created. In second case nitrocyclopentanecarbaldehydes were formed where three chiral centres were created. Yields of such developed reaction protocol reach up to 74 % and the reaction proceeds with excellent diastereo- and enantioselectivity (up to 19:1 d.r. and...

Among nature's creation, terpenoids are more versatile and exciting natural products. In a remarkable display of synthetic ingenuity and creativity, nature has endowed terpenes, more so sesquiterpenes, with a bewildering array of carbocyclic frameworks with unusual assemblage of rings and functionality. This phenomenal structural diversity of this class of natural products makes them ideal targets for developing and testing new synthetic strategies for efficient articulation of carbocyclic frameworks. The present thesis entitled "Synthesis of sesquiterpenes containing two vicinal quaternary carbon atoms" describes the synthesis of a number of herbertane sesquiterpenoids, antimicrobial sesquiterpenes enokipodins A and Bf and spirocyclic sesquiterpenes acorone and isoacorones based on ring-closing metathesis reaction. In the thesis, the compounds are sequentially numbered (bold), and references are marked sequentially as superscript and listed at the end of thesis. All the figures included in-the thesis were obtained by DIRECT XEROX OF THE ORIGINAL NMR SPECTRA, and in some of them uninformative areas have been cut to save the space. The herbertane sesquiterpenes are relatively a new class of aromatic sesquiterpenes, containing sterically crowded l-aryl-l,2,2-trimethylcyclopentane carbon framework incorporating two vicinal quaternary carbon atoms on a cyclopentane ring. The sterically crowded molecular framework coupled with the novel biological properties associated with the phenolic herbertanes made the herbertenoids challenging synthetic targets. In the present investigations, to begin with, a formal total synthesis of (±)-herbertenediol and (±)~ mastigophorenes A-D was developed starting from vanillin, based on a combination of Wacker oxidation and intramolecular aldol reactions. A general ring-closing metathesis (RCM) based methodology was developed for a-cuparenone and the herbertane sesquiterpenes herbertene, a-herbertenol, f)~herbertenol and herbertenediol starting from the appropriately substituted acetophenones. The acetophenones on Horner-Wadsworth-Emmons reaction followed by regioselective reduction generated 5-arylbut-2-enols, which on Claisen rearrangement furnished 3~aryl-3-methylpent-4-enals. Grignard reaction with vinylmagnesium bromide followed by RCM reaction and oxidation transformed 3-aryl-3-methylpent~4-enals into 4~aryl-4-methylcylopentenones, which were further transformed into 3-aryl-2,2,3-trimethylcyclopentanones, thus, completing the formal synthesis of the sesquiterpenes (±)-a-cuparenone, (±)-herbertene, (±)-a-herbertenol, (±)-pherbertenol and (±)'herbertenediol. In continuation of the synthesis of herbertane sesquiterpenes, a Claisen rearrangement and RCM reaction based strategy was developed for the synthesis of (±)~lt14-herbertenediol and (±)-71-epi-herbertenolide, and marine sesquiterpenes {£)-tochuinyl acetate and (±)-dihydrotochuinyl acetate. Ortho ester Claisen rearrangement of 3-arylbut-2~ enols generated 3-aryl~3-methylpent-4-enoates, which on allylation and RCM reactions generated 2~methyl-2-arylcyclopent-3-encarboxylates. Stereoselective alkylation followed by functional group manipulations transformed 2-methyl'2-arylcyclopent'3-encarboxylates into the marine sesquiterpenes (±)-tochuinyl acetate and (±)-dihydrotochuinyl acetate, (±)-ll-epiherbertenolide and (±)~l,,14-herbertenediol. Total synthesis of (±)-lt13-herbertenediol has been accomplished employing an RCM reaction as the key step. The requisite starting material 2-methoxy-5-methylphenyl acetate was obtained from p-cresol. Two sequential allylation reactions followed by RCM reaction transformed 2-methoxy-5-methylphenyl acetate into 1 -arylcyclopent-3-en-l-carboxylate. Allylic oxidation and alkylation followed by functional group manipulation transformed I-arylcyclopent-3-en-l-carboxylate into (±)-U3-herbertenediol. For the enantiospecific synthesis of (+)-a-herbertenol, an aromatic Claisen rearrangement based strategy was developed starting from the readily available monoterpene (R)-limonene. To begin with, limonene was converted into 5-isopropenyl-2-methylcyclopent-l-enemethanol which on Mitsunobu reaction with p-cresol followed by Claisen rearrangement of the resultant aryl ether generated a mixture of3-isopropenyl-3a,7,8b-trimethyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofurans. Degradation of the isopropenyl group and cleavage of the central ether ring transformed the major cyclopentabenzofuran into 3-aryl-2,3-dimethylcyclopentanone, which was further elaborated into (+)-a-herbertenol. The general RCM reaction methodology developed for the herbertenoids has been further extended to the first total synthesis of the antimicrobial sesquiterpenes (±)~ enokipodins A andB, and a formal total syntheses of (±)-cuparene-l,4-diol, (±)-cuparene-lt4-quinone and (±)~HM-1 methyl ether star*w« from 2,5~dimethoxy~4-methylacetophenone. It has been further extended to the formal synthesis of spirocydic sesquiterpenes (±)-acorone and (±)-isoacorones starting from cyclohexane-1,4-dione.

Es wird die enantioselektive Synthese eines substituierten Cyclopentanfragmentes beschrieben, welches zur Synthese einer Vielzahl von Diterpenen aus Euphorbiaceae genutzt werden kann. Schlüsselschritt hierbei ist eine intramolekulare Carbonyl-En-Reaktion. In zwei verschiedenen Syntheseansätzen wurde versucht, dieses zu einem Jatrophan-Diterpen umzusetzen. Versuche hinsichtlich einer Nozaki-Hiyama-Kishi-Kupplung werden beschrieben. Im zweiten Ansatz, wurde über eine Ringschlussmetathese bzw. eine Relay-Ringschlussmetathese versucht entsprechende Jatrophane herzustellen. Dies gelang bei einem Substrat, welches eine zweifach substituierte Doppelbindung beinhaltet. Somit konnte ein nichtnatürliches 17-Norjatrophan enantioselektiv synthetisiert werden. / The enantioselective synthesis of a highly substituted cyclopentan, useful for the synthesis of diterpenes from Euphorbiaceae is described. Key step is a intramolecular carbonyl-en reaction. Two different approaches towards Jatrophanes were examined. The first one envisioning a Nozaki-Hiyama-Kishi coupling didn´t work. The second one employed a ring-closing-metathesis which was successful in the case of a disubstituted double bond formed. The use of an relay-ring-closing-metathesis was also examined. The enantioselective synthesis of a nonnatural 17-Norjatrophane is described in all details.

Es wird die enantioselektive Synthese eines substituierten Cyclopentanfragmentes beschrieben, welches zur Synthese einer Vielzahl von Diterpenen aus Euphorbiaceae genutzt werden kann. Schlüsselschritt hierbei ist eine intramolekulare Carbonyl-En-Reaktion. In zwei verschiedenen Syntheseansätzen wurde versucht, dieses zu einem Jatrophan-Diterpen umzusetzen. Versuche hinsichtlich einer Nozaki-Hiyama-Kishi-Kupplung werden beschrieben. Im zweiten Ansatz, wurde über eine Ringschlussmetathese bzw. eine Relay-Ringschlussmetathese versucht entsprechende Jatrophane herzustellen. Dies gelang bei einem Substrat, welches eine zweifach substituierte Doppelbindung beinhaltet. Somit konnte ein nichtnatürliches 17-Norjatrophan enantioselektiv synthetisiert werden. / The enantioselective synthesis of a highly substituted cyclopentan, useful for the synthesis of diterpenes from Euphorbiaceae is described. Key step is a intramolecular carbonyl-en reaction. Two different approaches towards Jatrophanes were examined. The first one envisioning a Nozaki-Hiyama-Kishi coupling didn´t work. The second one employed a ring-closing-metathesis which was successful in the case of a disubstituted double bond formed. The use of an relay-ring-closing-metathesis was also examined. The enantioselective synthesis of a nonnatural 17-Norjatrophane is described in all details.