Chiral 1,2-amino alcohols were synthesized via newly developed &ldquo / intramolecular unsaturation transfer&rdquo / using cyclohexanone, propargyl bromide, and various chiral amino alcohols as starting components. These amino alcohols can be potential chiral ligands for many asymmetric transformation reactions. Therefore, their effectiveness as chiral ligands in diethylzinc addition to benzaldehyde and N-diphenylphosphinoyl imines were tested. Various parameters including temperature, solvent, ligand amount etc. were screened for the synthesized chiral ligands. In diethylzinc addition to benzaldehyde high enantioselectivity could not be obtained. When N-diphenylphosphinoyl imines were used as substrate good ee values up to 80% were achieved.

Nitrogen containing heterocycles have always constituted a subject of great interest due to their wide presence in biologically important compounds so the development of efficient methods for the preparation of pyrrole derivatives and formation of new pyrrole-based heterocyclic compounds are an attractive goal in heterocyclic chemistry. In this study, starting from dimethoxytetrahydrofurane and amino acid esters, unsubstituted pyrrole derivatives, and treatment of amino acid esters with convenient chloroenones 1,2-disubstituted and 1,2,4-trisubstituted pyrrole derivatives were synthesized without racemization. Reaction of unsubstituted pyrrole derivatives with norephedrine toward inter- and intramolecular cyclizations give new interesting heteropolycylic compounds with oxazole-pyrrole-pyrazine structures. Study continued with cyclization reaction of these synthesized substituted and unsubstituted pyrrole derivatives with BBr3 and new bicyclic pyrrole derivatives were obtained in moderate yield.

Synthesis and evaluation of catalytic performances of novel bifunctional 2- aminoDMAP-Thiourea/ Sulfonamide/ Squaramide organocatalysts derived from trans-(R,R)-cyclohexane-1,2-diamine forms the main goal of this thesis. For this purpose, direct selective mono-N-pyridilization of trans-(R,R)-cyclohexane-1,2- diamine via Pd and Cu catalysis is described successfully first. Facile preparation of chiral 2-aminoDMAP core catalaphore led to the development of various 2- aminoDMAP- Thiourea/ Sulfonamides/ Squaramides as bifunctional acid/base organocatalyst libraries (most in two-steps overall) which showed good results in asymmetric conjugate addition of 1,3-dicarbonyls to trans-(&beta / )-nitrostyrene. Enantiomeric excesses (ee) up to 93% were attained.

Cyclitols are cyclic compounds having hydroxyl groups which attached to different carbons on the ring. Cyclitols have attracted a great deal of attention for having diverse biological activities. Cyclic alcohols play an important role in biological processes such as inhibition of glycosidase, cellular recognition, and signal transduction. In addition to this, these compounds are very important molecules due to being capable of using while synthesizing natural products or pharmaceuticals. In this study, development of new methodology for the synthesis of bis-aminoinositol derivatives was aimed. The starting material, cis-diester, was synthesized from the Diels-Alder reaction of furan and maleic anhydride followed by reaction with MeOH. As a second key compound, trans-diester was obtained from the Diels-Alder reaction of furan and fumaryl chloride followed by esterification. The diester functionality in these two compounds was planned to be converted into the hydrazide upon treatment with hydrazine monohydrate. Before this reaction, double bond was protected via stereo selective oxidation reaction with m-CPBA due to preventing retro Diels-Alder reaction. Then, hydrazide functionality was converted into acyl azide through &beta / -nitroso hydrazide intermediate. Subsequent Curtius rearrangement reaction resulted in the formation of the isocyanate which was converted to the corresponding bis-urethane by treatment with MeOH. Attempt to cleave the oxa-bridge in urethane with sulfamic acid provided the unexpected tricyclic product 148. Furthermore, hydrolysis of isocyanate with aqueous HCl formed the diamine 156. However, O-bridge could not be opened with any reagents used for that of urethane derivative as described above. Then,the cis-diol 157 was synthesized to prevent the neighboring group participitation during the epoxide-opening reaction. Further ring-opening reactions are under investigation.

Pyrazoles, isoindolinones, benzodizepinones and dihydroquinolinones are very important heterocycles for their biological properties. Many pharmaceutical agents include these units as core structures. Reactive molecules such as acyl azides, free radicals and formyl groups are used as key step reactants in these studies. Regiospesific hydrolysis and esterifications are used to reach target starting materials. Two different methodology are used for critical ring closure steps. Benzodiazepinones, and isoindolinones are obtained by base mediated ring closure reactions whereas thionyl chloride mediated procedure is used for dihydroquinolinones. Moreover, chloroacetonylation of the double bonds is also examined. Addition of acetylacetone to various alkenes was performed with in the presence of Mn(OAc)3 and HCl. Removal of one of the acetyl groups with ammonia under very mild conditions provided compounds derived from chloroacetonylation of the double bonds.

Aminocyclitols are cyclitols in which at least one of the hydroxyl groups is exchanged with an amino functional group. In turn, they constitute a wide group of natural products with interesting biological properties and are widely distributed throughout. In particular, antibiotics containing an aminocyclitol unit have stimulated the development of synthetic methodologies in the search for analogues with enhanced pharmacological profiles. In this study, three different methods were applied to synthesize diaminoconduritol derivative 202. In the first method, 1,2,3,6-tetraphthalic anhydrate (196), derived from Diels-Alder reaction between of maleic anhydride and 3-sulfolene, was used as a starting compound. Starting with the opening of anhydride group with trimethyl silylazide, tetrazolinone derivative 205 instead of bisamino cyclohexane derivative 201 was obtained. v In the second method, we started the synthesis of target compound 202 by the Birch reduction of benzene. Lactame 218 was synthesized as a key compound. Functionalization of lactame 218 was started with the cleavage of bond between nitrogen and carbonyl group in 218. At the end of the method, imidazole derivative 215 was obtained instead of target compound 202. Diaminoconduritol 242 was synthesized successfully by bishydrazide method. In this strategy, 1,2,3,6-tetraphthalic anhydrate (196) was used as a starting material. After conversion of bisurethane 223 to acylazide derivative 230, Curtius degradation and phtooxygenation reactions were used to introduce the amine and oxygen functionalities into the cyclohexene ring.

In this thesis, an intramolecular Pauson-Khand reaction of chiral enynes derived from homoallyl, allyl and homopropargyl alcohols is described. For this purpose, 2-heteroaryl substituted homoallyl, allyl and homopropargyl alcohols are easily and efficiently resolved through enzymatic resolution in a high ee (91-99%) with a known stereochemistry. Each enantiomerically enriched enyne derived from homoallyl and homopropargyl alcohols affords the conformationally most stable diastereomeric cyclopenta[c]pyran ring system as a sole product, whereas enantiomerically enriched enynes derived from allyl alcohols give the diastereomeric cis:trans mixture of cyclopenta[c]furan ring system. In addition these, an intramolecular Pauson&ndash / Khand reaction of camphor tethered enynes derived from homoallyl, homomethallyl, and homopropargyl alcohols is also described. Accordingly, homoallyl, homomethallyl, and homopropargyl moieties are easily constructed on the camphor carbonyl group with excellent diastereoselectivity due to endo-face selectivity, and with known stereochemistry. Each enantiomerically pure enyne affords the conformationally most stable diastereomeric spirocyclic cyclopenta[c]pyran ring system.

In the first part of this thesis, the construction of the novel bifunctional proline-(1R,2R)-2-aminoDMAP organocatalyst backbone is described. Target compound has both Lewis base and Br&oslash / nsted acid catalaphoric sites. The Lewis base site is synthesized via selective mono-N-pyridilization of trans-(1R,2R)-cyclohexane-1,2-diamine by Cu catalysis and Br&oslash / nsted acid site is subsequently introduced by anchoring L-proline unit. In the second part, catalytic activities of organocatalysts are tested in asymmetric Michael addition reaction between a cyclic 1,3-dicarbonyl compound 4-hydroxycoumarin and various &alpha / ,&beta / -unsaturated ketones to afford optically active warfarin as anticoagulants, in one step. Reaction parameters such as solvent, temperature, equivalency, and cocatalyst were screened. Enantiomeric excess value (ee) up to 72% is attained.

Racemic metyhl 3-cyclohexene-1-carboxylate was resolved via enzymatic hydrolysis to afford the enantiomerically enriched 3-cyclohexene-1-carboxylic acid with PLE (S-configuration), HLE (S-configuration), CCL (S-configuration) and PPL (R-configuration) . The nucleoside&amp / #65533 / s precursor, 5-(hydroxymethyl)-2-cyclohexen-1-ol (19), was synthesized by iodolactonization, followed by iodine elimination and the reduction of the lactone. In connection with this work, alpha,beta-unsaturated and saturated cyclic ketones were selectively oxidized on alpha&#039 / - and alpha-positions using Mn(OAc)3 and Pb(OAc)4, respectively. The resultant racemic alpha&#039 / - and alpha-acetoxylated substrates were resolved into corresponding enantiomerically enriched alpha&#039 / - and alpha-hydroxylated and acetoxylated compounds via PLE hydrolysis.

Chiral cyclic alkenols with hydroxymethyl functionality are important structural units in many biologically active natural compouds such as prostaglandins, sesquiterpene antiviral agents, pentenomycins, xanthocidin, sarkomycin, etc. 1,3-cycloalkanediones are converted into bicyclic polyoxo derivatives with formaldehyde and trioxane in the presence of Lewis acid. Selective oxidation of the bicyclic compounds by using manganese(III)acetate followed by enzyme-catalyzed kinetic resolution afforded chiral bicyclic hydroxy ketones. Reduction of carbonyl group and cleavage of the ether functionality furnished the desired chiral cycloalkanols with hydroxymethyl group. This study is a model for the synthesis of these type of compounds.