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This thesis deals with the design and synthesis of chiralenantiopure nitrogencontaining ligands and the use of theseligands in asymmetric catalysis. A modular synthetic approachto enantiopure nitrogen-containing ligands was developed. Thesynthetic method is based on the ring-opening of activatedchiral aziridines by nitrogen nucleophiles. The aziridines areconveniently prepared from amino alcohols. The structure oftheaziridine and of the nucleophile can be extensively varied andlibraries of ligands are easily prepared. The use of primaryamines affords C2-symmetric bis(sulfonamides), whereas the use ofammonia affords C3-symmetric tris(sulfonamides) that can beelaborated into the corresponding tetra-amines. The C2- and C3-symmetric ligands were used in the asymmetrictitaniummediated addition of diethylzinc to benzaldehyderesulting in modest enantioselection, 76% ee. A thoroughinvestigation of the reaction conditions revealed that theamount of Ti(OiPr)4has a decisive effect on the reaction rate and thestereochemical outcome of the reaction. The reaction timedecreased from about 90 hours to 15 minutes and theenantioselectivity changed from 26% of the (R)- enantiomer to72% of the (S)-enantiomer when the Ti(OiPr)4:benzaldehyde ratio was increased from 0.125:1 to1.48:1. Moreover, the titanium-mediated addition of diethylzincto benzaldehyde was studied in the presence of chiraladditives. The bis(sulfonamides) were also used in thecyclopropanation of cinnamyl alcohol. However, only lowenantioselection was observed, 27% ee. The C3-symmetric tetra-amines were reacted to formazaphosphatranes. These weak acids were only partiallydeprotonated by the strong base KOtBu to form the correspondingproazaphosphatranes. The unexpectedly strong basicity of theproazaphosphatranes was believed to be due to steric effects assuggested by DFT calculations. The tetra-amines and thesulfonamides were used for the preparation of metal complexesof Lewis acidic metals such as titanium(IV) andzirconium(IV). <b>Keywords:</b>asymmetric catalysis, aziridine, benzaldehyde,diethylzinc, enantioselective, ligand, proazaphosphatrane,ring-opening, sulfonamide, symmetry, titanium, zirconium

Design of new chiral ligands for asymmetric synthesis is important. The ligand should be economical and efficient in enantioselective transformations. For the synthesis of some natural products and biologically active compounds, optically active amines are used as important intermediates. For this reason, it is significant to develop new catalyst system which can produce optically active amines in an economical and efficient way. Our group developed PFAM ligands and used successfully for the enantioselective synthesis of organic compounds. In this work, these ligands were tested as chiral catalysts for enantioselective synthesis of amines. N-sulphonyl and N-phosphinoyl imines synthesized from aromatic aldehydes were used as the starting material for enantioselective diethylzinc addition reaction in the presence of copper salt and PFAM ligands. By improving the known procedure, N-benzylidine sulphonylaldimine was obtained in excellent yield (98%). Asymmetric diethylzinc addition reaction to N-sulphonyl and N-phosphinoyl aryaldimines provided chiral amines in up to 81% enantioselectivity and 99% yield.

The asymmetric synthesis of chiral norbornene based 1,4-aminoalcohols and their applications in asymmetric diethylzinc addition reactions was perfomed starting from meso-anhydride 50. The desymmetrization of this meso-anhydride 50 was done by the usage of quinine or quinidine cinchona alkaloids with very high enantiomeric excess values (up to 98% ee) and chemical yields. The Quinidine-mediated desymmetrization of meso-anhydride 50 with methanol gave (2R,3S)-(+)-cis-monoester 51. The amination of this resulting compound with HMPTA was performed and by keeping the amine group constant, the amidoester was transformed into chiral ligands with Grignard reaction followed by LAH reduction. The effectiveness of 1,4-aminoalcohol type ligands, (2R,3S)-(-)-57, (2R,3S)-(-)-58, (2R,3S)-(-)-59 and (2S,3R)-(+)-60 as chiral catalysts in asymmetric diethylzinc addition reaction to benzaldehyde were examined and the ligand 60 gave the highest enantioselectivity (69% e.e.)

The asymmetric synthesis of N-aryl substituted chiral 1,4-aminoalcohols and their applications in asymmetric borane reduction and enantioselective diethylzinc addition to benzaldehyde reactions were performed starting from meso anhydride 51 that is the cycloadduct of cyclopentadiene and maleic anhydride. The desymmetrization of meso-anhydride 51 was achieved by using quinine or quinidine with very high enantiomeric excess value (up to 98% ee) and with high chemicalb yield. The quinine-mediated desymmetrization of meso-anhydride 51 with methanol gave (2S,3R)-(-)-cis-monoester 52. The hemiester was subjected to chemoselective amidation with various types of N-aryl substituted amines and then, it was treated with LAH and followed by hydrogenation in the presence of palladium catalyst to get the chiral 1,4-amino alcohols. The catalytic effectiveness of these chiral 1,4-amino alcohol ligands, (2S,3R)-60, (2S,3R)-61, (2S,3R)-62 and (2S,3R)-63 were examined in asymmetric borane reduction and enantioselective diethylzinc addition to benzaldehyde reactions. Keywords: Amino alcohol, chiral ligand, asymmetric reaction, borane reduction, diethylzinc addition

An unexpected tricyclic ether formation instead of acetate addition to the double bond of a norbornene derivative aroused our interest to explore the mechanism of this reaction. Mechanistic studies showed that methylene diacetate (MDA) was formed in the stock solution (NBu4OAc + dichloromethane) and decomposed to formaldehyde under Lewis or Br&oslash / nsted acid conditions. Formaldehyde and olefin condensation (Prins reaction) clearly explains the formation of the unexpected product. Same methodology was then successfully applied to develop a one-step procedure for the synthesis of 3-chloro-3-arylpropanols, which are important starting materials for the synthesis of biologically active benzanilide derivatives. Styrenes were reacted with MDA in the presence of boron trifluoride to give the corresponding 3-chloro-3-arylpropanols in 36&amp / #8211 / 84% yield. The second part of the thesis involves kinetic resolution of 3-chloro-3-arylpropanols by lipase mediated acylation which are described for the first time. Acylation with the CCL provided the best enantioselectivity amongst the enzymes used. Enantiomerically enriched products with up to 78% ee were obtained after two successive lipase-mediated acylations. Different substituents on the aromatic ring and bromide, instead of chloride, at the benzylic position of the substrates were found to have no drastic influence on the enantioselectivity of the reaction. In the last part, easily available ferrocenyl substituted aziridinylmethanols (FAM) were complexed with nickel to catalyze the enantioselective diethylzinc addition to various enones with ee&amp / #8217 / s reaching 82%. The ligands can be recovered and used without losing their activity. The sense of asymmetric induction was found to be dependent on the configuration of the aziridine ring.

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.

<p>This thesis deals with the design and synthesis of chiralenantiopure nitrogencontaining ligands and the use of theseligands in asymmetric catalysis. A modular synthetic approachto enantiopure nitrogen-containing ligands was developed. Thesynthetic method is based on the ring-opening of activatedchiral aziridines by nitrogen nucleophiles. The aziridines areconveniently prepared from amino alcohols. The structure oftheaziridine and of the nucleophile can be extensively varied andlibraries of ligands are easily prepared. The use of primaryamines affords C₂-symmetric bis(sulfonamides), whereas the use ofammonia affords C₃-symmetric tris(sulfonamides) that can beelaborated into the corresponding tetra-amines.</p><p>The C₂- and C₃-symmetric ligands were used in the asymmetrictitaniummediated addition of diethylzinc to benzaldehyderesulting in modest enantioselection, 76% ee. A thoroughinvestigation of the reaction conditions revealed that theamount of Ti(OiPr)₄has a decisive effect on the reaction rate and thestereochemical outcome of the reaction. The reaction timedecreased from about 90 hours to 15 minutes and theenantioselectivity changed from 26% of the (R)- enantiomer to72% of the (S)-enantiomer when the Ti(OiPr)₄:benzaldehyde ratio was increased from 0.125:1 to1.48:1. Moreover, the titanium-mediated addition of diethylzincto benzaldehyde was studied in the presence of chiraladditives. The bis(sulfonamides) were also used in thecyclopropanation of cinnamyl alcohol. However, only lowenantioselection was observed, 27% ee.</p><p>The C₃-symmetric tetra-amines were reacted to formazaphosphatranes. These weak acids were only partiallydeprotonated by the strong base KOtBu to form the correspondingproazaphosphatranes. The unexpectedly strong basicity of theproazaphosphatranes was believed to be due to steric effects assuggested by DFT calculations. The tetra-amines and thesulfonamides were used for the preparation of metal complexesof Lewis acidic metals such as titanium(IV) andzirconium(IV).</p><p><b>Keywords:</b>asymmetric catalysis, aziridine, benzaldehyde,diethylzinc, enantioselective, ligand, proazaphosphatrane,ring-opening, sulfonamide, symmetry, titanium, zirconium</p>

The synthetic strategy of this study mainly depends upon the asymmetric desymmetrization of meso norbornene type an anhydride. Asymmetric desymmetrization was achieved by using chinchona alkaloids under kinetically controlled conditions. The resultant mono ester carboxylic acid was epimerized to trans configuration. Subsequent esterification followed by lithium aluminum hydride reduction afforded the first chiral diol ligand with 98 % ee. Transformation of diol to corresponding trans diamine was achieved via Mitsunobu-Gabriel combination. The resultant diamine was first transformed into salen type ligand with 3,5-di-tert-butyl-2-hydroxybenzaldehyde. Throughout this process, no racemization was observed and all the ligands tested in asymmetric reactions have 98 % ee value. The second part of the thesis involves the asymmetric test reactions of the chiral ligands to check the effectiveness of them. The first testing method was diethylzinc addition to benzaldehyde. The ligands showed moderate effectiveness. The salen type ligand was tested in asymmetric epoxidation and aziridination reactions and it showed good effectiveness. Another applied method was desymmetrization of meso 2-cyclohexene-3,4-diol in which 2-(diphenylphosphino)benzoic acid attached trans-diol and trans-diamine type ligands were tested. Since norbornene type strained bicyclic systems are available in ring opening methathesis polymerization (ROMP) reactions, trans-diamine was subjected to ROMP to get an enlarged macromolecular system

An applicable method for the racemic synthesis of 1,2-amino alcohols having tertiary alcohol moiety was developed. This method can be used as a general method for the synthesis of various 1,2-amino alcohols with various tertiary alcohol moieties by changing chloroacetone with different monohalo ketones, and with different aryl halides or alkyl halides. The resultant racemic 1,2-aminoe alcohols were tried to resolve by using various hydrolase type enzymes under different conditions by changing the parameters i.e. solvent, temperature and substrate: enzyme ratios. Finally, poorly resolved amino alcohol 20 with 21 % was used as chiral ligand in diethyl zinc reaction to benzaldhyde and afforded (R)-1-phenylpropan-1-ol almost with 21 % e.e..