Thesis advisor: Marc L. Snapper / Chapter 1. Review of concept and methodology development for asymmetric allylation of carbonyls and imines. Chapter 2. Description of the catalytic asymmetric addition of allyltrichlorosilane to aldehydes catalyzed by a proline-based N-oxide catalyst. Chapter 3. Introduction of the first catalytic asymmetric silylation of alcohols for desymmetrization of meso-diols. Chapter 4. Presentation of asymmetric silylation for synthesis of chiral syn-1,2-diols by kinetic resolution or divergent reaction on a racemic mixture. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18092号 / 理博第3970号 / 新制||理||1572(附属図書館) / 30950 / 京都大学大学院理学研究科化学専攻 / (主査)教授 丸岡 啓二, 教授 大須賀 篤弘, 教授 時任 宣博 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

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

The asymmetric synthesis of cis-1,4-aminoalcohols with norbornene backbone was performed starting with simple and cheap anhydride 30. Quinine-mediated desymmetrization of anhydride 30 with methanol resulted in (2S,3R)-(-)-cis-hemiester 31 (98% e.e.). Chemoselective amination with HMPTA and NH4OH followed by LAH reduction afforded (2S,3R)-(+)-36 and (2S,3R)-(-)-37, respectively. The amidoester (2S,3R)-(-)-32 was transformed into chiral ligand (2S,3R)-(-)-35 with Grignard reaction followed by LAH reduction. The chiral ligands (2S,3R)-(-)-35, (2S,3R)-(+)-36 and (2S,3R)-(-)-37 were subjected to asymmetric diethylzinc addition reaction to examine their effectiveness as chiral catalyst. Among these, chiral ligand 36 exhibited the highest enantioselectivity (88% e.e.)

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18094号 / 理博第3972号 / 新制||理||1573(附属図書館) / 30952 / 京都大学大学院理学研究科化学専攻 / (主査)教授 丸岡 啓二, 教授 時任 宣博, 教授 大須賀 篤弘 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20944号 / 理博第4396号 / 新制||理||1631(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 依光 英樹, 教授 丸岡 啓二, 教授 大須賀 篤弘 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

A new phosphineoxy aziridiniyl phosphonates POAP were synthesized as potential organocatalysts and used for silicon based asymmetric Abramov-type phosphonylation of aldehydes with triethyl phosphite. Besides POAP organocatalyst, known chiral phosphineoxy ferrocenyl substituted aziridinyl methanol (POFAM) and aziridinyl phosphonates (AP) were also used for the same reaction. The product &alpha / -hydroxy phosphonates were obtained in good yields up to 99% but with poor enantioselectivities. Highest enantioselectivity (%34) was obtained with POAP organocatalyst. Optimization studies were done with different solvents, ligands, aldehydes, and concentrations.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19012号 / 工博第4054号 / 新制||工||1624(附属図書館) / 31963 / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 赤木 和夫, 教授 辻井 敬亘, 教授 古賀 毅 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

De nouveaux β-aminoalcools chiraux ont été synthétisés en 3 à 4 étapes avec de bons rendements globaux (19-42%). Ils ont été testés en tant que ligands dans la réaction de réduction de cétones aromatiques par transfert d’hydrogène. Des excès énantiomériques jusqu’à 91% ont été obtenus avec de bonnes conversions jusqu’à 99%. La réduction asymétrique de cétones aromatique par le borane a été également étudiée. Ces β-aminoalcools se sont montrés actifs mais pas très énantiosélectifs. Ces composés ont également été utilisés en tant que ligands dans la réaction d’addition du diéthylzinc sur des aldéhydes aromatique conduisant aux produits désirés avec de bons rendements (jusqu’à 98%) et de bonnes énantiosélectivités (jusqu’à 80%). En revanche, la réaction d’addition d’autres organométalliques (l’organozincique, le silane, l’étain et le nickel) sur aldéhydes montre de faible énantiosélectivité dans la plupart de cas.Dans la dernière partie de ce travail, un des β-aminoalcools synthétisés a été évalué dans la réaction de cyanation catalytique énantiosélective d’aldimines. Malgré des bonnes conversions obtenues, des faible énantiosélectivités ont été observées. / Chiral β-aminoalcohol compounds were prepared in 3 or 4 steps from isosorbide in good overall yields (19-42%). These compounds were used as ligands in the asymmetric transfer hydrogenation of aromatic ketones giving good enantioselectivities (up to 91% ee) and excellent conversions (up to 99%). The asymmetric reduction of aromatic ketones by borane complexes using these aminoalcohols was also evaluated. Good catalytic activity but low enantioselectivity were observed. Asymmetric addition of diethylzinc to aromatic aldehydes using these β-aminoalcohols was also studied leading to desired products in good yields (up to 98%) and good enantioselectivities (up to 80%). However, no asymmetric induction was observed when using other organometallics (organozinc, silane, nickel, tin).The last part of this work consisted in evaluating one of these β-aminoalcohols in the Titanium-catalyzed asymmetric cyanation of aldimines. Despite good conversions, low enantioselectivities were observed.