京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第18342号 / 農博第2067号 / 新制||農||1024(附属図書館) / 学位論文||H26||N4849(農学部図書室) / 31200 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 栗原 達夫, 教授 三上 文三, 教授 平竹 潤 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第19513号 / 理博第4173号 / 新制||理||1599(附属図書館) / 32549 / 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 依光 英樹 / 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(工学) / 甲第19726号 / 工博第4181号 / 新制||工||1645(附属図書館) / 32762 / 京都大学大学院工学研究科材料化学専攻 / (主査)教授 松原 誠二郎, 教授 吉田 潤一, 教授 中尾 佳亮 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19744号 / 工博第4199号 / 新制||工||1648(附属図書館) / 32780 / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 中條 善樹, 教授 赤木 和夫, 教授 松原 誠二郎 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20411号 / 工博第4348号 / 新制||工||1674(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 杉野目 道紀, 教授 村上 正浩, 教授 中尾 佳亮 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20714号 / 工博第4411号 / 新制||工||1685(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 杉野目 道紀, 教授 村上 正浩, 教授 松田 建児 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

This doctoral thesis focuses on applying different organocatalysts in several enantioselective reactions and aerobic photooxidations using visible light. Chapter 1 describes using a chiral primary amine-salicylamide derived from (1R,2R)-cyclohexane-1,2-diamine as chiral organocatalyst in the asymmetric conjugate Michael addition of aldehydes and ketones to maleimides, giving the corresponding enantioenriched succinimides. The same organocatalyst is used in the enantioselective Michael addition of aldehydes to nitroalkenes, yielding enantiopure γ-nitroaldehydes. Furthermore, these Michael additions of aldehydes to maleimides and nitroalkenes are carried out employing sustainable and environmentally friendly deep eutectic solvents (DES), being able to reuse the catalytic system for several cycles. Chapter 2 describes using a chiral primary-amine monocarbamate derived from (1R,2R)-cyclohexane-1,2-diamine as chiral organocatalyst in the enantioselective α-amination of aldehydes with azodicarboxylates, obtaining the corresponding α,α-disubstituted aldehydes with the absence of solvent under mild conditions. This simple orgacatalytic system’s applicability is demonstrated by preparing a chiral oxazolidinone precursor of amino acids. The reaction is also successfully scaled-up. In addition, theoretical calculations were performed to demonstrate how the absolute configuration of the final adducts is produced. Chapter 3 shows how riboflavin tetraacetate, a cheap vitamin B2 derivative, is an appropriate metal-free photocatalyst in the aerobic photooxidation of xanthenes, thioxanthenes and dihydroacridines under visible light irradiation. / This research work has been possible thanks to funding from the Spanish Ministerio de Economía y Competitividad (PGC2018-096616-B-100, CTQ201788171-P), the Generalitat Valenciana (AICO 2021/013) and the University of Alicante (VIGROB-173). The author wishes to express his gratitude to the Institute of Organic Synthesis for a research contract (I-PI/21-20) and to the University of Alicante-Banco Santander consortium for a grant to spend a three-months research period in the Chemistry Interdisciplinary Project research center (ChIP) of the University of Camerino (Italy) under the supervision of Dr. Matteo Tiecco.

No description available.

The objective of this research was to development new methodologies for the asymmetric syntheses of amine and natural products from enantiopure sulfinimines (N-sulfinyl imines). In this context, new methods was devised for the asymmetric synthesis of 2,5-cis and trans-disubstituted pyrrolidines from 3-oxo pyrrolidine 2-phosphonates, prepared by an intramolecular metal carbenoid N-H insertion from a sulfinimine derived delta-amino-alpha-diazo- beta-ketophosphonate. Horner-Wadsworth-Emmos reaction of the 3-oxo pyrrolidine 2-phosphonates and aldehydes provided pyrrolidine enones. Hydrogenation (Pd/H2) of the pyrrolidine enones gave cis-2,5-disubstituted pyrrolidines. Luche reduction the pyrrolidine enones followed by a TFA-NaBH3CN mediated hydroxy directed reduction provided the 2,5-trans products. (+)-Preussin, a potent antiviral and antitumor agent was prepared in 9 steps in 28% overall yield from the sulfinimine. An acid catalyzed intramolecular Mannich cyclization of a sulfinimine-derived N-sulfinyl syn-alpha-methyl-beta-amino ketones was employed for the asymmetric synthesis of 2,3,5,6-tetrasubstituted piperidinones. The beta-amino ketones were prepare by treatment of prochiral lithium Weinreb amide enolates with enantiopure (E)-N-(4-(benzyloxy)butylidene)-2,4,6-triisopropylbenzenesulfinamide. This new methodology was highlighted in the first asymmetric synthesis of the poison frog alkaloid (-)-indolizidine 221T. By manipulation of water concentration in tetrahydrofuran, syn- and anti-2,3-diamino esters were prepared by treatment of the lithium enolate of N-(diphenylmethylene) glycine ethyl ester with sulfinimines. Anhydrous THF afforded enantiopure syn-2,3-diamino esters with a syn/anti selectivity of better than 25:1. In a THF-H2O the anti-2,3-diamino esters were formed. The mechanism involves the generation of H2O-LDA species in the formation of enolate which inhibited the retro-Mannich fragmentation in the diamino ester species. (SR,2S,3R)-(-)-Ethyl-2-(N,N-dibenzylamino)-3-N-(p-toluenesulfinyl)amino-pent-4-enoate was employed in an improved total synthesis of the anti-tumor antibiotic (-)-agelastatin A. A series of N-sulfinyl aza-Morita-Baylis-Hillman products were prepared by addition of vinylaluminum and N-methylmorpholine-N-oxide reagents to enantiopure N-(p-toluenesufinyl)- and N-(2-methypropanesulfinyl)-derived sulfinimines from the least hindered direction via a non-chelation control mechanism. Hydrogenation of the these acrylates with a rhodium(I) catalyst afforded anti-alpha-substituted-beta-amino esters with a anti/syn selectivity of better than 17:1. This new methodology is useful for the asymmetric synthesis of anti-alpha-alkyl-beta-amino esters, which are valuable chiral building blocks for the preparation of biologically active nitrogen-containing natural products. / Chemistry

The research objective of this thesis research was to develop new methods for the asymmetric synthesis of amine derivatives using p-toluenesulfinimines. Enantiopure sulfinimines are versatile chiral building blocks for the asymmetric synthesis of alkaloids. Sulfinimines were prepared by the condensation of (S)- or (R)-p-toluenesulfinamide with aldehydes and ketones in good to excellent yields, which were prepared from the commercially available Anderson reagent. The first research project was the development of a new method for the preparation of enantiopure anti-anti- α-lkyl β-amino ketones and was accomplished by the stereoselective α-alkylation of enolates of sulfinimine derived β-amino esters. The anti- α-lkyl β-amino esters were transformed to their corresponding Weinreb amides by reacting with lithium dimethyl hydroxyl amine without epimerization. Reactions of the Weinreb amides with Grignard and organolithium reagents afforded the corresponding anti- α-lkyl β-amino ketones in modest yields and high optical purity. The modest yields are the results of competition between addition and reduction of the Weinreb amide. anti- α-lkyl β-amino ketones are important chiral building blocks for the asymmetric synthesis of nitrogen-containing biologically active molecules, such as pyrrolidines, piperidines and other alkaloids. To further illustrate the utility of sulfinimine -derived enantiopure N-sulfinyl anti- α-lkyl β-amino ketones, they was applied to the asymmetric synthesis of the unknown anti-C5, C6 derivative of 2,3,4,6-tetrasubsituted indolizidine 221-T. The key step in the synthesis was the stereoselective construction of the piperidine ring of the 5,6,8-tri-substituted indolizidine and was realized via the use of an acid-catalyzed intramolecular Mannich cyclization. The indolizidine was readily transformed in to the key intermediate 7-hydroxyl-2,3,4,6-tetrasubsituted indolizidine in high stereoselectivity and yield. Changing the sequence of chemical operation steps avoided the production of the side product β-pyrrole ketone. Reduction of the intermediate piperdinone, followed by ring-closing metathesis and reductive catalytic hydrogenation afford the bicyclic indolizidine with overall 76% yield of 3 steps. The C-2 branched cocaine analogs are thought to have varied bioactivities and potent therapeutical uses compared to other positions of substituted cocaine analogs. However, reports on the synthesis of such analogs are few. The first example of preparation of a cocaine analog having a dimethylphosphonate group at the C-2 position was reported. The key step in forming the required isoxazolidine intermediate, which controls the required cis stereochemistry at C-2 and C-3, was a novel microwave induce stereoselective [3+2] intramolecular cycloaddition of an α,β-unsaturated pyrrolidine nitrone. The use of the microwave irradiation techniques significantly reduce the time required for isoxazolidine formation from 96 hours to five hours. / Chemistry