Ⅰ. Synthesis of Pyrazinoindole-Based Lewis-Acid/Base Assembly, and Development of C-H Activation Reaction Using 2H-Azirine Ⅱ. Synthesis of Quinolizin-4-ones through C-H Activation III. Regioselective B-H Activation of o-Carborane : Chapter I. Synthesis of Pyrazinoindole-Based Lewis-Acid/Base Ass

Yonghyeon Baek 강원대학교 대학원 2020 국내박사

본 논문은 첫 번째로, 질소 원자를 포함하는 삼각-고리화합물인 2H-아지린 (2H-azirine)을 사용하여 루이스 산/염기 작용기를 피라지노인돌 (pyrazinoindole)에 도입한 어셈블리의 합성과 개발, 그리고 2H-아지린을 탄소-수소 활성화 반응의 반응물로 사용하여 선택적인 탄소-탄소 결합 형성반응의 개발을 다루고 있다. 두 번째는, 탄소-수소 활성화 반응을 통한 생리활성 물질인 퀴놀리진-4-온 (quinolizin-4-one) 유도체의 합성과 특징에 대해 설명한다. 마지막으로, 2차원 벤젠 시스템에서 더 확장된 3차원의 pseudo-aromatic 화합물인 오쏘-카보레인의 (o-carborane) 위치 선택적인 작용기화에 대해서 다루고 있다. Chapter Ⅰ. 2H-아지린을 이용한 루이스 산/염기 어셈블리의 합성과 탄소-수소 결합 활성화 반응의 개발 Part 1. 2H-아지린을 사용한 피라지노인돌 기반의 루이스 산/염기 어셈블리의 합성 피라지노인돌은 카바졸 (carbazole)유도체와 전자적으로 비슷한 특징을 나타내기 때문에 형광, 재료 화학 분야에서 다양한 연구가 수행되었다. 이에따라 피라지노인돌을 형광 코어로 사용하고 루이스 산/염기를 도입하여 특정이온의 검출에 따라 피라지노인돌의 형광의 흡수와 방출이 변하는지 연구하고자 했다. 이러한 피라지노인돌 기반의 루이스 산/염기 어셈블리의 합성은 위치선택적인 [3 + 3] 고리화 반응을 통하여 합성되었다. Part 2. 2H-아지린을 사용한 탄소-수소 결합 활성화 반응에서 선택적인 탄소-탄소 결합 형성 반응의 개발 이전에 2H-아지린은 주로 고리화 반응의 반응물로 사용되었다. 이때, 아지린이 갖는 핵심 중간체는 비닐-나이트렌이다. 이를 탄소-수소 활성화 반응에 이용된 사례가 없기 때문에 이를 연구하고자 하였다. 이때 형성될 수 있는 생성물은 탄소-탄소 커플링, 탄소-질소 커플링 화합물이 형성될 수 있다. 우리는 효율적인 접근은 위해 밀도함수이론 (DFT) 기반의 계산을 통하여 본 반응을 설계하였다. 놀랍게도 중간체의 안정성을 계산한 결과 탄소-탄소 커플링 반응이 선호되는 것으로 나타났다. 이후 실험을 통하여 아실메틸화 반응을 개발하였고, 메커니즘 연구를 통하여 반응의 현상에 대하여 규명하였다. 또한, 탄소-수소 활성화 반응에서 2H-아지린을 새로운 나이트렌의 전구체로 사용하여 선택적인 아실메틸화 반응을 개발한 점에서 의미가 크다. Chapter II. 탄소-수소 결합 활성화 반응을 통한 퀴놀리진-4-온의 합성 퀴놀리진-4-온은 생리활성 물질, 특정이온의 검출 혹은 생물학적 억제제에 사용되는 화합물로 알려져 있다. 기존의 합성법으로는 피리딘과 diene과의 Diels-Alder 반응을 통해 합성하거나, 연속적인 HWE 반응을 통하여 합성하였다. 그러나 위 반응들은 반응조건이 매우 가혹하며 치환체 적용범위가 낮다는 단점이 있다. 따라서 이를 개선하기 위하여 2-비닐피리딘과 다이아조 화합물과의 탄소-수소 활성화 반응과 분자내 고리화 반응을 통해 새로운 퀴놀리진-4-온의 합성법을 개발하였다. 더 나아가 합성된 퀴놀리진-4-온은 강한 형광을 방출하기 때문에 재료분야에서 이용가치가 높을 것이라 기대한다. Chapter III. 오쏘-카보레인의 위치선택적인 붕소-수소 결합 활성화 반응의 개발 로듐촉매를 사용한 위치선택적인 붕소-수소 활성화 반응을 통해 오쏘-카보레인의 보론 4번위치에 선택적으로 아마이드화 반응을 개발하였다. 카보레인의 경우에는 붕소중성자포획 치료에 사용되는 필수 붕소약물로써 다양한 작용기화 반응의 개발을 중요하다. 따라서 본 연구에서는 아마이드화에 사용되는 반응물로써 다이옥사졸론을 사용하였다. 또한 합성법 측면에서 응용가치를 높이기 위해 카보레인 클러스터가 이치환된 물질로부터 두 번의 아마이드화 반응을 수행하였으며, 독특한 구조의 카보레인 클러스터를 합성하였다. Chapter I. Synthesis of Pyrazinoindole-Based Lewis-Acid/Base Assembly, and Development of C–H Activation Reaction Using 2H-Azirine The heterocyclic compound 2H-azirine is useful for the organic synthesis of aza-heterocyclic compounds because of its unique reactivity with transition metals. They are easily converted by transition metal catalysts or heat to vinyl nitrene intermediates. Herein, we describe the synthesis of pyrazinoindole-based Lewis acid/base assemblies using nitrene intermediates generated by 2H-azirine using acylmethylation reactants in C–H activation reactions. The synthesis and characterization of pyrazinoindole-based assemblies are discussed in Part 1, and 2H-azirine, which is used as an acylmethylation reactant in C–H activation reactions is discussed in Part 2. Part 1. Synthesis of Pyrazinoindole-Based Lewis-Acid / Base Assembly Using 2H-Azirine Our group developed a regioselective synthetic method for the preparation of pyrazinoindole via a sequential Rh-catalyzed formal [3 + 3] cycloaddition and aromatization of a wide range of diazoindolinimines with 2H-azirines. Because the previously reported synthetic methods yielded mixtures of pyrazinoindole, the present method using asymmetrical azirines has a strong advantage from a regioselectivity viewpoint. Therefore, we synthesized pyrazinoindole-based Lewis acid/base assemblies using the previously developed synthesis of regioselective pyrazinoindole. The pyrazinoindole-based Lewis acid/base assemblies prepared via regioselective [3 + 3] cyclo-addition exhibit strong emission in THF solution, which is attributed to through-space intramolecular charge transfer (ICT) transitions. The dimesitylboryl group was selected as the Lewis acid to detect fluoride anion. Because the fluoride anion favors bonding with boron, the electronic effect is on the pyrazinoindole fluorophore after the formation of strong boron-fluorine bonds. These phenomena were validated by NMR titration studies, and more particularly by 19F NMR. Likewise, the dialkylamino group was selected as the Lewis base to detect proton ion and the protonation of the acid affected the pyrazinoindole fluorophore. These pyrazinoidole fluorophores are affected by the boron-fluoride bond formation and protonation. These results exhibit an electronic effect on the fluorophore, which greatly affects the absorption or emission of light, inducing a color change. Part 2. Selective C–C Bond Formation from C–H Activation Using 2H-Azirine A novel synthetic method for acylmethyl-substituted 2-arylpyridine derivatives using 3-aryl-2H-azirines was developed based on a prototype reaction using density functional theory (DFT) calculations and targeted experiments guided by the calculated mechanism. Initially, it was hypothesized that the 2H-Azirine ring was opened at the metal center to yield familiar metal nitrene complexes that undergo C–N coupling. Computational studies revealed and prototype experimental work confirmed that neither the formation of the expected metal nitrene complexes nor the C–N coupling were viable. Instead, azirine ring-opening followed by C–C coupling was highly favorable to yield imines that readily undergo hydrolysis under aqueous conditions to form acylmethyl-substituted products. This new method was highly versatile and selective toward a wide range of substrates with high functional group tolerance. The utility of the new method is demonstrated via a convenient one-pot synthesis of biologically relevant heterocycles such as pyridoisoindole and pyridoisoqunolinone. Chapter Ⅱ. Synthesis of Quinolizin-4-ones through C–H Activation Quinolizin-4-one is an important biologically active compound found primarily in the core molecular structure. Nevertheless, the general synthetic route of quinolizin-4-one has yet to be developed. In addition to its biological activity, quinolizin-4-one is characterized by fluorescence emission based on the specific molecular structure. However, previous studies were limited by the narrow pattern of substituents, which decreased the reaction yield and efficiency. Therefore, it is necessary to develop an efficient synthetic method using a wide range of substituents and to analyze the general synthetic mechanism. Accordingly, we have developed an efficient synthetic method for quinolysine via C–H bond activation. Quinolizin-4-one was synthesized in high yield from the 2-vinylpyridine derivative in one step via reaction with diazo Meldrum's acid (DM). In addition, the quinolizin-4-one obtained is a fluorescent material with characteristic absorption, emission, and fluorescence quantum yield data. Chapter III. Regioselective B–H Activation of o-Carborane o-Carborane is an important compound with three-dimensional structure of benzene and is used in material science and medical applications. It has been investigated as a substitute for the existing benzene system, and often exhibits renewed activity when it is replaced by carborane. In particular, it is used as an essential boron drug in agents for boron neutron capture therapy (BNCT), and o-carborane-based BNCT boron drugs are still under investigation. Therefore, the functionalization of carborane is important for the development of boron drugs. Amide and amine groups are key functional elements easily found in natural products and biologically active compounds, and therefore, reactions introducing amines or amides into carborane are significant. Nevertheless, few studies have reported facile amination and amidation reactions. Herein, regioselective amidation of cage B(4)-H bond in o-carboranes has been achieved for the first time using dioxazolone as the amidation reagent, where –COOH acts as a traceless directing group. A rhodium-catalyzed direct and regioselective amidation of the cage B(4)−H bond in a wide range of o-carboranes with alkyl-, aryl-, and heteroaryl-substituted dioxazolones has been demonstrated via activation of carboxylic acid-assisted B(4)−H bond in carborane clusters, resulting in a number of amidated o-carboranes in high yield with the release of carbon dioxide. Moreover, the selective two-fold decarboxylative amidation of the cage B(4)−H bond in o-carborane was performed.

Lewis Acid-Promoted Diastereoselective Cross-Coupling of Boronic Acids and Aryl-Substituted 1,2-Diols

유희선 아주대학교 2021 국내박사

A Lewis acid-promoted highly diastereoselective C(sp3)–C(sp2) cross-coupling reaction of aryl-substituted 1,2-diols and a variety of styryl, aryl, heteroaryl and polyaryl boronic acids as nucleophiles has been developed in a one-pot process under mild reaction conditions. The regioselective opening of aryl-substituted cyclic boronic esters promoted by a Brønsted or Lewis acid and subsequent intramolecular 1,4-transfer of the carbon ligand from boron atom to the same face of the resulting resonance-stabilized planar benzylic carbenium ion in a stereospecific fashion led to highly diastereoselective C–C bond formation at the benzylic carbon center. The synthetic value of this method has been demonstrated by a unified enantioselective total synthesis of 9-norneolignan natural products (–)-agatharesinol, (–)-agatharesinol acetonide, (–)-sugiresinol and (+)-hinokiresinol in 6 to 8 steps from the commercially available methyl 3-(4-hydroxyphenyl)acrylate.

Overcoming Limitations in Carbonyl-Olefin Metathesis using Novel Catalytic Approaches

Davis, Ashlee J ProQuest Dissertations & Theses University of Mich 2022 해외박사(DDOD)

Carbon-carbon bond forming reactions are among the most desirable transformations to synthetic organic chemists. Olefin−olefin metathesis is one of the most strategic methods available for the direct formation of carbon−carbon double bonds through the use metal alkylidene catalysts. The relative abundance of feedstocks available for this mode of reactivity has garnered olefin−olefin metathesis relevance in a wide range of applications from pharmaceuticals to materials. More recently, carbonyl−olefin metathesis has emerged as a key alternative to traditional olefin metathesis, with catalytic protocols relying on Lewis, Bronsted, and organocatalysts promoting renewed interest in the field.Chapter 1 provides a detailed look at the current methods available for carbonyl−olefin metathesis using Lewis acids. Early approaches relied on stoichiometric amounts of Lewis acids to promote the desired reactivity, while newer methods achieve the same reactivity in a catalytic fashion using a range of Lewis acids and mild reaction conditions. Chapter 2 presents the first general catalyst for the synthesis of larger ring systems from unreactive starting materials. The Al(III)-ion pair catalyst promotes ring-closing carbonyl−olefin metathesis through a unique and unprecedented carbonyl-ene/hydroalkoxylation pathway, as supported by NMR, KIE, and computational studies.Chapter 3 investigates the development and employment of metal complexes for carbonyl−olefin metathesis. The tunability of the Lewis acidic metal center promotes the ring-closing reaction on substrates that are sensitive to traditional catalytic systems such as bis-olefinic aryl ketones, and precursors to ring-closed products that are prone to isomerization under Lewis acidic conditions. NMR and IR studies demonstrate the formation of the active catalysts and quantify their Lewis acidic character. Chapter 4 expands the use of the metal complexes for ring-closing carbonyl−olefin metathesis for the synthesis of 7-membered rings. The increased potency of the Lewis acid catalyst is demonstrated on previously studied substrate classes, highlighting its superb catalytic activity.Lastly, chapter 5 focuses on the use of continuous flow reactors as enabling technology of the synthesis of 6-membered rings. This work restores the use of simple monomeric FeCl3 as the Lewis acid catalyst, eliminating the need for Ag(I) additives and costly air-free equipment and techniques. Mechanistic investigations reveal the reaction conditions promote a reversible carbonylene reaction, followed by an unprecedented stepwise hydroalkoxylation reaction to form the desired products.

루이스산에 의한 아릴(α-실릴메틸)바이닐 케톤의 고리화반응

이경란 부산대학교 2004 국내박사

The bismetallic reagent 2-stannyl-3-silylpropene (1) should be a versatile intermediates since both the vinylstannane and allylsilane moieties can be sequentially manipulated to construct more complicated and properly functionalized molecules. By modifying the vinylstannane moiety of 1 via the palladium-catalyzed cross coupling with aromatic acid chlorides and aryl halides gave aryl (α- silylmethyl)vinyl ketones 3 and 2-arylallylsilanes 5, respectively. Manipulation of the allylsilane moiety of 1 was achieved by the fluoride ion-catalyzed reaction; the reation of 1 with aldehydes in the presence of tetrabutylammonium (triphenylsilyl)difluorosilicate (TBAT) afforded 1-(2-hy droxyethyl)vinylstannes 7. When aryl (α-silymethyl)vinyl ketones 3 were treated with Lewis acids such as BF₃·OEt₂, AlCl₃, EtAlCl₂, InCl₃, and InBr₃ (α-silylmethyl) cyclopentanones 9 were produced via Nazarov cyclization. The reactions can be explained as follows: the Lewis acid-complexed, pentadienyl cation precursor undergoes a ring closure to cyclopentenyl cation followed by rapid loss of proton (rearomatization process) to afford (α-silylmethyl) cyclopentanones 9. The role of the silyl group of 3 in the reaction is rate enhancement due to the stabilization of cyclopentenyl cation by β-effect of silicon atom. Indeed Nazarov cyclization of aryl (1-methylvinyl) ketones 11a proceeded very slowly. On the contrary the reactions of 2-thienyl and 3-thienyl (α-silylmethyl)vinyl ketones 3a and 3b with FeCl₃ afforded α-methylenecyclopentanones 8a and 8b as major products, respectively. Such silicon-directed Nazarov reaction took place through the competitive rapid loss of the silicon electrofuge, not through the loss of proton from the cyclopentenyl cation. It is surprising because the removal of hydrogens from cyclopentenyl cation to regain aromaticity requires oxidants of some kinds. The resultant 2,3-dihydrothiophenes were supposed to be oxidized to α-methylenecyclo- pentanones 8a and 8b by ferric chloride. The role of FeCl₃ cannot be fully accounted at the present time. But it is almost certain that FeCl₃ serves as an oxidant in addition to a Lewis acid. When other aryl (α-silylmethyl)vinyl ketones where aryl group is phenyl, 3-methoxyphenyl, 3,5-dimethoxyphenyl, 1-naphthyl, 2-benzothienyl, or 2-benzofuryl were treacted with FeCl₃, silicon-directed Nazarov reation products α-methylenecyclopentanones 8 were obtained, though the yield of 8 were lower (3%~29%). (α-Silylmethyl)cyclopentanones 9 (15%~52%) were obtained along with 8. When 2-thienyl (α-trimethylsilylmethyl)vinyl ketones (3a) was treated with InCl₃ (0.1 equiv) in the presence of excess TMSCl (5 equiv), a 2:1 diastereomeric mixture of dimerized seven-membered cycloadducts 12 was obtained in 86% yield. The cycloadducts 12 seem to be formally resulted from the [4+2]cycloaddition between Lewis acid-complexed pentadienyl cation derived from 3a and carbon-carbon double bond of 3a. The structure of the cycloadduct 12 was confirmed by ¹H NMR, ^(13)C NMR, DEPT, ¹H-¹H COSY, HSQC, HMBC spectrum and high resolution mass spectrum. When other Lewis acids such as FeCl₃, BF₃·OEt₂, AlCl₃ were used under the same reaction conditions the same cycloadduct 12 was obtained in lower yield (34~42%). Along with this cyclic dimer Nazarov cyclization product 9a was produced in 17~21% yield. When the amounts of FeCl₃ was increased to 2 equivalents in the presence of excess TMSCl, however, no cycloadduct 12 was produced at all. Only Nazarov cyclization products 8a and 9a was obtained in 17% and 49% yield, respectively. The presence of excess TMSCl (5 molar excess) was essential for this cyclization. In the absence of it dimeric cycloadduct 12 was not formed either, although the role of the TMSCl in this reaction is yet to be clarified. The reaction of m-methoxyphenyl (α-silylmethyl)vinyl ketone (3c) was catalyzed similarly by InCl₃ (0.1 equiv) in the presence of TMSCl (5.0 equiv) the dimeric seven-membered cycloadduct 14 in 69% yield as a 2:1 diastereomeric mixture. In some extent a silyl group was removed from 14, and the desilylated product 15 was also formed in 13% yield. The similar treatment of 3,5-dimethoxyphenyl derivative 3d afforded the dimeric cycloadduct 16 and Nazarov cyclization product 9d in 41% and 28% yield, respectively. However the reaction of 3-thienyl (α-silylmethyl)vinyl ketone (3b) did not produce the dimeric cycloadduct at all even the same reaction conditions. Only Nazarov cyclization product was detected and 9b was formed in much higher yield. 2-Thienyl (1-methylvinyl) ketone (11a) and 4-methoxyphenyl (1-methylvinyl) ketone (28) underwent the similar cycloaddition to give 13 and 31 in 67% and 49% yields, respectively. Surprisingly none of the cycloadduct was formed in the reaction of aryl vinyl ketones without any alkyl substituent on the α-position of the vinyl group. In this reaction a small amount (14%) of 2-thienyl 1,3-dichloropropyl ketone, which indicates the involvement of solvent CH₂Cl₂, was formed. However the reaction mechanism is not clear. In order to understand the reaction mechanism and the limit of the cycloaddition, efforts were made to trap InCl₃-complexed pentadienyl cation with either electron rich or deficient olefins. From the reactions between aryl (1-methylvinyl) ketone (11a or 28) and an olefin, however, no [4+2] cycloaddition product was obtained at all. Dimeric cycloadduct 13 or 31 was product obtained. We found a new type of reaction which produces dimerized seven- membered cycloadducts 13, 14 and 39 from InCl₃-TMSCl induced reactions of aryl (1-alkyl)vinyl ketones, however, the scope of the reaction is not clear yet.

A Merged 1,2 and 1,3 Asymmetric Induction Model Describing Lewis Acid-Mediated Diastereoselective Reactions of Chiral N-Sulfonyl Imines and Nucleophilic Alkenes

Lo, Anna University of California, Davis ProQuest Dissertat 2022 해외박사(DDOD)

The exploitation of resident stereogenic centers to construct new stereogenic centers is a powerful strategy employed in the synthesis of complex organic molecules. Although the influence of both α- and β-stereogenic centers on the diastereoselective addition of nucleophiles to aldehydes has been thoroughly studied, analogous studies of α- and β-substituted imines are sparse. This dissertation describes the comprehensive study of how inherent asymmetry impacts diastereoselective nucleophilic additions to α- and β-chiral N-sulfonyl imines. Chapter one discusses the development of stereodivergent Lewis acid-mediated nucleophilic additions to α-chiral N-sulfonyl imines. From this study, two sets of optimized and generalizable conditions were developed, allowing access to either syn or anti diastereomeric outcomes in >95:5 diastereomeric ratios. Chapter two discusses the diastereoselective Lewis acid-mediated nucleophilic additions to β-chiral N-sulfonyl imines. These reactions typically proceed through a six-membered chelate and result in anti-products. Experimental and computational evidence lead to the construction of a generalizable stereoelectronic model that predicts for the magnitude of selectivity observed based on conformational preferences of the substrate-Lewis acid chelate. These two chapters together constitute a complete study of how 1,2 and 1,3 asymmetric induction affect diastereoselective nucleophilic additions to chiral N-sulfonyl imines.

A Study on Novel Catalysts for Upgrading Polycyclic Aromatic Hydrocarbons and Characterization using XAFS Spectroscopy

서혜련 단국대학교 대학원 2011 국내석사

본 연구는 다환식 방향족 탄화수소의 고부가화를 주 대상으로 하며, 세부적으로 탈황, 수첨분해, 카르복실화의 세 촉매반응으로 구분된다. 촉매활성을 증진시키기 위해 낮은 산화수를 가지는 인 전구체, 나노크기의 촉매합성, 그리고 촉매와 반응물의 인큐베이션단계를 적용하였다. 다양한 조건 및 방법으로 제조한 촉매는 BET, CO uptake, TPR, TEM, ICP-AES, 그리고 XAFS 등의 분석기법을 이용하여 특성을 조사하였다. 연구를 통하여 얻은 결과를 종합하면 다음과 같다. 첫째, 리간드 안정화법으로 제조한 Ni2P 나노결정의 형성 메커니즘 및 TOP와 TOPO의 역할에 대해 연구하였다. XANES 및 EXAFS 결과를 통해 Ni2P 나노결정 형성과정 중의 Ni은 착화물형성단계(complexation), 핵성장단계(nucleation), 그리고 인화물형성단계(phosphidation)를 거치는 것을 확인하였다. 또한 Ni-TOPO 복합체로부터 형성된 Ni2P 나노입자의 크기가 약 11 nm인 것과 비교해서, Ni-TOP 복합체로부터 더 작은 크기인 5 nm의 나노입자가 형성된 것을 통해 Ni-TOP 간 상호작용이 더 강하다는 것을 확인하였다. 둘째, 종래의 고온 환원법 (773 K, Ni2P/SiO2-HT)을 개선하여 Ni2P 활성상의 분산도를 높이기 위하여 낮은 산화가를 갖는 인 전구체를 사용하여 Ni2P촉매를 제조하였다. 673 K이하의 낮은 온도에서 환원되는 방식을 통해 실리카 담체상에 Ni2P 입자들의 분산도를 높일 수 있었으며 (Ni2P/SiO2-LT), 그에 따른 전환율의 향상효과를 거두었다: Ni2P/SiO2-HT(54%) < Ni2P/SiO2-LT(67%). EXAFS 분석결과를 통해 담체상의Ni2P 입자 및 두 종류의 Ni (tetrahedral Ni(I), square pyramidal Ni(II) 이 존재함을 확인하였으며, Ni2P의 분산도가 증가함에 따라 두 종류의 Ni 배위 가운데, square pyramidal Ni(II) 의 배위수가 증가하여 4,6-DMDBT 전환을 위한 반응활성점으로 작용함을 확인하였다. 셋째, 리간드 안정화법을 사용하여 제조한 나노입자 단위의 MoS2 의 입자형성 메커니즘 및 형상특성 제어를 위한 다양한 합성조건을 확립하였다. EXAFS 및 TEM결과를 통하여 Mo은 핵성장단계 (nucleation)에 이어 황화물 형성단계 (sulfidation)를 거쳐 판상의MoS2구조가 얻어짐을 확인하였다. 결과적으로, 핵성장 초기단계에서는1 nm 이하의 구형의 나노입자가 형성되고 온도가 증가할수록 5-7 nm까지 길이 방향으로 증가하며, 황화단계를 통하여 단일 판상형태 MoS2상으로 발달되었으며(573 K), 황화온도를 593 K이상으로 승온시 판상이 여러측으로 적층되는 거동을 확인하였다. 넷째, 리간드 안정화법을 사용하여 제조한 MoS2 나노입자 촉매를 감압 잔사유의 수첨분해반응에 적용하여 나노입자 형상특성에 따른 촉매적 활성을 비교평가하였다. 이를 통해 단층형 MoS2 나노입자 촉매의 경우 종래 전구체기반의 분산촉매 대비 감압잔사유의 경질화에 대한 우수한 수율 (52.4 % vs. 78.2 %)을 보여 가능성을 입증하였다. 또한 EXAFS 및 TEM 분석결과를 통해10 nm이하의MoS2 나노촉매가 수첨분해반응 (673 K, 10.0 MPa) 중에도 안정하게 형상특성을 유지함을 확인하였다. 다섯째, 이산화탄소 고정화를 통한 방향족화합물의 고부가화 연구를 위하여 AlCl3루이스 산 촉매를 사용하여 toluene 및 2-naphthol의 직접 카르복실화 반응에 적용하였다. 반응 율속단계에 해당하는 이산화탄소의 활성화 단계를 촉진시키기 위하여 촉매전처리 (이산화탄소 및 루이스산촉매 인큐베이션 단계)를 도입하여 반응 카르복실산에 대한 수율 향상 효과를 확인하였다 (6.9 % vs. 2.5 %). 한편 각 반응의 주생성물에 해당하는 para-Toluic acid및 2-Hydroxyl, 1-naphthoic acid의 선택도는 거의 99.9 %에 가깝게 얻어져 알킬 기능기를 가지는 방향족은para위치로, 하이드록실 기능기를 가지는 방향족은 ortho 위치로의 카르복실화가 우세함을 입증하였다. This study includes the catalysis for upgrading polycyclic aromatic hydrocarbons. In detail, the catalysis was classified with three types of reaction including the hydrodesulfurization (HDS), the hydrocracking (HCK) and the carboxylation. In order to increase the catalytic activity, three approaches have been made by adopting less oxidic phosphorous precursor to lower reduction temperature, synthesizing nano-scaled catalysts to provide better accessibility, and undergoing incubation of non-reactive CO2 with the Lewis acid catalyst. Characterizations were made by BET, CO uptake, TPR, TEM, ICP-AES and XAFS spectroscopy. First, a study has been conducted to demonstrate the formation mechanism of Ni2P nanocrystals and the role of coordinating solvents of TOP (trioctylphosphine) and TOPO (trioctylphosphine oxide). The Ni2P nanocrystals were successfully synthesized by a ligand stabilization method. The XANES and EXAFS results confirm that the Ni species undergo three consecutive steps of complexation, nucleation and phosphidation in the course of formation of Ni2P nanocrystals. The stronger interaction of Ni-TOP complex induced smaller Ni2P nanoparticles (5 nm) than those (11 nm) from Ni-TOPO complex. Second, the Ni2P catalysts were prepared by a new synthetic method with use of less oxidic phosphorus precursor in order to achieve high dispersion on silica support, and their structural properties and catalytic activity in HDS of 4,6-DMDBT were studied. Low temperature reduction technique led to better dispersion of Ni2P particles on SiO2 support. EXAFS analysis of the Ni2P samples confirmed the formation of Ni2P phase present on the silica support and the presence of two types of sites, tetrahedral Ni(I) sites and square pyramidal Ni(II) sites, with the latter growing in number in the same order as the reactivity Ni2P/SiO2-LT(67 % HDS) > Ni2P/SiO2-HT(54 % HDS), as the dispersion of Ni2P phase increased. These results thus suggest that the HDS activity of the Ni2P catalysts highly depend on the dispersion of the Ni2P phase. Third, MoS2 nanoparticles were synthesized by using the ligand stabilization method. Different temperature conditions for two consecutive synthesis steps of nucleation and sulfidation were applied to clarify the effect of synthetic conditions on the MoS2 nanoparticle formation. The EXAFS and TEM results confirm that the Mo species undergo the nucleation followed by the sulfidation in the course of formation of MoS2 particles. In the nucleation step, nuclei-like spherical nanoparticles below 1 nm in size were initially formed and were linked together into one-dimensional direction with 5-7 nm in length at a high temperature. In the sulfidation step, the development of MoS2 phase was promoted upon heating over 593 K with the formation of stacking structures comprising several layers of single slabs. Fourth, the oil-dispersible nanoscaled-MoS2 catalysts synthesized by the ligand stabilization method were applied for the hydrocracking of vacuum residue. TEM and EXAFS results revealed that the MoS2 phase of less than 10 nm in length remained stable in the course of the hydrocracking. The nanoscaled-MoS2 catalysts gave a good activity for the hydrocracking of vacuum reside with a yield to the liquid oil product of 78.2 % at 673 K and 10.0 MPa, which was much higher than the bulk MoS2 catalyst of 52.4 %. Fifth, the direct carboxylation of toluene and 2-naphthol was conducted by using AlCl3 as a Lewis acid catalyst. para-Toluic acid and 2-hydroxy,1-naphthoic acid were obtained with about both 100 % of selectivity and 16.9 % and 6.9 % of yield, respectively. Incubation step was beneficial to induce the CO2 activation and resulted in higher yield of carboxylic acid. This study verified that the aromatic compounds with alkyl group favor the para-carboxylation and those with hydroxyl group favor the ortho-carboxylation onto the adjacent site of hydroxyl group.

Ferric chloride-catalyzed chlorination of alcohol and carboxylic acid using α, α-dichlorodiphenylmethane

이수민 Graduate School, Yonsei University 2017 국내석사

알코올의 히드록시기나 카복실산의 카르복시기 의 수산기를 다른 작용기로 변환시키는 반응은 특히, 할로젠화 반응은 유기화학이나 유기합성 분야에 있어서 중요한 반응이다. 그 동안 일반적으로 이 반응을 위해 사용해 왔던 염소화 반응 시약으로는 염화티오닐, 포스포러스 트리클로라이드, 포스포러스 펜타클로라이드, 염화수소, 사염화탄소 / 트리페닐포스핀 등이 있다. 그러나 이 시약들의 경우 부식이나 독성으로 인해 다루기 힘들고 부산물이 많이 생성되는 문제점을 갖고 있었다. 따라서 온건한 반응 조건에서 반응성이 좋고 안정한 염소화 반응 시약을 찾는 실험들이 다양하게 진행되어 왔다. 현재까지는 다이할로이미다졸리다인다이온 (dihaloimidazoli¬dinedione), 사이클로헵타트리에닐리움 클로라이드(cycloheptatrienyliumchloride), 다이클로로다이페닐사이클로프로펜(dichlorodiphenylcyclopropene) 등의 시약들을 만들어 이용하는 방법이 알려져 있다. 본 연구에서는 염화철(Ⅲ) 촉매 하에 새로운 염소화 시약으로 α, α-다이클로로다이페닐메테인을 사용하여 온화한 조건에서 알코올과 카복실산의 염소화 반응을 진행하였다. 메커니즘으로는 알코올과 α, α-다이클로로다이페닐메테인이 FeCl3 촉매 하에서 탄소양이온 중간체를 생성하고 이때 생성되는 이 염소 이온이 중간체인 탄소양이온과 반응을 하면서 염화 생성물을 얻는다. 비대칭 알코올인 옥탄-2-올을 사용한 염소화 반응에서는 탄소양이온을 생성하지 않고 SN2반응 메커니즘으로 진행하여 입체 선택적인 생성물을 얻는다. 이는 카이랄 (S)-옥탄-2-올로 염소화 반응을 통해 얻은 (R)-2-클로로옥탄을 카이랄 가스 크로마토그래피(chiral gas chromatography)로 확인할 수 있었다. 산 염화물의 경우, 친핵체로 작용하는 아민과 1-헵탄올을 추가적으로 반응시켜 아마이드와 에스터의 합성으로 확인할 수 있었다. Chlorination reactions to replace hydroxyl groups with other functional groups are important in organic chemistry. Typically used chlorinating reagents include thionyl chloride, phosphorus trichloride, phosphorus pentachloride, hydrogen chloride, carbon tetrachloride / triphenylphosphine, and so on. However, these reagents are difficult to handle due to corrosion, toxicity, and the production of byproducts. Therefore, several studies have been conducted to discover stable and highly reactive chlorinating sources. To address these shortcomings, mild reagents such as dihaloimidazolidinedione, cycloheptatrienylium chloride, dichlorodiphenylcyclopropene, and others have been developed. This study investigated α, α-dichlorodiphenylmethane (DCDPM) as a new chlorinating source for chlorinating alcohol and carboxylic acid with ferric chloride as a catalyst under mild reaction conditions. Alcohol and DCDPM reacted to produce an intermediate, carbocation, and chloride ion under a FeCl3 catalyst. The chloride ion reacted with carbocation to obtain chlorinated product. Since chiral alcohol was not used to produce carbocation in the chlorination reaction, the reaction proceeded to the SN2 mechanism. The chlorination reaction of (S)-octan-2-ol proceeded to form (R)-2-chlorooctane, which was confirmed by chiral gas chromatography. In the case of carboxylic acid; an acid chloride was obtained through the reaction of carboxylic acid. Acid chloride reacted with other nucleophiles such as alcohol or amine to identify it. 1-heptanol or several nucleophilic amine reagents reacted with the acid chloride to form ester or amide, respectively.

Unveiling anisotropic chemical reactivity of 2D layered nanostructures

한재효 Graduate School, Yonsei University 2017 국내박사

2차원 층상 구조는 비등방성이라는 독특한 성질을 바탕으로 다양한 연구가 진행 되고 있다. 물리적으로는 방향에 따라 마찰력, 전자 이동속도가 큰 차이값을 보이며 화학적으로는 비등방적 화학구조에 따라 촉매 반응등의 효과가 다르게 나타난다. 좀더 자세히 말하면 2차원 전위 금속 칼코겐 화합물의 경우, 측면 부분에는 불포화 댕글링 메탈 황 본드들이 존재하게 되고 단면 부분에는 포화된 황 본드들이 3가의 형태로 존재하고 있다. 기존의 연구들 경우 측면 부분의 불포화 댕글링 본드들의 활용성에 맹점을 두고 분자의 흡착을 이용한 센서, 화학적 불안정성을 이용한 헤테로에피탁시알 성장, 높은 반응성을 이용한 산소 분해등의 연구가 중점적으로 연구되어 있다. 본 연구에서는 일반 화학에서 알려진 단분자들을 외부 자극으로 이용하여 측면과 단면부분에서 존재하는 화학적 비등방성의 차이를 먼저 이해하고 더 나아가 외부자극 정도에 따라 조절 하는 연구를 수행 하였다. 먼저, 친전자체/친핵체인 싱글렛 산소 (1O2)와 물 (H2O)을 이용하여 면간의 반응성 차이를 시간별로 관찰 하였다. 실험 결과 친전자체의 경우 상대적으로 전자가 많은 황물질로 구성된 단면과 선택적으로 반응하는 반면, 친핵체의 경우 전자가 부족한 측면의 댕글링 본드들과 선택적으로 반응 하는 것을 관찰 하였다. 더 나아가 측면에서의 반응은 아톰들의 이동과 재배열이 관찰되어 전위 금속 황/산화물의 복합체 설계가 가능함을 밝혀냈다. 앞서 친전자체로 사용된 싱글렛 산소의 경우 반응성이 매우 높아 그 과정에 대한 자세한 이해의 한계가 있었다. 이를 다음 연구에서는 일반 화학에서 쉽게 접근할 수 있는 루이스 산을 이용하여 단면의 황 아톰들을 활성화 시키고 그 결과물을 시간 별로 관찰 하였다. AlCl3 루이스 산을 사용하여 NbS2의 황과 복합체를 이루며 물질 내의 본드의 결합 절단이 발생 하여 선택적 에칭을 통한 다공형 구조를 개발 하였다. 다공형 구조의 경우 표면적이 증가하여 물성의 극대화가 관찰 되어 향후 개발된 루이스 산을 이용한 표면 반응을 이용한 다방면적 접근법을 제시하였다. 위 연구를 이용하여 차후 2차원 층상 구조의 선택적 반응 및 조절을 통해 결정 구조 재배열, 에칭, 성장을 유도 할 수 있고 이는 전하 분리, 전해질의 흡착도 상승, 표면적의 극대화로 이어져 차후 물성 극대화로 이어질 것을 예상한다. Anisotropy is a unique merit in 2D layered nanostructures that forms new physico/chemical behaviors. Anisotropic excitons and hall carrier mobility have been reported in the wide range of 2D layered nanostructure, for instance, order of magnitude high mobility has been observed from arm chair to zig-zag direction in black phosphorous. Not only in the physical behaviors but also anisotropy determines the chemical reactivity in 2D layered nanostructures. The anisotropic chemical reactivity determines the high catalytic reactivity of peripheral edge sites of 2D layered transition metal chalcogenides. Meanwhile, the fully saturated trivalent chalcogens in the basal plane is known to be chemically inert, at least under mild conditions. Harsh treatments such as radical species and plasma are necessary to initiate bond deformation, yet, chemical approaches to induce reactions in controlled manner has not been demonstrated until now. In this thesis, anisotropic chemical reacitivity of 2D layered nanostructure is studied based on Lewis acid-base reaction. In the first section, the general background of 2D layered TMC and chemical principles employed in the research are broadly discussed. In the second section, colloidal synthesis of 2D layered nanostructures in various chemical compositions and shapes are presented. The synthetic protocol is a must prequiste for this study as the particles are employed as a well defined model system. In the third section, unique nanoscale phenomena, including a “compositional metathesis” and a regioselective “morphological transformation”, promoted by subjecting 2D layered TMC nanocrystals to chemical stimuli is explored. Since acid and base are the most fundamental chemical characteristics, we choose to test their reactions with 2D layered titanium disulfide (TiS2) nanocrystals as an exemplary for understanding of their nanoscale chemical reactivity. TiS2 nanocrystals are exposed to either oxygen (O2) or water (H2O): more specifically (i) singlet oxygen (1O2) as electrophilic Lewis acid and (ii) water as a nucleophilc Lewis base that donates electrons. We demonstrate that these two chemical stimuli convert layered TiS2 into titanium dioxide (TiO2) as a final product, but via markedly different reaction pathways with distinct nanoscale morphologies. In the fourth section, Lewis acid promoted surface activation of NbS2 nanoseheet is presented. The fundamental understanding of interaction between molecular reagents and solid-state matter continues to fuel countless aspects of scientific discovery. One model that has recently received a great attention is chemically driven surface activations of 2D layered transition metal chalcogenides (TMCs) nanostructures due to their importance in understanding of stability, surface chemistry and materials properties. Especially, a prolonged attention has been given to the edge of plane where unsaturated metals and chalcogens are chemically active and some of examples include edge selective growth to a core-shell heterostructure, efficient hydrogen evolution catalysis and chemisorption for sensing applications. On the other hand, completely saturated trivalent sulfur and metal atoms of the basal plane are believed to be chemically inert and surface activation strategies remain elusive. Electrostatic potential mapping, Density functional theory (DFT) based Fukui function of slab model and transient energy profile of NbS2 nanosheets with group 13 metal chloride (MCl3, M= Al, Ga and In) Lewis acids is executed to understand the chemical reactivity of sulfurs in basal, edge and vertex sites toward Lewis acid as well as the mechanism of etching process, respectively. Lastly, the electrochemical energy storage property is measured that the performance of nanopore-NbS2 is increased by two times due to enlarged specific surface area that enormously large capacitance and the long-term stability is achieved with the capacitance of initial and porous NbS2 of 354 and 637 F/g, respectively.

Catalytic asymmetric roskamp reaction of diazo weinreb amides and α-silyloxymethyl diazoesters and synthetic studies of (-)-shikimic acid and epoxyquinomycin B

Shin, Sungho Sungkyunkwan university 2018 국내박사

A convenient one-pot procedure to synthesize a variety of highly optically active syn-α-aryl-β-hydroxy Weinreb amides and syn-α-silyloxymethyl-β-hydroxy esters using an asymmetric Roskamp/reduction strategy is described. An oxazaborolidinium ion catalyzed asymmetric Roskamp reaction of α-aryl diazo Weinreb amides with aldehydes produced α-phenyl-β-keto Weinreb amides, which were in situ reduced with zinc borohydride to give syn-α-aryl-β-hydroxy Weinreb amides in good yields (up to 87%) with high enantioselectivities (up to 99% ee) and syn stereoselectivities (>20:1). Also, an oxazaborolidinium ion catalyzed asymmetric Roskamp reaction of α-silyloxymethyl diazo esters with aldehydes produced α-silyloxymethyl-β-keto esters, which were in situ reduced with zinc borohydride to give syn-α-silyloxymethyl-β-hydroxy esters in good yields (up to 89%) with high enantioselectivities (up to 99% ee) and syn stereoselectivities (>20:1). These compounds would be valuable chiral intermediate for bioactive natural products. Other subject is synthetic studies. Tamiflu, a neuraminidase inhibitor, is an antiviral medication used to treat influenza virus in patients who have had symptoms for less than 2 days. The current key starting material for the production of Tamiflu is (-)-shikimic acid. However, limited availability of (-)-shikimic acid from natural Chinese star anise has led to the development of synthetic pathways to increase the supply of (-)-shikimic acid. Besides its industrial uses, (-)-shikimic acid is a pivotal intermediate in the biogenetic synthesis pathway of a variety of aromatic natural products in microorganisms and plants known as the shikimate pathway. Enantioselective Diels-Alder reactions with furans, we have found that the Diels-Alder reaction of furans with cationic chiral oxazaborolidinium catalyst provides 7-oxabicyclo[2.2.1]hept-5-enes with high endo-selectivity (91:9) and excellent enantioselectivity (99% ee). Another subject is synthetic studies of epoxyquinomycin B. Chiral cyclohexenone epoxide compounds, frequently found in natural products, exhibit wide range of interesting biologically active properties, including antibiotic, antimicotic, and antitumoral activities. Among them, epoxyquinomycin B has received considerable attention from the synthetic community because of therapeutic potential as anti-inflammatory agents and for the treatment of rheumatoid arthritis. As synthetic strategy, we have been studied on an asymmetric epoxidation with benzoquinone monoketal derivatives. Synthetic study of (+)-epoxyquinomycin has been approached from the readily available stereocontrolled Diels−Alder adduct of cyclopentadiene and 1,4-benzoquinone monoketal through an efficient series of steps and asymmetric Sharpless epoxidation of 1,4-benzoquinone monoketal.

Charge Transfer Complex로 본 Cholesterol과 Lewis Acid와의 Interration에 관하여

홍은경 이화여자대학교 대학원 1961 국내석사