Looking for treasure in stereochemistry-land. A path marked by curiosity, obstinacy, and serendipity

Over the past 40 years, much of my research has evolved around various topics of conformational analysis and asymmetric synthesis. This Perspective describes some of my salient contributions in eight different areas of organic stereochemistry: (1) conformational analysis of six-membered rings, (2) evaluation of stereoelectronic interactions in (1)J(C-H) one-bond coupling constants in six-membered rings, (3) eclipsed conformation in cis-2-tert-butyl-5-(tert-butylsulfonyl)-1,3-dioxane, (4) determination of enthalpic and entropic contributions to ΔG°(CH(2)Ph) and ΔG°(t-Bu), (5) study of the "attractive gauche effect" in O-C-C-O segments, (6) examination of salt effects on conformational equilibria, (7) asymmetric synthesis of β-amino acids, and (8) asymmetric organocatalysis and "Green" chemistry. It will be appreciated that a basic understanding of the principles of physical organic chemistry has been essential in all projects. Furthermore, curiosity, enthusiasm, obstinacy, and paying attention to unexpected observations will lead to many new (stereo)chemical discoveries.     

Fun with photons, reactive intermediates, and friends. Skating on the edge of the paradigms of physical organic chemistry, organic supramolecular photochemistry, and spin chemistry

This Perspective presents a review and survey of the science and philosophy of my research career over the past five decades at Columbia as a physical organic chemist and photochemist. I explore the role of paradigms, structure, and geometric thinking in my own cognitive and intellectual development. The Perspective describes my investigations of high energy content molecules in electronically excited states and the development of electronic spin and supramolecular photochemistry chemistry. Current research dealing with the nuclear spin chemistry of H(2) incarcerated in buckyballs is illustrated. In the second part of this Perspective, I recount a personal role of the philosophy and history of science and the scientific communities' use of paradigms in their every day research and intellectual activities. Examples are given of the crucial role of geometry and structure in the rapid development of organic chemistry and physical organic chemistry over the past century.     

Organofluorine chemistry: synthesis and conformation of vicinal fluoromethylene motifs

The C-F bond is the most polar bond in organic chemistry, and thus the bond has a relatively large dipole moment with a significant -ve charge density on the fluorine atom and correspondingly a +ve charge density on carbon. The electrostatic nature of the bond renders it the strongest one in organic chemistry. However, the fluorine atom itself is nonpolarizable, and thus, despite the charge localization on fluorine, it is a poor hydrogen-bonding acceptor. These properties of the C-F bond make it attractive in the design of nonviscous but polar organic compounds, with a polarity limited to influencing the intramolecular nature of the molecule and less so intermolecular interactions with the immediate environment. In this Perspective, the synthesis of aliphatic chains carrying multivicinal fluoromethylene motifs is described. It emerges that the dipoles of adjacent C-F bonds orientate relative to each other, and thus, individual diastereoisomers display different backbone carbon chain conformations. These conformational preferences recognize the influence of the well-known gauche effect associated with 1,2-difluoroethane but extend to considering 1,3-fluorine-fluorine dipolar repulsions. The synthesis of carbon chains carrying two, three, four, five, and six vicinal fluoromethylene motifs is described, with an emphasis on our own research contributions. These motifs obey almost predictable conformational behavior, and they emerge as candidates for inclusion in the design of performance organic molecules.     

我在“化学拔尖计划”有机化学课堂教学上的三项小尝试

The goal of the Ministry of Education's "Top Talent Training Program" is to train top innovative talents for China and prepare them to be the leading figures in the field of chemical research. This paper summarizes the author's three attempts to reform organic chemistry teaching in the "Top Talent Training Program"; including (1) to present the report of the minireview of organic chemistry as a true academic report; (2) to stimulate students' interest by practical comprehensive structural determination of organic compounds; (3) to create more active learning atmosphere through displaying interesting research stories and new research directions. We also discussed how to stimulate the students' interest in scientific research through these three teaching reforms.     

Application of physical organic methods to the investigation of organometallic reaction mechanisms

For the past 75 years, physical organic chemistry has been the foundation for the elucidation of mechanisms, and the understanding of structure/activity relationships, in organic chemistry. The rational design of experiments and the critical analysis of data have been the hallmarks of this field. In this Perspective, we revisit some of the studies carried out during the past 30 years in which our group has used the tools of physical organic chemistry to investigate the mechanisms of a variety of organometallic reactions. The Perspective covers a broad spectrum of metal-mediated reactions including organic reductions, alkene, carbon monoxide and nitric oxide migratory insertion reactions, C-H bond activation, and the reactions of metal-heteroatom bonds with organic molecules. These studies, along with similar ones carried out in other groups, have demonstrated that the principles and methods of physical organic chemistry have adapted well to the study of organometallic reaction mechanisms. The understanding obtained in this way has aided the development of useful metal-mediated reactions in a wide range of areas, especially in industrial catalysis and in applications to problems in organic synthesis.     

The Huisgen Reaction: Milestones of the 1,3‐Dipolar Cycloaddition

The concept of 1,3‐dipolar cycloadditions was presented by Rolf Huisgen 60 years ago. Previously unknown reactive intermediates, for example azomethine ylides, were introduced to organic chemistry and the (3+2) cycloadditions of 1,3‐dipoles to multiple‐bond systems (Huisgen reaction) developed into one of the most versatile synthetic methods in heterocyclic chemistry. In this Review, we present the history of this research area, highlight important older reports, and describe the evolution and further development of the concept. The most important mechanistic and synthetic results are discussed. Quantum‐mechanical calculations support the concerted mechanism always favored by R. Huisgen; however, in extreme cases intermediates may be involved. The impact of 1,3‐dipolar cycloadditions on the click chemistry concept of K. B. Sharpless will also be discussed.     

Glaser反应研究新进展

Glaser偶联反应是合成二炔化合物的重要反应,广泛应用于有机合成、材料化学等领域.介绍了近年来Glaser偶联反应中溶剂、氧化剂、底物等领域的研究新进展,指出Glaser偶联反应在不断加深其各方面绿色化研究的同时,多功能团底物的Glaser偶联反应与不对称的Glaser偶联反应也值得关注.     

Polyvalent iodine in organic chemistry

Tricoordinate, I(III), and pentacoordinate, I(V), polyvalent iodine compounds have been known for over a century. In the last twenty years, new polyvalent iodine reagents have been introduced along with synthetic methodologies, based on these and derived reagents, that play an ever increasing role in contemporary organic chemistry. In this Perspective, an overview of these developments is provided with emphasis on the chemistry and uses of aryl-, alkenyl-, and alkynyliodonium salts in preparative and synthetic organic chemistry. It is hoped that this brief overview, along with recent more comprehensive reviews of the field, will stimulate further developments and applications of this useful class of compounds across a broad spectrum of organic chemistry.     

Bioorthogonal organic chemistry in living cells: novel strategies for labeling biomolecules

The chemical labeling of biomolecules continues to be an important tool for the study of their function and cellular fate. Attention is increasingly focused on labeling of biomolecules in living cells, since cell lysis introduces many artefacts. In addition, with the advances in biocompatible synthetic organic chemistry, a whole new field of opportunity has opened up, affording high diversity in the nature of the label as well as a choice of ligation reactions. In recent years, several different two-step labeling strategies have emerged. These rely on the introduction of a bioorthogonal attachment site into a biomolecule, then ligation of a reporter molecule to this site using bioorthogonal organic chemistry. This Perspective focuses on these techniques, their implications and future directions.     

Five-membered oxaza heterocyclic compounds on the basis of epoxides and aziridines

The review summarizes methods for the synthesis of 1,3-oxazolidin-2-ones, 1,3-oxazolidines, and dihydro-1,3-oxazoles from epoxides and aziridines. Possible applications of N,O-containing heterocycles in medicinal and organic chemistry as biologically active substances and intermediate products for their preparation are considered.     

Diradical mechanisms for the cycloaddition reactions of 1,3-butadiene,benzene, thiophene,ethylene, and acetylene on a Si(111)-7x7 surface

The cycloaddition chemistry of several representative unsaturated hydrocarbons (1,3-butadiene, benzene, ethylene, and acetylene) and a heterocyclic aromatic (thiophene) on a Si(111)-7x7 surface has been explored by means of density functional cluster model calculations. It is shown that (i) 1,3-butadiene, benzene, and thiophene can undergo both [4+2]-like and [2+2]-like cycloadditions onto a rest atom-adatom pair, with the former process being favored over the latter both thermodynamically and kinetically; (ii) ethylene and acetylene undergo [2+2] cycloaddition-like chemisorptions onto a rest atom-adatom pair; and (iii) all of these reactions adopt diradical mechanisms. This is in contrast to the [4+2] cycloaddition-like chemisorptions of conjugated dienes on a Si(100) surface and to the prototype [4+2] cycloadditions in organic chemistry, which were believed to adopt concerted reaction pathways. Of particular interest is the [4+2]-like cycloaddition of s-trans-1,3-butadiene, whose stereochemistry is retained during its chemisorption on the Si(111) surface.     

Polyoxoniobate chemistry in the 21st century

Polyoxometalate (POM) chemistry of W, Mo and V is rich and diverse; and new discoveries are frequent and abundant. The prolificacy of this POM chemistry is attributed to rich redox chemistry, an acidic nature that is compatible with addendum metal cations, and most importantly an understanding and ability to control solution behavior. In contrast, the POM chemistry of Nb and Ta (PONb, POTa) is hindered by minimal redox chemistry, alkalinity that is incompatible with the solubility of most metal cations, and a relatively poor understanding of the behavior in aqueous media. Despite these hurdles, considerable advancements in PONb chemistry (and to a much lesser extent POTa chemistry) have been made in the last decade. These include synthesis of the first heteropolyniobate Keggin derivatives, utilization of organic countercations to obtain unprecedented PONb geometries and compositions, and investigation of PONb solution behavior using advanced techniques such as nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI MS) and small-angle X-ray scattering (SAXS). This Perspective article summarizes the recent successes, continued shortcomings, and some unique and potentially exploitable features of PONb chemistry. More importantly, this annotated compilation of recent PONb literature has revealed the most logical and promising directions for the continued growth of the most challenging of polyoxometalate chemistries.     

核磁共振技术(NMR)在组合化学中的应用

对科学产生最大影响的分析方法是核磁共振技术(NMR),它被广泛用于许多领域.本文结合作者的研究结果评述了NMR在组合化学中的应用,着重于NMR在固相合成的应用、液态NMR和NMR在高通量筛选中的应用.     

Chemistry of carbon dioxide relevant to its utilization: a personal perspective

This presentation provides a review of the author's research group's contributions to the organometallic chemistry of carbon dioxide with a focus on incorporating this information into the development of an effective means for producing chemicals from this greenhouse gas. The types of chemistry addressed include insertion reactions of CO(2) into M-H, M-C, and M-O bonds as well as seminal contributions related to the copolymerization reactions of CO(2) and cyclic ethers. Relevant to this latter subject, efforts were made to place the author's achievements into perspective with the accomplishments of other investigators, but these efforts were not meant to be exhaustive.     

The Mechanism and Stereochemistry of Wittig Reactions of Phosphonium Ylide-Anions

Abstract

Schmidbaur's group have extensively investigated¹ the coordination properties of phosphonium 1,3-ylide-anions (1) in organometallic chemistry and more recently Cristau² has reported the potential usefulness of these compounds in synthetic organic chemistry. There have been a few studies³ of specific phosphonium 1,1-ylide-anions (2), however their only use in the Wittig reaction appears to be that of (2a).⁴ We have set out to study the stereochemistry and mechanism of Wittig reactions of (1) and (2) and to carry out some preliminary investigations on the arsenic analogues (3).     

1,3-dipolar cycloadditions of azides and alkynes: a universal ligation tool in polymer and materials science

In 2001, Sharpless and co-workers introduced "click" chemistry, a new approach in organic synthesis that involves a handful of almost perfect chemical reactions. Among these carefully selected reactions, Huisgen 1,3-dipolar cycloadditions were shown to be the most effective and versatile and thus became the prime example of click chemistry. Hence, these long-neglected reactions were suddenly re-established in organic synthesis and, in particular, have gained popularity in materials science. The number of publications dealing with click chemistry has grown exponentially over the last two years. The Minireview discusses whether click chemistry is a miracle tool or an ephemeral trend.     

单细胞分析的研究

单细胞分析是分析化学、生物学和医学之间渗透发展形成的跨学科前沿领域。近年来,毛细管电泳及微流控芯片用于单细胞分析已取得显著进展,特别表现在微流控芯片用于细胞的培养、分选、操纵、定位、分离及检测细胞的组分,实时监测细胞释放,及高通量阵列检测等方面。芯片的单元操作可根据需要灵活组合,显示出其独特的优点。本文重点介绍作者研究组的工作,并对近三年来国内外在毛细管电泳及芯片毛细管电泳用于单细胞分析的新进展进行评论。最后从毛细管电泳与微流控芯片、微流控芯片与细胞界面以及量子点用于探测活细胞等方面,展望了单细胞分析的发展前景。     

International research supported by the German Research Foundation (DFG)--examples of activities in the field of chemistry

Chemical sciences play an important role in addressing global challenges such as energy supply and storage, health, or environment. Research in these complex areas requires more and more international collaborative work. In fact collaborative research has been common practice for many years in the field of chemistry. This situation is also reflected by the increasing number of German funding programs, which promote international and joint research collaborations, in order to achieve a more effective use of both national and international resources in the field of chemistry.