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Bi(III)-Initiated Chemistry: Mechanistic Investigations of Catalytic Activity

Bi(III) 引发的化学：催化活性的机理研究

基本信息

批准号：
7252877
负责人：
ROBERT J HINKLE
金额：
$ 21.21万
依托单位：
COLLEGE OF WILLIAM AND MARY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-01 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7252877
关键词：
3-hydroxybutanal Acetals Acidity Acids Age Antifungal Agents Area Bismuth Bismuth Subsalicylate Catalysis Chemistry Complex Condition Cyclization Data Development Ethers Ethyl Ether Evaluation Flowers Foundations Future Gas Chromatography Glean Goals In Situ Individual Investigation Ions Kinetics Label Laboratories Lethal Dose 50 Ligands Mass Chromatography Mediating Metals Methodology NMR Spectroscopy Nitrogen Numbers Organic Synthesis Oxygen Pharmaceutical Preparations Pharmacologic Substance Procter &amp Gamble brand of bismuth subsalicylate Protocols documentation Range Reaction Reagent Relative (related person)Role Salts Solutions Solvents Source Spectrometry Students Sulfur System Techniques Temperature Toxic effect Variant Work base catalyst chelation enol ketene progenitor rapid growth reaction rate research study solid state toxic metal

项目摘要

DESCRIPTION (provided by applicant): Bismuth compounds have recently blossomed as very useful reagents for organic synthesis and catalytic quantities initiate a wide-range of reactions. Some more recently developed Bi(III)-initiated methodologies have been used in the synthesis of antitumor and antifungal agents. Outside of these latest uses of bismuth catalysts, many of the previously documented reactions were simple carbonyl protection and deprotection protocols via intermediate oxocarbenium ions. The actual catalytically-active species in most of these reactions, however, is uncertain and currently under considerable debate. The growing use of bismuth(III) compounds is largely due to the facts that they are inexpensive, have very low toxicity (the LD50 for BiBr3 is comparable to that of NaCl), are relatively stable in the solid-state, and are fairly easy to handle under typical laboratory conditions (hygroscopic). In fact, bismuth compounds have been widely utilized in pharmaceutical preparations for over 400 years. Perhaps the most widely-known, medicinally important bismuth(III) compound is bismuth subsalicylate, the active ingredient in Pepto-Bismol (r). The specific aims of this project are to investigate the mechanisms of reaction non-toxic bismuth(III) compounds by studies in the following areas: (1) stoichiometric interactions between Bi(III) compounds and reactive organic substrates; reaction rates, yields, turnover numbers and molecularity of aldol and allylation reactions; (2) evaluation of the degree of crossover in Mukaiyama aldol reactions with ketene silyl acetals in efforts to document the true catalyst; and (3) the evaluation of Bi(III) in potentially diastereomeric reactions and direct comparisons to diastereoselectivities obtained using other Lewis and BrOnsted acids as initiators. The proposed studies will attempt to document the true source of the high catalytic activity in bismuth salts. These investigations are crucial to understanding this versatile metalloid and will provide the foundation for the development of new synthetic methodologies in potentially asymmetric syntheses. The organic synthesis of pharmaceuticals and materials often relies upon metals as catalysts for a number of key transformations. With increasing needs for medications and materials as Baby Boomers age, chemists are working toward finding more environmentally- friendly catalysts such as those based on non-toxic metals like bismuth. As Bi(III) compounds recently have enjoyed rapid growth in synthetic methodology, their role(s) as catalysts should be assessed to determine if they are, in fact, unique catalysts and if they are beneficial compared to other catalyst systems. We pose a number of mechanistic questions and propose experiments to answer those questions.

描述（由申请人提供）：铋化合物最近已成为非常有用的有机合成试剂，并且催化量可引发广泛的反应。一些最近开发的 Bi(III) 引发的方法已用于合成抗肿瘤和抗真菌药物。除了铋催化剂的这些最新用途之外，许多先前记录的反应都是通过中间体氧碳鎓离子进行的简单的羰基保护和脱保护方案。然而，大多数这些反应中实际的催化活性物质是不确定的，目前处于相当大的争论中。铋(III)化合物的使用不断增长，很大程度上是因为它们价格低廉、毒性极低（BiBr3的LD50与氯化钠相当）、固态相对稳定，并且在典型实验室条件（吸湿性）下相当容易处理。事实上，铋化合物广泛应用于药物制剂已有 400 多年的历史。也许最广为人知、具有药用价值的铋(III) 化合物是次水杨酸铋，它是 Pepto-Bismol (r) 中的活性成分。本项目的具体目标是通过以下领域的研究，探讨无毒的铋（III）化合物的反应机理：（1）Bi（III）化合物与反应性有机底物之间的化学计量相互作用；羟醛和烯丙基化反应的反应速率、产率、周转数和分子数； (2) 评估Mukaiyama羟醛反应与烯酮甲硅烷基缩醛的交叉程度，以努力记录真正的催化剂； (3) Bi(III) 在潜在非对映异构反应中的评估，以及与使用其他路易斯酸和布朗斯台德酸作为引发剂获得的非对映选择性的直接比较。拟议的研究将尝试记录铋盐高催化活性的真正来源。这些研究对于理解这种多功能非金属至关重要，并将为潜在不对称合成中新合成方法的开发奠定基础。药物和材料的有机合成通常依赖金属作为许多关键转化的催化剂。随着婴儿潮一代的年龄增长，对药物和材料的需求不断增加，化学家正在努力寻找更环保的催化剂，例如基于铋等无毒金属的催化剂。由于 Bi(III) 化合物最近在合成方法中得到了快速发展，因此应评估它们作为催化剂的作用，以确定它们实际上是否是独特的催化剂，以及与其他催化剂体系相比它们是否有益。我们提出了许多机械问题，并提出了实验来回答这些问题。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bi(OTf)3-, TfOH-, and TMSOTf-mediated, one-pot epoxide rearrangement, addition, and intramolecular silyl-modified Sakurai (ISMS) cascade toward dihydropyrans: comparison of catalysts and role of Bi(OTf)3.

DOI：
10.1021/jo201478d
发表时间：
2011-11-18
期刊：
JOURNAL OF ORGANIC CHEMISTRY
影响因子：
3.6
作者：
Lambert, R. Frederick;Hinkle, Robert J.;Ammann, Stephen E.;Lian, Yajing;Liu, Jia;Lewis, Shane E.;Pike, Robert D.
通讯作者：
Pike, Robert D.

Synthesis of 2,6-disubstituted dihydropyrans via an efficient BiBr(3)-initiated three component, one-pot cascade.