Enantioselective Catalytic Boronate Reactions

对映选择性催化硼酸酯反应

基本信息

批准号：
8818674
负责人：
Scott Edward Schaus
金额：
$ 28.94万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
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：
2007-04-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8818674
关键词：
Acetals Acids Address Aldehydes Area Biological Factors Boron Boronic Acids Boxing Breathing Carbon Carboxylic Acids Catalysis Chemicals Chemistry Collection Coupling Cyanides Development Diels Alder reaction Drug Compounding Glycols Goals Health Isomerism Ligands Methodology Methods Modality Natural Product Drug Organic Synthesis Pathway interactions Pharmaceutical Preparations Pharmacologic Substance Physical condensation Process Property Reaction Reagent Research Seminal carbanion carbon compound catalyst design enantiomer human disease improved innovation insight interest novel organic acid prevent programs quinone methide

Acetals Acids Address Aldehydes Area Biological Factors Boron Boronic Acids Boxing Breathing Carbon Carboxylic Acids Catalysis Chemicals Chemistry Collection Coupling Cyanides Development Diels Alder reaction Drug Compounding Glycols Goals Health Isomerism Ligands Methodology Methods Modality Natural Product Drug Organic Synthesis Pathway interactions Pharmaceutical Preparations Pharmacologic Substance Physical condensation Process Property Reaction Reagent Research Seminal carbanion carbon compound catalyst design enantiomer human disease improved innovation insight interest novel organic acid prevent programs quinone methide

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项目摘要

DESCRIPTION (provided by applicant): The development of new chemical methodologies is an important objective of organic synthesis. An area that continues to inspire chemists is the chemistry of organoboranes and boronates. The unique properties of boron and the ability to activate organic boronates to deliver carbon nucleophiles has yielded an impressive array of chemical methods and processes. We will extend the ability of organoboranes and boronates to deliver carbanion equivalents in novel condensation reactions including chemoselective carbonyl condensations and multicomponent reactions. The reactions will be rendered asymmetric through the development of asymmetric catalysts and chiral boronate reagents and the utility of the methods developed demonstrated by the asymmetric synthesis of pharmaceuticals and natural products. Significant advances have been made in the mechanistic understanding of boronate activation via ligand exchange with chiral diols. We will use the mechanistic insight we have obtained to expand the repertoire of reactions catalyzed by dynamic ligand exchange processes to include acyl cyanides as electrophiles, borono-Petasis reactions, and ortho-quinone methide chemistry. Our continued interest in reaction discovery has led to the identification of chiral diol acid catalysts capable of promoting the enantioselectie addition reactions to acetals. We seek to explore this reactivity and expand it to include types of functionalized nucleophiles in additions to oxoniums and iminiums and boronate hetero-Diels-Alder reactions. Goals of the research program include developing a breadth of reactivity, providing access to novel chiral blocks, and new reaction development. Bond constructions are selected to access chiral synthetic intermediates that could be used in the construction of pharmaceuticals and natural products. The results will transform the way boronate nucleophiles are utilized in enantioselective synthesis.

描述（由申请人提供）：新化学方法的发展是有机合成的重要目标。继续激发化学家的区域是有机菜和硼酸盐的化学。硼的独特特性以及激活有机硼酸盐以输送碳接ch的能力，产生了令人印象深刻的化学方法和过程。我们将扩展有机鸟烷和硼酸盐在新型冷凝反应中提供碳纤维当量的能力，包括化学选择性羰基冷凝和多组分反应。这些反应将通过不对称催化剂和手性硼酸酯试剂的发展以及通过药物和天然产物的不对称合成所证明的方法而变得不对称。在通过手性二醇通过配体交换对硼酸盐激活的机械理解中，已经取得了重大进展。我们将使用所获得的机械洞察力扩大由动态配体交换过程催化的反应的曲目，将酰基氰化物作为电力，硼诺酸 - 别发反应和正质甲基甲基甲基化学。我们对反应发现的持续兴趣导致鉴定出能够促进对乙酰乙酰基反应反应的手性二醇催化剂。我们试图探索这种反应性并将其扩展到包括功能化的亲核试剂除氧和亚米氮和硼酸盐杂二烷 - alder反应外。研究计划的目标包括发展广度的反应性，提供对新型手性障碍的访问以及新的反应发展。选择键合构造以获取可用于制造药物和天然产品的手性合成中间体。结果将改变硼酸核亲核试剂在对映选择性合成中的使用方式。