Novel Organoboron Chemistry Utilizing Tetrahydroxydiborane

利用四羟基乙硼烷的新型有机硼化学

基本信息

批准号：
8849455
负责人：
GARY A MOLANDER
金额：
$ 33.83万
依托单位：
UNIVERSITY OF PENNSYLVANIA
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：
2007-09-07 至 2017-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The goal of the research proposed is to facilitate the construction of organic molecules by developing new reagents and subsequently exploiting the novel reactivity patterns of those reagents. Herein are described protocols for novel syntheses of organoboron compounds that will increase the productivity and efficiency of chemists in the synthesis of organic molecules. The development of tetrahydroxydiborane [(HO)2B-B(OH)2] and its commercial synthetic precursor, (Me2N)2B-B(NMe2)2, will reduce dependency on the wholly inefficient bis(pinacoloato)diboron (B2pin2). Proposed are unique, more cost effective, and environmentally sound procedures for the synthesis of boronic acids and diverse derivatives. Most importantly, new vistas for chemical reactivity will be developed. As a result of the studies described, novel methods for the introduction of boron into organic molecules will be realized; processes that are far more sustainable than previous methods. Direct access to boronic acids will make these protocols more versatile in two important ways: 1) Sequential reactions that require reactive but unstable boronic acids can be carried out without a tedious and inefficient hydrolysis procedure, thus permitting rapid and more sustainable access to high value-added products. Not only would this address significant efficiencies inherent to the multi-step protocol generally employed, but it would also extend synthetic methods both to novel organoborons as well as those boronic acids that are prone to significant degradation by protodeboronation during routine handling. 2) A variety of more useful and robust organotrifluoroborates can be directly synthesized without the wasteful hydrolysis methods required with protocols employing pinacolboronates. Novel approaches to organoborons that take advantage of boryl anion-like reactivity patterns of bisbora compounds and avoid expensive transition metal catalysts represent another centerpiece of the described research. These protocols will enable the formation of novel organoboron reagents in a direct approach. Importantly, these useful new reagents will be employed in unprecedented bond-forming reactions, including the engagement of nucleophilic umpolung reagents, polyfluoroalkyltrifluoroborates, and ¿-trifluoroborato- substituted nitrogen- and oxygen heterocycles that will provide solutions to long-standing challenges in organic synthesis. Using the novel methods developed, a number of unique 2¿ alkylating reagents, including amino alkylating and alkoxy alkylating agents, will be synthesized in enantiopure form, and protocols for their cross-coupling, based on secondary interactions with embedded functional groups, will be developed. These distinctive reagents will allow unprecedented bond constructions and insertion of stereocenters with complete stereochemical fidelity into organic substrates via cross-coupling.

描述（由适用提供）：提出的研究的目的是通过开发新试剂并随后利用这些试剂的新反应性模式来促进有机分子的构建。此处描述了有机体化合物的新型合成的方案，这些方案将提高化学家在有机分子合成中的生产力和效率。四氢羟基二吡喃的发展[（HO）2B-B（OH）2]及其商业合成前体（ME2N）2B-B（NME2）2，将减少对完全低效率BIS（Pinacoloato）Diboron（B2Pin2）的依赖性。提出的是独特的，更具成本效益和环境合理的程序，用于合成硼酸和潜水衍生物。最重要的是，将开发新的化学反应性远景。后果描述的研究将实现将硼引入有机分子中的新方法；比以前的方法更可持续的过程。直接进入硼酸将通过两种重要方式使这些方案更具用途：1）可以进行反应性但不稳定的硼酸的顺序反应，而无需进行乏味且效率低下的水解程序，从而可以快速且更可持续地访问高增值产品。这种不仅可以解决通常采用的多步协议固有的显着效率，而且还将将合成方法扩展到新颖的有机体以及那些在常规处理过程中易于通过蛋白质碳化而显着降解的硼酸。 2）可以直接合成各种更有用和鲁棒的有机氟氟甲叶酸盐，而无需使用使用Pinacolboronates的协议所需的浪费水解方法。利用Boryl阴离子样的Bisbora化合物并避免昂贵的过渡金属催化剂的有机龙的新方法是该研究的另一个核心。这些方案将使新的有机龙试剂以直接的方法形成。重要的是，这些有用的新试剂将用于前所未有的形成键的反应，包括核umpolung试剂，多流氟烷基三氟甲酸酯和€trifluoroborato-trifluoroborato替代的氮气和氧气杂质为长期有组织的求解效果，将其提供为长期合成的质量。使用开发的新方法，将开发许多独特的2烷基化试剂，包括氨基烷基化和烷基烷基化剂，以对映异构形式合成，并基于与嵌入式功能组的二级相互作用的协议，用于交叉耦合方案。这些独特的试剂将允许通过交叉耦合将其完全立体化学保真度插入具有完全立体化学保真度到有机底物中的立体构建体。

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Copper(II)-mediated O-arylation of protected serines and threonines.

DOI：
10.1021/ol5024689
发表时间：
2014-09-19
期刊：
Organic letters
影响因子：
5.2
作者：
El Khatib M;Molander GA
通讯作者：
Molander GA

Copper-mediated N-Arylation of Methyl 2-Aminothiophene-3-carboxylate with Organoboron Reagents.

使用有机硼试剂对 2-氨基噻吩-3-甲酸甲酯进行铜介导的 N-芳基化。

DOI：
10.1016/j.tetlet.2015.10.080
发表时间：
2015
期刊：
Tetrahedron letters
影响因子：
1.8
作者：
Rizwan,Komal;Karakaya,Idris;Heitz,Drew;Zubair,Muhammad;Rasool,Nasir;Molander,GaryA
通讯作者：
Molander,GaryA

Accessing an azaborine building block: synthesis and substitution reactions of 2-chloromethyl-2,1-borazaronaphthalene.