实用和天生的碳-功能化异环
Yuta Fujiwara1, Janice A Dixon, Fionn O'Hara
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|December 4, 2012
概括
硫酸盐使得基直接添加到医学上重要的异环环. 这种温和且操作简单的方法为在药物发现中合成有价值的C-C键提供了一条新的途径.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 合成化学 合成化学
背景情况:
- 富含的异环环在许多药品中都是关键的支架.
- 异环的直接C-H功能化是具有挑战性的,因为它们具有固有的特性,限制了药物合成.
- 现有的方法通常需要预先功能化的基板或恶劣的条件.
研究的目的:
- 开发一种温和而直接的方法,用于医学上重要的异环体的C-H功能化.
- 在没有预先功能化的情况下,将基组引入异环核.
- 为现有的C-H功能化策略提供一种补充方法.
主要方法:
- 使用硫酸盐作为基基的前体.
- 采用适度反应条件 (≤50°C),与敏感功能群体相容.
- 测试各种各样的天然产品,药物分子和构建块的反应性.
主要成果:
- 基基的成功转移到各种异环,形成新的C-C键.
- 展示了温和,直接和操作上简单的功能化.
- 与水和空气的兼容性,以及适用于单联体反应的适用性.
- 与Minisci,电友芳香替代和过渡金属介导方法相比,互补的反应性.
结论:
- 硫酸盐为 heterocycles 的直接 C-H 化提供了一个有效和多功能工具.
- 这种方法简化了与药物发现相关的复杂异环化合物的合成.
- 该方法克服了以前的功能化技术的局限性,提供了广泛的适用性.
相关概念视频
01:32Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction mixture.
01:16Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
03:02Organic Compounds
All living things are formed mostly of carbon compounds called organic compounds. The category of organic compounds includes both natural and synthetic compounds that contain carbon. Although a single, precise definition has yet to be identified by the chemistry community, most agree that a defining trait of organic molecules is the presence of carbon as the principal element, bonded to hydrogen and other carbon atoms. However, some carbon-containing compounds such as carbonates, cyanides, and...
02:08Introduction to Functional Groups
Functional groups are group of atoms with specific chemical properties that occur within organic molecules and sometimes denoted as “R”. Functional groups are found along the carbon backbone of macromolecules can form chains or rings of carbon atoms. Functional groups can “functionalize” a compound by enabling it to adopt different physical and chemical properties.
Types of common functional groups
The table below summarizes some of the major functional groups in organic chemistry. (The...
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.