一个简单的,单一的方法,用于脱氧化基化甲基化的脱氧化基化
Shane Plunkett1, Justin B Diccianni2, James Mulhearn2
1Discovery Process Research, Johnson & Johnson R&D, Spring House, Pennsylvania 19477, United States.
Organic letters
|October 9, 2025
概括
一种新方法使使用酒精的C(sp2) -C(sp3) 交叉合反应成为可能. 这种在位酒精激活与N-异环碳素提供了药物样分子的高效合成.
科学领域:
- 有机化学 有机化学
- 催化剂是一种催化剂.
- 合成方法论 合成方法论
背景情况:
- 在合成复杂分子时,C(sp2) -C(sp3) 交叉合至关重要.
- 酒精是有吸引力的,可持续的原料,但很难激活.
- 现有的方法通常需要单独的酒精激活步骤.
研究的目的:
- 开发一种有效的C(sp2) -C(sp3) 交叉合的in situ酒精激活方法.
- 探索使用N-异环碳 (NHCs) 进行酒精激活.
- 为了优化反应条件,使其具有广泛的适用性,特别是在极性,类似药物的酒精中.
主要方法:
- 使用高通量实验来发现和优化反应条件.
- N-异环碳被用于DMA中酒精的局部激活.
- 优化,无修复的协议与传统方法进行了验证.
主要成果:
- 在DMA中使用NHC识别了一种新的in situ酒精激活策略.
- 在优化的条件下,与单独的激活方法相比,反应能力相当或更强.
- 该方法成功合成了48种测试中的45种具有类似药物特性的极性酒精.
结论:
- 开发的 in situ 激活方法提供了一种高效和实用的方法,用于使用酒精的C(sp2) -C(sp3) 交叉合.
- 这项工作扩大了酒精作为模拟合成原料的实用性.
- 无处理协议为简化合成过程提供了优势.
相关概念视频
Radical Substitution: Allylic Bromination
6.4K
In organic synthesis, the formation of products can be altered by changing the reaction conditions. For example, a dibromo addition product is formed when propene is treated with bromine at room temperature. In contrast, propene undergoes allylic substitution in non-polar solvents at high temperatures to give 3-bromopropene. In order to avoid the addition reaction, the bromine concentration must be kept as low as possible throughout the reaction. This can be achieved using N-bromosuccinimide...
6.4K
Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
20.7K
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.
20.7K
Hydroboration-Oxidation of Alkenes
11.1K
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
11.1K
Preparation of Alkynes: Alkylation Reaction
12.0K
Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
12.0K
Radical Anti-Markovnikov Addition to Alkenes: Mechanism
4.6K
The reaction of hydrogen bromide with alkenes in the presence of hydroperoxides or peroxides proceeds via anti-Markovnikov addition. The radical chain reaction comprises initiation, propagation, and termination steps.
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
4.6K
Halogenation of Alkenes
18.4K
Halogenation is the addition of chlorine or bromine across the double bond in an alkene to yield a vicinal dihalide. The reaction occurs in the presence of inert and non-nucleophilic solvents, such as methylene chloride, chloroform, or carbon tetrachloride.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
18.4K


