烯烃和酮类中C(sp3)-C(sp2)键断裂合成。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2025-05-06 Epub Date: 2025-04-15 DOI:10.1021/acs.accounts.5c00156
Michal Šimek, Jeremy H Dworkin, Ohyun Kwon
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引用次数: 0

摘要

最近,对官能团附近的C-C键进行均溶裂解已成为复杂有机分子骨架重组的一种流行策略。与传统的极性键断裂反应性不同,均裂断裂提供了碳中心自由基,可与多种亲根试剂进行控制终止。除了标准的自由基捕获,过渡金属催化促进复杂的C-C和c -杂原子成键反应。多年来,人们一直致力于研究羧酸和醇的相邻C-C键的断裂。尽管烯烃和酮类在天然产物、原料化学品和常见的合成中间体中无处不在,但很少有人注意开发它们在使萜烯和萜类等手性池材料多样化方面的潜力。这种方式的去功能化是合成高价值化学品和高级合成中间体的有力方法,因为它可以重建和进一步修饰手性碳骨架。出于合成需要,自2018年以来,我们集团专注于开发基于臭氧分解的脱烷基分子多样化,并于2025年扩展到脱烷基。在本报告中,我们记录了我们最初的动机,描述了历史背景,并总结了我们在脱烷基和脱烷基合成方面的研究。我们的脱烷基方法利用臭氧在甲醇中分解烯烃,生成α-甲氧基氢过氧化物,并与还原剂反应。它们的还原通过单电子转移,由过渡金属介导,导致烷氧基的形成,经过快速的β-断裂,提供碳中心自由基和由缩醛碳原子衍生的酯基。产生的自由基可以被亲自由基战略性地终止,从而传递重塑的手性分子。利用这一概念,我们开发了氢脱烷基化(通过苯硫醇的氢原子转移)、脱烷基化噻吩化(通过二芳基二硫化物的噻基转移)、烯基化(通过硝基苯乙烯的加成/消除)和氧脱烷基化(通过TEMPO处理然后氧化)。此外,动力学分析使FeII/维生素C催化体系能够用于脱烷基烷基化和卤代脱烷基化。臭氧分解和铜催化的协同作用最近通过净氧化还原-中性C-C裂解和C-N键形成实现了氨基脱烯化。虽然臭氧相对于有机化合物的高氧化电位使得烯烃到过氧化物的转化成为可能,但它也限制了脱烯化技术对具有臭氧敏感官能团的底物的适用性。我们最近克服了这一限制,首先将Isayama-Mukayiama过氧化作用应用于烯烃,然后使用一种新的催化体系──用化学计量的γ-萜烯催化FeIII和PhSH──进行无臭氧氢脱烯化。除烯烃外,我们还开发了一种直接的方法,用于酮类的均溶脱酰裂解,包括环烷酮。该方法适用于全合成和含酮的复杂天然产物的后期修饰。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis through C(sp3)-C(sp2) Bond Scission in Alkenes and Ketones.

ConspectusThe homolytic cleavage of C-C bonds adjacent to functional groups has recently become a popular strategy for restructuring the skeletons of complex organic molecules. In contrast to the traditional reactivity profiles of polar bond disconnections, homolytic scission furnishes carbon-centered free radicals primed for controlled termination with a diverse range of radicophiles. Beyond standard radical capture, transition-metal catalysis facilitates sophisticated C-C and C-heteroatom bond-forming reactions. Intensive efforts have been focused over many years into the cleavage of the neighboring C-C bonds of carboxylic acids and alcohols. Despite the ubiquity of alkenes and ketones in natural products, feedstock chemicals, and common synthetic intermediates, much less attention has been paid to exploiting their potential in diversifying chiral pool materials, such as terpenes and terpenoids. Defunctionalization in this manner is a powerful approach for synthesizing high-value chemicals and advanced synthetic intermediates because of the possibility to reconstruct and further decorate chirality-bearing carbon skeletons. Motivated by synthetic necessity, since 2018 our group has focused on developing ozonolysis-based dealkenylative molecular diversification, and we expanded into deacylation in 2025. In this Account, we chronicle our initial motivation, describe the historical background, and summarize our research into dealkenylative and deacylative synthesis. Our dealkenylative approach capitalizes on the ozonolysis of alkenes in MeOH to generate α-methoxyhydroperoxides primed for a reaction with reducing agents. Their reduction through single electron transfer, mediated by a transition metal, leads to the formation of an alkoxyl radical that undergoes rapid β-scission, furnishing both a carbon-centered free radical and an ester group derived from the acetal carbon atom. The produced free radical can be strategically terminated by radicophiles, thereby delivering remodeled chiral molecules. Using this concept, we have developed hydrodealkenylation (through hydrogen atom transfer from benzenethiol), dealkenylative thiylation (through thiyl group transfer from diaryl disulfides), alkenylation (through addition/elimination with nitrostyrenes), and oxodealkenylation (through treatment with TEMPO followed by oxidation). Furthermore, kinetic analysis has enabled the development of a catalytic FeII/vitamin C system for dealkenylative alkynylation and halodealkenylation. Synergizing ozonolysis and copper catalysis has recently enabled aminodealkenylation through net-redox-neutral C-C cleavage followed by C-N bond formation. Although the high oxidation potential of ozone relative to organic compounds makes alkene-to-peroxide conversion possible, it also limits the applicability of dealkenylative techniques for substrates featuring ozone-sensitive functional groups. We recently overcame this constraint by first applying Isayama-Mukayiama peroxidation to olefins and then using a novel catalytic system─catalytic FeIII and PhSH with stoichiometric γ-terpinene─for ozone-free hydrodealkenylation. Beyond alkenes, we have developed a straightforward methodology for the homolytic deacylative cleavage of ketones as well, including cycloalkanones. This process is applicable in total syntheses and in the late-stage modifications of complex ketone-containing natural products.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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