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学科主题: 氟化学
题名: Shelf-Stable Electrophilic Reagents for Trifluoromethylthiolation
其他题名: 稳定的亲电三氟甲硫基化试剂
作者: Shao XX(邵欣欣); Xu CF(徐春发); Lv L(吕龙); Shen QL(沈其龙)
通讯作者: 沈其龙
刊名: Accounts Chem. Res.
发表日期: 2015
DOI: 10.1021/acs.accounts.5b00047
卷: 48, 期:5, 页:1227-1236
收录类别: SCI
文章类型: 论文
英文摘要: Fluorine, which is the most electronegative element and has a small atomic radius, plays a key role in pharmaceutical, agrochemical,. and materials sciences. One of the fluoroalkyl groups, the trifluoromethylthio group (CF3S-), has been well-recognized as an important structural motif in the design of lead compounds for new drug discovery because of its high lipophilicity (Hansch lipophilicity parameter pi = 1.44) and strong electron-withdrawing properties, which could improve the drug molecule's cell-membrane permeability and enhance its chemical and metabolic stability. While classic methods for the preparation of trifluoromethylthiolated compounds typically involve halogen fluorine exchange reactions of polyhalogenomethyl thioethers or trifluoromethylation of sulfur-containing compounds under harsh reaction conditions, an alternative but more attractive strategy is direct trifluoromethylthiolation of the substrate at a late stage by employing an electrophilic trifluoromethylthiolating reagent. Although several electrophilic trifluoromethylthiolating reagents have been reported previously, these reagents either require a strong Lewis acid/Bronsted acid as an activator or suffer from a toxic nature or limited substrate scope. To address these problems, in late 2011 we initiated a project with the aim to develop new, shelf-stable, and highly reactive electrophilic trifluoromethylthiolating reagents that could easily install the trifluoromethylthio group at the desired positions of the drug molecule at a late stage of drug development. Inspired by the broad reactivity of the hypervalent iodine reagent, we initially discovered a highly reactive trifluoromethylthiolating reagent, trifluoromethanesulfenate 1a. Structure reactivity studies disclosed that the iodine atom of reagent 1a does not play an important role in this reagent's reactivity. Consequently, a simplified second-generation electrophilic reagent, trifluoromethanesulfenate 1b, was developed. In parallel, we developed another shelf-stable, highly reactive electrophilic reagent with a broad substrate scope, N-trifluoromethylthiosaccharin (2). In this Account, we mainly describe our discovery of these two different types of electrophilic trifluoromethylthiolating reagents, trifluoromethanesulfenates 1a and 1b and N-trifluoromethylthiosaccharin 2. Systematic studies showed that both types of reagents are highly reactive toward a wide range of nucleophiles, yet the substrate scopes of thee two different types of reagents are complementary. In particular, reagents la and 1b are more reliable in transition-metal-catalyzed reactions such as copper-catalyzed trifluoromethylthiolation of aryl/vinyl/alkylboronic acids and silver-catalyzed decarboxylative trifluoromethylthiolation of aliphatic carboxylic acids as well as in the organocatalytic asymmetric trifluoromethylthiolation of beta-keto esters and oxindoles. Reagent 2 is more electrophilic than reagents 1a and 1b, and 2 very attractive as ...
语种: 英语
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WOS记录号: WOS:000355055700004
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/39724
Appears in Collections:中科院有机氟化学重点实验室_期刊论文

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作者单位: 中科院上海有机化学研究所, 有机氟化学重点实验室

Recommended Citation:
Shao XX,Xu CF,Lv L,et al. Shelf-Stable Electrophilic Reagents for Trifluoromethylthiolation[J]. Accounts Chem. Res.,2015,48(5):1227-1236.
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