鎳催化苯甲醇的動態交叉親電芳基化反應
作者：
小柯機器人發布時間：2021/1/3 15:40:53
蘭州大學舒興中團隊報導了一種鎳催化苯甲醇的動態交叉親電芳基化反應策略。 相關研究成果發表在2020年12月28日出版的《美國化學會志》。
通過金屬催化的交叉偶聯反應催化醇的轉化是非常重要的，但它通常依賴於一個多步驟的過程。
該文報導了一種直接功能化醇的動態動力學交叉偶聯方法。通過鎳催化的苯甲醇與（雜）芳基親電試劑的交叉親電芳基化反應，證明了該方法的可行性。反應在兩個偶聯劑的廣泛底物範圍內進行。富電子、貧電子和鄰位/間位/對位取代（雜）芳基親電試劑（例如Ar–OTf、Ar–I、Ar–Br和惰性Ar–Cl）都很好地耦合。大多數功能，包括醛、酮、醯胺、酯、腈、碸、呋喃、噻吩、苯並噻吩、吡啶、喹諾酮類、Ar–SiMe3、Ar–Bpin和Ar–SnBu3，都是耐受的。該方法的動力學性質使得苯甲醇在各種親核基團（包括未活化的伯/仲/叔醇、酚和游離吲哚）存在下能夠直接芳基化。
因此，它提供了一個強大的替代現有方法，精確合成二芳基甲烷。生物活性分子的簡明合成及其在肽修飾和結合中的應用證明了該方法的合成實用性。初步的機理研究表明，原位生成的草酸苄酯與鎳的反應，可能通過自由基過程，是與芳基親電試劑反應的初始步驟。
附：英文原文
Title: Dynamic Kinetic Cross-Electrophile Arylation of Benzyl Alcohols by Nickel Catalysis
Author: Peng Guo, Ke Wang, Wen-Jie Jin, Hao Xie, Liangliang Qi, Xue-Yuan Liu, Xing-Zhong Shu
Issue&Volume: December 28, 2020
Abstract: Catalytic transformation of alcohols via metal-catalyzed cross-coupling reactions is very important, but it typically relies on a multistep procedure. We here report a dynamic kinetic cross-coupling approach for the direct functionalization of alcohols. The feasibility of this strategy is demonstrated by a nickel-catalyzed cross-electrophile arylation reaction of benzyl alcohols with (hetero)aryl electrophiles. The reaction proceeds with a broad substrate scope of both coupling partners. The electron-rich, electron-poor, and ortho-/meta-/para-substituted (hetero)aryl electrophiles (e.g., Ar–OTf, Ar–I, Ar–Br, and inert Ar–Cl) all coupled well. Most of the functionalities, including aldehyde, ketone, amide, ester, nitrile, sulfone, furan, thiophene, benzothiophene, pyridine, quinolone, Ar–SiMe3, Ar–Bpin, and Ar–SnBu3, were tolerated. The dynamic nature of this method enables the direct arylation of benzylic alcohol in the presence of various nucleophilic groups, including nonactivated primary/secondary/tertiary alcohols, phenols, and free indoles. It thus offers a robust alternative to existing methods for the precise construction of diarylmethanes. The synthetic utility of the method was demonstrated by a concise synthesis of biologically active molecules and by its application to peptide modification and conjugation. Preliminary mechanistic studies revealed that the reaction of in situ formed benzyl oxalates with nickel, possibly via a radical process, is an initial step in the reaction with aryl electrophiles.
DOI: 10.1021/jacs.0c12462
Source: https://pubs.acs.org/doi/10.1021/jacs.0c12462