手性伯胺/酮協同催化過氧化氫不對稱α羥基化反應
作者：
小柯機器人發布時間：2021/1/9 22:54:17
中科院羅三中團隊揭示了手性伯胺/酮協同催化過氧化氫不對稱α羥基化反應。 相關研究成果發表在2021年1月5日出版的國際學術期刊《美國化學會志》。
羰基、有機胺是有機催化中的「陰/陽」兩面，同時能夠互相激活和轉化。因此當作為共催化劑時，這兩種分子能夠相互反應和結合，進而消除單獨的反應活性。氨基催化和羰基催化雖然在許多重要的催化策略中得到了廣泛的應用，但並不能很好地共存，因此，胺/羰基雙催化的協同作用在本質上仍是未知的。
該文報導了一種伯胺-酮協同雙催化方法，用於β-酮羰基與H2O2的不對稱α-羥基化反應。除了參與典型的烯胺催化循環外，還發現手性伯胺催化劑與酮催化劑協同作用，通過從原位生成的酮亞胺（ketimine）得到惡唑烷中間體活化H2O2分子。最終，這種烯胺-惡氮雜環丙烷的偶聯促進了幾種β-酮羰基的高度可控的α-羥基化反應，具有良好的產率和對映選擇性。
值得注意的是，肽醯醯胺或手性酯的後期羥基化也可以實現高立體選擇性。除了操作簡單和溫和的條件外，這種協同的胺/酮催化方法還為過氧化氫的催化活化提供了一種新的策略，並擴展了包括這種具有挑戰性的典型的胺和羰基催化的領域。
附：英文原文
Title: Chiral Primary Amine/Ketone Cooperative Catalysis for Asymmetric α-Hydroxylation with Hydrogen Peroxide
Author: Mao Cai, Kaini Xu, Yuze Li, Zongxiu Nie, Long Zhang, Sanzhong Luo
Issue&Volume: January 5, 2021
Abstract: Carbonyls and amines are yin and yang in organocatalysis as they mutually activate and transform each other. These intrinsically reacting partners tend to condense with each other, thus depleting their individual activity when used together as cocatalysts. Though widely established in many prominent catalytic strategies, aminocatalysis and carbonyl catalysis do not coexist well, and, as such, a cooperative amine/carbonyl dual catalysis remains essentially unknown. Here we report a cooperative primary amine and ketone dual catalytic approach for the asymmetric α-hydroxylation of β-ketocarbonyls with H2O2. Besides participating in the typical enamine catalytic cycle, the chiral primary amine catalyst was found to work cooperatively with a ketone catalyst to activate H2O2 via an oxaziridine intermediate derived from an in-situ-generated ketimine. Ultimately, this enamine–oxaziridine coupling facilitated the highly controlled α-hydroxylation of several β-ketocarbonyls in excellent yield and enantioselectivity. Notably, late-stage hydroxylation for peptidyl amide or chiral esters can also be achieved with high stereoselectivity. In addition to its operational simplicity and mild conditions, this cooperative amine/ketone catalytic approach also provides a new strategy for the catalytic activation of H2O2 and expands the domain of typical amine and carbonyl catalysis to include this challenging transformation.
DOI: 10.1021/jacs.0c11787
Source: https://pubs.acs.org/doi/10.1021/jacs.0c11787