Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, China.
Angew Chem Int Ed Engl. 2020 Nov 9;59(46):20455-20458. doi: 10.1002/anie.202008952. Epub 2020 Sep 2.
The enantioselective desymmetrizing C-H activation of α-gem-dialkyl acyclic amides remains challenging because the availability of four chemically identical unbiased methylene C(sp)-H bonds and increased rotational freedoms of the acyclic systems add tremendous difficulties for chemo- and stereocontrol. We have developed a method for the synthesis of acyclic aliphatic amides with α,β-contiguous stereogenic centers via Pd-catalyzed asymmetric arylation of unbiased methylene C(sp)-H, in good yields and with high levels of enantio-, chemo- and diastereoselectivity (up to >99 % ee and >20:1 d.r.). Successive application of this method enables the sequential arylation of the gem-dialkyl groups with two different aryl iodides, giving a range of β-Ar-β'-Ar-aliphatic acyclic amides containing three contiguous stereogenic centers with excellent diastereoselectivity.
通过 Pd 催化的非对称芳基化反应，实现了α-位，β-位紧邻手性中心的脂肪族酰胺的合成，该方法具有高对映选择性、化学选择性和非对映选择性（高达>99%ee 和>20:1d.r.）。通过连续应用这种方法，可以对两个不同的芳基碘化物进行gem-二烷基的连续芳基化，得到一系列含有三个连续手性中心的β-Ar-β'-Ar-脂肪族酰胺，具有极好的非对映选择性。
