Catalytic Asymmetric 1,3-Dipolar Cycloaddition of b-Fluoroalkylated a,b-Unsaturated 2-Pyridylsulfones with Nitrones for Chiral Fluoroalkylated Isoxazolidines and g-Amino Alcohols
Catalytic Asymmetric 1,3-Dipolar Cycloaddition of b-Fluoroalkylated a,b-Unsaturated 2-Pyridylsulfones with Nitrones for Chiral Fluoroalkylated Isoxazolidines and g-Amino Alcohols
复制标题
b-氟烷基化 a,b-不饱和 2-吡啶基砜与硝酮的催化不对称 1,3-偶极环加成反应生成手性氟烷基化异恶唑烷和 g-氨基醇
DOI：
10.1002/anie.201610605
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Norio Shibata
中科院分区：
文献类型：
--
作者：
Xing Yang;Feng Cheng;Ying-Da Kou;Shuai Pang;Yong-Cun Shen;Yi-Yong Huang;Norio Shibata
在手性NiII/双（恶唑啉）催化剂的作用下，2 -吡啶砜和氟烷基化基团活化的烯烃在各种芳族和脂肪族硝基上进行了高效的非映对和对映选择性1,3 -偶极环加成。通过4种Å分子筛、手性双（恶唑啉）配体、反应溶剂和温度对反应过程进行了调整。获得了一系列光学纯净的氟烷基化异恶唑烷，从而促进了对映体富集的克级α -三氟甲基化γ -氨基醇的不对称合成，以及具有潜在药用价值的1,3 -恶嗪酮- 2 - 1的三氟甲基化衍生物。基于一个加合物的绝对构型和一些对照实验，假设了一个立体化学模型来解释观察到的内端和对映体选择性。
2‐Pyridylsulfone‐ and fluoroalkylated group‐activated olefins underwent highly efficient diastereo‐ and enantioselective 1,3‐dipolar cycloadditions across various aromatic and aliphatic nitrones in the presence of a chiral NiII/bis(oxazoline) catalyst. The process was tuned by 4 Å molecular sieves, chiral bis(oxazoline) ligands, reaction solvents, and temperature. A wide array of optically pure fluoroalkylated isoxazolidines were obtained, thus facilitating the asymmetric synthesis of an enantioenriched α‐trifluoromethylated γ‐amino alcohol in gram‐scale and a trifluoromethylated derivative of 1,3‐oxazinan‐2‐one with potential pharmaceutical interest. A stereochemical model, based on the absolute configuration of one adduct and some control experiments, was postulated to account for the observed endo‐ and enantioselectivity.