CN104672189A - 一种多手性中心芳香醇的合成方法 - Google Patents

一种多手性中心芳香醇的合成方法 Download PDF

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CN104672189A
CN104672189A CN201410766620.6A CN201410766620A CN104672189A CN 104672189 A CN104672189 A CN 104672189A CN 201410766620 A CN201410766620 A CN 201410766620A CN 104672189 A CN104672189 A CN 104672189A
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aromatic alcohol
isobenzofuran
synthetic method
multichiral
ones
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刘国华
叶群群
程探宇
金荣华
徐溥群
汪磊
马俊
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Shanghai Normal University
University of Shanghai for Science and Technology
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Shanghai Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
    • C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B57/00—Separation of optically-active compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/005—General concepts, e.g. reviews, relating to methods of using catalyst systems, the concept being defined by a common method or theory, e.g. microwave heating or multiple stereoselectivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明公开了多手性中心芳香醇的合成方法，包括以下步骤：(1)isobenzofuran-1(3H)-ones、RuCl[(S,S)-TsDPEN](mesitylene)、HCOOH:NEt3(摩尔比5:2)、CH2Cl2混合，40℃下机械搅拌反应约4～5h；(2)用饱和食盐水洗涤并用二氯甲烷萃取，收集有机相，干燥、蒸干溶剂，过柱分离即得到相应的多手性醇。本发明在有关不对称氢转移反应诱导动态动力学拆分文献综述的基础上，设计合成了一系列isobenzofuran-1(3H)-ones，对其进行不对称氢转移反应，实现了β位的动态动力学拆分，实现了以高产率、高ee值和dr值合成相应的多手性中心芳香醇。

Description

一种多手性中心芳香醇的合成方法
技术领域
本发明涉及一种多手性中心芳香醇的合成方法。
背景技术
动态动力学拆分是从外消旋的底物制备光学纯化合物的有效方法，从理论上讲可以获得定量的产率和接近100％的ee值，近年来引起了化学工作者的广泛关注。不对称氢转移反应是选择性地还原醛、酮及亚胺等化合物的重要方法之一，条件温和，操作简便。文献已有一些通过不对称氢转移反应来实现动态动力学拆分的报道。在这些报道中，绝大部分是通过不对称氢转移反应来实现α位的动态动力学拆分，而对于β位的动态动力学拆分的报道却甚少。
发明内容
本发明目的是介绍一种合成多手性中心芳香醇的方法，利用不对称氢转移动态动力学拆分一系列isobenzofuran-1(3H)-ones，以合成高产率、高ee值和dr值的多手性中心芳香醇。
本发明技术方案是：
(1)将isobenzofuran-1(3H)-ones、RuCl[(S,S)-TsDPEN](mesitylene)、氢源、CH2Cl2混合，40℃下机械搅拌反应约4～5h；
(2)用饱和食盐水洗涤并用二氯甲烷萃取，收集有机相，干燥、蒸干溶剂，过柱分离即得到相应的多手性醇。
所述isobenzofuran-1(3H)-ones的结构式为：
其中R为-H，4-甲基，4-甲氧基，4-异丙基，4-氟，4-氯，4-溴，4-硝基，4-三氟甲基，4-氰基，3-氟，3-氯，3-溴，3-甲氧基，3-甲基，2,4-二甲基，2-噻吩基，2-呋喃基，2-萘基，2-甲氧基。
上述方法可以用反应方程式表示如下：
本发明在有关不对称氢转移反应诱导动态动力学拆分文献综述的基础上，设计合成了一系列isobenzofuran-1(3H)-ones，对其进行不对称氢转移反应，实现了β位的动态动力学拆分，实现了以高产率、高ee值和dr值合成相应的多手性中心芳香醇。
附图说明
图1为实施例1制备的多手性中心芳香醇的核磁共振氢谱图；
图2为该多手性中心芳香醇的外消旋体的高效液相色谱图；
图3为该多手性中心芳香醇对应异构体的高效液相色谱图。
具体实施方式
下面结合实施方式对本发明进行具体的描述，有必要在此指出的是本发明只用于对本发明进行进一步说明，不能理解为对本发明保护范围的限制。
实施例1:
方法：
将isobenzofuran-1(3H)-ones 1a(0.1mmol)、RuCl[(S,S)-TsDPEN](mesitylene)(0.2μmol)、HCOOH:NEt3(摩尔比5:2)(0.2ml)、CH2Cl2(2ml)加入干净的试管中，40℃下机械搅拌反应约4h。
反应结束后，往反应器中加入5mL二氯甲烷，用5mL×3的饱和食盐水洗涤上述溶液，收集有机相并用无水硫酸钠干燥，浓缩有机相，残余物用柱色谱分离纯化得到相应的多手性中心芳香醇1b(98％收率，99％ee,83:17dr)。
实施例2:
方法：
将isobenzofuran-1(3H)-ones 2a(0.1mmol)、RuCl[(S,S)-TsDPEN](mesitylene)(0.2μmol)、HCOOH:NEt3(摩尔比5:2)(0.2ml)、CH2Cl2(2ml)加入干净的试管中，40℃下机械搅拌反应约4h。
反应结束后，往反应器中加入5mL二氯甲烷，用5mL×3的饱和食盐水洗涤上述溶液，收集有机相并用无水硫酸钠干燥，浓缩有机相，残余物用柱色谱分离纯化得到相应的手性异苯并呋喃醇2b(94％收率，99％ee,80:20dr)。
实施例3：
方法：
将isobenzofuran-1(3H)-ones 3a(0.1mmol)、RuCl[(S,S)-TsDPEN](mesitylene)(0.2μmol)、HCOOH:NEt3(摩尔比5:2)(0.2ml)、CH2Cl2(2ml)加入干净的试管中，40℃下机械搅拌反应约4h。
反应结束后，往反应器中加入5mL二氯甲烷，用5mL×3的饱和食盐水洗涤上述溶液，收集有机相并用无水硫酸钠干燥，浓缩有机相，残余物用柱色谱分离纯化得到相应的手性异苯并呋喃醇3b(96％收率，99％ee,77:23dr)。
实施例4：
方法：
将isobenzofuran-1(3H)-ones 4a(0.1mmol)、RuCl[(S,S)-TsDPEN](mesitylene)(0.2μmol)、HCOOH:NEt3(摩尔比5:2)(0.2ml)、CH2Cl2(2ml)加入干净的试管中，40℃下机械搅拌反应约4h。
反应结束后，往反应器中加入5mL二氯甲烷，用5mL×3的饱和食盐水洗涤上述溶液，收集有机相并用无水硫酸钠干燥，浓缩有机相，残余物用柱色谱分离纯化得到相应的手性异苯并呋喃醇4b(96％收率，99％ee,77:23dr)。

Claims (4)

1.多手性中心芳香醇的合成方法，其特征在于，包括以下步骤：
(1)将isobenzofuran-1(3H)-ones、RuCl[(S,S)-TsDPEN](mesitylene)、氢源、CH2Cl2混合，40℃下机械搅拌反应约4～5h；
(2)用饱和食盐水洗涤并用二氯甲烷萃取，收集有机相，干燥、蒸干溶剂，过柱分离即得到相应的多手性醇。
2.根据权利要求1所述的多手性中心芳香醇的合成方法，其特征在于，所述isobenzofuran-1(3H)-ones的结构式为：
其中R为-H，4-甲基，4-甲氧基，4-异丙基，4-氟，4-氯，4-溴，4-硝基，4-三氟甲基，4-氰基，3-氟，3-氯，3-溴，3-甲氧基，3-甲基，2,4-二甲基，2-噻吩基，2-呋喃基，2-萘基，2-甲氧基。
3.根据权利要求1所述的多手性中心芳香醇的合成方法，其特征在于，氢源为摩尔比5:2的HCOOH和Et3N的混合物。
4.根据权利要求1所述的多手性中心芳香醇的合成方法，其特征在于，所述催化剂RuCl[(S,S)-TsDPEN](mesitylene)与isobenzofuran-1(3H)-ones的摩尔比为1:500。
CN201410766620.6A 2014-12-11 2014-12-11 一种多手性中心芳香醇的合成方法 Pending CN104672189A (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112371192A (zh) * 2021-01-14 2021-02-19 江苏欣诺科催化剂有限公司 复合型钌催化剂及其制备方法和应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080300415A1 (en) * 2007-05-31 2008-12-04 Taheebo Japan Co., Ltd. Preparation of optically active 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4, 9-diones having anticancer activities

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080300415A1 (en) * 2007-05-31 2008-12-04 Taheebo Japan Co., Ltd. Preparation of optically active 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4, 9-diones having anticancer activities

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112371192A (zh) * 2021-01-14 2021-02-19 江苏欣诺科催化剂有限公司 复合型钌催化剂及其制备方法和应用

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Application publication date: 20150603