一种简单、 高效合成α-卤代甲基酮化合物的新方法

doi:10.7503/cjcu20130799

高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (6): 1236.doi: 10.7503/cjcu20130799

一种简单、高效合成α-卤代甲基酮化合物的新方法

刘开建()

湖南工学院材料与化学工程系, 衡阳 421002

收稿日期:2013-08-19 出版日期:2014-06-10 发布日期:2014-01-23
作者简介:联系人简介: 刘开建, 男, 博士, 讲师, 主要从事有机合成及金属催化方面的研究. E-mail:liukaijian_1982@163.com
基金资助:
湖南省重点建设学科项目和湖南省科技计划项目(批准号: 2014FJ3053)资助

Mild and Efficient Method for Synthesis of α-Halomethylketones^†

LIU Kaijian^*()

Department of Materials and Chemical Engineering, Hunan Institute of Technology, Hengyang 421002, China

Received:2013-08-19 Online:2014-06-10 Published:2014-01-23
Contact: LIU Kaijian E-mail:liukaijian_1982@163.com
Supported by:
† Supported by the Construct Program of the Key Discipline in Hunan Province, China and the Science and Technology Planning Project of Hunan Province, China(No. 2014FJ3053).

摘要/Abstract

摘要：

发展了一种简单、高效、温和的卤代炔烃水合反应体系. 在阳离子金催化剂的催化作用下, 以二氯乙烷为溶剂, 室温下卤代炔烃发生水合反应, 高收率、高区域选择性地得到单一的α-卤代甲基酮化合物(收率≥91%). 该方法具有底物适用范围广、反应条件温和和环境友好等优点, 为含α-卤代甲基酮结构单元的天然产物及复杂药物分子的合成提供了新方法.

关键词: 卤代甲基酮, 卤代炔烃, 金催化, 水合反应

Abstract:

α-Halomethylketones are building blocks for the synthesis of various compounds due to their selective transformations with different reagents. Moreover, a wide range of α-halomethylketone derivatives attract increasing interests in pharmaceutical chemistry. α-Halomethylketones are also widespread used as intermediates in organic synthesis, such as in Favorskii rearrangement and Reformatsky reaction. However, their direct synthesis from the corresponding methylktones by N-halosuccinimides, molecular halogen and metal halides has been plagued by poor regioselectivity and over-halogenation. For the above reasons, a simple, convenient and environmentally benign protocol to synthesize the α-halomethylketones was developed by catalytic hydration of haloalkynes, which can be easily prepared in one step from commercial terminal alkynes. In the presence of 3%(molar fraction) BrettPhosAuNTf₂ and 3 mmol H₂O in dichloroethane at room temperature, a broad range of haloalkynes were converted into α-halomethylketones in excellent yield through gold-catalyzed hydration reaction. The presented methodology will provide new strategies for α-halomethylketones-type drug design and synthesis, which has important academic significance and application value.

Key words: a-Halomethylketone, Haloalkyne, Gold-catalysis, Hydration reaction

中图分类号:

O625

TrendMD:

刘开建. 一种简单、高效合成α-卤代甲基酮化合物的新方法. 高等学校化学学报, 2014, 35(6): 1236.

LIU Kaijian. Mild and Efficient Method for Synthesis of α-Halomethylketones^†. Chem. J. Chinese Universities, 2014, 35(6): 1236.

图/表 4

参考文献 26

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Entry	Gold catalyst	Catalyst content, x(%)	n(H₂O)/mmol	Solution	Time/h	Yield(%)^b
1	Ph₃PAuNTf₂	3	0.1	DCE	72	20
2	Ph₃PAuNTf₂	3	0.3	DCE	15	64
3	Ph₃PAuNTf₂	3	1.0	DCE	12	64
4	(4-CF₃Ph)₃P AuNTf₂	3	0.3	DCE	16	66
5	(4-MeOPh)₃P AuNTf₂	3	0.3	DCE	15	67
6	IPrAuNTf₂	3	0.3	DCE	15	69
7	Et₃PAuNTf₂	3	0.3	DCE	24	34
8	LAuNTf₂	3	0.3	DCE	15	72
9	MePhos AuNTf₂	3	0.3	DCE	15	77
10	XPhos AuNTf₂	3	0.3	DCE	15	88
11	BrettPhos AuNTf₂	3	0.3	DCE	15	94^c
12	BrettPhos AuNTf₂	2	0.3	DCE	24	83
13	BrettPhos AuNTf₂	1	0.3	DCE	72	40
14	BrettPhos AuNTf₂	3	0.3	DCM	16	88
15	BrettPhos AuNTf₂	3	0.3	THF	48	15
16	BrettPhos AuNTf₂	3	0.3	DME	48	25
17	BrettPhos AuNTf₂	3	0.3	1,4-Dioxane	48	22
18	BrettPhos AuNTf₂	3	0.3	CH₃CN	48	20
19	BrettPhos AuNTf₂	3	0.3	DMF	48	20
20	AgNTf₂	20	0.3	DCE	48
21	HNTf₂	20	0.3	DCE	48
22^d	BrettPhos AuNTf₂	3	0.3	DCE	15	94
23^e	BrettPhos AuNTf₂	3	0.3	DCE	16	94

Entry	Gold catalyst	Catalyst content, x(%)	n(H₂O)/mmol	Solution	Time/h	Yield(%)^b
1	Ph₃PAuNTf₂	3	0.1	DCE	72	20
2	Ph₃PAuNTf₂	3	0.3	DCE	15	64
3	Ph₃PAuNTf₂	3	1.0	DCE	12	64
4	(4-CF₃Ph)₃P AuNTf₂	3	0.3	DCE	16	66
5	(4-MeOPh)₃P AuNTf₂	3	0.3	DCE	15	67
6	IPrAuNTf₂	3	0.3	DCE	15	69
7	Et₃PAuNTf₂	3	0.3	DCE	24	34
8	LAuNTf₂	3	0.3	DCE	15	72
9	MePhos AuNTf₂	3	0.3	DCE	15	77
10	XPhos AuNTf₂	3	0.3	DCE	15	88
11	BrettPhos AuNTf₂	3	0.3	DCE	15	94^c
12	BrettPhos AuNTf₂	2	0.3	DCE	24	83
13	BrettPhos AuNTf₂	1	0.3	DCE	72	40
14	BrettPhos AuNTf₂	3	0.3	DCM	16	88
15	BrettPhos AuNTf₂	3	0.3	THF	48	15
16	BrettPhos AuNTf₂	3	0.3	DME	48	25
17	BrettPhos AuNTf₂	3	0.3	1,4-Dioxane	48	22
18	BrettPhos AuNTf₂	3	0.3	CH₃CN	48	20
19	BrettPhos AuNTf₂	3	0.3	DMF	48	20
20	AgNTf₂	20	0.3	DCE	48
21	HNTf₂	20	0.3	DCE	48
22^d	BrettPhos AuNTf₂	3	0.3	DCE	15	94
23^e	BrettPhos AuNTf₂	3	0.3	DCE	16	94

Compd.	MS(ES⁺), m/z(Ref.)	Compd.	MS(ES⁺), m/z(Ref.)
2a	162.7(162.7)^[24]	2l	184.1(184.1)^[24]
2b	169.0(169.0)^[25]	2m	172.3(172.3)^[26]
2c	241.1(241.1)^[26]	2n	233.4(233.4)^[24]
2d	251.1(251.1)^[26]	2o	233.4(233.4)^[26]
2e	193.1(193.1)^[26]	2p	222.4(222.4)^[26]
2f	305.1(305.1)^[26]	2q	199.4(199.4)^[24]
2g	182.1(182.1)^[24]	2r	168.1(168.1)^[24]
2h	280.1(280.1)^[26]	2s	349.0(349.0)^[24]
2i	161.1(161.1)^[26]	2t	263.1(263.1)^[26]
2j	155.0(155.0)^[26]	2u	198.9(198.9)^[26]
2k	168.1(168.1)^[24]

Compd.	MS(ES⁺), m/z(Ref.)	Compd.	MS(ES⁺), m/z(Ref.)
2a	162.7(162.7)^[24]	2l	184.1(184.1)^[24]
2b	169.0(169.0)^[25]	2m	172.3(172.3)^[26]
2c	241.1(241.1)^[26]	2n	233.4(233.4)^[24]
2d	251.1(251.1)^[26]	2o	233.4(233.4)^[26]
2e	193.1(193.1)^[26]	2p	222.4(222.4)^[26]
2f	305.1(305.1)^[26]	2q	199.4(199.4)^[24]
2g	182.1(182.1)^[24]	2r	168.1(168.1)^[24]
2h	280.1(280.1)^[26]	2s	349.0(349.0)^[24]
2i	161.1(161.1)^[26]	2t	263.1(263.1)^[26]
2j	155.0(155.0)^[26]	2u	198.9(198.9)^[26]
2k	168.1(168.1)^[24]

一种简单、高效合成α-卤代甲基酮化合物的新方法

Mild and Efficient Method for Synthesis of α-Halomethylketones^†

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一种简单、 高效合成α-卤代甲基酮化合物的新方法

Mild and Efficient Method for Synthesis of α-Halomethylketones†

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一种简单、高效合成α-卤代甲基酮化合物的新方法

Mild and Efficient Method for Synthesis of α-Halomethylketones^†