β-二羰基化合物与靛红衍生的α,β-不饱和酮之间的Michael加成/半缩酮化串联反应构建3,4'-吡喃-螺环氧化吲哚类化合物

doi:10.6023/cjoc202406026

摘要/Abstract

3,4'-吡喃-螺环氧化吲哚结构单元存在于一些天然产物和具有生物活性的合成化合物中, 而多官能团化3,4'-吡喃-螺环氧化吲哚的合成鲜有文献报道. 本工作发展了一种4-二甲氨基吡啶(DMAP)催化作用下β-二羰基化合物与靛红衍生的α,β-不饱和酮之间的Michael加成/半缩酮化串联反应, 在温和条件下, 以最高99%的产率和大于20∶1的非对映选择性成功地合成了一系列多官能团化3,4'-吡喃-螺环氧化吲哚类化合物. 该研究为高效构建多官能团化的3,4'-吡喃-螺环氧吲哚类化合物提供了一个简单、温和的方法.

关键词: 串联反应, 催化, Michael加成, 吡喃, 螺环氧化吲哚

3,4'-Pyran-spirooxindole is a structural unit existing in many natural products and bioactive synthetic compounds. The synthesis of multifunctionalized 3,4'-pyran-spirooxindole derivatives has rarely been reported. Herein a Michael addition/hemiketalization cascade reaction between β-dicarbonyl compounds and isatin-derived α,β-unsaturated ketones catalyzed by 4-dimethylaminopyridine (DMAP) is presented. A variety of multifunctionalized 3,4'-pyran-spirooxindoles were obtained in high yields (up to 99%) with excellent diastereoselectivities (dr>20∶1) under mild conditions. This methodology provides a simple and convenient method for the syntheses of multifunctionalized 3,4'-pyran-spirooxindoles.

Key words: cascade reaction, catalysis, Michael addition, pyran, spirooxindole

引用此文

张明美, 沙风, 伍新燕. β-二羰基化合物与靛红衍生的α,β-不饱和酮之间的Michael加成/半缩酮化串联反应构建3,4'-吡喃-螺环氧化吲哚类化合物[J]. 有机化学, 2025, 45(4): 1369-1378.

Mingmei Zhang, Feng Sha, Xin-Yan Wu. Michael Addition/Hemiketalization Cascade Reaction Between β-Dicarbonyl Compounds and Isatin-Derived α,β-Unsaturated Ketones to Construct 3,4'-Pyran-spirooxindoles[J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1369-1378.

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图/表 8

图1. 含3,4'-吡喃-螺环氧化吲哚结构单元的生物活性分子举例

Figure 1. Examples of bioactive molecules possessing 3,4'- pyran spirooxindole scaffold

图式1. 3,4'-吡喃-螺环氧化吲哚的构建

Scheme 1. Construction of 3,4'-pyran spirooxindoles

Entry	Catalyst	Solvent	Time/h	Yield^b/%	Dr ^c
1	—	CH₂Cl₂	—	N.R.	—
2	DABCO	CH₂Cl₂	42	80	>20∶1
3	Et₃N	CH₂Cl₂	72	92	>20∶1
4	DIPEA	CH₂Cl₂	120	96	>20∶1
5	TMG	CH₂Cl₂	24	88	>20∶1
6	Na₂CO₃	CH₂Cl₂	12	89	>20∶1
7	DMAP	CH₂Cl₂	24	98	>20∶1
8	DMAP	CHCl₃	72	92	>20∶1
9	DMAP	DMF	5	89	>20∶1
10	DMAP	EtOAc	60	97	>20∶1
11^d	DMAP	Toluene	72	89	>20∶1
12^d	DMAP	Et₂O	72	48	>20∶1
13^d	DMAP	THF	72	76	>20∶1
14^d	DMAP	EtOH	72	48	>20∶1
15	DMAP	MeCN	10	99	>20∶1
16^e	DMAP	MeCN	10	98	>20∶1
17^f	DMAP	MeCN	8	96	>20∶1
18^g	DMAP	MeCN	24	96	>20∶1

表1. 反应条件的优化a

Table 1. Optimization of reaction conditions

表2. 反应底物拓展a

Table 2. Scope of the substrates

表3. 不对称催化Michael加成/半缩酮化串联反应a

Table 3. Asymmetric Michael addition/hemiketalization cascade reaction

图式2. 克级反应

Scheme 2. Gram-scale reaction

图2. 产物3a的单晶结构

Figure 2. X-ray crystal structure of product 3a

图3. 催化反应的关键中间体

Figure 3. Key intermediates of the cascade reaction

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