无过渡金属参与的醚、醛和酰胺C—H键自由基炔基化和烯丙基化反应

doi:10.6023/cjoc202207014

有机化学 ›› 2022, Vol. 42 ›› Issue (12): 4340-4349.DOI: 10.6023/cjoc202207014 上一篇下一篇

所属专题：自由基化学专辑

研究论文

无过渡金属参与的醚、醛和酰胺C—H键自由基炔基化和烯丙基化反应

许耀辉^a, 吴镇^a, 吴新鑫^a, 朱晨^a^,^b^,^*()

a 苏州大学材料与化学化工学部江苏苏州 215123
b 中国科学院上海有机化学研究所天然产物有机合成重点实验室上海 200032

收稿日期:2022-07-06 修回日期:2022-08-14 发布日期:2022-09-01
通讯作者: 朱晨
作者简介:
^†共同第一作者
基金资助:
国家自然科学基金(21971173); 国家自然科学基金(22171201)

Transition-Metal Free Radical-Mediated C—H Bond Alkynylation and Allylation of Ethers, Aldehydes and Amides

Yaohui Xu^a, Zhen Wu^a, Xinxin Wu^a, Chen Zhu^a^,^b()

a College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Received:2022-07-06 Revised:2022-08-14 Published:2022-09-01
Contact: Chen Zhu
About author:
^†These authors contributed equally to this work.
Supported by:
National Natural Science Foundation of China(21971173); National Natural Science Foundation of China(22171201)

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摘要/Abstract

醚、醛和酰胺类化合物广泛存在于天然产物和药物分子中, 并作为常见廉价原料应用于合成化学中. 通过自由基反应途径实现杂原子α位C—H键官能化为这些化合物的结构改造提供了高效策略. 报道了一例通过二三氟醋酸碘苯(PIFA)在光照下直接攫氢产生碳自由基实现C—H键炔基化和烯丙基化反应的新策略. 该方法操作简单, 能够以中等到良好的产率实现醚、醛和酰胺C—H键的炔基化和烯丙基化反应. 反应条件温和, 不需要使用过渡金属催化剂, 官能团兼容性广, 适用于醚、醛和酰胺以及形式多样的炔基和烯丙基砜试剂.

关键词: 自由基反应, 炔基, 烯丙基, 无过渡金属, C—H键官能化

Ethers, aldehydes, and amides are widely found in natural products and pharmaceutical molecules, and employed as inexpensive materials in synthetic chemistry. Radical-mediated heteroatomic α-C—H bond functionalization provides an efficient strategy for structural modification of ethers, aldehydes, and amides. New approaches of C—H alkynylation and allylation through phenyliodine bis(trifluoroacetate) (PIFA) induced hydrogen atom transfer (HAT) under visible-light irradiation are reported. The method is operationally simple, leading to the corresponding alkynylated and allylated products in moderate to good yields. The protocol features mild and transition-metal free conditions, broad functional group compatibility, and is adapted to a diversity of ethers, aldehydes, and amides as well as various alkynylating and allylating reagents.

Key words: radical reaction, alkynylation, allylation, transition-metal free, C—H bond functionalization

引用此文

许耀辉, 吴镇, 吴新鑫, 朱晨. 无过渡金属参与的醚、醛和酰胺C—H键自由基炔基化和烯丙基化反应[J]. 有机化学, 2022, 42(12): 4340-4349.

Yaohui Xu, Zhen Wu, Xinxin Wu, Chen Zhu. Transition-Metal Free Radical-Mediated C—H Bond Alkynylation and Allylation of Ethers, Aldehydes and Amides[J]. Chinese Journal of Organic Chemistry, 2022, 42(12): 4340-4349.

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图/表 10

图1. 含有α-炔基醚结构的生物活性分子

Figure 1. Biologically active molecules containing α-alkynyl ether moiety

图2. 醚和酰胺的C—H键官能团化反应

Figure 2. C—H alkynylation of ethers and amides

图3. 合成炔基酮的相关报道

Figure 3. Relevant works on ynone synthesis

图4. PIFA攫氢的C—H键官能团化反应

Figure 4. C—H functionalization via PIFA-mediated hydrogen abstraction

Entry	PIFA/ equiv.	THF/mL	K₂CO₃/ equiv.	Solvent	Yield/%
1^b	1.5	—	1.5	MeCN	36
2^b	1.5	—	1.5	PhCF₃	21
3^b	1.5	—	1.5	DCM	14
4^b	1.5	—	1.5	DCE	14
5^b	1.5	—	1.5	DMSO	29
6^b	1.5	—	1.5	Acetone	44
7^b	1.5	—	1.5	EtOAc	47
8^b^,^c	1.5	—	1.5	EtOAc	41
9^b^,^d	1.5	—	1.5	EtOAc	28
10	1.5	2	1.5	—	68
11^e	1.5	2	1.5	—	65
12	1.5	2	—	—	19
13	1.5	1	1.5	—	54
14	1.5	5	1.5	—	78
15	1.5	10	1.5	—	78
16^e	1.5	10	1.5	—	66
17^e	2	10	2	—	76
18^e	2	5	2	—	77

表1. 醚的炔基化反应条件筛选a

Table 1. Reaction condition screening of C—H alkynylation of ether

表2. THF的炔基化反应a

Table 2. Alkynylation of THF

表3. 醚和酰胺的炔基化反应

Table 3. Alkynylation of ethers and amides

表4. 醛的炔基化反应

Table 4. Alkynylation of aldehydes

表5. C—H键烯丙基化反应

Table 5. Allylation of C—H bonds

图5. C—H键官能化的反应机理

Figure 5. Reaction mechanism of the functionalization of C—H bonds

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无过渡金属参与的醚、醛和酰胺C—H键自由基炔基化和烯丙基化反应

Transition-Metal Free Radical-Mediated C—H Bond Alkynylation and Allylation of Ethers, Aldehydes and Amides

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