荧光染料和镍协同催化的脱羧羰基化反应

doi:10.6023/cjoc202110018

摘要/Abstract

在荧光染料与镍协同催化下, 以N-苯甲酰基琥珀酰亚胺类化合物为羰基化试剂, 实现了α-氨基酸的脱羧羰基化反应. 该反应以较好的收率(最高可达78%)合成了16种含α-氨基酮的衍生物, 光转化效率最高可达3.25×10^–1 mmol/ (kW•h). 此外, 提出了该光催化反应的可能机理: α-氨基羧酸在可见光催化下生成α-氨基烷基自由基, 并进入镍催化循环中, 经过氧化加成和还原消除过程后生成α-氨基酮类化合物. 该反应可以在温和条件下合成不同种类的α-氨基酮类化合物, 显示了良好的底物适应性, 可能在含有α-氨基酮的药物分子合成及肽的化学修饰等方面具有很广泛的应用价值.

关键词: 光催化, 镍催化, 单电子转移, 脱羧偶联反应

The decarboxylative carbonylation of α-amino acids was carried out with N-benzoyl succinimide as the carbonylation reagent under the synergistic catalysis of fluorescent dye/nickel catalysts. In this reaction, 16 kinds of α-amino ketone-containing derivatives were synthesized with good yields (up to 78%), and the light conversion efficiency was up to 3.25×10^–1 mmol/(kW•h). In addition, the possible mechanism of the photocatalytic reaction was proposed: α-amino carboxylic acid was catalyzed by visible light to form α-amino alkyl radicals, which entered the nickel catalytic cycle and produced α-amino ketone target compound via oxidation addition and reduction elimination process. The reactions could generate a variety of α-amino ketones with broad substrate scope under mild conditions and might have widespread use in synthesis of α-amino ketone-containing drug molecules and peptide modifications.

Key words: photocatalysis, nickel catalysis, single electron transfer, decarboxylative coupling reaction

引用此文

余卫国, 王灵娜, 俞晓聪, 罗书平. 荧光染料和镍协同催化的脱羧羰基化反应[J]. 有机化学, 2022, 42(4): 1216-1223.

Weiguo Yu, Lingna Wang, Xiaocong Yu, Shuping Luo. Fluorescent Dye/Nickel Synergistic Catalytic Decarboxylative Carbonylation Reaction[J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1216-1223.

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图/表 9

图1. 含有α-氨基酮单元的代表性生物活性化合物和药物

Figure 1. Typical biologically active compounds and drugs containing α-amino ketone units

Entry	Photocatalyst	Yield^b/% of 3a
1	4CzIPN	53
2	4DPAIPN	24
3	4CzIPA	15
4	5CzBN	n.r.^c
5	3CzClIPN	n.r.^c
6	3DPAIPN	n.r.^c

表1. 光催化反应的光敏剂筛选a

Table 1. Photosensitizers optimization for photocatalytic reactions

Entry	Solvent	Yield^b/% of 3a
1	DMAc	53
2	DMF	12
3	DMSO	18
4	THF	n.r.^c
5	CH₃CN	n.r.^c
6	PhCH₃	16
7	1,4-Dioxane	n.r.^c

表2. 光催化反应的溶剂筛选a

Table 2. Solvent optimization for photocatalytic reactions

Entry	Base	Yield^b/% of 3a
1	Cs₂CO₃	53
2	K₂HPO₄	17
3	DIPEA	n.r.^c
4	K₂CO₃	32
5	Et₃N	n.r. ^c
6	Pyridine	n.r. ^c

表3. 光催化反应的碱筛选a

Table 3. Base optimization for photocatalytic reactions

Entry	PC (2 mol%)	Metal catalyst and ligand	Yield^b/% of 3a
1	4CzIPN	Ni(acac)₂/dtbbpy	53
2	4CzIPN	NiCl₂•DME/dtbbpy	68
3	4CzIPN	NiCl₂•DME/dppf	10
4	4CzIPN	NiCl₂•DME/1,10-phen	n.r.^c
5	4CzIPN	NiCl₂•DME	n.r.^c
6	4CzIPN	dtbbpy	n.r.^c
7	None	NiCl₂•DME/dtbbpy	n.r.^c
8^d	4CzIPN	NiCl₂•DME/dtbbpy	n.r.^c
9^e	4CzIPN	NiCl₂•DME/dtbbpy	n.r.^c
10^f	4CzIPN	NiCl₂•DME/dtbbpy	n.r.^c

表4. 以Cs2CO3为碱的光反应条件筛选a

Table 4. Optimization for photocatalytic reactions using Cs2CO3 as base

图式1. 光催化偶联反应底物的拓展

Scheme 1. Expansion of substrates for photocatalytic coupling reaction n.r. means no product

图1. 荧光淬灭实验图

Figure 1. Fluorescence quenching experiment diagram

图式2. 自由基的捕捉实验

Scheme 2. Experiment of free radical capture n.r. means no product

图式3. 反应的可能机理

Scheme 3. Possible mechanism of reaction

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