α-氧代羧酸、炔和伯胺的多组分碳氢环化构筑异喹啉鎓骨架

doi:10.6023/cjoc202507007

摘要/Abstract

开发了Rh(III)催化α-氧代羧酸、炔和伯胺的三组分C—H键活化/环化反应, 一步构筑二、四并环的异喹啉鎓盐衍生物. 伯胺与α-氧代羧酸通过酮胺缩合原位生成α-亚胺酸, 从而将α-氧代羧酸的弱氧导向转变成强氮导向. 当烷基胺为氮源时, α-亚胺酸与炔烃发生氮导向的C—H键活化/环化反应, 以较高的产率得到二并环的N-烷基异喹啉鎓盐(离子液). 当芳胺作为氮源时, α-亚胺酸与炔烃发生氮导向的C—H环化后, 可以进一步发生羧基导向的C—H键活化/环化反应, 从而以中等至良好的产率得到四并环的二苯并[a,f]喹嗪鎓盐. 通过时间依赖的ESI-MS成功检测到7个关键中间体, 其中包括3个羧基保留的物种, 证明了羧基在该反应中的重要性, 并以此提出包含了酮胺缩合、脱羧、C—H键活化、炔烃插入及还原消除等过程的反应机理.

关键词: α-氧代羧酸, C—H键活化/环化, 多组分, 铑催化, 异喹啉鎓

The Rh(III)-catalyzed three-component C—H activation/annulation reaction of α-oxocarboxylic acids, alkynes, and primary amines to construct bicyclic and tetracyclic isoquinolinium derivatives is reported. The in-situ generated α-imino acid intermediates from keto-amine condensation between α-oxocarboxylic acid and primary amine enable a directing group switch from weak oxygen to strong nitrogen. By using alkylamines as N-source, N-directed C—H activation of α-imino acids and alkynes afforded bicyclic N-alkyl isoquinolinium salts (ionic liquids) in high yields. When using arylamines instead, the sequential N- and carboxyl-directed C—H activation/annulation process furnished tetracyclic dibenzo[a,f]quinolizinium salts with moderate to good yields. Seven key intermediates, including three carboxylate-retained species, have been characterized by time-dependent ESI-MS analysis, supporting a plausible mechanism involving keto-amine condensation, decarboxylation, C—H activation, alkyne insertion, and reductive elimination.

Key words: α-oxocarboxylic acids, C—H activation/annulation, multi-component, rhodium-catalysis, isoquinolinium

引用此文

曾依玲, 梁方鹏, 李辉, 刘荣荣, 李世清. α-氧代羧酸、炔和伯胺的多组分碳氢环化构筑异喹啉鎓骨架[J]. 有机化学, 2026, 46(2): 554-563.

Yiling Zeng, Fangpeng Liang, Hui Li, Rongrong Liu, Shiqing Li. Multi-component C—H Annulation of α-Oxocarboxylic Acids, Allynes and Primary Amines to Yield Isoquinolinium Skeletons[J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 554-563.

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图/表 5

图式1. α-氧代羧酸的邻位碳氢活化/环化反应

Scheme 1. ortho-C—H activation/annulation of α-oxocarboxy- lic acids

Entry	Variation from above conditions^a	3a/4a^b/%
1	None	74/trace
2	[(p-cymene)RuCl₂] as catalyst	0/0
3	[Cp*Co(CO)I₂] as catalyst	0/0
4	[Cp*RhCl₂]₂ (2.5 mol%)	10/47
5	Cu(OTf)₂ instead of Cu(OAc)₂	21/0
6	AgOAc instead of Cu(OAc)₂	12/31
7	Cu(OAc)₂ (2 equiv.)	26/55
8	Without Cu(OAc)₂	9/56
9	Without NaOAc	<5/48
10	HOAc instead of NaOAc	25/51
11	PivOH instead of NaOAc	26/50
12	CsOAc instead of NaOAc	29/36
13	NaBF₄ instead of Zn(OTf)₂	66/<5
14	NaSbF₆ instead of Zn(OTf)₂	67/<5

表1. 芳基胺N-1体系条件优化a

Table 1. Screening of reaction conditions of N-1 system

图式2. 使用芳胺N-1的双环化底物范围

Scheme 2. Scope of di-annulation with anilines N-1

图式3. 使用烷基胺N-2的单环化底物范围

Scheme 3. Scope of mono-annulation with alkylamines N-2

图式4. 芳基胺体系的机理研究和可能的反应机理

Scheme 4. Mechanistic studies and possible mechanism of the aniline system

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