铜催化1-苯甲酰基-2,3-二氢吡啶-4(1H)-酮的对映选择性硼氢化反应

doi:10.6023/cjoc202602002

摘要/Abstract

报道了一种高效的铜催化1-苯甲酰基-2,3-二氢吡啶-4(1H)-酮的不对称硼氢化反应. 该方法具有广泛的底物适用范围, 可耐受多种N-酰基取代基(芳基、萘甲酰基、杂芳基、新戊酰基)及取代苯甲酰基片段, 产物环状α-氨基硼酸酯的产率最高可达99%, 对映体过量值为84%~96%. 克级规模合成及下游转化实验证明了其合成应用价值. 提出了一种合理的反应机理, 涉及硼基铜中间体及σ键复分解过程, 这一特征使其有别于典型的铜催化烯烃硼氢化反应.

关键词: 硼氢化, 铜, α-氨基硼酸酯

An efficient copper-catalyzed asymmetric hydroboration of 1-benzoyl-2,3-dihydropyridin-4(1H)-ones is reported. This protocol features a broad substrate scope, tolerating various N-acyl substituents (aryl, naphthoyl, heteroaryl, pivaloyl) and substituted benzoyl moieties, affording cyclic α-aminoboronate esters with up to 99% yield and ee values of 84%~96%. Gram-scale synthesis and downstream transformations demonstrated synthetic utility. A plausible mechanism involving a borylcopper intermediate and σ-bond metathesis is proposed, distinguishing this process from typical Cu-catalyzed alkene hydroborations.

Key words: hydroboration, copper, α-aminoboronate esters

引用此文

吴晓飞, 孙伟, 徐森苗. 铜催化1-苯甲酰基-2,3-二氢吡啶-4(1H)-酮的对映选择性硼氢化反应[J]. 有机化学, 2026, 46(7): 2816-2824.

Xiaofei Wu, Wei Sun, Senmiao Xu. Copper-Catalyzed Enantioselective Hydroboration of 1-Benzoyl-2,3-dihydropyridin-4(1H)-ones[J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2816-2824.

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Entry	Ligand	[Cu]	Solvent	Yield^b/%	ee^c/%
1	L1	CuCl	Toluene	56	44
2	L2	CuCl	Toluene	22	75
3	L3	CuCl	Toluene	71	93
4	L4	CuCl	Toluene	9	45
5	L5	CuCl	Toluene	Trace	—
6	L6	CuCl	Toluene	Trace	—
7	L3	CuCl	Benzene	20	89
8	L3	CuCl	THF	45	91
9	L3	CuCl	Et₂O	19	93
10	L3	CuCl	MCPE	42	92
11	L3	CuCl	1,4-Dioxane	34	91
12	L3	CuCl	CH₂Cl₂	Trace	—
13	L3	CuCl	CH₃CN	20	91
14	L3	CuCl	n-Hexane	Trace	—
15	L3	CuBr	Toluene	63	93
16	L3	CuTc	Toluene	30	93
17	L3	CuOAc	Toluene	Trace	—
18	L3	Cu(CH₃CN)₄PF₆	Toluene	Trace	—
19	L3	CuCl₂	Toluene	Trace	—
20^d	L3	CuCl	Toluene	72	92

Entry	Ligand	[Cu]	Solvent	Yield^b/%	ee^c/%
1	L1	CuCl	Toluene	56	44
2	L2	CuCl	Toluene	22	75
3	L3	CuCl	Toluene	71	93
4	L4	CuCl	Toluene	9	45
5	L5	CuCl	Toluene	Trace	—
6	L6	CuCl	Toluene	Trace	—
7	L3	CuCl	Benzene	20	89
8	L3	CuCl	THF	45	91
9	L3	CuCl	Et₂O	19	93
10	L3	CuCl	MCPE	42	92
11	L3	CuCl	1,4-Dioxane	34	91
12	L3	CuCl	CH₂Cl₂	Trace	—
13	L3	CuCl	CH₃CN	20	91
14	L3	CuCl	n-Hexane	Trace	—
15	L3	CuBr	Toluene	63	93
16	L3	CuTc	Toluene	30	93
17	L3	CuOAc	Toluene	Trace	—
18	L3	Cu(CH₃CN)₄PF₆	Toluene	Trace	—
19	L3	CuCl₂	Toluene	Trace	—
20^d	L3	CuCl	Toluene	72	92