氧化铝促进的咪唑并[1,2-a]吡啶与α,β-不饱和酮的Michael加成

doi:10.6023/cjoc202503008

摘要/Abstract

开发了一种以酸性氧化铝为路易斯酸, 咪唑并[1,2-a]吡啶与α, β-不饱和酮的直接Michael加成反应. 酸性氧化铝表面丰富的路易斯酸位点(Al^3⁺)能够高效活化α,β-不饱和酮的羰基, 显著提高β-碳的亲电性, 从而促进咪唑并[1,2-a]吡啶C3位的选择性烷基化. 该方法具有优异的官能团兼容性、温和的反应条件、低廉的试剂成本和操作方便等特点, 为烷基化的咪唑并[1,2-a]吡啶的高效合成提供了新策略.

关键词: 路易斯酸, 咪唑并[1,2-a]吡啶, α,β-不饱和酮, Michael加成

A direct Michael addition reaction between imidazo[1,2-a]pyridines and α,β-unsaturated ketones using acidic alumina as a C(sp³)—H acid catalyst has been developed. The abundant C(sp³)—H acid sites (Al³⁺) on the acidic alumina surface effectively activate the carbonyl group of α,β-unsaturated ketones, significantly enhancing the electrophilicity of the β-carbon and thereby facilitating selective alkylation at the C3 position of imidazo[1,2-a]pyridines. This method demonstrates excellent functional group compatibility, mild reaction conditions, low reagent costs, and operational simplicity, providing a novel strategy for the efficient synthesis of alkylated imidazo[1,2-a]pyridine derivatives.

Key words: C(sp³)—H acid, imidazo[1,2-a]pyridine, α,β-unsaturated ketone, Michael addition

引用此文

孙亚栋, 周海, 郑土才, 王守才, 及方华. 氧化铝促进的咪唑并[1,2-a]吡啶与α,β-不饱和酮的Michael加成[J]. 有机化学, 2025, 45(9): 3361-3369.

Yadong Sun, Hai Zhou, Tucai Zheng, Shoucai Wang, Fanghua Ji. Alumina-Promoted Michael Addition of Imidazo[1,2-a]pyridines with α,β-Unsaturated Ketones[J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3361-3369.

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参考文献 16

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Entry	Al₂O₃	Solvent	T/^oC	Yield^b/%
1^a	Acidic	n-Hexane	68	85
2	Neutral	n-Hexane	68	17
3	Basic	n-Hexane	68	21
4	Acidic	Heptane	68	75
5	Acidic	PhMe	68	55
6	Acidic	DCM	68	60
7	Acidic	CH₃CN	68	20
8	Acidic	n-Butanol	68	0
9	Acidic	Ethanol	68	0
10	Acidic	THF	68	30
11	Acidic	Acetone	68	15
12	Acidic	DMSO	68	0
13	Acidic	dioxane	68	0
14	Acidic	n-Hexane	48	65
15	Acidic	n-Hexane	88	81
16	Acidic	n-Hexane	108	78
17^c	Acidic	n-Hexane	68	70
18^d	Acidic	n-Hexane	68	56
19	—	n-Hexane	68	0

Entry	Al₂O₃	Solvent	T/^oC	Yield^b/%
1^a	Acidic	n-Hexane	68	85
2	Neutral	n-Hexane	68	17
3	Basic	n-Hexane	68	21
4	Acidic	Heptane	68	75
5	Acidic	PhMe	68	55
6	Acidic	DCM	68	60
7	Acidic	CH₃CN	68	20
8	Acidic	n-Butanol	68	0
9	Acidic	Ethanol	68	0
10	Acidic	THF	68	30
11	Acidic	Acetone	68	15
12	Acidic	DMSO	68	0
13	Acidic	dioxane	68	0
14	Acidic	n-Hexane	48	65
15	Acidic	n-Hexane	88	81
16	Acidic	n-Hexane	108	78
17^c	Acidic	n-Hexane	68	70
18^d	Acidic	n-Hexane	68	56
19	—	n-Hexane	68	0