基于硅氧键断裂的N-酰基吲哚类酰胺的脱保护

doi:10.6023/cjoc202510032

摘要/Abstract

保护基策略在有机合成与药物合成领域占据重要地位, 其中酰胺的脱保护一直受到广泛关注. 然而, 由于酰胺键的稳定性较高, 在脱除酰基保护基时通常需要苛刻的条件. 为了解决这一难题, 发展了一种温和条件下脱除酰基保护基的方法, 即烷氧基硅烷促进的N-酰基吲哚类化合物的酰胺键断裂反应. 硅烷的Si—O键发生断裂, 原位产生亲核试剂进攻酰胺键, 成功地实现了酰基保护基的脱除. 该反应具有条件温和、底物适用范围广、操作简单、产率高以及所用试剂廉价易得等优点, 可以为脱去酰胺的酰基保护基提供一种绿色且实用的新方法.

关键词: N-酰基吲哚类酰胺, 硅氧键断裂, 脱保护基, 绿色合成

The protecting group strategy represents a pivotal approach in organic synthesis, in which the deprotection of amides has garnered considerable attention. However, due to the high stability of the amide bond, harsh conditions are often required for the deprotection of amides. A method for deprotection of amides under mild conditions has been developed, namely the silane-promoted deprotection of N-acyl indole type amides. The Si—O bond of silane undergoes cleavage, generating a nucleophile in situ that attacks the amide bond, thereby successfully achieving the deprotection of amides. The mild conditions, broad substrate scope, operational simplicity, high yields, and the use of inexpensive and readily available reagents, make this protocol a green and practical strategy for deprotection of amides.

Key words: N-acyl indole-type amide, Si—O bond cleavage, deprotection, green synthesis

引用此文

杨鹏飞, 马雨婷, 徐婉欣, 孙雨蒙, 仰海凌. 基于硅氧键断裂的N-酰基吲哚类酰胺的脱保护[J]. 有机化学, 2026, 46(5): 2112-2120.

Pengfei Yang, Yuting Ma, Wanxin Xu, Yumeng Sun, Hailing Yang. Deprotection of N-Acyl Indole-Type Amides Based on Si—O Bond Cleavage[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2112-2120.

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Entry	Deviation from standard conditions	Yield^b/%
1	None	95 (90)^c
2	w/o silane	N.R.
3	w/o K₂CO₃	N.R.
4	(EtO)₃SiH instead of (MeO)₃SiH	93
5	(EtO)₄Si instead of (MeO)₃SiH	67
6	2.0 equiv. of (EtO)₄Si instead of (MeO)₃SiH	94
7	Ph₂SiH₂instead of (MeO)₃SiH	N.R.
8	Et₃SiH instead of (MeO)₃SiH	N.R.
9	NaHCO₃ instead of K₂CO₃	N.R.
10	KHCO₃ instead of K₂CO₃	N.R.
11	Na₂CO₃ instead of K₂CO₃	N.R.
12	CsCO₃ instead of K₂CO₃	94
13	Toluene instead of DMF	N.R.
14	Ethyl acetate instead of DMF	6
15	CH₂Cl₂ instead of DMF	5
16	THF instead of DMF	15
17	0.50 mL of DMF	90

Entry	Deviation from standard conditions	Yield^b/%
1	None	95 (90)^c
2	w/o silane	N.R.
3	w/o K₂CO₃	N.R.
4	(EtO)₃SiH instead of (MeO)₃SiH	93
5	(EtO)₄Si instead of (MeO)₃SiH	67
6	2.0 equiv. of (EtO)₄Si instead of (MeO)₃SiH	94
7	Ph₂SiH₂instead of (MeO)₃SiH	N.R.
8	Et₃SiH instead of (MeO)₃SiH	N.R.
9	NaHCO₃ instead of K₂CO₃	N.R.
10	KHCO₃ instead of K₂CO₃	N.R.
11	Na₂CO₃ instead of K₂CO₃	N.R.
12	CsCO₃ instead of K₂CO₃	94
13	Toluene instead of DMF	N.R.
14	Ethyl acetate instead of DMF	6
15	CH₂Cl₂ instead of DMF	5
16	THF instead of DMF	15
17	0.50 mL of DMF	90