Deprotection of N-Acyl Indole-Type Amides Based on Si—O Bond Cleavage

doi:10.6023/cjoc202510032

Abstract

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

Cite this article

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.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 5

References 25

[1]	(a) Vitaku E.; Smith D. T.; Njardarson J. T. J. Med. Chem. 2014, 57, 10257. doi: 10.1021/jm501100b pmid: 27689804
	(b) Didas S. A.; Choi S.; Chaikittisilp W.; Jones C. W. Acc. Chem. Res. 2015, 48, 2680. doi: 10.1021/acs.accounts.5b00284 pmid: 27689804
	(c) Ruiz-Castillo P.; Buchwald S. L. Chem. Rev. 2016, 116, 12564. pmid: 27689804
	(d) Patel A. R.; Patel I.; Banerjee S. Curr. Org. Chem. 2024, 28, 375. doi: 10.2174/0113852728296565240221082253 pmid: 27689804
	(e) Yi R.-N.; He W.-M. Chin. J. Org. Chem. 2021, 41, 1267 (in Chinese). doi: 10.6023/cjoc202100022 pmid: 27689804
	(易荣楠, 何卫民, 有机化学, 2021, 41, 1267.) doi: 10.6023/cjoc202100022 pmid: 27689804
	(f) Ge Y.-X.; Yan Q.-Q.; Tian Y.-F.; Wang H.-J.; Zhang C.-F.; Li Z.-J. Chin. J. Org. Chem. 2021, 41, 3106 (in Chinese). doi: 10.6023/cjoc202102035 pmid: 27689804
	(葛雅欣, 闫芹芹, 田云飞, 王海军, 张春芳, 李泽江, 有机化学, 2021, 41, 3106.) doi: 10.6023/cjoc202102035 pmid: 27689804
	(g) Wang X.; Xu X.; Wang Z.; Fang P.; Mei T. Chin. J. Org. Chem. 2020, 40, 3738 (in Chinese). doi: 10.6023/cjoc202003022 pmid: 27689804
	(王向阳, 徐学涛, 王振华, 方萍, 梅天胜, 有机化学, 2020, 40, 3738.) doi: 10.6023/cjoc202003022 pmid: 27689804
[2]	(a) Costello C. A.; Kreuzman A. J.; Zmijewski M. J. Tetrahedron Lett. 1996, 37, 7469. doi: 10.1016/0040-4039(96)01752-2
	(b) Rathi J. O.; Shankarling G. S. ChemistrySelect 2020, 5, 6861. doi: 10.1002/slct.v5.23
[3]	(a) Baran P. S.; Corey E. J. J. Am. Chem. Soc. 2002, 124, 7904. pmid: 12095326
	(b) Wen J.; Wang F.; Zhang X. M. Chem. Soc. Rev. 2021, 50, 3211. doi: 10.1039/D0CS00082E pmid: 12095326
	(c) Jiang X.-L.; Zhu S.-L. Chin. J. Org. Chem. 2021, 41, 3745 (in Chinese). doi: 10.6023/cjoc202100068 pmid: 12095326
	(江晓莉, 朱少林, 有机化学, 2021, 41, 3745.) pmid: 12095326
	(d) Chen T.; Zou Y.; Hu Y. Zhang Z. Wei H. Wei L. Zhang W. Angew. Chem. Int. Ed. 2023, 62, e202303488. doi: 10.1002/anie.v62.26 pmid: 12095326
	(e) Yang P.-F.; Zhao H.-T.; Chen X.-Y.; Shu W. Nat. Synth. 2024, 3, 1360 doi: 10.1038/s44160-024-00609-2 pmid: 12095326
[4]	(a) Wuts P. G. M.; Greene T. W. Protective Groups in Organic Synthesis, 4th ed., Wiley-Interscience, Hoboken, 2006, pp. 773-789.
	(b) Yoo M.; Jung K.-W. ChemistrySelect 2018, 3, 1527. doi: 10.1002/slct.v3.5
[5]	(a) Spaggiari A.; Blaszczak L. C.; Prati F. Org. Lett. 2004, 6, 3885. pmid: 15496055
	(b) Koenig S. G.; Vandenbossche C. P.; Zhao H.; Mousaw P.; Singh S. P.; Bakale R. P. Org. Lett. 2009, 11, 433. doi: 10.1021/ol802482d pmid: 15496055
	(c) Chen H.; Chen D.-H.; Huang P.-Q. Sci. China Chem. 2020, 63, 370. doi: 10.1007/s11426-019-9665-5 pmid: 15496055
	(d) Kita Y.; Nishii Y.; Onoue A.; Mashima K. Adv. Synth. Catal. 2013, 355, 3391. doi: 10.1002/adsc.v355.17 pmid: 15496055
	(e) Liu S.-Z.; Liu W.-H.; Deng Y.; Li Q.; Dou M.-Y.; Cui Y.; Dou J.-M. Org. Chem. Front. 2025, 12, 5438. doi: 10.1039/D5QO00603A pmid: 15496055
	(f) Ban Y.; Wang E.; Ren K.; He L.; Hou K.; Zhou L.; Gao M.; Yang. L; Yang X. J. Org. Chem. 2025, 90, 1968. doi: 10.1021/acs.joc.4c02711 pmid: 15496055
[6]	Sultane P. R.; Mete T. B.; Bhat R. G. Org. Biomol. Chem. 2014, 12, 261. doi: 10.1039/C3OB41971A
[7]	Wang A.-E.; Chang Z.; Liu Y.-P.; Huang P.-Q. Chin. Chem. Lett. 2015, 26, 1055. doi: 10.1016/j.cclet.2015.05.033
[8]	Manas C.; Nandita G.; Khasnobis S.; Chakrabarty M. Synth. Commun. 2002, 32, 265. doi: 10.1081/SCC-120002011
[9]	Shimizu Y.; Morimoto H.; Zhang M.; Ohshima T. Angew. Chem., Int. Ed. 2012, 51, 8564.
[10]	Han Q.; Xu K.; Tian F.; Huang S.; Zeng C. Chin. J. Org. Chem. 2022, 42, 1123 (in Chinese). doi: 10.6023/cjoc202112007
	(韩群, 徐坤, 田发宁, 黄胜阳, 曾程初, 有机化学, 2022, 42, 1123.) doi: 10.6023/cjoc202112007
[11]	(a) Buslov I.; Song F.; Hu X. Angew. Chem. Int. Ed. 2016, 55, 12295. doi: 10.1002/anie.201606832 pmid: 27612210
	(b) Carney J. R.; Dillon B. R.; Campbell L.; Thomas S. P. Angew. Chem. Int. Ed. 2018, 57, 10620. doi: 10.1002/anie.v57.33 pmid: 27612210
	(c) Yang P.-F.; Liang J.-X.; Zhao H.-T.; Shu W. ACS Catal. 2022, 12, 9638. doi: 10.1021/acscatal.2c02892 pmid: 27612210
	(d) Yang P.-F.; Shu W. Angew. Chem. Int. Ed. 2022, 61, e202208018. pmid: 27612210
	(e) Yang P.-F.; Zhu L.; Liang J.-X.; Zhao H.-T.; Zhang J.-X.; Zeng X.-W.; Ouyang Q.; Shu W. ACS Catal. 2022, 12, 5795. doi: 10.1021/acscatal.2c00665 pmid: 27612210
[12]	(a) Li G.; Lei P.; Szostak M. Org. Lett. 2018, 20, 5622. doi: 10.1021/acs.orglett.8b02323
	(b) Huang C.; Li J.; Wang J.; Zheng Q.; Li Z.; Tu T. Sci. China Chem. 2021, 64, 66. doi: 10.1007/s11426-020-9883-3
[13]	Inoue F.; Saito T.; Semba K.; Nakao Y. Chem. Commun. 2017, 53, 4497. doi: 10.1039/C7CC00852J
[14]	He K.-H.; Tan F.-F.; Zhou C.-Z.; Zhou G.-J.; Yang X.-L.; Li Y. Angew. Chem. Int. Ed. 2017, 56, 3080. doi: 10.1002/anie.v56.11
[15]	Shen Y.; Chen F.; Du Z.; Zhang H.; Liu J.; Liu N. J. Org. Chem. 2024, 89, 4530. doi: 10.1021/acs.joc.3c02768
[16]	Ahmad A.; Dutta H. S.; Kumar M.; Khan A. A.; Raziullah; Koley D. Org. Lett. 2020, 22, 5870. doi: 10.1021/acs.orglett.0c01963
[17]	Liang J.-X.; Yang P.-F.; Shu W. Organometallics 2022, 41, 3795. doi: 10.1021/acs.organomet.2c00509
[18]	Yan Y.; Wang P.; Wang Y.; Dong J.; Li G.; Wang C.; Xue D. Org. Lett. 2024, 26, 1370. doi: 10.1021/acs.orglett.3c04294
[19]	Abe T.; Yamada K. Org. Lett. 2016, 18, 6504. doi: 10.1021/acs.orglett.6b03466
[20]	Lin D.-Z.; Huang J.-M. Org. Lett. 2019, 21, 5862. doi: 10.1021/acs.orglett.9b01971
[21]	Wang S.-D.; Yang B.; Zhang H.; Qu J.-P.; Kang Y.-B. Org. Lett. 2023, 25, 816. doi: 10.1021/acs.orglett.2c04346
[22]	Pang M.; Ramazani A.; Zhang Z.; Zhang G. Org. Biomol. Chem. 2025, 23, 2812. doi: 10.1039/D5OB00030K
[23]	Wang Z.; Chen T.; Liu H.; Zhao X.-L.; Hu W.-B.; Yang H.; Liu Y. A.; Wen K. J. Org. Chem. 2021, 86, 6467. doi: 10.1021/acs.joc.1c00314
[24]	Oh Y. S.; Kohn H. J. Org. Chem. 1992, 57, 3662. doi: 10.1021/jo00039a028
[25]	Zhang C.; Feng P.; Jiao N. J. Am. Chem. Soc. 2013, 135, 15257. doi: 10.1021/ja4085463 pmid: 24032593

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

基于硅氧键断裂的N-酰基吲哚类酰胺的脱保护