Direct 1,3-Azidoheteroarylation of [1.1.1]Propellane with Cyclic Aldimines and Azidotrimethylsilane (TMSN3) under Mild Conditions

doi:10.6023/cjoc202504022

Abstract

A practical method for the 1,3-azidoheteroarylation of [1.1.1]propellane with cyclic aldimines and azidotrimethylsilane (TMSN₃) is presented. A broad spectrum of 1-azido-3-heteroaryl bicyclo[1.1.1]pentanes (BCPs) can be synthesized in moderate-to-good yields under standard conditions. The versatility of this method is further confirmed by its applicability to large-scale synthesis, product derivatizations, and late-stage functionalization of pharmaceutically relevant molecules. Mechanistic studies reveal that a radical relay mechanism initiated by a single-electron transfer (SET) process is operational.

Key words: heteroarene, [1.1.1]propellane, bicyclo[1.1.1]pentane (BCP), oxidant, difunctionalization

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Yuxin Wang, Jingyi Zhang, Yibo Wang, Binye Cao, Xinchang Wang, Jiabin Shen, Yihan Gao, Wanmei Li. Direct 1,3-Azidoheteroarylation of [1.1.1]Propellane with Cyclic Aldimines and Azidotrimethylsilane (TMSN₃) under Mild Conditions[J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3797-3806.

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Entry	Oxidant	Solvent	Yield^b/%
1	PIDA	MeCN	40
2	PIFA	MeCN	18
3	m-CPBA	MeCN	0
4	H₂O₂	MeCN	0
5	—	MeCN	0
6	PIDA	DMSO	67
7	PIDA	NMP	36
8	PIDA	DMF	72
9	PIDA	EA	20
10	PIDA	MeOH	Trace
11	PIDA	DCM	25
12^c	PIDA	DMF	70
13^d	PIDA	DMF	38
14^e	PIDA	DMF	0
14^f	PIDA	DMF	61
15^g^,^h^,ⁱ	PIDA	DMF	60, 62, 65

Entry	Oxidant	Solvent	Yield^b/%
1	PIDA	MeCN	40
2	PIFA	MeCN	18
3	m-CPBA	MeCN	0
4	H₂O₂	MeCN	0
5	—	MeCN	0
6	PIDA	DMSO	67
7	PIDA	NMP	36
8	PIDA	DMF	72
9	PIDA	EA	20
10	PIDA	MeOH	Trace
11	PIDA	DCM	25
12^c	PIDA	DMF	70
13^d	PIDA	DMF	38
14^e	PIDA	DMF	0
14^f	PIDA	DMF	61
15^g^,^h^,ⁱ	PIDA	DMF	60, 62, 65

温和条件下[1.1.1]螺桨烷与环状醛亚胺和叠氮三甲基硅烷(TMSN₃)的直接1,3-叠氮杂芳基化

Direct 1,3-Azidoheteroarylation of [1.1.1]Propellane with Cyclic Aldimines and Azidotrimethylsilane (TMSN₃) under Mild Conditions

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温和条件下[1.1.1]螺桨烷与环状醛亚胺和叠氮三甲基硅烷(TMSN3)的直接1,3-叠氮杂芳基化