溶剂介导吡咯并[1,2-a]喹喔啉选择性C—H键碘代

doi:10.6023/cjoc202107033

摘要/Abstract

开发了一种溶剂介导吡咯并[1,2-a]喹喔啉和N-碘代丁二酰亚胺(NIS)的区域选择性C—H碘化, 分别以CHCl₃和N,N-二甲基甲酰胺(DMF)为溶剂, 选择性地生成了1-碘吡咯并[1,2-a]喹喔啉和3-碘吡咯并[1,2-a]喹喔啉. 此外,吡咯并[1,2-a]喹喔啉与N-溴代丁二酰亚胺(NBS)的溴代反应得到主要产物为1,3-二溴吡咯并喹喔啉. 该方法具有反应条件简单温和、区域选择性好、底物范围广、克级合成等特点. 此外,还通过钯和碘催化的C—X (X=C, S)键形成反应研究了卤化吡咯并[1,2-a]喹喔啉产物的进一步转化.

关键词: 溶剂介导, 区域选择性, 吡咯并[1,2-a]喹喔啉, C—H键碘代

A solvent mediated regioselective C—H iodination of pyrrolo[1,2-a]quinoxaline with N-iodo-succininide (NIS) has been developed. 1-Iodopyrrolo[1,2-a]quinoxalines and 3-iodopyrrolo[1,2-a]quinoxalines could be selectively synthesized by using CHCl₃ and N,N-dimethylformamide (DMF) as solvents, respectively. Furthermore, 1,3-dibromopyrroloquinoxalines were obtained as the main products by the bromination of pyrrolo[1,2-a]quinoxaline with N-bromo-succinimide (NBS). The method features simple and mild reaction conditions, good regioselectivity, broad substrate scope, and gram-scale synthesis. In addition, the further transformation of halogenated pyrrolo[1,2-a]quinoxaline products has also been investigated through palladium and iodine catalyzed C—X (X=C, S) bond formation reactions.

Key words: solvent-mediated, regioselectivity, pyrrolo[1,2-a]quinoxaline, C—H bond iodination

引用此文

刘亚丽, 杨振, 李阳, 刘岩, 刘平. 溶剂介导吡咯并[1,2-a]喹喔啉选择性C—H键碘代[J]. 有机化学, 2021, 41(12): 4789-4797.

Yali Liu, Zhen Yang, Yang Li, Yan Liu, Ping Liu. Solvent Mediated Selective C—H Bond Iodination of Pyrrolo[1,2-a]quinoxaline[J]. Chinese Journal of Organic Chemistry, 2021, 41(12): 4789-4797.

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图/表 10

Scheme 1. Selective halogenations of pyrrolo[1,2-a]quinoxalines

Entry	[I] (equiv.)	Solvent	t/h	Yield^b/%
Entry	[I] (equiv.)	Solvent	t/h	2a	3a
1^c	NIS (1.2)	CHCl₃	24	17	—
2	NIS (1.2)	CHCl₃	24	81	—
3	NIS (1.2)	CHCl₃	12	76	—
4	I₂ (1.2)	CHCl₃	12	nr	—
5	TBAI (1.2)	CHCl₃	12	nr	—
6	NIS (1)	DMF	6	—	72
7	NIS (1)	DMSO	6	—	56
8	NIS (1)	MeCN	6	—	52
9	NIS (1)	EtOH	6	—	51
10	NIS (1)	MeOH	6	—	39
11	NIS (1)	DCM	6	—	trace
12	NIS (1)	Toluene	6	—	nr
13	I₂ (1)	DMF	6	—	21
14	NIS (2)	DMF	6	—	40
15	NIS (1)	DMF	10	—	73
16	NIS (1)	DMF	3	—	76

Table 1. Optimization of the reaction conditions

Table 2. Scope of selective C—H iodination of pyrrolo[1,2-a]-quinoxalines with NISa

Table 3. Bromination of pyrrolo[1,2-a]quinoxaline with NBSa

Figure 1. Cystal structure of 4a (CCDC: 2073986)

Scheme 2. TBAI-promoted the sulfenylation of 4a

Figure 2. Crystal structure of 5a (CCDC: 2062352)

Scheme 3. Gram-scale synthesis of 2a

Table 4. Pd-catalyzed Suzuki-Miyaura reactions of 2aa

Table 5. Pd-catalyzed Sonogashira reactions of 2aa

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