Visible Light-Catalyzed Synthesis of Difluoroalkylated Polycyclic Indoles

doi:10.6023/cjoc202212032

Abstract

Polycyclic indoles are widely found in natural products and pharmaceutical molecules, and have a wide range of applications in the pharmaceutical, pesticide and dye industries. Although considerable development has been made in the synthesis of indole polycycles, it is still of great scientific interest and value to explore more efficient and milder experimental strategies for the synthesis of highly-functionalized polycyclic indoles. Herein, a one-step radical tandem cyclization reaction to synthesize difluoroalkylindoles with quaternary carbon centers by using difluorobromoesters as the fluorine source and 3-alkenyl indoles as the substrates under visible light-catalyzed conditions was developed. The method is easy-to-operate and mild in conditions, with a wide range of substrate adaptability and good yields, providing a green and efficient synthetic route for fluorine-containing polycyclic indoles.

Key words: visible light catalysis, polycyclic indole, radical reaction, difluoroalkylation, cascade cyclization

Cite this article

Jinxiao Zhao, Tonghui Wei, Sen Ke, Yi Li. Visible Light-Catalyzed Synthesis of Difluoroalkylated Polycyclic Indoles[J]. Chinese Journal of Organic Chemistry, 2023, 43(3): 1102-1114.

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Entry	Photocatalyst	Solvent	Base	Yield^b/% of 3a
1	fac-Ir(ppy)₃	THF	Na₂HPO₄	99 (95)
2	Ir(dtbpy)(ppy)₂	THF	Na₂HPO₄	81
3	[Ru(bpy)₃]Cl₂	THF	Na₂HPO₄	N.R.
4	Eosin Y	THF	Na₂HPO₄	N.R.
5	fac-Ir(ppy)₃	DCM	Na₂HPO₄	93
6	fac-Ir(ppy)₃	Toluene	Na₂HPO₄	39
7	fac-Ir(ppy)₃	DMSO	Na₂HPO₄	N.R.
8	fac-Ir(ppy)₃	THF	K₂HPO₄	95
9	fac-Ir(ppy)₃	THF	Na₂CO₃	91
10	fac-Ir(ppy)₃	THF	DBU	87
11	None	THF	Na₂HPO₄	N.R.
12	fac-Ir(ppy)₃	THF	none	N.R.
13^c	fac-Ir(ppy)₃	THF	Na₂HPO₄	N.R.

Entry	Photocatalyst	Solvent	Base	Yield^b/% of 3a
1	fac-Ir(ppy)₃	THF	Na₂HPO₄	99 (95)
2	Ir(dtbpy)(ppy)₂	THF	Na₂HPO₄	81
3	[Ru(bpy)₃]Cl₂	THF	Na₂HPO₄	N.R.
4	Eosin Y	THF	Na₂HPO₄	N.R.
5	fac-Ir(ppy)₃	DCM	Na₂HPO₄	93
6	fac-Ir(ppy)₃	Toluene	Na₂HPO₄	39
7	fac-Ir(ppy)₃	DMSO	Na₂HPO₄	N.R.
8	fac-Ir(ppy)₃	THF	K₂HPO₄	95
9	fac-Ir(ppy)₃	THF	Na₂CO₃	91
10	fac-Ir(ppy)₃	THF	DBU	87
11	None	THF	Na₂HPO₄	N.R.
12	fac-Ir(ppy)₃	THF	none	N.R.
13^c	fac-Ir(ppy)₃	THF	Na₂HPO₄	N.R.

可见光催化合成二氟烷基取代的多环吲哚化合物