I2 -Catalyzed Cycloisomerization of Ynamides: Chemoselective and Divergent Access to Indole Derivatives

Bo-Han Zhu; Sheng-Bing Ye; Min-Ling Nie; Zhong-Yang Xie; Yi-Bo Wang; Peng-Cheng Qian; Qing Sun; Long-Wu Ye; Long Li

doi:10.1002/anie.202215616

I₂ -Catalyzed Cycloisomerization of Ynamides: Chemoselective and Divergent Access to Indole Derivatives

Angew Chem Int Ed Engl. 2023 Feb 13;62(8):e202215616. doi: 10.1002/anie.202215616. Epub 2023 Jan 16.

Authors

Bo-Han Zhu^{1

2}, Sheng-Bing Ye^{1

2}, Min-Ling Nie^{1

2}, Zhong-Yang Xie^{1

2}, Yi-Bo Wang^{1

2}, Peng-Cheng Qian^{1

2}, Qing Sun³, Long-Wu Ye⁴, Long Li^{1

2

4}

Affiliations

¹ College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou, 325035, China.
² Wenzhou Key Laboratory of Technology and Application of Environmental Functional Materials, Institute of New Materials & Industry Technology, Wenzhou University, Wenzhou, 325000, China.
³ Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle, Nanchang Hangkong University, Nanchang, 330063, China.
⁴ State Key Laboratory of Physical Chemistry of Solid Surfaces and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.

PMID: 36573021
DOI: 10.1002/anie.202215616

Abstract

Herein, an I₂ -catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom-economy. This protocol not only represents the first molecular-iodine-catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine-ynamides involving distinctively different C(sp³ )-C(sp³ ) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I₂ . Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5-exo-dig cyclization/rearrangement process.

Keywords: Alkynes; Cycloisomerization; Heterocycles; Iodine; Rearrangement.

Abstract

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