Divergent synthesis of N-heterocycles via controllable cyclization of azido-diynes catalyzed by copper and gold

Wen-Bo Shen,Long-Wu Ye,Bo Zhou,Long Li,Qing Sun,Juan-Zhu Yan,Xin Lu,Xin Liu

doi:10.1038/s41467-017-01853-1

Abstract

Gold-catalyzed intermolecular alkyne oxidation by an N–O bond oxidant has proven to be a powerful method in organic synthesis during the past decade, because this approach would enable readily available alkynes as precursors in generating α-oxo gold carbenes. Among those, gold-catalyzed oxidative cyclization of dialkynes has received particular attention as this chemistry offers great potential to build structurally complex cyclic molecules. However, these alkyne oxidations have been mostly limited to noble metal catalysts, and, to our knowledge, non-noble metal-catalyzed reactions such as diyne oxidations have not been reported. Herein, we disclose a copper-catalyzed oxidative diyne cyclization, allowing the facile synthesis of a wide range of valuable pyrrolo[3,4-c]quinolin-1-ones. Interestingly, by employing the same starting materials, the gold-catalyzed cascade cyclization leads to the divergent formation of synthetically useful pyrrolo[2,3-b]indoles. Furthermore, the proposed mechanistic rationale for these cascade reactions is strongly supported by both control experiments and theoretical calculations.

Highlights

Gold-catalyzed intermolecular alkyne oxidation by an N–O bond oxidant has proven to be a powerful method in organic synthesis during the past decade, because this approach would enable readily available alkynes as precursors in generating α-oxo gold carbenes
AReaction conditions: the reaction was performed with 1a (0.1 mmol), 4 (0.15 mmol), and catalyst (2–10 mol%) in DCE (2 mL) at 25−80 °C in vials bMeasured by 1H NMR using diethyl phthalate as the internal standard c2 h dIn CH3NO2, 5 min eIn CH3NO2, 30 min diazo carbonyls as precursors in generating α-oxo metal carbenes[18,19,20,21,22,23,24,25,26,27,28,29,30]
These alkyne oxidations have been mostly limited to noble metal catalysts, and, to our knowledge, non-noble metal-catalyzed such as diyne oxidation has not been reported

Summary

Introduction

Gold-catalyzed intermolecular alkyne oxidation by an N–O bond oxidant has proven to be a powerful method in organic synthesis during the past decade, because this approach would enable readily available alkynes as precursors in generating α-oxo gold carbenes. Gold-catalyzed oxidative cyclization of dialkynes has received particular attention as this chemistry offers great potential to build structurally complex cyclic molecules These alkyne oxidations have been mostly limited to noble metal catalysts, and, to our knowledge, non-noble metal-catalyzed reactions such as diyne oxidations have not been reported. Notable is that haloalkynes are typically required for this strategy Such a goldcatalyzed oxidative diyne cyclization has been well exploited in the synthesis of various functionalized O-heterocycles by Zheng and Zhang[33] and Ji et al.[34] In addition, Tang et al disclosed that rhodium could catalyze this type of diyne oxidation (Fig. 2b)[35]. The mechanistic rationale for these cascade reactions, in particular accounting for the distinct selectivity, is well supported by density functional theory (DFT) calculations

Methods

Results

Conclusion