Synthesis Of α-Carbolines Via Metal-Free[2+2+2] Cycloaddition Of Ynamides

Due to their combined stability and peculiar reactivity,ynamides have emerged as remarkably useful building blocks for organic chemical synthesis.The lone pair of electrons on the nitrogen atom in ynamide produces a conjugation effect with the electrons on the alkynyl group,causing a difference in the electrical properties of the α-and β-carbons on the alkynyl group,so when ynamides participate in a reaction,its regioselectivity is higher.In this paper,we will introduce a method for the synthesis of α-carbolines by TMSOTf-catalyzed [2 + 2 + 2] cycloaddition reaction of alkyne-cyanamides with ynamides.Carbolines composed of indole and pyridine ring are widely found in nature products and pharmaceuticals.This two ring systems has proven to be privileged pharmacophores for use in the design of compounds with wide ranging pharmacological properties such as antibacterial,antitumor,anxiolytic,anti-inflammatory,central nervous system stimulating,and kinase inhibitory properties.However,conventional methods for synthesizing α-carbolines usually suffer from serious disadvantages such as harsh reaction conditions,tedious procedures,and low yields.Therefore,it is of great significance to explore methods for synthesizing α-carbolines,especially for the efficient synthesis of amino-substituted α-carbolines.After research,we have found that a metal-free [2 + 2 + 2] cycloaddition of alkyne-cyanamides with ynamides is disclosed for the efficient synthesis of amino-substituted α-carbolines.This strategy provides a straightforward way to furnish 2-amino-α-carbolines in high to excellent yields with wide diversity and functional group tolerance.More importantly,this method first realized the synthesis of 2-amino-α-carbolines via cycloaddition of alkyne-cyanamides with ynamides with excellent selectivities.