Water vs. Organic Solvents: Water‐Controlled Divergent Reactivity of 2‐Substituted Indoles

Abstract

Water is not a good solvent for most organic compounds, yet water can offer many benefits to some organic reactions, hence enriching organic chemistry. Herein, the unique divergent reactivity of 2‐substituted indoles with •NO sources is presented. The amount of water solvent was harnessed for a scalable, benign, and expedient synthesis of indolenine oximes, albeit with water’s inability to dissolve the reactants. 2‐Methoxyethyl nitrite, which has been tailored for reactions in water, empowered this protocol by enhancing the product selectivity. We further report on chemoselective transformations of the products that rely on their structural features. Our findings are expected to offer access to an underexplored chemical space. The platform is also applicable to oximinomalonate synthesis. Mechanistic studies revealed the important role of water in the reversal of stability between oxime and nitroso compounds, promoting the proton transfer.

Direct Aromatic Nitrosation Using 2-Methoxyethyl Nitrite as a NO Cation Source

“…Building on our recent work demonstrating the efficacy of 2-methoxyethyl nitrite (MOE-ONO) as a nitrating and oximating reagent in water, we propose its use as a NO cation source for aromatic electrophilic nitrosation (Scheme d). Compared to the commonly used tert -butyl nitrite, MOE-ONO exhibits higher activity and selectivity.…”