Surfactant Micelles Enable Metal‐Free Spirocyclization of Keto‐Ynamides and Access to Aza‐Spiro Scaffolds in Aqueous Media

Abstract

Micellar solutions of cetyltrimethylammonium bromide (CTAB) surfactant allow the spirocyclization of keto‐ynamides in an aqueous medium without recourse to transition‐metal catalysis, enabling access in water to naturally occurring aza‐spiro compounds with potential in drug discovery. The reaction was monitored by dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo‐TEM), which determined the morphology and change in size of the micelles before and after incorporation of the substrate and achievement of 5‐endo‐dig cyclization inside the micelles.

Surfactants Accelerate Isotope Exchange-Based 18F-Fluorination in Water

“…With or without the addition of the liposoluble substrate 1 (10 mmol/L), the micelles formed by the selected surfactants (30 mmol/L in water) were well dispersed with particle sizes less than 30 nm (Figure , determined by DLS and observed by cryo-TEM) . The sizes of the micelles formed in the presence of the substrate were overall larger than those formed in the absence of the substrate.…”

Micellar Mechanisms for Desymmetrization Reactions in Aqueous Media

“…Reactions mediated by micelle or micellar substances have been sometimes reported in the aqueous media as environmentally benign reactions. Classical examples include selective monohydroxymerculation of dienes in the presence of surfactants such as sodium lauryl sulfate (SLS), and more recently, several studies about reactions with the use of surfactants combined with Lewis acid, iodine, and other metals have been reported. − They are found to accelerate the reaction rates or promote the selectivities in water solvent due to the amphiphilic nature. However, in this selective monohydrolysis reaction, the reaction intermediate from the starting material itself forms micellar aggregates and governs the selectivity without requiring a special additive under environmentally benign conditions.…”

Cascade Processes with Micellar Reaction Media: Recent Advances and Future Directions

“…After 48 h at 30 °C, 100% conversion of the substrate was observed. The desired reaction mixture contained the spiro ester and spiro acid; the desired E isomer of the spiro ester was recovered with a 75% yield [ 37 ].…”