Controlling the Site Selectivity in Acylations of Amphiphilic Diols: Directing the Reaction toward the Apolar Domain in a Model Diol and the Midecamycin A Macrolide Antibiotic.

Seeking to improve the site selectivity of acylation of amphiphilic diols, which is induced by imidazole-based nucleophilic catalysts and directs the reaction toward apolar sites, as we recently reported, we examined a new improved catalytic design and an alteration of the acylating agent. The new catalysts performed slightly better selectivity-wise in the model reaction, compared to the previous set, but notably could be prepared in a much more synthetically economic way. The change of the acylating agent from anhydride to acyl chloride, particularly in combination with the new catalysts, accelerated the reaction and increased the selectivity in favor of the apolar site.

Base- and Catalyst-Induced Orthogonal Site Selectivities in Acylation of Amphiphilic Diols.

Seeking to selectively functionalize natural and synthetic amphiphiles, we explored acylation of model amphiphilic diols. The use of a nucleophilic catalyst enabled a remarkable shift of the site selectivity from the polar site, preferred in background noncatalyzed or base-promoted reactions, to the apolar site. This tendency was significantly enhanced for organocatalysts comprising an imidazole active site surrounded by long/branched tails.

Finding Lead Catalytic Systems for a Rare Version of Enantioselective Robinson Annulation: Integration of Fluorogenic Assays in Catalyst Screening.

Among the several variants of the highly useful and versatile Robinson annulation, a particular variation that involves ketones reacting with nonenolizable enones, while the α-carbons of the ketones act as nucleophiles at both steps of this cascade process, remains largely unexplored. Moreover, such a catalytic enantioselective reaction is exceptionally rare. While pursuing catalysis of this transformation, we developed two fluorogenic assays that, in combination with other analytic techniques, enabled rapid screening of several sets of catalysts.