Experimental and Computational Studies on Regiodivergent Chiral Phosphoric Acid Catalyzed Cycloisomerization of Mupirocin Methyl Ester.

This article presents a new strategy for achieving regiocontrol over the endo- vs. exo- modes of cycloisomerizations of epoxide-containing alcohols that lead to the formation of 5- or 6-membered cyclic ethers. Unlike traditional methods relying on achiral reagents or enzymes, our approach utilizes chiral phosphoric acids to catalyze the regiodivergent selective formations of either tetrahydrofuran- or tetrahydropyran-containing products. Using methyl ester of epoxide-containing antibiotic mupirocin as the substrate, we demonstrate that catalytic chiral phosphoric acids ( R )-TCYP and ( S )-TIPSY could be used to achieve the selective formation of either the 6-membered endo -product (95:5 r.r.) or the 5-membered exo -product (77:23 r.r.), correspondingly. This cyclization was found to be unselective under the standard conditions involving various achiral acids, bases or buffers. The subsequent mechanistic studies using state-of-the-art quantum chemical solutions provided the description of the potential energy surface that is fully consistent with the experimental observations. Based on these results, we obtained highly detailed reaction paths and propose a concerted and highly synchronous mechanism for the formation of both exo- and endo- products.
PMID: 31905253 [PubMed - as supplied by publisher]

Source: Chemistry - January 5, 2020 Category: Chemistry Authors: Wang S, Arguelles AJ, Tay JH, Hotta M, Zimmerman PM, Nagorny P Tags: Chemistry Source Type: research