Asymmetric Epoxidation of 1,4-Naphthoquinones Catalyzed by Guanidine–Urea Bifunctional Organocatalyst

Abstract

An enantioselective nucleophilic epoxidation of 2-substituted 1,4-naphthoquinones in the presence of a newly developed guanidine-bisurea bifunctional organocatalyst with tert-butyl hydroperoxide (TBHP) as an oxidant is presented. 1,4-Naphthoquinones bearing substituents at C6, C7, and C2 were available for the reaction, and the corresponding epoxides were obtained with 88:12-95:5 er in 71-98% yields. DFT calculations indicated that substituents at C2 and C6 in the terminal Ar group of the catalyst 9k play a key role in controlling the stereochemical outcome.

Enantioselective Epoxidation of 2,3-Disubstituted Naphthoquinones by a Side Chain Truncated Guanidine–Urea Bifunctional Organocatalyst

“…In the epoxidation catalyzed by 9, the epoxide-forming step, i.e., cyclization step, is the reaction rate-and stereochemistry-determining step, based upon our preliminary calculation. 7 Thus, we explored two diastereomeric TS structures for the cyclization step (Si- face (TS major ) and Re-face (TS minor ) modes leading to the major and minor enantiomers of 8a, respectively) at the B3LYP/6-31G* level in the presence of a simplified catalyst model of 9. To estimate dispersion interactions, single-point energy calculations of the B3LYP-optimized structures were conducted at the M06-2X/6−311 + G** level.…”

An Overview of Saturated Cyclic Ethers: Biological Profiles and Synthetic Strategies

“…Nevertheless, it is difficult to apply AE on quinones because of their highly symmetric and planar structures with two carbonyl groups; therefore, differentiating the si - and re -faces of the olefins with chiral oxidants or catalysts is challenging. Kawaguchi et al [56] developed an asymmetric epoxidation of 1,4-naphthoquinones catalyzed by guanidine−urea bifunctional organocatalysts with TBHP as an oxidant, resulting in the desired epoxides with 85:15−95:5 er in 71%−98% yields (Scheme 5).…”

Recent Advances in Chiral Guanidine‐Catalyzed Enantioselective Reactions

“…They werea pplied to the asymmetric epoxidation of 1,4-naphthoquinones (Scheme 55). [73] Substrates with either methoxy-or chloro-substituents at C-6o rC-7 positions underwent epoxidation efficiently to afford epoxides in 71-97 %y ield with er highert han 91:9.A sf or the epoxidation of compounds with nPr, iBu, iPr,B n, 4-MeBn, and 4-ClBn groups at C-2, epoxidesw ere synthesized with 76-90 % ee values in 71-98 %y ield.…”

“…Bifunctional guanidine-urea catalysts 28 developedbyt he Nagasawa group. [73] Scheme55. Asymmetric epoxidationo f1,4-naphthoquinones catalyzed by guanidine-ureab ifunctional catalysts 28 k.…”

“…Recently, Nagasawa and co‐workers reported a series of guanidine‐urea bifunctional catalysts 28 (Figure ), which were derivatives of their previously‐designed guanidine‐thiourea catalysts. They were applied to the asymmetric epoxidation of 1,4‐naphthoquinones (Scheme ) …”