Catalytic Asymmetric Epoxidation of α,β-Unsaturated Amides:  Efficient Synthesis of β-Aryl α-Hydroxy Amides Using a One-Pot Tandem Catalytic Asymmetric Epoxidation−Pd-Catalyzed Epoxide Opening Process

Abstract

The catalytic asymmetric epoxidation of alpha,beta-unsaturated amides using Sm-BINOL-Ph3As=O complex was succeeded. Using 5-10 mol % of the asymmetric catalyst, a variety of amides were epoxidized efficiently, yielding the corresponding alpha,beta-epoxy amides in up to 99% yield and in more than 99% ee. Moreover, the novel one-pot tandem process, one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process, was developed. This method was successfully utilized for the efficient synthesis of beta-aryl alpha-hydroxy amides, including beta-aryllactyl-leucine methyl esters. Interestingly, it was found that beneficial modifications on the Pd catalyst were achieved by the constituents of the first epoxidation, producing a more suitable catalyst for the Pd-catalyzed epoxide opening reaction in terms of chemoselectivity.

Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: Application of catalytic asymmetric phase-transfer reaction

“…Thus, we planned to use this PTC to synthesize the three of four ␣-amino acid portions (Leu, Choi, and Argol portions) of 1a and its analogs. For the synthesis of the Hpla portion and the following coupling reaction with the Leu portion, we chose a strategy based on the catalytic asymmetric epoxidation of an ␣,␤-unsaturated imidazolide (18,19,22) and the subsequent one-pot process including a peptide coupling reaction of the corresponding ␣,␤-epoxy peroxyester and ␤-selective epoxide opening reaction (20,22).…”

“…34 and 35). We recently reported the catalytic asymmetric epoxidation of ␣,␤-unsaturated imidazolides by the LaOBINOLOPh 3 AsAO (1:1:1) complex 19 or LaOBINOLOPh 3 PAO (1:1:3) complex 20 and efficient transformations of the corresponding epoxidation products (18)(19)(20)22). This is the first example of a general catalytic asymmetric epoxidation of ␣,␤-unsaturated carboxylic acid derivatives.…”

“…In fact, a coupling reaction of the D-Hpla portion and the D-Leu portion was accomplished just by mixing 5 and 7a in THF without any reagent (15). After completion of the coupling reaction, the crude dipeptide was directly treated with a catalytic amount of palladium on charcoal under hydrogen atmosphere to give the desired left dipeptide: D-Hpla-D-Leu portion 21a in very high yield as a mixture of diastereomers (97%, two steps, 11:1) (20,22). Diastereomers were separated by flash column chromatography at this stage.…”

“…To address this issue, we applied asymmetric phase-transfer catalysis (PTC) promoted by two-center catalysts, which were recently developed by our group (14), to the syntheses of 1a as well as its analogs. Here, we report the enantioselective syntheses of aeruginosin 298-A and its analogs (15) by using asymmetric PTC and the catalytic asymmetric epoxidation of an ␣,␤-unsaturated imidazolide, which was also recently developed by our group (16)(17)(18)(19)(20)(21)(22). Moreover, serine protease inhibitory activities of 1a and its analogs were examined, leading to the future discovery of analogs possessing higher and more selective protease inhibitor potencies than those of the natural products.…”

Enantioselective Total Syntheses of Several Bioactive Natural Products Based on the Development of Practical Asymmetric Catalysis

“…Catalytic Asymmetric Epoxidation of a a,b b-Unsaturated Simple Amides: Enantioselective Syntheses of Several 1,3-Polyol Natural Products [145][146][147] Chiral a,b-epoxy amides are very important compounds because they can be converted into useful chiral building blocks such as a-and b-hydroxy amides. Many chiral a,b-epoxy amides can be synthesized from the corresponding a,b-epoxy peroxy esters (Chart 7).…”