For the synthesis of ,-diamino ester.aentry 1 2 3 four 5 6 7 8 9 ten 11 12 13 14 15aReactionAr C6H5 C
For the synthesis of ,-diamino ester.aentry 1 two 3 4 five 6 7 eight 9 10 11 12 13 14 15aReactionAr C6H5 C6H5 4-CH3-C6H4 4-Br-C6H4 4-Cl-C6H4 4-F-C6H4 4-CF3O-C6H4 3-CH3O-C6H4 3-Cl-C6H4 3-F-C6H4 2-Cl-C6H4 2-F-C6H4 2,6-di-Cl-C6H3 1-naphthyl 3-CF3-C6H4 2-Br-C6HR Me Et Me Me Me Me Me Me Me Me Me Me Me Me Me Meproduct 5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k 5l 5m 5n 5o 5pyield ( )b 79 70 67 72 68 78 80 70 67 75 63 83 53 64 74anti:syn c 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:circumstances: 1) ten mol Cu(OTf)two, 0.5 mmol cinnamic ester 4, 1.0 mmol TsNCl2, 250 mg 4 molecular sieves in three.0 mL acetonitrile at room temperature for 24 h; 2) Quenched by three mL saturated Na2SO3 for 30 min; 3) Benzylamine 2.0 mL at area temperature for 1 h. bIsolated yield. cDetermined by 1H NMR.substituted substrates, which indicates that the steric hindrance impacts the formation with the solution. In addition, great stereoselectivity was obtained for all the examined cinnamic ester substrates, and only the anti-isomers had been observed. To establish the structure of product 5, single crystals were ready. Thankfully, the crystals of solution 5o had a superb crystallinity and were suitable for single crystal X-ray analysis (Figure 1). Crystallographic evaluation has revealed that the antivicinal diamino ester was obtained. Consequently, the stereochemistry on the other products was assigned (anti-isomer) depending on the similarity of their properties. Lastly, some reactions have been additionally performed to achieve insight in to the CXCR3 Species reaction mechanism. Initial, we ready the aziridine 6 based on the reported system with cinnamic ethyl ester as starting material [33]. Then, we applied the aziridine 6 as beginning material to react with benzylamine under equivalent reaction situations on the third step of this one-pot reaction (Scheme three). To our delight, aziridine six was converted into the corresponding diamino acid ester 5b with 73 chemical yield. As a result, aziridine most likely might be the intermediate in this reaction.Figure 1: ORTEP diagram of compound 5o.According to the above final results, a proposed reaction mechanism for this one-pot reaction is illustrated in Scheme four, which contains the sequence of aminochlorination, aziridination and followed by the S N 2 nucleophilic ring-opening. The first step could be the Cu-catalyzed aminochlorination reaction of methyl cinnamate 1a resulting in anti-chloroamine intermediate A. The secondBeilstein J. Org. Chem. 2014, ten, 1802807.affording the target products in good-to-excellent chemical yields. Furthermore, this reaction offers virtually total stereochemical outcomes, and only the LTC4 Source anti-isomer is discovered for all the situations, which provides an easy access to ,-diamino acid derivatives.Scheme 3: Ring-opening of aziridine 6.ExperimentalGeneral process for the one-pot synthesis of ,-diamino esters: Into a dry vial was added cinnamic ester four (0.50 mmol) and freshly distilled acetonitrile (three.0 mL). The reaction vial was loaded with freshly activated 4 molecular sieves (250 mg), TsNCl2 (1.0 mmol) and Cu(OTf)two (ten mol ). The option in the capped vial was stirred at room temperature for 24 h without the need of argon protection. The reaction was lastly quenched by dropwise addition of saturated aqueous Na2SO3 resolution (three.0 mL). Following quench for 30 min, benzylamine (two.0 mL) was added for the mixture exposed to air. Yet another one particular hour was necessary until conversion was complete. Then the phases have been separated, and the aqueous phase was extracted with ethyl a.