For the synthesis of ,-diamino ester.aentry 1 2 3 4 5 six 7 8 9 ten 11 12 13 14 15aReactionAr C6H5 C
For the synthesis of ,-diamino ester.aentry 1 two 3 4 5 six 7 eight 9 ten 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 two,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 ADAM8 Formulation 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:situations: 1) ten mol Cu(OTf)2, 0.five mmol cinnamic ester 4, 1.0 mmol TsNCl2, 250 mg 4 molecular sieves in 3.0 mL acetonitrile at area temperature for 24 h; two) Quenched by three mL saturated Na2SO3 for 30 min; three) Benzylamine 2.0 mL at space temperature for 1 h. bIsolated yield. cDetermined by 1H NMR.substituted substrates, which indicates that the steric hindrance affects the formation of the solution. In addition, excellent stereoselectivity was obtained for all the examined cinnamic ester substrates, and only the anti-isomers have been observed. To determine the structure of product five, single crystals have been ready. Luckily, the crystals of solution 5o had an excellent crystallinity and were appropriate 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. Ultimately, some reactions have been additionally conducted to obtain insight in to the reaction mechanism. Initial, we prepared the aziridine 6 based on the reported system with cinnamic ethyl ester as beginning material [33]. Then, we employed the aziridine 6 as starting material to react with benzylamine beneath equivalent reaction conditions from the third step of this one-pot reaction (Scheme three). To our delight, aziridine 6 was converted into the corresponding diamino acid ester 5b with 73 chemical yield. Hence, aziridine most likely could possibly be the intermediate in this reaction.Figure 1: ORTEP diagram of compound 5o.Based on the above results, a proposed reaction mechanism for this one-pot reaction is illustrated in Scheme 4, which consists of the sequence of aminochlorination, aziridination and followed by the S N two nucleophilic ring-opening. The initial step would 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 merchandise in good-to-excellent chemical yields. Furthermore, this reaction gives virtually complete stereochemical CK2 supplier outcomes, and only the anti-isomer is identified for each of the circumstances, which offers 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 4 (0.50 mmol) and freshly distilled acetonitrile (3.0 mL). The reaction vial was loaded with freshly activated 4 molecular sieves (250 mg), TsNCl2 (1.0 mmol) and Cu(OTf)two (10 mol ). The resolution inside the capped vial was stirred at room temperature for 24 h without having argon protection. The reaction was lastly quenched by dropwise addition of saturated aqueous Na2SO3 solution (three.0 mL). After quench for 30 min, benzylamine (two.0 mL) was added for the mixture exposed to air. Yet another one particular hour was needed until conversion was total. Then the phases were separated, as well as the aqueous phase was extracted with ethyl a.