For the synthesis of ,-diamino ester.aentry 1 2 three four five six 7 8 9 ten 11 12 13 14 15aReactionAr C6H5 C
For the synthesis of ,-diamino ester.aentry 1 two three four 5 6 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 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)2, 0.five mmol cinnamic ester four, 1.0 mmol TsNCl2, 250 mg 4 molecular sieves in 3.0 mL acetonitrile at space LPAR1 supplier temperature for 24 h; two) Quenched by 3 mL saturated Na2SO3 for 30 min; 3) Benzylamine two.0 mL at area temperature for 1 h. bIsolated yield. cDetermined by 1H NMR.substituted substrates, which indicates that the steric hindrance affects the formation from the item. Moreover, outstanding stereoselectivity was obtained for all of the examined cinnamic ester substrates, and only the anti-isomers have been observed. To decide the structure of solution five, single crystals had been prepared. Thankfully, the crystals of item 5o had an excellent crystallinity and had been appropriate for single crystal X-ray evaluation (Figure 1). Crystallographic evaluation has revealed that the antivicinal diamino ester was obtained. As a result, the stereochemistry from the other merchandise was assigned (anti-isomer) determined by the similarity of their properties. Finally, some reactions have been additionally carried out to gain insight in to the reaction mechanism. 1st, we ready the aziridine 6 based on the reported system with cinnamic ethyl ester as beginning material [33]. Then, we used the aziridine six as beginning material to react with benzylamine under similar reaction conditions on 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. Thus, aziridine probably may be the HSP90 web intermediate within this reaction.Figure 1: ORTEP diagram of compound 5o.Based on the above benefits, 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 is definitely 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. In addition, this reaction offers practically total stereochemical outcomes, and only the anti-isomer is identified for all the circumstances, which offers a simple access to ,-diamino acid derivatives.Scheme three: Ring-opening of aziridine six.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 (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 resolution in the capped vial was stirred at area temperature for 24 h devoid of argon protection. The reaction was ultimately quenched by dropwise addition of saturated aqueous Na2SO3 solution (three.0 mL). Immediately after quench for 30 min, benzylamine (two.0 mL) was added to the mixture exposed to air. A further 1 hour was required till conversion was total. Then the phases have been separated, as well as the aqueous phase was extracted with ethyl a.
