Outcomes, a proposed reaction mechanism for this one-pot reaction is illustrated in Scheme four, which

Outcomes, a proposed reaction mechanism for this one-pot reaction is illustrated in Scheme four, which includes the sequence of aminochlorination, aziridination and followed by the S N two nucleophilic ring-opening. The initial step will be the Cu-catalyzed β-lactam Chemical drug aminochlorination reaction of methyl cinnamate 1a resulting in anti-chloroamine intermediate A. The secondBeilstein J. Org. Chem. 2014, 10, 1802807.affording the target merchandise in good-to-excellent chemical yields. Additionally, this reaction offers virtually complete stereochemical outcomes, and only the anti-isomer is identified for each of the circumstances, which supplies an easy access to ,-diamino acid derivatives.Scheme 3: 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 (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 solution in the capped vial was stirred at area temperature for 24 h without having argon protection. The reaction was finally quenched by dropwise addition of saturated aqueous Na2SO3 answer (3.0 mL). Soon after quench for 30 min, benzylamine (2.0 mL) was added for the mixture exposed to air. Yet another one particular hour was necessary till conversion was total. Then the phases have been separated, as well as the aqueous phase was extracted with ethyl acetate (3 ten mL). The combined organic layers have been washed with brine, dried more than anhydrous sodium sulfate, and concentrated to SIRT2 Activator Purity & Documentation dryness. Purification by flash chromatography (EtOAc/hexane, from 1:20 to 1:three, v/v) provided final products five.step includes a typical intramolecular SN2 substitution reaction of intermediate A with all the aid of benzylamine, to provide the aziridine intermediate B. The intermediate B undergoes a S N 2 nucleophilic procedure attacked by benzylamine, major towards the formation on the final item 5a. The great stereoselectivity and formation of only anti-isomer is often explained by the formation of aziridine intermediate and complete geometry manage of the following SN2 nucleophilic attack. The formation of the unexpected diamino ester, instead of aziridine, might be because of the relative robust nucleophilicity of benzylamine. Considering the fact that the final product 5a is anti as well as the aminohalogenation item intermediate A can also be anti, the only method to clarify the stereochemistry of solution 5 will be the double inversion via aziridine formation. The direct substitution on the Cl atom is doable, nevertheless it will cause the syn solution five. As a result we think that the interpretation from the observed stereochemical outcome need to involve the intermediate aziridine formation.Supporting InformationSupporting Details FileExperimental information and spectral information. [http://beilstein-journals.org/bjoc/content/ supplementary/1860-5397-10-189-S1.pdf]ConclusionIn conclusion, a brand new one-pot system for the synthesis of ,differentiated diamino esters directly from ,-unsaturated esters has been developed. The reaction sequence consists of copper-catalyzed aminochlorination, aziridination and S N 2 nucleophilic ring-opening reaction. This one-pot reaction is operationally practical and may tolerate a variety of substratesAcknowledgementsWe gratefully acknowledge the monetary help in the National Natural Science Foundation of China (No. 21102071)Scheme four: Proposed mechanism.Beilstein J. Org. Chem. 2014, ten, 1802807.along with the Fundamental Investigation Funds.