Trybase (mL)T ( )time (min)item ( )b 3a 5a1 2 3aReaction1,2-ethanediamine (2) methylamine (two) dimethylamine (two) ammonia resolution (two)conditions: 1a (0.5 mmol), acetonitrile (3 mL), base.rt rt rt rtbIsolated30 30 30yieldsplex mixture 88 83After having the optimized conditions, we then combined the aminohalogenation as well as the therapy of benyzlamine to develop a one-pot procedure with ,-unsaturated esters as beginning supplies. Around the initial reaction step the cinnamic ester underwent a copper(II) trifluoromethanesulfonate-catalyzed aminohalogenation reaction with TsNCl2 as nitrogen source. Soon after being quenched by saturated sodium sulfite, the resulting mixture was stirred with benzylamine. Various ,-unsaturated esters have been studied to evaluate the yield and stereochemical outcome of these reactions (Table 3). As shown in Table 3, nearly all the tested substrates worked well below the optimized conditions providing rise to the corresponding ,-diamino ester items, even though the aromatic ring was substituted by powerful elec-tron-withdrawing groups (fluoro, Table 3, entries 6, 10 and 12; trifluoromethyl, entry 15) or an electron-donating group (methoxy, Table three, entry eight). Inside the case of ethyl ester, the reaction showed decrease reactivity (Table 3, entry 2), and 70 chemical yield was obtained comparing to 79 yield from methyl ester (Table three, entry 1).1025796-31-9 In stock A cinnamic ester with double-substituted aromatic ring 4m was also tolerated in this reaction along with a moderate chemical yield (53 , Table three, entry 13). Notably, when the phenyl was replaced by 1-naphthyl 4n (Table 3, entry 14), it was also well performing within this reaction giving rise to the target solution in 64 yield.5-Bromonicotinaldehyde Order For the substrates with ortho-substituents (Table 3, entries 13 and 16), the yields were a little bit bit reduced than the yields from the meta- and para-Beilstein J.PMID:23460641 Org. Chem. 2014, 10, 1802?807.Table three: One-pot reaction for the synthesis of ,-diamino ester.aentry 1 two 3 four 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 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:conditions: 1) 10 mol Cu(OTf)2, 0.five mmol cinnamic ester four, 1.0 mmol TsNCl2, 250 mg four ?molecular sieves in 3.0 mL acetonitrile at space temperature for 24 h; 2) 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 impacts the formation of the solution. In addition, fantastic stereoselectivity was obtained for all the examined cinnamic ester substrates, and only the anti-isomers had been observed. To decide the structure of item 5, single crystals were prepared. Luckily, the crystals of product 5o had a superb crystallinity and have been appropriate for single crystal X-ray evaluation (Figure 1). Crystallographic analysis has revealed that the antivicinal diamino ester was obtained. As a result, the stereochemistry of the other solutions was assigned (anti-isomer) depending on the similarity of their properties. Finally, some reactions have been moreover performed to gain insight into the reaction mechanism. 1st, we prepared the aziridi.