Highly Enantioselective Organocatalytic aza-Henry Reaction of Nitroalkanes to N-Boc Isatin Ketimines

doi:10.6023/A14040335

Abstract

We report a highly enantioselective aza-Henry reaction of nitroalkanes with N-Boc isatin ketimines 1. A cinchona alkaloid derived bifunctional catalyst C5, featuring a C6 hydroxy group, is identified as a powerful catalyst for this reaction. Accordingly, under an atmosphere of nitrogen, to a 10 mL Schlenk tube are added C5 (0.03 mmol, 14.6 mg), MS5Å (120 mg), nitromethane (4.5 mmol, 244 μL) and 3.0 mL of toluene successively, followed by the addition of N-Boc isatin ketimine 1 (0.3 mmol). The resulting mixture is stirred at 20 ℃ till the full consumption of the ketimine, monitored by TLC analysis. After the solvent is removed under reduced pressure, the residue is directly subjected to column chromatography, using an eluent of dichloromethane and acetone (10:1, V/V), to afford the desired product 3. Under this condition, a variety of differently substituted N-Boc isatin ketimines work well with MeNO₂ to provide the Mannich adduct in up to 91% ee. A 1.0 mmol scale reaction of 1a and MeNO₂ is examined, giving adduct 3a in 87% yield and 90% ee. Unfortunately, unprotected isatin derived N-Boc isatin ketimine 1j provides the corresponding product in only 66% ee, suggesting the importance of the N-protecting group of isatin in securing high enantioselectivity. Nitroethane and nitropropane are also viable for this reaction, affording the corresponding products in high yield and excellent ee value, albeit with moderate diastereoselectivity.

Key words: organocatalysis, aza-Henry reaction, isatin ketimine, nitroalkane, quaternary aminooxindoles

Cite this article

Wang Yuhui, Cao Zhongyan, Niu Yanfei, Zhao Xiaoli, Zhou Jian. Highly Enantioselective Organocatalytic aza-Henry Reaction of Nitroalkanes to N-Boc Isatin Ketimines[J]. Acta Chimica Sinica, 2014, 72(7): 867-872.

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高对映选择性的有机催化的硝基烷烃对N-Boc靛红亚胺的不对称aza-Henry反应