Synthesis of (2-Nitro-1-AfAlemphenylethyl)malononitriles by Michael Addition of Masked Acyl Cyanides to Nitroalkenes

Haoyi Sun; Yongcheng Guo; Huajie Li; Meiling Wang; Tiandi Ding; Ying Zhi; Kun Zhao; Qingqiang Yao

doi:10.1055/s-0041-1738437

Synlett, Table of Contents

Synlett 2023; 34(20): 2396-2400
DOI: 10.1055/s-0041-1738437

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Special Issue Dedicated to Prof. Hisashi Yamamoto

Synthesis of (2-Nitro-1-AfAlemphenylethyl)malononitriles by Michael Addition of Masked Acyl Cyanides to Nitroalkenes

Haoyi Sun‡

^aSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, P. R. of China

,

Yongcheng Guo‡

^aSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, P. R. of China

,

Huajie Li

^aSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, P. R. of China

,

Meiling Wang

^aSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, P. R. of China

,

Tiandi Ding

^aSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, P. R. of China

,

Ying Zhi ∗

^aSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, P. R. of China

,

Kun Zhao∗

^bKey Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, P. R. of China

,

Qingqiang Yao∗

^aSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, P. R. of China

› Author Affiliations

Abstract

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Abstract

A highly efficient method has been developed for the synthesis of (2-nitro-1-phenylethyl)malononitriles through a Michael addition reaction between substituted nitroolefins and masked acyl cyanide reagents, serving as carbon monoxide equivalents. Under mild conditions, the reaction took place with excellent yields (90–98%), providing a short entry into a series of the title compounds in a scalable fashion. An asymmetric version of this reaction has also been briefly explored.

Key words

Umpolung - masked acyl cyanides - nitroalkenes - Michael addition reaction - malononitriles - asymmetric catalysis

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References

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7 (2-Nitro-1-phenylethyl)malononitriles 3a–p; General Procedure A 10 mL glass tube equipped with a stirrer bar was charged with 1 (0.5 mmol, 1.0 equiv), 2 (75.7 mg, 0.6 mmol, 1.2 equiv), and DCM (2.5 mL). Catalyst A (0.1 mmol, 10 mol%) was added, and the mixture was stirred at r.t. for 12 h, then directly purified by column chromatography (silica gel). (Methoxymethyl)(2-nitro-1-phenylethyl)malononitrile (3a) White solid; yield: 135 mg (98%); mp154–156 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.48–7.39 (m, 5 H), 5.09 (dd, J = 13.2, 8.8 Hz, 1 H), 5.06 (s, 2 H,), 4.95 (dd, J = 13.2, 5.6 Hz, 1 H), 4.31 (dd, J = 8.8, 5.6 Hz, 1 H), 3.50 (d, J = 1.0 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 130.4, 130.0, 129.5 (2 C), 129.3 (2 C), 111.6, 111.2, 96.9, 74.2, 68.6, 57.7, 51.5. ESI-HRMS: m/z [M + H]⁺ calcd for C₁₃H₁₄N₃O₄: 276.0984; found: 276.0980.
8 CCDC 2205805 contains the supplementary crystallographic data for compound 3a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures

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