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

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

Publication History

Received: 14 February 2023

Accepted after revision: 12 April 2023

Article published online:
08 May 2023

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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.
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