Mander’s Reagent for the Deoxycyanation of β-Diketones: A Direct Synthesis of Oxoalkenenitriles

In the memory of Prof. Lewis N. Mander

Abstract

Ethyl cyanoformate and methyl cyanoformate (Mander’s reagent) are both routinely used to perform C-selective ketone alkoxycarbonylations. Interestingly, both reagents were found to yield oxoalkenenitriles through an unprecedented deoxycyanation of 1,3-dicarbonyl compounds (e.g., 2-methylcyclohexane-1,3-dione). Although this method is not general, this is the first time that both Mander’s reagent and ethyl cyanoformate have been used for the deoxycyanation of 1,3-dicarbonyl compounds for the preparation of synthetically useful oxoalkenenitriles. Limitations on the substrate scope of the present method are discussed.

Key words

Mander’s reagent - alkyl cyanoformates - deoxycyanation - oxoalkenenitriles - β-diketones

Publication History

Received: 24 February 2022

Accepted after revision: 26 March 2022

Accepted Manuscript online:
26 March 2022

Article published online:
29 April 2022

• References and Notes

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The C-carboxymethylation of ketones is the main application of Mander’s reagent; apart from the formation of carbonated cyanohydrins (see ref. 2), there are few methods in which cyanoformates are used as a cyanation reagents, see:
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• 27 Also, 8b1 and 8b2 were revealed to be plausible intermediates: after exposing 8b1 to Mander’s reagent for 2 h, a mixture of 37% of the oxonitrilic product 4b and ~40% of recovered 8b1 was detected.
• 28 After stirring for 2 h, a ~1:1 mixture of Et₃N and ethyl cyanoformate remained virtually unchanged. On the other hand, stirring a 1:3 mixture of Et₃N and Mander’s reagent for 1 h gave a 50% yield of acylated Et₃N; see ref. 23.
• 29 Unfortunately, attempts to prepare cyclic oxonitrile 4g by using the carbonate derivative methyl (3-oxocyclopent-1-en-1-yl) carbonate were also unfruitful (see SI).
• 30 The C-carboxymethyl product would be expected to form under thermodynamic conditions if access to carbonate 8b and oxonitrile 4b is kinetically hampered.
• 31 2-Methyl-3-oxocyclohex-1-ene-carbonitrile (4a); Typical Procedure In a Schlenk flask, Et₃N (1 equiv) was added dropwise to a solution of 2a (1 equiv) in anhyd CH₂Cl₂ (0.1 M), and the mixture was stirred for 10 min at rt. Ethyl cyanoformate (3 equiv) was added in one portion, and the resulting mixture was stirred for 6 h at rt. The mixture was then diluted with H₂O and extracted with CH₂Cl₂ (3×). The organic layer was washed with distilled water, dried (Na₂SO₄), and concentrated by vacuum distillation at rt. The resulting oil was distilled in a Kugelrohr apparatus to give a colorless oil; yield: 48%. ¹H NMR (500 MHz, CDCl₃): δ = 2.05–2.12 (m, 5 H) 2.51–2.59 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 15.2, 22.4, 28.3, 37.8, 117.1, 125.5, 146.7, 196.8.