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Mander’s Reagent for the Deoxycyanation of β-Diketones: A Direct Synthesis of OxoalkenenitrilesThis work was supported by Fondo SEP-Cinvestav 2018 (069). We also thank Conacyt for a Ciencia de Frontera 2019 grant (51493).
In the memory of Prof. Lewis N. Mander
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.
Received: 24 February 2022
Accepted after revision: 26 March 2022
Accepted Manuscript online:
26 March 2022
Article published online:
29 April 2022
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References and Notes
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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.
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: