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Synlett 2020; 31(13): 1273-1276
DOI: 10.1055/s-0040-1707811
DOI: 10.1055/s-0040-1707811
letter
Dialkyl Diazomalonates in Transition-Metal-Free, Thermally Promoted, Diastereoselective Wolff β-Lactam Synthesis
This research was supported by the Russian Foundation for Basic Research (Grant No. 20-03-00922).Further Information
Publication History
Received: 03 April 2020
Accepted after revision: 04 May 2020
Publication Date:
19 May 2020 (online)
![](https://www.thieme-connect.de/media/synlett/202013/lookinside/thumbnails/st-2020-b0190-l_10-1055_s-0040-1707811-1.jpg)
Abstract
Metal-free, thermally promoted synthesis of 3-alkoxy-3-alkoxycarbonyl-2-azetidinones via the Wolff-Staudinger β-lactam synthesis using dialkyl diazomalonates is described. The reaction appears fairly general and delivers only one diastereomer.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707811.
- Supporting Information
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References and Notes
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- 15 General Procedure for the Preparation of Lactams 6a–p In a 25 mL round-bottom flask, amine (0.8 mmol, 1.0 equiv) and aldehyde (0.9 mmol, 1.1 equiv) were dissolved in 10 mL of chlorobenzene and refluxed with azeotropic removal of water. After 1 h, half of the solvent was distilled off and 2-diazomalonates 4a–e (1.6 mmol, 2.0 equiv) was added. The mixture was then refluxed overnight, and the reaction progress was followed via TLC. When no more diazo compound was detectable (20–24 h), the solvent was evaporated in vacuo, and the resulting mixture was purified by column chromatography on silica gel with a linear gradient (0–20%) of acetone in n-hexane (total volume of eluent, 450 mL) to provide pure compounds 6a–p. In case of volatile aldehyde or amine, they were reacted in chlorobenzene at room temperature overnight in the presence of 4 Å MS. The latter was filtered off before proceeding with the addition of 4 and heating. Compounds 6a,d,g,l,n,p were prepared with the use of presynthesized imines.
- 16 Characterization Data of Representative Compounds Compound 6i: white powder (231 mg, 72%); mp 113–115 °C. 1H NMR (400 MHz, CDCl3): δ = 7.30 (d, J = 8.9 Hz, 2 H), 6.95 (d, J = 8.5 Hz, 1 H), 6.87–6.82 (m, 2 H), 6.49 (d, J = 2.4 Hz, 1 H), 6.35 (d, J = 8.5 Hz, 1 H), 5.50 (s, 1 H), 3.89 (s, 3 H), 3.78 (d, J = 2.0 Hz, 6 H), 3.75 (s, 3 H), 3.39 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 166.3, 161.2, 161.1, 158.6, 156.5, 130.5, 128.6, 119.0, 114.4, 112.4, 104.0, 98.5, 94.5, 60.1, 55.9, 55.8, 55.5, 55.3, 51.9 ppm. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H23NaNO7: 424.1367; found: 424.1378. Compound 6l: yellow powder (202 mg, 66%); mp 97–99 °C. 1H NMR (400 MHz, CDCl3): δ = 7.21 (d, J = 8.7 Hz, 2 H), 7.01–6.68 (m, 2 H), 4.63 (s, 1 H), 4.08 (dq, J = 8.9, 7.0 Hz, 1 H), 3.92 (dq, J = 10.8, 7.1 Hz, 1 H), 3.81 (s, 3 H), 3.78–3.63 (m, 1 H), 2.93 (s, 3 H), 1.30 (t, J = 7.0 Hz, 3 H), 0.99 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 166.3, 165.0, 160.1, 128.6, 124.4, 113.9, 95.2, 67.8, 64.1, 61.4, 55.3, 27.4, 15.4, 13.8 ppm. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C23H27NNaO7: 452.1680; found: 452.1683. Compound 6n: yellow oil (206 mg, 42%). 1H NMR (400 MHz, CDCl3): δ = 7.51–7.46 (m, 2 H), 7.42–7.26 (m, 8 H), 7.24–7.01 (m, 2 H), 6.80 (d, J = 8.0 Hz, 2 H), 5.35–5.09 (m, 2 H), 4.94 (d, J = 12.2 Hz, 1 H), 4.86–4.77 (m, 2 H), 4.54 (d, J = 18.0 Hz, 1 H), 3.81 (s, 3 H), 3.74 (s, 3 H), 3.65 (d, J = 18.0 Hz, 1 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 167.9, 165.9, 164.8, 160.2, 137.0, 134.7, 128.6, 128.4, 128.4, 128.3, 128.2, 128.0, 123.6, 114.1, 95.7, 70.3, 67.1, 66.4, 55.2, 52.5, 41.3 ppm. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C28H27NNaO7: 512.1680; found: 512.1700.
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