Access to Ynamides via CuO-Mediated Oxidative Amidation of Alkynes

Abstract

Copper(II) oxide mediated the direct coupling of terminal alkynes and amides by way of C–H functionalization to afford ynamides as useful building blocks. Some alkali halides such as KCl were discovered to play a key role as additive in the coupling reaction, while other salts could suppress the formation of products.

Key words

alkylation - amides - copper - cross-coupling - oxidation

• References and Notes

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• 25 General Procedures for the Synthesis of Ynamides In a dry 25 mL round-bottom flask, CuO (1.93 mmol), KCl (0.154 mmol), 4-PPY (0.154 mmol), and the 2-oxazolidinone (3.85 mmol) were added to dry toluene (5 mL) under argon. The flask was placed in an oil bath, and 4-ethynylanisole (0.77 mmol) was added. Then, the reaction mixture was stirred for 36 h at 80 °C. After the crude mixture was filtered and concentrated under vacuum, the mixture was separated on a silica gel column using hexanes–EtOAc (2:1) as eluent to afford the ynamide. Analytical Data of Selected Compounds
  Ynamide 7 ^27a Colorless acicular crystal. ¹H NMR (500 MHz, CDCl₃): δ = 7.42 (d, J = 9.1 Hz, 2 H), 7.35–7.28 (m, 3 H), 7.24–7.23 (m, 2 H), 6.85 (d, J = 9.1 Hz, 2 H), 4.33 (m, 2 H), 4.14 (m, 1 H), 3.80 (s, 3 H), 3.25 (dd, J = 14.0, 3.5 Hz, 1 H), 3.00 (m, 1 H); [α]_D ¹⁸ +82.1 (c 3.01, CHCl₃); known compound. Ynamide 8 Colorless acicular crystal. ¹H NMR (500 MHz, CDCl₃): δ = 7.39 (d, J = 8.8 Hz, 2 H), 6.83 (d, J = 8.8 Hz, 2 H), 4.42 (t, J = 8.8 Hz, 1 H), 4.19 (d, J = 8.8, 6.0 Hz, 1 H), 4.03 (m, 1 H), 3.81 (s, 3 H), 2.29 (m, 1 H), 1.03 (d, J = 6.6 Hz, 3 H), 1.02 (d, J = 6.6 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 159.6, 156.1, 133.4, 114.3, 113.9, 77.0, 71.9, 64.8, 62.1, 55.3, 29.2, 17.2, 15.2. ESI-HRMS: m/z calcd [M + H]⁺ = 260.1286; found: 260.1281; [α]_D ¹⁸ +28.2 (c 2.57, CHCl₃). Ynamide 9 ^27b Colorless acicular crystal. ¹H NMR (500 MHz, CDCl₃): δ = 7.39–7.29 (m, 5 H), 7.12 (d, J = 8.7 Hz, 2 H), 6.66 (d, J = 8.7 Hz, 2 H), 5.05–5.01 (m, 1 H), 4.70–4.66 (m, 1 H), 4.20 (dd, J = 9.0, 7.2 Hz, 1 H), 3.67 (m, 3 H); [α]_D ¹⁸ +154.9 (c 1.36, CHCl₃); known compound.
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• 27b Yao B, Liang Z, Niu T, Zhang Y. J. Org. Chem. 2009; 74: 4630