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DOI: 10.1055/a-2185-0673
Synthesis of 2,4-Disubstituted Oxazoles by a Copper-Catalyzed [3+2] Annulation/Olefination Cascade between Amides and IIII/PV Hybrid Ylides
This work was funded by the National Natural Science Foundation of China (22101079), the Natural Science Foundation of Hunan Province (2022JJ40040).
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Abstract
We report a novel and efficient method for oxazole synthesis through a copper-catalyzed [3+2] annulation/olefination cascade between readily available iodonium–phosphonium hybrid ylides and amides. An unprecedented α-phosphonium Cu carbenoid acts as the key intermediate. This method features excellent regioselectivity with mild reaction conditions and a broad substrate scope. Its synthetic utility is demonstrated by its application in late-stage functionalizations and the rapid synthesis of a chiral ligand based on an oxazole motif.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2185-0673.
- Supporting Information
Publication History
Received: 24 August 2023
Accepted after revision: 02 October 2023
Accepted Manuscript online:
02 October 2023
Article published online:
06 November 2023
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- 22 2-(4-Methylphenyl)-4-phenyl-1,3-oxazole (3a); Typical Procedure A dry clean test-tube equipped with a stirrer bar was charged with p-methylbenzamide 2a (16.2 mg, 0.12 mmol), Na2CO3 (25.4 mg, 0.24 mmol), IIII/PV hybrid ylide 1a (67.0 mg, 0.1 mmol), Cu(acac)2 (1.31 mg, 5 mol%), and 3 Å MS (50 mg). DCE (1.0 mL) was then added from a syringe under a N2 atmosphere. The resulting mixture was stirred for 3 h at 40 °C (water-bath temperature), then cooled to r.t. After removal of the volatiles under reduced pressure, the residue was purified by column chromatography [silica gel, PE–EtOAc (20:1)] to give a white solid; yield: 21.2 mg (90%). 1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 7.3 Hz, 2 H), 7.95 (s, 1 H), 7.83 (d, J = 7.9 Hz, 2 H), 7.43 (t, J = 7.5 Hz, 2 H), 7.34 (dd, J = 6.8 Hz, 1 H), 7.29 (d, J = 7.9 Hz, 2 H), 2.42 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 162.3, 142.0, 140.8, 133.3, 131.4, 129.6, 128.9, 128.2, 126.6, 125.8, 125.0, 21.7. HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H14NO: 236.1070; found: 236.1069.
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