Metal-Free sp³ C–H Functionalization: PABS/I₂-Promoted Synthesis of Polysubstituted Oxazole Derivatives from Arylethanones and 2-Amino-2-alkyl/arylacetic Acid

Abstract

A nonmetal-catalyzed process for the synthesis of polysubstituted oxazoles from inexpensive and readily available α-amino acids and methyl ketones is established. This reaction is proposed to achieve oxidative cleavage of C(sp³)–H bonds, followed by decarboxylation and annulation. The mild reaction conditions employed in both cases enable the tolerance of a wide range of functional groups as well as high reaction efficiency.

Key words

nonmetal-catalyzed - oxazoles - sp³ C–H functionalization - high yield - amino acids

• References and Notes

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• 30 Typical Procedure for the Preparation of 2,5-Diphenyloxazole A test tube was charged with 1a (0.32 mmol), 2a (0.38 mmol), I₂ (2.0 equiv), and PABS (0.5 equiv). Then DMSO (2 mL) was added to the reaction system. The reaction was stirred at 100 °C for 5 h. After cooling to r.t., the solvent diluted with EtOAc (10 mL) and washed with brine (5 mL) and dried over anhydrous Na₂SO₄. After the solvent was evaporated in vacuo, the residues were purified by column chromatography, eluting with PE–EtOAc to afford pure 3aa as a yellow solid (64 mg, 90%); mp 58–60 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.11–8.08 (m, 2 H), 7.70–7.68 (m, 2 H), 7.48–7.39 (m, 6 H), 7.30 (t, J = 7.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 161.02, 151.14, 130.20, 128.81, 128.70, 128.31, 127.91, 127.37, 126.18, 124.08, 123.37. ESI-HRMS: m/z calcd for C₁₅H₁₂NO [M + H]⁺: 222.0914; found: 222.0916.