New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore-560064, Karnataka, India.
J Org Chem. 2012 Dec 7;77(23):10752-63. doi: 10.1021/jo3021192. Epub 2012 Nov 16.
An efficient two-step synthesis of 2-phenyl-4,5-substituted oxazoles involving intramolecular copper-catalyzed cyclization of highly functionalized novel β-(methylthio)enamides as the key step has been reported. These enamides are obtained by nucleophilic ring-opening of newly synthesized 4-[(methylthio)hetero(aryl)methylene]-2-phenyl-5-oxazolone precursors by alkoxides, amines, amino acid esters and aryl/alkyl Grignard reagents, thus leading to the introduction of an ester, N-substituted carboxamide or acyl functionalities at 4-position of the product oxazoles. Synthesis of two naturally occurring 2,5-diaryloxazoles, i.e., texamine and uguenenazole, via two-step hydrolysis-decarboxylation of the corresponding 2,5-diaryloxazole-4-carboxylates has also been described. Similarly, three of the serine-derived oxazole-4-carboxamides were elaborated to novel trisubstituted 4,2'-bisoxazoles through DAST/DBU-mediated cyclodehydration-dehydrohalogenation sequence. The present protocol is complementary and an improvement to our previously reported silver carbonate-induced cyclization of β-bis(methylthio)enamides to 2-phenyl-5-(methylthio)-4-substituted oxazoles.
一种高效的两步法合成 2-苯基-4,5-取代恶唑的方法，涉及分子内铜催化高度官能化新型β-（甲硫基）烯酰胺的环化反应，这是关键步骤。这些烯酰胺是通过新合成的 4-[(甲硫基)杂芳基亚甲基]-2-苯基-5-恶唑啉前体的亲核开环得到的，通过烷氧基化物、胺、氨基酸酯和芳基/烷基格氏试剂，从而在产物恶唑的 4-位引入酯、N-取代的羧酰胺或酰基官能团。通过相应的 2,5-二芳基恶唑-4-羧酸酯的两步水解-脱羧反应，也合成了两种天然存在的 2,5-二芳基恶唑，即 texamine 和 uguenenazole。同样，通过 DAST/DBU 介导的环脱水-脱卤化序列，三种丝氨酸衍生的恶唑-4-羧酰胺被精心设计成新型三取代的 4,2'-双恶唑。本方案是对我们之前报道的碳酸银诱导β-双（甲硫基）烯酰胺环化合成 2-苯基-5-（甲硫基）-4-取代恶唑的补充和改进。
