A metal-free, biomimetic catalytic protocol for the cyclization of N-(2-hydroxyethyl)amides to the corresponding 2-oxazolines (4,5-dihydrooxazoles), promoted by the 1,3,5,2,4,6-triazatriphosphorine (TAP)-derived organocatalyst tris(o-phenylenedioxy)cyclotriphosphazene (TAP-1) has been developed. This approach requires less precatalyst compared to the reported relevant systems, with respect to the phosphorus atom (the maximum turnover number (TON) ∼ 30), and exhibits a broader substrate scope and higher functional-group tolerance, providing the functionalized 2-oxazolines with retention of the configuration at the C(4) stereogenic center of the 2-oxazolines. Widely accessible β-amino alcohols can be used in this approach, and the cyclization of N-(2-hydroxyethyl)amides provides the desired 2-oxazolines in up to 99% yield. The mechanism of the reaction was studied by monitoring the reaction using spectral and analytical methods, whereby an ¹⁸O-labeling experiment furnished valuable insights. The initial step involves a stoichiometric reaction between the substrate and TAP-1, which leads to the in situ generation of the catalyst, a catechol cyclic phosphate, as well as to a pyrocatechol phosphate and two possible active intermediates. The dehydrative cyclization was also successfully conducted on the gram scale.

中文翻译：

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磷基有机催化N-(2-羟乙基)酰胺脱水环化成2-恶唑啉

由 1,3,5,2,4,6-三氮杂三膦促进的N- (2-羟乙基)酰胺环化为相应的 2-恶唑啉 (4,5-二氢恶唑) 的无金属仿生催化方案（TAP）衍生的有机催化剂三（邻苯二氧基）环三磷腈（TAP- 1）已被开发出来。与报道的相关系统相比，这种方法需要较少的预催化剂，就磷原子而言（最大转换数（TON）~30），并且表现出更广泛的底物范围和更高的官能团耐受性，提供了功能化的 2-恶唑啉保留在 2-恶唑啉的 C(4) 立体中心的构型。在这种方法中可以使用广泛易得的 β-氨基醇，并且N的环化-(2-羟乙基)酰胺以高达 99% 的收率提供所需的 2-恶唑啉。通过使用光谱和分析方法监测反应来研究反应机理，其中¹⁸ O-标记实验提供了有价值的见解。初始步骤涉及底物和 TAP- 1之间的化学计量反应，这导致催化剂、邻苯二酚环磷酸盐以及邻苯二酚磷酸盐和两种可能的活性中间体的原位生成。脱水环化也成功地以克级进行。