Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, Canada, M5S 3H6.
J Org Chem. 2022 Sep 2;87(17):11329-11349. doi: 10.1021/acs.joc.2c00803. Epub 2022 Aug 15.
The reaction of the HCl or trifluoroacetic acid salts of primary amines with carbonyldiimidazole (CDI) is shown to be a preparatively useful method for forming monosubstituted carbamoylimidazoles (28 examples) without the formation of symmetrical urea side products. The utility of these air- and water-stable crystalline carbamoylimidazole reagents was demonstrated by their reactions as blocked or masked isocyanate equivalents. Reaction with various classes of nucleophiles provides access to useful functional groups including ureas, carbamates, thiocarbamates, hydantoins, and oxazolidinones. A parallel synthesis library of 30 ureas was generated by the reaction of 6× carbamoylimidazole intermediates with 5× amines and triethylamine. The unsymmetrical urea-containing natural products macaurea A and pygmaniline A were also prepared in good yields (95% over four steps and 79% over three steps, respectively) using this approach. The reaction of carbamoylimidazoles with amino acid methyl esters followed by microwave irradiation in aqueous media gives hydantoins in high yields, further demonstrating the ability of carbamoylimidazoles as isocyanate surrogates. Three hydantoin-containing natural products including macahydantoin D and meyeniihydantoin A were prepared in nearly quantitative yields from proline methyl ester and carbamoylimidazoles. The reaction of carbamoylimidazoles with alcohols and thiols under basic conditions affords carbamates and thiocarbamates, respectively, in good yields. Lastly, a method for the preparation of chiral oxazolidinone heterocycles from chiral epoxy alcohols is demonstrated using a double displacement approach. The reactions occur with high regio- and stereoselectivity (dr ≥ 15:1 by H NMR) via a domino attack of the corresponding alkoxides with carbamoylimidazoles followed by an intramolecular attack of the generated urea anion at the proximal position of the epoxide group.
伯胺的 HCl 或三氟乙酸盐与羰基二咪唑 (CDI) 的反应被证明是一种有用的制备方法，可以形成单取代的碳酰胺咪唑 (28 个实例)，而不会形成对称的脲副产物。这些空气稳定和水稳定的结晶碳酰胺咪唑试剂的用途通过它们作为封闭或掩蔽异氰酸酯等价物的反应得到证明。与各种类别的亲核试剂的反应提供了获得有用的官能团的途径，包括脲、氨基甲酸酯、硫代氨基甲酸酯、海因、恶唑烷酮。通过 6×碳酰胺咪唑中间体与 5×胺和三乙胺的反应，生成了 30 个脲的平行合成文库。不对称脲含有的天然产物 macaurea A 和 pygmaniline A 也通过该方法以良好的收率（四步总收率 95%，三步总收率 79%）制备。碳酰胺咪唑与氨基酸甲酯的反应，然后在水介质中进行微波辐射，可高产率得到海因，进一步证明了碳酰胺咪唑作为异氰酸酯替代物的能力。三种含海因的天然产物，包括 macahydantoin D 和 meyeniihydantoin A，从脯氨酸甲酯和碳酰胺咪唑以近乎定量的产率制备。碳酰胺咪唑与醇和硫醇在碱性条件下的反应分别以高产率得到氨基甲酸酯和硫代氨基甲酸酯。最后，通过双取代反应方法展示了从手性环氧醇制备手性恶唑烷酮杂环的方法。反应以高区域和立体选择性（通过 1H NMR 观察 dr ≥ 15:1）进行，通过相应烷氧基与碳酰胺咪唑的级联攻击，随后生成的脲阴离子在环氧基团的近端位置进行分子内攻击。
