Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA.
J Am Chem Soc. 2012 Oct 24;134(42):17412-5. doi: 10.1021/ja307948m. Epub 2012 Oct 11.
2,4-Oxazole is an important structural motif in various natural products. An efficient modular synthesis of this structure has been achieved via a [3 + 2] annulation between a terminal alkyne and a carboxamide using a gold-catalyzed oxidation strategy. The postulated reactive intermediate, a terminal α-oxo gold carbene, previously known to be highly electrophilic and hence unlikely to be trapped by stoichiometric external nucleophiles, is coerced to react smoothly with the carboxamide en route to the oxazole ring by a P,N- or P,S-bidentate ligand such as Mor-DalPhos; in stark contrast, often-used ligands such as monodentate phosphines and N-heterocyclic carbenes are totally ineffective. The role of these bidentate phosphines in this reaction is attributed to the formation of a tricoordinated gold carbene intermediate, which is less electrophilic and hence more chemoselective when reacting with nucleophiles. The success in using bidentate phosphine ligands to temper the reactivities of in situ-generated gold carbenes is likely to open many new opportunities to apply oxidative gold catalysis to the development of novel methods, and the implication of tricoordinated gold intermediates in homogeneous gold catalysis should stimulate further advances in gold catalysis.
2,4-噁唑是各种天然产物中的重要结构基序。通过使用金催化氧化策略，在末端炔烃和羧酰胺之间进行[3 + 2]环加成，实现了这种结构的有效模块化合成。假定的反应性中间体，末端α-氧金卡宾，以前被认为是高反应性的，因此不太可能被化学计量的外部亲核试剂捕获，被 P，N-或 P，S-双齿配体（如 Mor-DalPhos）强制与羧酰胺反应，从而顺利地反应到噁唑环中；与此形成鲜明对比的是，通常使用的配体，如单齿膦和 N-杂环卡宾，完全无效。这些双齿膦配体在该反应中的作用归因于形成三配位金卡宾中间体，其在与亲核试剂反应时具有较低的反应性和较高的化学选择性。成功地使用双齿膦配体来调节原位生成的金卡宾的反应性，可能会为将氧化金催化应用于新型方法的开发开辟许多新机会，而三配位金中间体在均相金催化中的作用应该会刺激金催化的进一步发展。
