Oxazole Synthesis by Sequential Asmic-Ester Condensations and Sulfanyl–Lithium Exchange–Trapping

Oxazoles are rapidly assembled through
a sequential deprotonation–condensation
of Asmic, anisylsulfanyl­methyl­isocyanide, with esters
followed by sulfanyl–lithium exchange–trapping. Deprotonating
Asmic affords a metalated isocyanide that efficiently traps esters
to afford oxazoles bearing a versatile C-4 anisylsulfanyl substituent.
Interchange of the anisylsulfanyl substituent is readily achieved
through a first-in-class sulfur–lithium exchange–electrophilic
trapping sequence whose versatility is illustrated in the three-step
synthesis of the bioactive natural product streptochlorin.

恶唑（Oxazoles）可通过以茴香硫基甲基异氰（anisylsulfanylmethyl isocyanide，简称Asmic）与酯类为底物，经连续去质子化-缩合、随后硫基-锂交换-捕获的串联过程快速合成。对Asmic进行去质子化可得到金属化异氰中间体，该中间体可高效捕获酯类，进而得到带有多功能C-4位茴香硫基取代基的恶唑产物。该茴香硫基取代基可通过一类首创的硫-锂交换-亲电捕获序列实现便捷置换，该序列的通用性通过生物活性天然产物链氯菌素（streptochlorin）的三步合成得到实例验证。