Development of a Flexible and Robust Synthesis of Tetrahydrofuro[3,4-]furan Nucleoside Analogues.

In the context of a PRMT5 inhibitor program, we describe our efforts to develop a flexible and robust strategy to access tetrahydrofuro[3,4-]furan nucleoside analogues. Ultimately, it was found that a Wolfe type carboetherification from an alkenol derived from d-glucofuranose diacetonide was capable of furnishing the B-ring and installing the desired heteroaryl group in a single step. Using this approach, key intermediate was delivered on a gram scale in a 62% yield and 9.

Low temperature organocopper-mediated two-component cross coupling/cycloisomerization approach toward N-fused heterocycles.

Organocopper reagents smoothly react with heterocyclic propargyl mesylates at low temperature to produce N-fused heterocycles. The copper reagent plays a "double duty" in this novel cascade transformation, which proceeds via an SN2' substitution followed by a subsequent cycloisomerization step.