Part Ⅰ. Study on Cyclization of Ketyl Radical Promoted by Pyridine-Boryl Radical: Synthesis of Indanols, Indoles, and Chromanols Part Ⅱ. Geminal Fluorocyclization of 1,2-Diketones Mediated by Phosphoramidite

Abstract

Part Ⅰ. Indanol, indole, and chromanol are common structural motifs in bioactive compounds, and thus their synthetic routes have advanced for decades. Nonetheless, it is still desirable to develop mild, operationally simple, and sustainable methods that require neither precious metals nor special equipment. In this work, a persistent pyridine-boryl radical was studied to generate a ketyl radical and promote the radical cyclization under mild conditions. Although the ketyl radical could not be employed for 5-endo- and 5-exo-cyclizations for indanol and indole synthesis, respectively, 6-exo-cyclization for chromanol synthesis could be conducted. Reaction conditions were optimized with various diboron reagents and hydrogen donors. Additionally, an unusual 3,3-sigmatropic rearrangement of allylic boric acid was observed to form an isomerized product. Part Ⅱ. Fluorinated heterocycles are significant structures as bioisosteres with diverse applications in pharmaceutical, agrochemical, medicinal, and material chemistry. However, there are only a few examples that introduce fluorine and form a heterocycle in a single step. It was aimed to achieve simultaneous 1,1-addition by sequential electrophilic fluorination and nucleophilic cyclization with a tethered functional group onto dioxaphospholene, a carbene surrogate. The reaction conditions were optimized using various fluorenium sources and additives, and N-fluorobenzenesulfonimide was determined as a superior electrophilic fluorinating reagent in the absence of additives. Ethers and esters served as competent internal nucleophiles, but thioethers interfered with electrophilic fluorination. A substrate survey of diverse symmetric and unsymmetric 1,2-diketones is underway. Additionally, a regioselective variant will be examined with α-keto thioesters.