Iron‐Catalyzed Reductive Cyclization of Alkenyl Vinylogous Carbonates for Stereoselective Synthesis of Substituted Tetrahydrofurans, Tetrahydropyrans, and Chromans

Abstract

A method for the stereoselective synthesis of substituted tetrahydrofurans (THFs), tetrahydropyrans (THPs), as well as chromans using intermolecular hydrogen atom transfer (HAT) followed by intramolecular radical cyclization of alkenyl vinylogous carbonates is described. This Fe(acac)3‐catalyzed reaction uses PhSiH3 as H‐source and works under ambient conditions in HFIP/ethylene glycol (5:1 mixture) as solvent. The methodology developed has broad substrate scope and is amenable to gram‐scale synthesis. The method gives ready access to even hexa‐substituted cyclic ethers containing two quaternary carbons. This strategy is used in the construction of oxaspirocyclic systems. Diastereoselective synthesis of fused bicyclic as well as tricyclic motifs could be achieved. The stereochemistry of the products was assigned using NOE experiments and was further confirmed by single‐crystal X‐ray diffraction studies on two derivatives.

Visible-light-promoted C(sp3)–H thiolation of aliphatic ethers with thiosulfonates

“…Aliphatic ethers such as tetrahydrofuran (THF) and tetrahydropyran (THP) are valuable building blocks ubiquitous in numerous natural products, bioactive molecules and pharmaceuticals. 1 Due to their importance in medicinal chemistry, direct functionalization of the α-C(sp 3 )–H bonds in aliphatic ethers to synthesize more usable molecules has attracted significant attention in the past few years. 2 Compared to the construction of C–C, 3 C–N 4 and C–O 5 bonds, the construction of C–S bonds through direct C(sp 3 )–H thiolation has been less explored.…”

Fe-Catalyzed Hydroallylation of Unactivated Alkenes with Vinyl Cyclopropanes

“…Conversion of the olefin feedstock to complex and functionalized alkanes is of considerable interest for expedient access to valuable compounds. Generating a carbon-centered radical through metal-catalyzed hydrogen atom transfer (MHAT) from an early metal hydride to an unactivated alkene is the key step for a number of interesting olefin hydrofunctionalization reactions that have become prominent over the past several years. − Such an olefin-borne carbon radical can add to radical acceptors and engage in cross-coupling reactions or radical-polar crossover . Considering the unique mechanistic framework of the weak field MHAT reaction platform for forming a metallo/organic radical pair from olefins and the salient features, including high chemoselectivity and functional group tolerance―which largely differ from those of classical radical chemistrywe questioned if reaction between such a carbon-centered radical and electron-poor VCP could be harnessed for an efficient polarity-matched C–C bond-forming process (Figure c), which to date has proven to be a formidable task.…”