Synthesis and palladium-catalysed isomerisation of fused polycyclic tetrahydrofurans: efficient and stereoselective one-pot domino construction of functionalised bridged bicyclo[n.2.1] ring systems

Abstract

A new one-pot domino reaction for a general entry to functionalised bridged bicyclo[n.2.1] ring systems from alpha, alpha'-diactivated cyclic ketones and trans-1,4-dihalides is described. The sequence combines a base promoted C-O cycloalkylation reaction leading to fused polycyclic enol ethers and their in situ palladium-catalysed isomerisation.

Palladium‐catalyzed Synthesis of Fused Carbo‐ and Heterocycles

“…Rodriguez group described palladium‐catalyzed synthesis of bridged bicyclo[n.2.1] ring systems from α , α ’‐diactivated cyclic ketones and trans ‐1,4‐dihalides (Scheme 65). [81] Under optimal reaction conditions, α,α’ ‐diactivated ketone 209 reacted with 1,4‐dibromobutene 210 in presence of 6 equiv. K 2 CO 3 , 5 mol% of Pd(dppe) 2 , in N,N ‐dimethylsulfoxide at 80 °C for few hours to produce bridged bicycloalkanones 211 in 65–87% yields.…”

“…Synthesis of bridged bicycle-ring systems by Rodriguez group. [81] Scheme 66. Silylene transfer to 2-alkenylindoles via palladium-catalyst by Suginome and Ohmura group.…”

Syntheses and Applications of Functionalized Bicyclo[3.2.1]octanes: Thirteen Years of Progress

“…In this area, palladium-catalyzed intramolecular coupling reactions clearly lead the way, and some elegant approaches to bicyclo[3.2.1]octane derivatives essentially based on cycloisomerization or intramolecular Heck coupling have been reported in recent years. In 2000 the group of Langer and more recently Rodriguez and co-workers reported the stereoselective synthesis and palladium-catalyzed rearrangement of bicyclic 2-alkylidene-5-vinyl-tetrahydrofurans for the preparation of bicyclo[3.2.1]octan-8-ones. Under the Tsuji–Trost reaction conditions, the substrates 273 and 275 underwent initial ring-opening of the furan to form the corresponding π-allyl palladium(0) complex enolates, which then cyclized by nucleophilic addition of the carbon atom of the enolate onto the π-allyl palladium complex to give 274 and 276 in good yields, respectively (Scheme ).…”