Oxidopyrylium-Alkene [5 + 2] Cycloaddition Conjugate Addition Cascade (C³) Sequences: Scope, Limitation, and Computational Investigations

Abstract

Oxidopyrylium-alkene [5 + 2] cycloaddition conjugate addition cascade (C) sequences are described. Intramolecular cycloadditions involving terminal alkenes, enals, and enones were investigated. Substrates with tethers of varying lengths delivered five- and six-membered carbocycles and heterocycles thus demonstrating the scope and limitation of the cycloaddition-conjugate addition cascade. Several experiments and theoretical calculations provide evidence for the proposed mechanistic pathway.

Pathway Bifurcation in the (4 + 3)/(5 + 2)-Cycloaddition of Butadiene and Oxidopyrylium Ylides: The Significance of Molecular Orbital Isosymmetry

“…We determined the endo -configured TS-1 to be the lowest energy transition state structure, with a free energy barrier of 16.1 kcal/mol. This is consistent with the reaction conditions reported by Sammes and Street, whereby the transformation occurs easily at, or slightly below (0 °C), room temperature. , Alternative structures, which may be more clearly recognized as (4 + 3)- or (5 + 2)-cycloaddition transition states ( TS-3 and TS-6 to TS-8 ), were found to be higher in energy. The preference for TS-1 can again be ascribed to the favorable “secondary orbital interactions” between OP and BD .…”

Highly Diastereoselective Intramolecular Asymmetric Oxidopyrylium-olefin [5 + 2] Cycloaddition and Synthesis of 8-Oxabicyclo[3.2.1]oct-3-enone Containing Ring Systems

“…Treatment of acetoxy­hydro­pyranones 14 with base will lead to the formation of the aromatic oxidopyrylium ion 15 containing an α-chiral center bearing an alkyl substituent and an alkoxy tether with a terminal alkene. The O -allyl chain with the phenyl group will adopt a transition-state 15a where the bulky phenyl group would occupy a pseudoequatorial position in the envelope conformation of the developing five-membered ring. , The alkyl groups on the tether act as a stereochemical handle to orient the pyranone ring at the bottom so that the terminal alkene can approach from the top face. As the bulkiness of the alkyl substituent (R-group) on the side chain decreases, the preference of 15a over the alternative diastereomeric transition state would also decrease and that would lead to lower diastereoselectivity for the cycloadducts.…”

Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae

“…As part of our research program directed toward [5+2] cycloadditions, [78][79][80][81][82][83][84] we explored mechanistic pathways of acetoxypyranone-derived oxidopyrylium species en route to [5+2] cycloadditions [81] that led to the discovery of polycyclic ether-benzopyran 4 (Scheme 1). Commercially available aldehyde 2 was treated with 2-furyllithium to provide the desired alcohol (not shown) in quantitative yield.…”