Investigation of Transfer Group, Tether Proximity, and Alkene Substitution for Intramolecular Silyloxypyrone-Based [5 + 2] Cycloadditions

Abstract

Systematic investigation of intramolecular silyloxypyrone-based [5 + 2] cycloadditions revealed three significant factors impacting conversion to cycloadduct: (1) the silyl transfer group has a substantial influence on the rate of reaction, and the robust t-butyldiphenylsilyl group was found to be more effective overall than the conventional t-butyldimethylsilyl group; (2) α,β-unsaturated esters were generally more reactive than terminal olefins and afforded appreciable quantity of cycloadduct even at room temperature; and (3) the proximity of the tether to the silyl transfer group revealed a critical alignment trend between the pyrone and the alkene. Taken together, these investigations provided insight regarding the steric and electronic parameters that impact the scope and limitation of these reactions.

Experimental and Theoretical Investigation of the Synchronicity of Ambident Silyloxypyrone-Based (5 + 2) Cycloadditions

“…Limited precedence for ambident reactivity of oxidopyrylium intermediates derived from acetoxypyranones is also known (Scheme , eq 3), and a stepwise hetero-(5 + 2) cycloaddition between oxidopyrylium ylides and imines was recently reported . Herein, we report evidence for ambident silyloxypyrone-based cycloadditions , (Scheme , eq 4) supported by qualitative rate studies, Hammett linear free energy relationship (LFER) studies, and theoretical calculations, revealing a spectrum of reactivity that passes through the borderlands of concerted and stepwise …”

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.…”

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

“…Trivedi and co-workers reported an asymmetric cycloaddition of acetate derivative 9 to provide cycloadduct 10 with very high diastereoselectivity (dr 97%) . Several other oxidopyrylium-alkene cycloadditions have been reported with high selectivity in the literature. − We became interested in the oxidopyrylium-alkene cycloaddition reaction to provide access to structurally intriguing oxabicyclo­[3.2.1]­octane heterocyclic ring systems. We recently incorporated a variety of similar stereochemically defined cyclic ether-derived ligands and structural templates in the design of exceptionally potent HIV-1 protease inhibitors. − Herein, we report our studies on an asymmetric intramolecular cycloaddition reaction of the oxidopyrylium ylide bearing an α-chiral center and a number of alkoxy-alkene tethers for construction of five- to seven-membered ring systems.…”