Intramolecular Photoreactions of (5S)-5-Oxymethyl-2(5H)-furanones as a Tool for the Stereoselective Generation of Diverse Polycyclic Scaffolds

Abstract

The photoactivated evolution of a series of enantiomerically pure 5-oxymethyl-2(5H)-furanones has been investigated. The observed intramolecular photoreactions have proven to be a straightforward entry to diverse and stereochemically rich fragment-molecules, most of which contain the privileged tetrahydropyran (THP) scaffold. The formation of the THP involves a 1,5-hydrogen atom transfer process, leading to a diradical intermediate that recombines to form a new σ C-C bond. These reactions take place under both sensitized and nonsensitized conditions, and they are highly stereoselective. When the substrate contains an allyl residue, the intramolecular [2 + 2] cycloaddition leading to cyclobutanes competes advantageously. When the substrate contains a THP residue, the cyclization involves the concomitant formation of [6,6]-spiroketals with nonanomeric relationships.

Intramolecular Photocycloaddition of 2(5H)-Furanones to Temporarily Tethered Terminal Alkenes as a Stereoselective Source of Enantiomerically Pure Polyfunctionalyzed Cyclobutanes

“…First, the intramolecular [2 + 2] photocycloaddition of 5 was investigated using experimental conditions usually applied in our laboratories for intermolecular photoreactions (Table , entry 1) . However, the irradiation of 5 in acetone through a Pyrex filter at different temperatures (from rt to −78 °C) did not afford any of the expected photoproducts.…”

“…Our studies on the preparation of bicyclic tetrahydropyrans (THPs) by an intramolecular photoreaction of enantiomerically pure 5-oxymethyl-2­( 5H )-furanones showed that the photoreaction of lactone 1 bearing an allyloxymethyl substituent at C5 delivers mainly a regioisomeric mixture of [2 + 2] photocycloadducts 3 and 4 , along with targeted THP 2 (Scheme a) . In all of the assayed reactions, head to tail ( HT ) isomer 3 was slightly favored over head to head ( HH ) isomer 4…”

Photochemical Electron and Hydrogen Transfer in Organic Synthesis: The Control of Selectivity

“…The same type of hydrogen abstraction was also observed in furanone derivatives carrying a benzyl or allyl moiety on the side chain. 35,40 The addition of alkoxyl and ketyl radicals to furanones in their ground state generally occurs at the β-position, as was previously discussed for α-aminoalkyl radicals. Both types of radicals are nucleophilic and their behavior therefore resembles nucleophiles in the Michael addition.…”

“…The same reaction was also carried out using direct excitation via light absorption of 23. 35 The re-sulting 3 ππ* state 25 is characterized by the suppression of the π-bond of the α,β-unsaturated carboxyl system. The spin density at the β-position is high while the electron at the α-position is delocalized over the carboxyl function.…”

(S)-γ-Hydroxymethyl-α,β-butenolide, a Valuable Chiral Synthon: Syntheses, Reactivity, and Applications

“…Previous work has already shown that [2+2] photocycloaddition occurred with vinyl-substituted derivatives. 72 First of all, they have tested terminal alkenes with different temperatures and solvents. To achieve good yields and selectivities, acetone proved to be the best solvent at -78 °C.…”