Origins of Selective Formation of 5-Vinyl-2-methylene Furans from Oxyallyl/Diene (3+2) Cycloadditions with Pd(0) Catalysis

Abstract

The (3+2) cycloadditions between electron-deficient Pd-oxyallyls and conjugated dienes have been investigated with density functional theory calculations. A stepwise mechanism with C–C bond formation occurring first is supported by computations. The key electron-withdrawing ester substituent on the Pd-oxyallyl species decreases the migratory insertion barrier by both lowering the LUMO energy and enabling a less-strained six-membered coordination mode. The lack of (3+2) reactivity with monoenes is attributed to higher migratory insertion barriers due to a lower-energy HOMO, as well as high C–O reductive elimination barriers, which become rate-determining. Conjugated dienes enable the formation of a highly electrophilic η3 Pd-allyl species and greatly facilitates C–O formation.

Ambiphilic Reactivity of Vinyl Pd-Oxyallyl for Expeditious Construction of Highly Functionalized Cyclooctanoids

“…The formation of a diene product 5 was observed when carbonate 1z was used for the reaction probably due to the β-elimination of the palladium intermediate A (see Figure and Scheme ). These results (Figures and ) further demonstrated that the generation and reactivities of oxyallyl cations/Pd-oxyallyl hinge heavily on its substituents, as observed and calculated by others. ,, …”

“…We now report the catalytic generation, identification, and reaction of vinyl Pd-oxyallyl intermediate T4 . Interestingly, in contrast with the nucleophilic reactivity of Pd-oxyallyl reported previously, − this vinyl Pd-oxyallyl T4 displayed both electrophilic and nucleophilic properties which enabled the first efficient intermolecular [5 + 3] annulations for the construction of various highly functionalized nonbridged cyclooctanoids . Eight-membered carbocycles are well-known medium-sized rings and are encountered in some bioactive and natural products; their diverse synthesis via intermolecular annulation is often difficult due to the high ring strain, complex conformational properties, and repulsive transannular interactions .…”

“…In contrast, catalytic generation and cycloaddition of oxyallyl cations has been much less investigated despite the fact its synthetic potential has been unveiled as early as the 1990s . Recent work by Trost and co-workers, in combination with calculations by the Houk group, uncovered intermolecular (3 + 2) annulations between Pd-oxyallyl species and electron-rich dienes; this pioneering work demonstrated that the reactivities of the Pd-oxyallyl intermediate vary with substituents; , the use of appropriate ligands also proved to be crucial for efficient reactions in this Pd-based catalytic system. The Zi group recently reported an intriguing synthesis of carbocycles via the intermediacy of Pd-oxyallyls featuring an electron-withdrawing group in the presence of a Lewis acid .…”

“…The Zi group recently reported an intriguing synthesis of carbocycles via the intermediacy of Pd-oxyallyls featuring an electron-withdrawing group in the presence of a Lewis acid . Though synthetically capable, oxyallyl intermediates typically exhibit electrophilic properties in cycloadditions, and favor the electron-rich alkenes or dienes as partners (Scheme a). − This greatly limits their application in synthesis. Accordingly, the exploration of nucleophilic reactivities of Pd-oxyallyl species is quite challenging (Scheme a).…”

Enantioselective Inverse Electron Demand (3 + 2) Cycloaddition of Palladium-Oxyallyl Enabled by a Hydrogen-Bond-Donating Ligand

“…In this elegant work, they combined a protected ester-substituted enol ether with a Pd(0) catalyst to generate a Pd-oxyallyl, which cyclizes with 1,3-dienes to produce (3 + 2) cycloaddition products. Density functional theory (DFT) calculations by Chen and Houk revealed that the electron-withdrawing ester substituent is crucial because it decreases the energy of the LUMO of the Pd-oxyallyl species, leading to a more favorable energy match with the HOMO of the diene . Trost’s pioneering work paved the way for the discovery of new catalytic Pd-oxyallyl cycloaddition reactions .…”