Over the past few years our group has described a new type of alkene difunctionalization reaction in which aryl or alkenyl triflates bearing tethered alkenes are coupled with various nucleophiles to afford carbocyclic products. The products are formed in moderate to good chemical yield, with generally high levels of stereoselectivity. Our progress to date in this area, which includes reactions of amine, alcohol, enolate, and indole nucleophiles, is described in this review. Scheme 4. Optimization of the Enantioselective Reaction Scheme 5. Enantioselective alkene carboamination reactions Scheme 6. Carboamination reactions of cyclic alkenyl triflates Review Isr. J. Chem. 2020, 60, 259 -267 66 % yield, reproducible Scheme 13. Reactions of indole nucleophiles
The Pd-catalyzed coupling of malonate nucleophiles with alkenes bearing tethered aryl or alkenyl triflates is described. These alkene difunctionalization reactions afford malonate-substituted cyclopentanes that contain fused aryl or cycloalkenyl rings. The transformations generate a fivemembered ring, two CC bonds, and provide products bearing up to three stereocenters with good chemical yield and generally high diastereoselectivity.
Regiodivergent palladium-catalyzed alkene difunctionalization reactions between diethyl malonate and 1,5-dienes bearing a triflate group at C2 are described. Use of tris(2,4-di-tert-butylphenyl)phosphite as a ligand leads to 4-exo-cyclization/ functionalization to afford malonate-substituted methylene cyclobutanes. In contrast, the 1,2-bis(diphenylphosphino)benzene ligand provides methylene cyclopentanes via 5-endo-cyclization/functionalization. The five-membered ring-forming reactions occur via anticarbopalladation of the enolate nucleophile, whereas four-membered ring-forming reactions proceed through syn-4-exo-migratory insertion of the tethered alkene, followed by C(sp 3 )−C(sp 3 ) bond-forming reductive elimination from an (alkyl)Pd(II)(malonate) complex.
Palladium-catalyzed alkene difunctionalization reactions between alkenes bearing tethered aryl or alkenyl triflates and enolate nucleophiles are described. The transformations form two C−C bonds, a ring, and up to two stereocenters while producing substituted cyclopentane derivatives that contain appended carbonyl functionality. Products are formed with up to >20:1 diastereoselectivity, and the formation of sterically congested bonds between quaternary carbon atoms is feasible.
The Pd-catalyzed coupling of 1,5-diene-2-yl triflates with amine nucleophiles affords exomethylenecyclobutanes bearing dialkylaminomethyl groups at C2. The strained carbocyclic products are obtained in moderate to excellent yields, with regioselectivities of up to >95:5 for four-membered ring formation. The mechanism of these reactions, which provides products resulting from anti-addition to alkenes, differs from related reactions involving malonate nucleophiles that provide syn-addition products.
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