Palladium(0)‐Catalyzed Allylation Reaction with Dimethyl 2‐fluoromalonate

Abstract

The palladium(0)‐catalyzed allylation reaction of dimethyl 2‐fluoromalonate with allylic carbonates proceeds smoothly under neutral conditions to give the SN2 allylation product. However, using the nucleophile NaCF(CO2Et)2 under basic conditions increased the chemical yield. Moreover, the SN2′ allylation product was increased up to 75% yield.

Stereoselective Allylic Alkylations of Amino Ketones and Their Application in the Synthesis of Highly Functionalized Piperidines

“…This might be the reason why these types of allylic substrates have been used only very sporadically in palladium-catalyzed allylic alkylations. [22] The corresponding methyl-substituted allylic substrates can easily be obtained from O-protected lactic acid ester via Dibal reduction/H orner-Wadsworth-Emmons( HWE) olefination, which providest he corresponding a,b-unsaturated ester 7a and ketone 8a as single (E)-isomer,w hile in case of nitrile 9a a 3:7( E/Z)-mixture was obtained, whichc ould easily be separated by flash chromatography.I faBoc-protecting group was used on the lactate, the leaving group for the allylic alkylation could directly be introduced. In case of other carbamates it is recommended to introducet his leaving group after the HWE reaction, because Dibal reduction in this case resulted in the formation of side products.…”

“…In addition, these allylic substrates might undergo deprotonation of the π‐allyl Pd intermediate under the basic reaction conditions, providing electron‐poor dienes, which might also cause side reactions. This might be the reason why these types of allylic substrates have been used only very sporadically in palladium‐catalyzed allylic alkylations …”

Transition‐Metal‐Catalyzed Monofluoroalkylation: Strategies for the Synthesis of Alkyl Fluorides by C−C Bond Formation

“…In 1999, Kitazume and co-workers reported the allylation of afluorinated C-nucleophile catalyzed by atransition-metal complex in neutral and basic conditions.I nt he presence of Pd(PPh 3 ) 4 ,d iethyl 2-fluoromalonate underwent allylation with av ariety of substituted primary and secondary allylic carbonates in moderate to excellent yield and with high selectivity for nucleophilic attack at the less hindered terminus (Scheme 31). [58] Thea uthors noted that, although "palladium-catalyzed allylation reactions have been recognized to be useful for organic synthesis,t heir synthetic value in fluorine chemistry still appears to be underestimated." Indeed, this initial report set the stage for many subsequent developments with this class of reaction.…”

Copper-Catalyzed Monofluoroalkylation of Allyl Phosphates with Nucleophilic Ethyl 2-Fluoro-2-(trimethylsilyl)acetate

“…For a long time, it has been stuck on palladium-catalyzed and iridium-catalyzed reagents, in which the nucleophilic reagents are also very limited. For example, since CHF­(CO 2 Et) 2 and CF 3 CH­(F)­CO 2 Et were used in the palladium-catalyzed allyl monofluoroalkylation reaction in 1999, palladium-catalyzed asymmetric allyl monofluoroalkylation reactions were also developed by using EtO 2 CCHFPO­(OEt) 2 , CHF­(CO 2 Me) 2 , , or PhO 2 SCHFCO 2 Me as a nucleophilic reagent (Scheme A). Similarly, the use of (PhCO)­CFHCO 2 Et, and CHF­(CO 2 Me) 2 as nucleophilic reagents in iridium-catalyzed asymmetric allyl monofluoroalkylation reactions has been reported (Scheme B).…”