Asymmetric Allylic Alkylation of Cyclic Vinylogous Esters and Thioesters by Pd‐Catalyzed Decarboxylation of Enol Carbonate and β‐Ketoester Substrates

Abstract

Excellent yields and enantioselectivities were achieved for the palladium‐catalyzed asymmetric allylic alkylation of vinylogous thioesters. The close‐to‐neutral reaction conditions ensure that this reaction can tolerate a wide range of functionalities. Furthermore, this approach provides a convenient protocol for the synthesis of synthetically important α,α‐ and γ,γ‐disubstituted cycloalkenones.

A cooperative N-heterocyclic carbene/palladium catalysis system

“…The substitution of the allyl moiety was also explored and found to be detrimental to reactivity. This limitation is similar to many reported transition metal-catalyzed allylation methods 16 and is likely a result of unfavorable steric interactions. Investigations to understand this current restriction with our NHC/Pd platform are ongoing.…”

Metal catalyzed allylic alkylation: its development in the Trost laboratories

“…The use of the allyl ester of a methylated β-ketoester as in eq 71, which derives by methylation of the unsubstituted β- ketoester, works best when the enol substituent is phenoxy. 72 Replacing phenoxy by phenylthio ( 54 , eq 72, path b) gives an even better process. The most reactive substrate is enol thioether 55 which gives a quantitative yield of allylated product 56 .…”

Asymmetric Dearomatization/Cyclization Enables Access to Polycyclic Chemotypes

“…For Tsuji-Trost allylic alkylations involving prochiral π-allyl complexes, a wall/flap cartoon mnemonic aids in predicting stereochemical outcomes. [10] This model has also been used to predict the facial discrimination of simple prochiral enolates. [10b-d] Lloyd-Jones, Norrby, and coworkers have reported computational and NMR studies indicating that, in contrast to the C 2 -symmetric geometry assumed in the wall/flap model, experimental evidence suggests that the allyl group is situated remotely from the DACH ligand in a complex that is not symmetric on the NMR timescale.…”