The first regio-, diastereo- and enantioselective allylic alkylation of acyclic β-ketoesters to form vicinal tertiary and all-carbon quaternary stereocenters is reported. Critical to the successful development of this method was the employment of iridium catalysis in concert with N-aryl-phosphoramidite ligands. Broad functional group tolerance is observed at the keto-, ester-, and α-positions of the nucleophile. Various transformations demonstrating the utility of this method for rapidly accessing complex enantioenriched compounds are reported.
Highly congested vicinal stereocenters comprised of tertiary and all-carbon quaternary centers were generated via Ir-catalyzed asymmetric allylic alkylation of β-ketoesters. These catalytic reactions proceed in excellent yields with a broad scope on either reaction partner, and with outstanding regio-, diastereo-, and enantiocontrol. Implementation of a subsequent Pd-catalyzed alkylation affords dialkylated products with pinpoint stereochemical control of both chiral centers.
No Strain, No Gain! The first transition metal-catalyzed enantioselective α-alkylation of cyclobutanones is reported. This method employs palladium catalysis and an electron deficient PHOX type ligand to afford all–carbon α-quaternary cyclobutanones in good to excellent yields and enantioselectivities.
The development of (trimethylsilyl)ethyl
ester protected enolates
is reported. The application of this class of compounds in palladium-catalyzed
asymmetric allylic alkylation is explored, yielding a variety of α-quaternary
six- and seven-membered ketones and lactams. Independent coupling
partner synthesis engenders enhanced allyl substrate scope relative
to traditional β-ketoester substrates; highly functionalized
α-quaternary ketones generated by the union of (trimethylsilyl)ethyl
β-ketoesters and sensitive allylic alkylation coupling partners
serve to demonstrate the utility of this method for complex fragment
coupling.
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