Bulky Chiral Carbene Ligands and Their Application in the Palladium‐Catalyzed Asymmetric Intramolecular α‐Arylation of Amides

Abstract

Bring on the big cats: New, C2-symmetric bulky N-heterocyclic carbene ligands bring major improvements in the palladium-catalyzed asymmetric intramolecular α-arylation of amides to give oxindoles (see picture, dba=trans,trans-dibenzylideneacetone), which are formed in high yield and excellent enantiomeric purity

The Palladium Catalyzed Asymmetric Addition of Oxindoles and Allenes: An Atom-Economical Versatile Method for the Construction of Chiral Indole Alkaloids

“…Hydrogenolysis 23 of allylic acetate 18 led to 19a and 19b as an inseparable 7:1 mixture. Comparison of the optical rotation of this mixture to that in the literature 10d, 17b established the ( R )-configuration at the α-quaternary stereocenter of oxindole 17 . Additionally, it should be noted that partial racemization occurred during the hydrogenolysis, presumably due to Pd-catalyzed retro-allylic alkylation of 19a followed by non-selective recombination.…”

“…7 Because of the importance of this structural motif, and due to the significant challenge in preparing quaternary stereocenters in an asymmetric fashion, 8 there has been a significant interest by the chemical community to develop methodologies that lead to 3,3-disubstituted oxindoles in an asymmetric fashion. 9–18 Asymmetric syntheses of these oxindole units have been realized using the intramolecular Heck reaction, 9 α-arylation 10 or α-alkylation 11 reactions, intramolecular acyl migration, 12 Pd-catalyzed cyanoamidation, 13 Pd- and Mo-catalyzed allylic alkylation, 14 aldol 15 processes, cycloaddition reactions, 16 Claisen rearrangements, 17 and through the use of a variety of organocatalytic methods. 18 Thus, we reasoned that a catalyst controlled addition of oxindole nucleophiles to allenes would be an important addition to this list of reactions to enable preparation of 3,3-disubstituted oxindoles in nonracemic form.…”

Palladium(II)-Catalyzed Alkene Functionalization via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications

“…While 7-NHC 175 gave products with moderate levels of enantioselectivity, the bicyclic products were formed in only 35% yield. The chiral, cyclometalated five-membered NHC complex 176 132 catalyzed the reaction in similar yield, though without asymmetric induction.…”

Organocatalytic Michael Addition of Malonates to Isatylidene‐3‐acetaldehydes: Application to the Total Synthesis of (−)‐Debromoflustramine E

“…Oxindoles bearing a quaternary carbon stereocenter at the 3‐position are ubiquitous in nature and have been shown to be valuable building blocks for alkaloid synthesis 1. Several strategies have been developed to achieve the enantioselective synthesis of 3,3′‐disubstituted oxindoles, including 1) the direct functionalization of 3‐substituted oxindoles;2 2) intramolecular coupling reactions (Heck3 and arylation reactions4); 3) the rearrangement of indolyl acetates and carbonates;5 and 4) the alkylation of 3‐halooxindoles or 3‐hydroxyoxindoles 6…”