Diastereo‐ and Enantioselective Construction of Vicinal All‐Carbon Quaternary Stereocenters via Iridium/Europium Bimetallic Catalysis

Abstract

The diastereo-and enantioselective construction of vicinal all-carbon quaternary stereocenters is a formidable task. We here report a synergistic bimetallic catalysis via a chiral N,N'-dioxide-europium (Eu) complex and a phosphoramidite-iridium (Ir) catalyst for the asymmetric allylation of oxindole derivatives by using challenging trisubstituted allylic esters. The allylated products bearing vicinal all-carbon quaternary stereocenters were obtained with good diastereoselectivities (up to 20 : 1 dr) and excellent enantioselectivities (up to 99 % ee). Control experiments showed that the complementary diastereomers of the products were not accessible by the change of the stereochemistry of the chiral N,N'-dioxide ligand.

Catalytic stereodivergent allylic alkylation of 2-acylimidazoles for natural product synthesis

“…1b ) 13 – 23 . Remarkable advancements have been made in this domain through the synergistic interplay of discrete catalytic processes to achieve stereodivergent product formation 24 – 33 . Various nucleophilic substrates, including α-hydroxy ketones 34 , aldimine esters 35 – 37 , pentafluorophenyl esters 38 – 40 , azaaryl acetamides 41 – 43 , and oxindoles 44 have been successfully employed in these dual-catalyzed stereodivergent synthesis.…”

Asymmetric Synthesis of Hydroindoles via Desymmetrizing [3+2] Annulation of p-Quinamines and Arylalkylketenes

“…Using a chiral NHC catalyst to deliver enantiocontrol of quaternary carbon-based hydroindoles resulted in moderate results . Quaternary stereogenic centers are also privileged structural features, whose enantioselective construction represents significant synthetic challenge . Although asymmetric annulation of ketenes to construct quaternary carbon centers has been achieved in the reactions with oxaziridines, ketones, or α,β-unsaturated carbonyls, the reaction with p -quinamines remains challenging because the enantioselective control also involves a desymmetrization issue.…”

Catalytic Asymmetric Synthesis of Vicinal Quaternary Stereocenters Enabled by Alkylation of α,α-Disubstituted Aldehydes with 3-Bromooxindoles

“…Generally, strategies for C3 functionlization of oxindoles or 3-bromooxindoles are often adopted for this purpose. For oxindoles, elegant methodologies for reverse allylation and ring opening of aziridines have been reported (Scheme a), while 3-bromooxindoles are used as precursors to o -azaxylylene (indol-2-one) intermediates whose electrophilicity can be maneuvered and applied in a number of asymmetric conjugate addition reactions . In particular, the stereoselective formation of vicinal quaternary carbon centers between 3-bromooxindoles and 3-substituted indoles and oxindoles, β-naphthols, silyl ketene imines, and allyl stannanes has been established (Scheme b).…”