We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular SAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand O-SpiroPAP derived from O-SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H.
A NiH-catalyzed thioether-directed
cyclometalation strategy is
developed to enable remote methylene C–H bond amidation of
unactivated alkenes. Due to the preference for five-membered nickelacycle
formation, the chain-walking isomerization initiated by the NiH insertion
to an alkene can be terminated at the γ-methylene site remote
from the alkene moiety. By employing 2,9-dibutyl-1,10-phenanthroline
(L4) as the ligand and dioxazolones as the reagent, the
amidation occurs at the γ-C(sp3)–H bonds to
afford the amide products in up to 90% yield (>40 examples) with
remarkable
regioselectivity (up to 24:1 rr).
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