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Enantioselective Cleavage of Cyclobutanols Through Ir‐Catalyzed C−C Bond Activation: Mechanistic and Synthetic Aspects
Author(s) -
Ratsch Friederike,
Strache Joss Pepe,
Schlundt Waldemar,
Neudörfl JörgMartin,
Adler Andreas,
Aziz Sarwar,
Goldfuss Bernd,
Schmalz HansGünther
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202004843
Subject(s) - desymmetrization , enantioselective synthesis , chemistry , catalysis , toluene , reductive elimination , bond cleavage , chirality (physics) , stereochemistry , hydride , transition state , ligand (biochemistry) , medicinal chemistry , combinatorial chemistry , organic chemistry , metal , biochemistry , chiral symmetry breaking , physics , receptor , quantum mechanics , quark , nambu–jona lasinio model
The Ir‐catalyzed conversion of prochiral tert ‐cyclobutanols to β‐methyl‐substituted ketones proceeds under comparably mild conditions in toluene (45–110 °C) and is particularly suited for the enantioselective desymmetrization of β‐oxy‐substituted substrates to give products with a quaternary chirality center with up to 95 % ee using DTBM‐SegPhos as a chiral ligand. Deuteration experiments and kinetic isotope effect measurements revealed major mechanistic differences to related Rh I ‐catalyzed transformations. Supported by DFT calculations we propose the initial formation of an Ir III hydride intermediate, which then undergoes a β‐C elimination (C−C bond activation) prior to reductive C−H elimination. The computational model also allows the prediction of the stereochemical outcome. The Ir‐catalyzed cyclobutanol cleavage is broadly applicable but fails for substrates bearing strongly coordinating groups. The method is of particular value for the stereo‐controlled synthesis of substituted chromanes related to the tocopherols and other natural products.