McGrew GI, Stanciu C, Zhang J, Carroll PJ, Dreher SD, * Walsh PJ. * University of
Pennsylvania, Philadelphia and Merck and Co. Inc., Rahway, USA
Asymmetric Cross-Coupling of Aryl Triflates to the Benzylic Position of Benzylamines.
Angew. Chem. Int. Ed. 2012;
51: 11510-11513
Key words
iridium - hydrogenation - pyridinium salts
Significance
The authors previously described the application of (η6-C6H5CH2R)Cr(CO)3 complexes as nucleophile precursors in Pd-catalyzed allylic substitution reactions
(J. Am. Chem. Soc. 2011, 133, 20552). They now report the first catalytic asymmetric cross-coupling of benzyllithiums
α to tertiary amines using [Cr(CO)3] activation of benzylic C–H bonds. The stabilized organolithium undergoes Pd-catalyzed
coupling with aryl triflates by dynamic kinetic resolution to yield enantioenriched
Cr-coordinated diarylmethylamines in good to high yield, which can be de-complexed
by exposure to sunlight and air.
Comment
Development of an enantioselective version of the previously reported transformation
is challenging as it requires the enantioenriched palldium catalyst to select for
one of the chromium adducts faster than the other, and also requires the products
to be impervious to racemization. High-throughput screening identified the chiral
ligand Cy-Mandyphos, and that the addition of PMDETA and toluene as co-solvents increased
the yield. The authors report future plans to close the catalytic cycle by focusing
on an arene exchange between the chromium-complexed product and the free arene to
liberate the product and regenerate the substrate.
