We report Pd-catalyzed ortho-C−H methoxylation and chlorination of benzaldehydes by employing monodentate transient directing groups (TDGs) as an alternative strategy to bidentate TDGs. More importantly, a single crystal of benzaldehyde imine ortho-cyclopalladium intermediate was successfully obtained, and its structure was unambiguously determined by X-ray diffraction, which clearly showed that it was a binuclear palladium species bridged by a pyridone ligand. The utility of this approach was further demonstrated through the synthesis of key intermediates of natural products and drugs.
Commercially available 3,5-bis(trifluoromethyl)aniline was found to be a highly efficient monodentate transient directing group (MonoTDG) for the palladium-catalyzed direct dehydrogenative cross-coupling of benzaldehydes with arenes. A diverse set of symmetrical and unsymmetrical 9-fluorenones was readily obtained in yields of 32−72% along with excellent regioselectivities and broad functional group compatibility as well as high atom economy under mild conditions via a dual carbon−hydrogen (C−H) bond activation sequence. Article pubs.acs.org/joc
A diversity-oriented synthesis of useful spirocyclic pyrrolidines was successfully accomplished via late-stage cascade reactions of o-succinimide-substituted benzaldehydes. A catalytic amount of aniline as a transient directing group was efficient for the ruthenium-catalyzed ortho-C(sp)-H alkylation of benzaldehyde with maleimide. The in situ formed imine overrided a series of other traditional directing groups with excellent site selectivities. More importantly, only 0.5 mol % of ruthenium catalyst was sufficient for a 100 mmol scale-up reaction without column chromatography purification.
Benzidine was found to be a novel
transient directing group to
enable Pd-catalyzed direct selenylation of inert C(sp2)–H
bonds of benzaldehydes. Diverse diarylselenides were readily constructed
in high efficiency and satisfactory yields with good functional group
tolerance. The practical usage of the method was further demonstrated
by enlarged reaction to gram scale and application in the facile access
to two selenoxanthenes and one fluorescent probe.
2-Fluoro-5-(trifluoromethyl)aniline
was found to be a suitable
monodentate transient directing group (MonoTDG) to enable Ru(II)-catalyzed
intermolecular direct ortho-C(sp2)–H
imidation of benzaldehydes. N-Tosyloxyphthalimide
was used as an alternative azide-free amidation reagent to achieve
high efficiency and good functional group tolerance. Moreover, the
reaction could be enlarged to gram scale, and the amidated product
could be readily converted into useful quinazoline and fused isoindolinone
scaffolds by one-step derivatization.
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