Palladium‐Catalyzed ortho C−H Arylation of Benzaldehydes Using ortho‐Sulfinyl Aniline as Transient Auxiliary

Abstract

A Pd -catalyzed ortho-(Csp )-H arylation reaction of benzaldehydes using a catalytic amount of 2-(methylsulfinyl)aniline as transient auxiliary was developed. This reaction is compatible with a broad range of benzaldehyde and aryl iodide substrates. Compared with other related reaction systems, an excellent regioselectivity for ortho-C(sp )-H bonds over benzylic C(sp )-H bonds was obtained for ortho-alkyl-benzaldehyde substrates.

Hexafluoroisopropanol: the magical solvent for Pd-catalyzed C–H activation

“… 71 This result was the outcome of the cooperative effect between the transient directing group and external pyridone ligands in HFIP solvent medium. In addition, other research groups like Jin, 72 Ge and Li, 73 and Chen in collaboration with He, 74 Wei, 75 and Zhang 76 also contributed with their valuable results to enrich this area. However, the exact role of HFIP in the aforementioned reactions is still unknown, presumably due to the lack of computational and mechanistic studies.…”

Monodentate Transient Directing Group Enabled Pd-Catalyzed Ortho-C–H Methoxylation and Chlorination of Benzaldehydes

“…Omitting the covalent installation and removal of the stoichiometric directing groups, transient directing groups (TDGs), which form reversible linkages with the substrates in situ, constitute a promising alternative approach to direct metal-catalyzed C–H functionalizations . Since Yu’s breakthrough work employing amino acids as bidentate transient directing groups (BiTDGs) for Pd-catalyzed arylation of o -alkyl benzaldehydes and ketones, a set of small organic molecules, such as 3-aminopropanoic acid, acetohydrazide, 2-amino-2-methyl-propionic acid, anthranilic acid, , orthanilic acid, o -sulfinyl aniline, and 2-hydroxynicotinaldehyde, have been successfully utilized as suitable BiTDGs to enable Pd-catalyzed various C–H functionalizations by our and other groups. Generally, for the above BiTDG activation models, the imine provides the first neutral coordinating site, while the second coordinating site is required to form the stable 5- or 6-membered cyclopalladium intermediate, and most of the achievements for BiTDG-assisted Pd catalysis are restricted in C–H arylation (Scheme a) .…”

“…It is well-known that a multitude of nitrogen-based motifs, such as heterocycles, imines, and azo groups, have been widely employed as monodentate directing groups due to their strong coordination to various metals . However, Pd-catalyzed C–H functionalization using a structurally similar monodentate transient directing group (MonoTDG) remain rare and give generally low yields. , Therefore, the investigation of a new MonoTDG strategy allowing flexible and diverse reactivities is of great importance and highly desirable. Our continuous focus on TDG-mediated C–H functionalizations , prompted us to develop a new catalytic strategy for direct ortho -C–H functionalizations of benzaldehydes via Pd catalysis.…”

Transient Directing Groups in Metal−Organic Cooperative Catalysis

“…In this case also, the reaction would proceed via a fairly stable fused 5,5-membered palladabicycle that could be isolated as its acetate complex in 85 % and further characterized by X-ray diffraction analysis (Scheme 22, f). [49] Overall, these processes presumably proceeded through a similar mechanism, as depicted in Scheme 21.…”