Palladium-Catalyzed Site-Selective C(sp³)–H Arylation of Phenylacetaldehydes

Abstract

We describe a Pd-catalyzed selective C–H arylation reaction of phenylacetaldehydes using l-valine as the transient directing group. This process showed a broad substrate scope and excellent selectivity in which a ligand-controlled functionalization of the unactivated β-C­(sp3)–H bond. In addition, enantioselective arylation of phenylacetaldehydes was preliminarily explored by utilizing a bulky chiral transient directing group.

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

“…Recently, Gou et al depicted site-selective C(sp 3 )–H arylation of phenylacetaldehydes centered on a similar idea. 64 Later, in 2017, the same group reported ortho -C(sp 2 )–H arylation of substituted benzaldehydes, where HFIP was used as the key solvent ( Scheme 12B ). 65 α-Substituted amino acids were found to be extremely proficient as a transient moderator ( TDG 2 ) for such transformation.…”

A dual role for acetohydrazide in Pd-catalyzed controlled C(sp3)–H acetoxylation of aldehydes

“…To date only one example of aldehyde-directed ortho-hydroxylations of benzaldehydes via C(sp 2 )-H activation has been reported. 13 Very recently, the transient directing group (TDG) approach has been extended to the palladium-catalyzed ortho-C(sp 3 )-H bond arylations of aldehydes by the groups of Yu, 14 Hu 15 , Chen, 16 Bull, 17 Ge, 18 Wang 19 and Wei. 20 Notably, all these processes called for stoichiometric quantities of silver salts as oxidants and the CHO functional group is not oxidized in the reaction process.…”

Transient Directing Groups in Metal−Organic Cooperative Catalysis

“…These mediators include 2methoxyethylamine, a cheap and efficient mediator reported by the Bull group to promote the β-arylation of aldehydes with iodoarenes as well as an intramolecular version yielding indanes (Scheme 63, a) [111] and L-valine, which was shown to be efficient for the chemoselective C(sp 3 )À H β-arylation of 2,2-alkylmethyl arylacetaldehydes with iodoarenes with good levels of efficiency, although with over-arylations in some cases (Scheme 63, b). [112] In this case, the selectivity observed for the activation of the C(sp 3 )À H over the C(sp 2 )À H bonds was rationalized by the relative stabilities of the corresponding 5-and 6-membered ring palladium intermediates, respectively. Noteworthy, substituting L-valine for L-tert-leucine as the transient directing mediator gave rise to a moderate but promising 40 % ee.…”