Transient imines as ‘next generation’ directing groups for the catalytic functionalisation of C–H bonds in a single operation

Abstract

C-H functionalisation promises a paradigm shift in synthetic planning. However, the additional steps often required to install and remove directing groups currently detract from the efficiency. The strategy of reversible installation of a directing group via an imine linkage has recently emerged, with the imine formed and hydrolysed in situ. Such transient directing groups can promote transition metal catalysed functionalisation of unactivated C-H bonds of aldehydes, ketones and amines. This approach removes additional steps usually required for covalent directing groups and can use catalytic quantities of the imine forming component. This review updates the rapidly developing field of transient directing groups for C-H functionalisation on sp and sp carbon centres, to form new C-C and C-X bonds. We focus on the structures of the transient directing groups as mono or bidentate coordinating groups for various metal catalysts.

Rhodium‐Catalyzed C(sp2)‐ or C(sp3)−H Bond Functionalization Assisted by Removable Directing Groups

“…[16,42,43] Fore xample,awell-known directing group for functionalizing an alcohol is ap hosphinite or carbamate group.I mines were also explored as directing groups for carbonyl-containing compounds,a st hese permit the original carbonyl group to be regenerated after hydrolysis. [16,42,43] Fore xample,awell-known directing group for functionalizing an alcohol is ap hosphinite or carbamate group.I mines were also explored as directing groups for carbonyl-containing compounds,a st hese permit the original carbonyl group to be regenerated after hydrolysis.…”

“…An enormous number of studies based on the two approaches shown in Scheme 1h ave been reported to date and as eries of directing groups have been used (Scheme 2). [16,42,43] Fore xample,awell-known directing group for functionalizing an alcohol is ap hosphinite or carbamate group.I mines were also explored as directing groups for carbonyl-containing compounds,a st hese permit the original carbonyl group to be regenerated after hydrolysis.…”

“…Since this research area is atopic of current interest, numerous research groups have focused on the directed functionalization of C(sp 2 )ÀHaswell as C(sp 3 )ÀHbonds. [42][43][44][45] Avariety of transition-metal complexes including first, second, and third row,a nd even lanthanides have been used in directed CÀHfunctionalization reactions.Among them, the most popular are Fe,Co, Ni, Cu, Ru, Rh, Pd, and Ir catalysts. [39][40][41] Furthermore,atransient directing group directed C À H functionalization related to this Review was also reviewed by several research groups.…”

“…[39][40][41] Furthermore,atransient directing group directed C À H functionalization related to this Review was also reviewed by several research groups. [42][43][44][45] Avariety of transition-metal complexes including first, second, and third row,a nd even lanthanides have been used in directed CÀHfunctionalization reactions.Among them, the most popular are Fe,Co, Ni, Cu, Ru, Rh, Pd, and Ir catalysts. [46,47] One of the characteristic features in the case of Rh catalysts is that various rhodium complexes in various oxidation states (0, 1, 2, and 3), such as Rh 4 (CO) 12 ,R hCl(PPh 3 ) 3 ,[ Rh(OAc) 2 ] 2 ,a nd [Cp*RhCl 2 ] 2 are readily available that actively catalyze various catalytic reactions.G iven such av ariety of catalytic systems,R hcatalyzed directed CÀHfunctionalization reactions have been extensively studied in regard to anumber of transformations, including alkylation, arylation, alkenylation, alkynylation, halogenation, chalcogenation, acylation, inter-orintramolecular annulation.…”

Access to indolines from primary phenylethylamines by an unexpected palladium-catalyzed C–H functionalization process

“…The in situ formation of imines to promote the metal-catalyzed C-H activation has been recently used to functionalize sp 2 and sp 3 C-H bonds. 14 Accordingly, we next explored the possibility of the in situ preparation of the imine followed by the indoline formation reaction. Our rst attempt using DCE and molecular sieves for Scheme 2 Indolines formation.…”