Weinreb Amides as Directing Groups for Transition Metal-Catalyzed C-H Functionalizations

Abstract

Weinreb amides are a privileged, multi-functional group with well-established utility in classical synthesis. Recently, several studies have demonstrated the use of Weinreb amides as interesting substrates in transition metal-catalyzed C-H functionalization reactions. Herein, we review this part of the literature, including the metal catalysts, transformations explored so far and specific insights from mechanistic studies.

Rhodium-Catalyzed Oxidative Annulation of 2- or 7-Arylindoles with Alkenes/Alkynes Using Molecular Oxygen as the Sole Oxidant Enabled by Quaternary Ammonium Salt

“…A similar yield was obtained when Me 4 NOAc (1 equiv.) was added (entry 3), while other quaternary ammonium salts gave inferior results (entries [4][5][6][7][8][9][10][11]. Control experiments have shown that no reaction occurred in the absence of rhodium catalyst or molecular oxygen (entry 12).…”

“…C-H functionalization, including the reaction of a C-H bond with a (pseudo)halide, the reaction of a C-H bond with an organometallic reagent, and cross-coupling between two C-H bonds (CDC reaction), has gained tremendous popularity in recent years as a methodology for the construction of C-C bonds or C-heteroatom bonds [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Among these reactions, the CDC reaction is especially noteworthy because this reaction precludes both coupling partners from pre-functionalization, and as a result has high step economy and atom economy [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

C–H Functionalization of Aromatic Amides

“…Interestingly, there are few related comments in this field. In 2016, Yu's group used a large number of examples to comment and summarize the C–H activation reaction using N ‐methoxyamide as a versatile directing group; In 2017, Kapur and co‐workers published a review on the proximal C–H functional groups of aromatic amides and anilines using amides as weak coordination groups; In 2019, the Pilarski team summarized Weinreb amide‐directed C–H functionalization from the perspective of catalyst and mechanism . However, in the few examples mentioned above, the scope of coverage is relatively narrow, either to comment on the functionalization of a specific directing group or to summarize the functionalization of a specific reaction site.…”

Ruthenium (II) Catalyzed C(sp2)−H Bond Alkenylation of 2‐Arylbenzo[d]oxazole and 2‐Arylbenzo[d]thiazole with Unactivated Olefins

“…The reports on the Pd(II)‐catalyzed aryl C−H alkenylation for late stage functionalization to generate analogs of the COX‐2 selective anti‐inflammatory drug celecoxib, [8] the Ru(II)‐catalyzed aromatic ring alkenylation [9] via C−H activation directed by the oxazolidinone heterocycle, essential pharmacophoric feature of diverse therapeutic agents, [10] and the late‐stage arylation of pharmaceuticals by cyclo‐metallated ruthenium catalyst [11] caught our attention. Furthermore, assistance of directing groups (DGs) [4a–i] are required for C−H activation to enhance the selectivity and reactivity but often the pendant DG is not required in the product. Thus, the incorporation of the DGs and their post C−H activation removal require additional synthetic steps undermining the proclaimed step‐economical advantage of the C−H activation strategy.…”