Ruthenium‐Catalyzed Carbonylation of ortho CH Bonds in Arylacetamides: CH Bond Activation Utilizing a Bidentate‐Chelation System

Abstract

Given that CÀH bonds are ubiquitous in organic chemistry, substrate functionalization by means of CÀH bond activation appears as a challenging, yet straightforward method in organic synthesis, which can eliminate the multiple steps and limitations associated with the preparation of pre-functionalized starting materials. [1] A wide variety of transformations of CÀH bonds have been developed thus far and they have had a significant impact on organic synthesis, not only in academia, but also industrial processes. [2] Regioselectivity is the most important issue that must be addressed in the transformation of CÀ H bonds because organic molecules can have many different types of CÀH bonds. The use of a directing group can, for the most part, overcome the regio-control issues by allowing the catalyst to come into close proximity with the targeted CÀH bonds, which, in most cases, are ortho CÀH bonds. A wide variety of directing groups, such as ketones, esters, aldehydes, cyano, pyridine, and oxazoline derivatives, have been used in the chelation-assisted transformation of CÀH bonds. However, in most cases, structurally simple directing groups that can coordinate to a metal by a monodentate system were utilized. A well-designed bidentate directing group can potentially be used for the exploration of new catalytic reactions that have not yet been achieved using conventional directing groups. The first successful example of a bidentate, directing-group assisted transformation of CÀH bonds was reported by Daugulis et al., who discovered the Pd II -catalyzed arylation of CÀH bonds in amides, which consists of a 8-aminoquinoline moiety. [3] Following such a pioneering finding, a number of reactions using 8-aminoquinoline and picolinamide-based bidentate directing groups have been developed, especially in the case of Pd II -catalyzed reactions. [4] This bidentate directing system is also applicable to other transition-metal-catalyzed transformations of CÀH bonds. In a previous study, we reported that the Ru 0 -catalyzed CÀH bond carbonylation of aromatic amides with a 2-pyridinylmethylamine moiety as the bidentate directing group results in the formation of phthalimides, [5] the formation of which involves the carbonylation of the ortho CÀ H bonds. This new directing group was also applicable to the Ru-catalyzed carbonylation of unactivated C(sp 3 )ÀH bonds in alipthatic amides [6] and the Ni 0 -catalyzed oxidative annulation [a] K. Scheme 1. Carbonylation of phenylacetic amide 1 a. Scheme 2. Screening of directing groups.

Copper‐Mediated CH/CH Biaryl Coupling of Benzoic Acid Derivatives and 1,3‐Azoles

“…Results of control experiments with some structurally similar but monodentate directing groups suggest that an N , N ‐bidentate directing group is crucial for good conversion ( A – C ). Also notable is the inefficiency of other bidentate coordinating groups, such as (2‐pyridylmethyl)amino6a,b,e, 8 and (2‐methylthiophenyl)amino groups4b,d, 7e ( D and E ). In addition to the bidentate nature, the relatively acidic NH in 1 a is also believed to play a pivotal role in the coupling 17…”

Catalytic Functionalization of C(sp2)H and C(sp3)H Bonds by Using Bidentate Directing Groups

“…Chatani and co‐workers reasoned that a bidentate system would bind tightly to the catalyst even under a higher CO pressure, thereby permitting the catalyst to come into proximity to a CH bond, which may then be cleaved. They further successfully applied these reaction conditions to the ortho ‐carbonylation of aromatic acetamides (Scheme with n =1),45 thereby affording a six‐membered cycle. Extension of the reaction to the carbonylation of unactivated C(sp 3 )H bonds was successful (Scheme ) 46.…”

Transition Metal-Catalyzed Carbonylative CH Bond Functionalization of Arenes and C(sp3)H Bond of Alkanes

“…[26] Chatani and coworkers have shown the rutheniumcatalyzed carbonylation of ortho-CAH bonds in arylacetamides using a bidentate-chelation system (Scheme 20). [27,28] The presence of a 2-pyridynylmethyl amine moiety as the bidentate directing group in the substrates is essential for the success of the reaction. The effect of a directing group on the progress of the carbonylation of the CAH bond of phenylacetic amides was examined.…”