Decoding Directing Groups and Their Pivotal Role in C−H Activation

Abstract

Scheme 2. Amides derived from the acetylation of anilines used as directing group in metal-catalyzed CÀ H activations.

Transient Directing Groups in Metal−Organic Cooperative Catalysis

“…In this process, various benzaldehydes as well as benzothiophene-and thiophene-3-carbaldehydes could be heteroarylated in moderate to good yields (Scheme 26). [54] As a note, the authors could observe that the substrates underwent a double CÀ H activation towards benzo [4,5]thieno [3,2-c]isoquinolines under the reaction conditions with a range of benzothiophenes when using βalanine as the transient directing mediator in HFIP.…”

“…In this context, the direct functionalization of C(sp 2 )À H bonds in arenes has received a great deal of attention over the last decades and still constitutes a challenge of utmost importance. [4,7,8] For arenes whose innate reactivity cannot be used for the selective functionalization of one of their C(sp 2 )À H bonds or to bypass this innate reactivity, the use of directing groups is usually the best option and has been extensively studied. In most cases however, the directing group needs to be installed and cleaved -whenever possible -in at least two separate steps, diminishing the attractiveness and utility of the overall process.…”

“…Among all possible transient directing groups that could be reversibly installed onto an arene, imines have been the most studied, which has resulted in the development of efficient and selective processes for the functionalization of C(sp 2 )À H bonds in benzaldehydes. [7i,j,m] While their functionalization typically relies on the use of either uncleavable directing groups or intrinsic aldehyde weak coordinating groups in the cases of ortho-functionalization, [4] the use of imine transient directing groups has enabled the development of a range of transformations such as arylations, alkylations, aminations, or even selenations: these will be discussed in the following sections, starting with arylation reactions.…”

“…[3] The other and probably more general strategy is based on the use of directing groups embedded in the substrate, either acting as mono-or bidentate ligands for a transition-metal catalyst that will, upon coordination of the latter, bring the metallic center in close proximity to a specific, relatively inert, CÀ H bond to be activated and enable its selective functionalization (Scheme 1, a). [4] While this strategy is highly attractive, avoiding the prefunctionalization of the substrate mentioned above, the directing group moiety needs, most of the time, to be installed before and cleaved after the CÀ H bond functionalization event, therefore requiring at least two additional and unwanted synthetic transformations. Moreover, the cleavage of the directing group often turns out to be rather tricky, requiring harsh conditions, or even not possible.…”

Ruthenium‐Catalyzed Sulfoalkenylation of Acetanilides and Dual‐Use of the Catalyst Directing Group

“…[5][6][7] The oxidative coupling of alkenes and arenes was originally discovered by Fujiwara and Moritani more than fifty years ago for Pd(II) catalysts. [8][9] The reaction lay dormant until the early 2000's when De Vries, van Leeuwen and co-workers found that benzoquinone is a suitable oxidant and that a catalyst-directing group (CDG) [10] facilitates the reaction and enables regioselectivity. [11] Our interest in this chemistry stems from earlier investigations into the dual use of acetamides as catalyst-directing groups in CÀ H-activation reactions and their subsequent traceless removal through the deacetylation-diazotation-coupling sequence (DDC-sequence) [12] previously developed in our group.…”