{"doi":"10.1021/jacs.3c04223","title":"Enhancing Substrate–Metal Catalyst Affinity via Hydrogen Bonding: Pd(II)-Catalyzed β-C(sp<sup>3</sup>)–H Bromination of Free Carboxylic Acids","abstract":"The achievement of sufficient substrate–metal catalyst affinity is a fundamental challenge for the development of synthetically useful C–H activation reactions of weakly coordinating native substrates. While hydrogen bonding has been harnessed to bias site selectivity in existing C(sp 2 )–H activation reactions, the potential for designing catalysts with hydrogen bond donors (HBDs) to enhance catalyst–substrate affinity and, thereby, facilitate otherwise unreactive C(sp 3 )–H activation remains to be demonstrated. Herein, we report the discovery of a ligand scaffold containing a remote amide motif that can form a favorable meta -macrocyclic hydrogen bonding interaction with the aliphatic acid substrate. The utility of this ligand scaffold is demonstrated through the development of an unprecedented C(sp 3 )–H bromination of α-tertiary and α-quaternary free carboxylic acids, which proceeds in exceedingly high mono -selectivity. The geometric relationship between the NHAc hydrogen bond donor and the coordinating quinoline ligand is crucial for forming the meta -macrocyclophane-like hydrogen bonding interaction, which provides a guideline for the future design of catalysts employing secondary interactions.","journal":"Journal of the American Chemical Society","year":2023,"id":324029,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":641128,"name":"Guangrong Meng","orcid":"0000-0002-3023-0654","position":1,"is_corresponding":false},{"id":351359,"name":"Xiangyang Chen","orcid":"0000-0002-6981-7022","position":2,"is_corresponding":false},{"id":1039430,"name":"Joseph S Yoon","orcid":"0000-0003-4045-195X","position":3,"is_corresponding":false},{"id":1039431,"name":"Jing‐Ran Shan","orcid":"0009-0007-7968-7595","position":4,"is_corresponding":false},{"id":876368,"name":"Nikita Chekshin","orcid":"0000-0002-9687-3310","position":5,"is_corresponding":false},{"id":1025119,"name":"Daniel A. Strassfeld","orcid":"0000-0003-3598-0793","position":6,"is_corresponding":false},{"id":857601,"name":"Tao Sheng","orcid":"0000-0001-5339-9834","position":7,"is_corresponding":false},{"id":351360,"name":"Zhe Zhuang","orcid":"0000-0001-6679-0496","position":8,"is_corresponding":false},{"id":647889,"name":"Rodolphe Jazzar","orcid":"0000-0002-4156-7826","position":9,"is_corresponding":false},{"id":647888,"name":"Guy Bertrand","orcid":"0000-0003-2623-2363","position":10,"is_corresponding":false},{"id":292448,"name":"K. N. Houk","orcid":"0000-0002-8387-5261","position":11,"is_corresponding":false},{"id":321507,"name":"Jin‐Quan Yu","orcid":"0000-0003-3560-5774","position":12,"is_corresponding":false},{"id":857603,"name":"Liang Hu","orcid":"0000-0002-2960-9560","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:08:06.496579Z","pmid":"37487009","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}