{"doi":"10.1002/ange.202400509","title":"Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization","abstract":"Abstract In 2001, our curiosity to understand the stereochemistry of C−H metalation with Pd prompted our first studies in Pd(II)‐catalyzed asymmetric C−H activation (RSC Research appointment: 020 7451 2545, Grant: RG 36873, Dec. 2002). We identified four central challenges: 1. poor reactivity of simple Pd salts with native substrates; 2. few strategies to control site selectivity for remote C−H bonds; 3. the lack of chiral catalysts to achieve enantioselectivity via asymmetric C−H metalation, and 4. low practicality due to limited coupling partner scope and the use of specialized oxidants. These challenges necessitated new strategies in catalyst and reaction development. For reactivity , we developed approaches to enhance substrate–catalyst affinity together with novel bifunctional ligands which participate in and accelerate the C−H cleavage step. For site‐selectivity , we introduced the concept of systematically modulating the distance and geometry between a directing template, catalyst, and substrate to selectively access remote C−H bonds. For enantioselectivity , we devised predictable stereomodels for catalyst‐controlled enantioselective C−H activation based on the participation of bifunctional ligands. Finally, for practicality , we have developed varied catalytic manifolds for Pd(II) to accommodate diverse coupling partners while employing practical oxidants such as simple peroxides. These advances have culminated in numerous C−H activation reactions, setting the stage for broad industrial applications.","journal":"Angewandte Chemie","year":2024,"id":467420,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":392234,"name":"Nelson Y. S. Lam","orcid":"0000-0002-9307-0619","position":1,"is_corresponding":false},{"id":1025119,"name":"Daniel A. Strassfeld","orcid":"0000-0003-3598-0793","position":2,"is_corresponding":false},{"id":351358,"name":"Zhoulong Fan","orcid":"0000-0003-1457-5967","position":3,"is_corresponding":false},{"id":321502,"name":"Jennifer X. Qiao","orcid":"0000-0002-6685-2092","position":4,"is_corresponding":false},{"id":1299792,"name":"Tao Liu","orcid":"0000-0001-8960-8925","position":5,"is_corresponding":false},{"id":1202173,"name":"Dean Stamos","orcid":null,"position":6,"is_corresponding":false},{"id":321507,"name":"Jin‐Quan Yu","orcid":"0000-0003-3560-5774","position":7,"is_corresponding":false},{"id":956710,"name":"Kevin Wu","orcid":"0000-0003-1751-0018","position":0,"is_corresponding":true}],"reference_count":128,"raw_metadata":null,"created_at":"2026-07-19T02:05:10.907983Z","pmid":null,"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":[]}