{"doi":"10.1021/jacs.4c12907","title":"Catalyst-Controlled Chemoselective γ-C(sp<sup>3</sup>)–H Lactonization of Carboxylic Acid: Methyl versus Methylene","abstract":"Despite recent advances in ligand-enabled C(sp 3 )–H functionalization of native substrates, controlling chemoselectivity in the presence of methyl and methylene C(sp 3 )–H bonds remains a significant challenge. Herein, we report the first example of the Pd(II)-catalyzed chemoselective lactonization of γ-methyl and methylene C(sp 3 )–H bonds of carboxylic acids. Exclusive chemoselectivity of methyl or methylene γ-lactonization was achieved by using two different classes of Quinoline-Pyridone ligands. The bidentate ligand coordinating with Pd(II) via five-membered chelation favors γ-methyl C–H lactonization, whereas the ligand forming six-membered chelation affords γ-methylene C–H lactonization exclusively. Taking into account our previous findings, we show that the impact of ligand bite angle on chemoselectivity is different for five-membered and six-membered cyclopalladation processes. This method provides simple and versatile access to γ-lactones, including spiro- and fused ring systems. Deuterium incorporation experiments suggest that this observed chemoselectivity arises from both the C–H activation and C–O bond forming steps.","journal":"Journal of the American Chemical Society","year":2024,"id":423476,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9399,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"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":857603,"name":"Liang Hu","orcid":"0000-0002-2960-9560","position":1,"is_corresponding":false},{"id":1218624,"name":"Yilin Lu","orcid":"0009-0001-5862-6570","position":2,"is_corresponding":false},{"id":321507,"name":"Jin‐Quan Yu","orcid":"0000-0003-3560-5774","position":3,"is_corresponding":false},{"id":1218623,"name":"Jie-Lun Yan","orcid":"0000-0003-3340-2746","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T01:57:56.814994Z","pmid":"39412381","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":[]}