{"doi":"10.1021/jacs.3c06423","title":"Synthesis of β,γ-Unsaturated Aliphatic Acids via Ligand-Enabled Dehydrogenation","abstract":"α,β-Dehydrogenation of aliphatic acids has been realized through both enolate and β-C-H metalation pathways. However, the synthesis of isolated β,γ-unsaturated aliphatic acids via dehydrogenation has not been achieved to date. Herein, we report the ligand-enabled β,γ-dehydrogenation of abundant and inexpensive free aliphatic acids, which provides a new synthetic disconnection as well as a versatile platform for the downstream functionalization of complex molecules at remote γ-sites. A variety of free aliphatic acids, including acyclic and cyclic systems with ring sizes from five-membered to macrocyclic, undergo efficient dehydrogenation. Notably, this protocol features good chemoselectivity in the presence of more accessible α-C-H bonds and excellent regioselectivity in fused bicyclic scaffolds. The utility of this protocol has been demonstrated by the late-stage functionalization of a series of bioactive terpene natural products at the γ-sites. Further functionalization of the β,γ-double bond allows for the installation of covalent warheads, including epoxides, aziridines, and β-lactones, into complex natural product scaffolds, which are valuable for targeted covalent drug discovery.","journal":"Journal of the American Chemical Society","year":2023,"id":323751,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"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":1025118,"name":"Guowei Kang","orcid":"0000-0002-8334-0339","position":1,"is_corresponding":false},{"id":351360,"name":"Zhe Zhuang","orcid":"0000-0001-6679-0496","position":2,"is_corresponding":false},{"id":876368,"name":"Nikita Chekshin","orcid":"0000-0002-9687-3310","position":3,"is_corresponding":false},{"id":857602,"name":"Zhen Wang","orcid":"0000-0001-8125-8019","position":4,"is_corresponding":false},{"id":857603,"name":"Liang Hu","orcid":"0000-0002-2960-9560","position":5,"is_corresponding":false},{"id":321507,"name":"Jin‐Quan Yu","orcid":"0000-0003-3560-5774","position":6,"is_corresponding":false},{"id":857601,"name":"Tao Sheng","orcid":"0000-0001-5339-9834","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:08:06.496579Z","pmid":"37698388","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":[]}