{"doi":"10.1021/jacs.2c13520","title":"Pd-Catalyzed Amination of Base-Sensitive Five-Membered Heteroaryl Halides with Aliphatic Amines","abstract":"We report a versatile and functional-group-tolerant method for the Pd-catalyzed C–N cross-coupling of five-membered heteroaryl halides with primary and secondary amines, an important but underexplored transformation. Coupling reactions of challenging, pharmaceutically relevant heteroarenes, such as 2- H -1,3-azoles, are reported in good-to-excellent yields. High-yielding coupling reactions of a wide set of five-membered heteroaryl halides with sterically demanding α-branched cyclic amines and acyclic secondary amines are reported for the first time. The key to the broad applicability of this method is the synergistic combination of (1) the moderate-strength base NaOTMS, which limits base-mediated decomposition of sensitive five-membered heteroarenes that ultimately leads to catalyst deactivation, and (2) the use of a GPhos-supported Pd catalyst, which effectively resists heteroarene-induced catalyst deactivation while promoting efficient coupling, even for challenging and sterically demanding amines. Cross-coupling reactions between a wide variety of five-membered heteroaryl halides and amines are demonstrated, including eight examples involving densely functionalized medicinal chemistry building blocks.","journal":"Journal of the American Chemical Society","year":2023,"id":317305,"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":80,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9448,"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":650134,"name":"Kaibo Feng","orcid":"0000-0002-8558-4396","position":1,"is_corresponding":false},{"id":1022616,"name":"Aaron C. Sather","orcid":"0000-0002-1737-7512","position":2,"is_corresponding":false},{"id":285943,"name":"Stephen L. Buchwald","orcid":"0000-0003-3875-4775","position":3,"is_corresponding":false},{"id":1022615,"name":"Elaine C. Reichert","orcid":"0000-0002-9293-4382","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:06:50.336418Z","pmid":"36719903","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":[]}