{"doi":"10.1002/chem.202500353","title":"Development of a Highly Selective Synthesis of 4‐Substituted Tetrahydroquinolines: Substrate Scope and Mechanistic Study","abstract":"Herein, we describe a general and selective deprotonation functionalization reaction of tetrahydroquinolines at the 4-position using organolithiums and phosphoramide ligands. In addition to the development of a direct deprotonation alkylation reaction with primary and secondary alkyl halides, a Negishi cross-coupling protocol was realized to afford products with a range of aromatic halides. These methods were applied to the late-stage installation of tetrahydroquinolines into a variety of substrates including pharmaceuticals as well as natural product analogues. The use of thorough mechanistic investigations revealed the aggregation state of the newly formed tetrahydroquinoline anion to be a separated ion pair, which proved critical to optimizing the reaction conditions.","journal":"Chemistry - A European Journal","year":2025,"id":527989,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9347,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1304915,"name":"Lupita S. Aguirre","orcid":"0000-0001-8754-1608","position":1,"is_corresponding":false},{"id":1304916,"name":"Levi T. Litwiller","orcid":"0000-0002-1679-1500","position":2,"is_corresponding":false},{"id":1406009,"name":"Hải Bằng Lý","orcid":null,"position":3,"is_corresponding":false},{"id":1063011,"name":"Michael P. Crockett","orcid":"0000-0002-6165-2841","position":4,"is_corresponding":false},{"id":1063013,"name":"Andy A. Thomas","orcid":"0000-0001-6336-5566","position":5,"is_corresponding":false},{"id":1063012,"name":"Jeanette Piña","orcid":"0000-0003-3970-9263","position":0,"is_corresponding":true}],"reference_count":120,"raw_metadata":null,"created_at":"2026-07-19T02:50:44.062153Z","pmid":"39899756","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":[]}