{"doi":"10.1021/jacs.4c07777","title":"Expanding the Clip-and-Cleave Concept: Approaching Enantioselective C–H Hydroxylations by Copper Imine Complexes Using O<sub>2</sub> and H<sub>2</sub>O<sub>2</sub> as Oxidants","abstract":"Copper-mediated aromatic and aliphatic C–H hydroxylations using benign oxidants (O 2 and H 2 O 2 ) have been studied intensively in recent years to meet the growing demand for efficient and green C–H functionalizations. Herein, we report an enantioselective variant of the so-called clip-and-cleave concept for intramolecular ligand hydroxylations by the application of chiral diamines as directing groups. We tested the hydroxylation of cyclohexanone and 1-acetyladamantane under different oxidative conditions (Cu I /O 2; Cu I /H 2 O 2; Cu II /H 2 O 2 ) in various solvents. As an outstanding example, we obtained ( R )-1-acetyl-2-adamantol with a yield of 37% and >99:1 enantiomeric excess from hydroxylation in acetone using Cu I and O 2 . Low-temperature stopped-flow UV–vis measurements in combination with density functional theory (DFT) computations revealed that the hydroxylation proceeds via a bis(μ-oxido) dicopper intermediate. The reaction product represents a rare example of an enantiopure 1,2-difunctionalized adamantane derivative, which paves the way for potential pharmacological studies. Furthermore, we found that 1-acetyladamantane can be hydroxylated in a one-pot reaction under air with isolated yields up to 36% and enantiomeric ratios of 96:4 using Cu II /H 2 O 2 in MeOH.","journal":"Journal of the American Chemical Society","year":2024,"id":437216,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"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":1246663,"name":"Kevin F. Kirchgeßner-Prado","orcid":null,"position":1,"is_corresponding":false},{"id":370208,"name":"David A. Hiller","orcid":null,"position":2,"is_corresponding":false},{"id":1246060,"name":"Kim A. Eisenlohr","orcid":"0009-0002-9463-1331","position":3,"is_corresponding":false},{"id":1246664,"name":"Giacomo Rubin","orcid":null,"position":4,"is_corresponding":false},{"id":1246665,"name":"Christian Würtele","orcid":null,"position":5,"is_corresponding":false},{"id":1246666,"name":"Remy Goldberg","orcid":null,"position":6,"is_corresponding":false},{"id":1246061,"name":"Dominic Schatz","orcid":"0000-0002-1352-8045","position":7,"is_corresponding":false},{"id":1246062,"name":"Max C. Holthausen","orcid":"0000-0001-7283-8329","position":8,"is_corresponding":false},{"id":751414,"name":"Isaac Garcia‐Bosch","orcid":"0000-0002-6871-3029","position":9,"is_corresponding":false},{"id":1246063,"name":"Siegfried Schindler","orcid":"0000-0002-9991-9513","position":10,"is_corresponding":false},{"id":1246662,"name":"Alexander Petrillo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:00:29.872940Z","pmid":"39240225","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":[]}