{"doi":"10.1021/jacs.5c01166","title":"Enantioselective Hydrodifluoroalkylation of Alkenes with Conformationally Tuned Peptidyl Hydrogen Atom Transfer Catalysts","abstract":"We report the enantioselective hydrodifluoroalkylation of alkenes proceeding via an asymmetric hydrogen atom transfer (HAT) event catalyzed by thiol-containing tetrapeptides. Photocatalytic generation of a difluoroacetyl radical followed by carbon–carbon bond formation results in a prochiral carbon-centered radical that engages with the chiral catalyst. A trialkylamine reductant is proposed to turn over the catalyst in this net-reductive transformation. Notably, incorporating an ( S )-β-methyl-substituted cysteine as the N -terminal residue improved selectivity relative to that of the native N -terminal cysteine (Cys) residue, and X-ray crystallographic analysis supports the conformational underpinning of this effect. A range of enantioenriched γ-substituted amides were synthesized in up to a 96:4 enantiomeric ratio, demonstrating the broad functional group tolerance of this method. Models accounting for asymmetric induction are proposed with supporting DFT calculations.","journal":"Journal of the American Chemical Society","year":2025,"id":510302,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"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":814335,"name":"Eric P. Geunes","orcid":"0000-0002-6837-0679","position":1,"is_corresponding":false},{"id":1027000,"name":"Huiling Shao","orcid":"0000-0001-8007-6408","position":2,"is_corresponding":false},{"id":1366500,"name":"Yiran Zhang","orcid":"0000-0002-9554-6078","position":3,"is_corresponding":false},{"id":1367341,"name":"Jinkai Cheng","orcid":null,"position":4,"is_corresponding":false},{"id":1367342,"name":"Samantha V. Magpantay","orcid":null,"position":5,"is_corresponding":false},{"id":488914,"name":"Brandon Q. Mercado","orcid":"0000-0002-1940-3497","position":6,"is_corresponding":false},{"id":513494,"name":"James M. Mayer","orcid":"0000-0002-3943-5250","position":7,"is_corresponding":false},{"id":292448,"name":"K. N. Houk","orcid":"0000-0002-8387-5261","position":8,"is_corresponding":false},{"id":241562,"name":"Robert R. Knowles","orcid":"0000-0003-1044-4900","position":9,"is_corresponding":false},{"id":620725,"name":"Scott J. Miller","orcid":"0000-0001-7817-1318","position":10,"is_corresponding":false},{"id":1366499,"name":"Marcus Vinicius Pinto Pereira","orcid":"0000-0003-2718-7218","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:47:36.538276Z","pmid":"40111502","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":[]}