{"doi":"10.1021/jacs.5c06239","title":"Enantioselective Synthesis of Spirocyclic Nitrogen-Containing Heterocycles Catalyzed by an Iridium-Containing Cytochrome","abstract":"In the past decade, thousands of synthetic building blocks, intermediates, and drug candidates containing a spirocyclopropane core with at least one nitrogen atom have been investigated for a range of biological activities. These compounds create three-dimensional architectures that maintain the rigidity of their more sp 2 -rich analogs. Most examples contain simple core structures with unsubstituted cyclopropyl moieties, and only one has been made enantioselectively. Therefore, a straightforward method to produce more complex spirocyclic amines with high stereoselectivity would be of great synthetic utility. Here, we report the stereoselective cyclopropanation of methylene-substituted saturated heterocycles catalyzed by an iridium-containing cytochrome. After just four rounds of mutagenesis, we identified a variant that forms spiroazetidines, spiropyrrolidines, and spiropiperidines with enantioselectivities up to 99%. These results demonstrate an expeditious route to valuable, rigid, sp 3 -rich amino acid linchpins.","journal":"Journal of the American Chemical Society","year":2025,"id":526424,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9472,"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":560170,"name":"Brandon J. Bloomer","orcid":"0000-0002-6965-3654","position":1,"is_corresponding":false},{"id":1212476,"name":"John N. Brunn","orcid":"0000-0002-9892-9453","position":2,"is_corresponding":false},{"id":1402550,"name":"Andrew P. Quest","orcid":null,"position":3,"is_corresponding":false},{"id":1401982,"name":"Sukriyo Chakraborty","orcid":"0000-0002-8010-8358","position":4,"is_corresponding":false},{"id":588189,"name":"Joseph E. Schneider","orcid":"0000-0001-5487-7009","position":5,"is_corresponding":false},{"id":412247,"name":"Douglas S. Clark","orcid":"0000-0003-1516-035X","position":6,"is_corresponding":false},{"id":242491,"name":"John F. Hartwig","orcid":"0000-0002-4157-468X","position":7,"is_corresponding":false},{"id":1401981,"name":"Jingtong Xu","orcid":"0000-0003-0957-3297","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:50:30.402772Z","pmid":"40749167","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":[]}