{"doi":"10.1021/jacs.4c06067","title":"Computational Studies of Reactions of 1,2,4,5-Tetrazines with Enamines in MeOH and HFIP","abstract":"The reaction between 1,2,4,5-tetrazines and alkenes in polar solvents proceeds through a Diels-Alder cycloaddition along the C-C axis (C3/C6 cycloaddition) of the tetrazine, followed by dinitrogen loss. By contrast, the reactions of 1,2,4,5-tetrazines with enamines in hexafluoroisopropanol (HFIP) give 1,2,4-triazine products stemming from a formal Diels-Alder addition across the N-N axis (N1/N4 cycloaddition). We explored the mechanism of this interesting solvent effect through DFT calculations in detail and revealed a novel reaction pathway characterized by C-N bond formation, deprotonation, and a 3,3-sigmatropic rearrangement. The participation of an HFIP molecule was found to be crucial to the N1/N4 selectivity over C3/C6 due to the more favored initial C-N bond formation than C-C bond formation.","journal":"Journal of the American Chemical Society","year":2024,"id":452620,"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":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":528962,"name":"Dennis Svatunek","orcid":"0000-0003-1101-2376","position":1,"is_corresponding":false},{"id":1275312,"name":"Zixi Zhu","orcid":null,"position":2,"is_corresponding":false},{"id":761914,"name":"Dale L. Boger","orcid":"0000-0002-3966-3317","position":3,"is_corresponding":false},{"id":218928,"name":"Xin‐Hua Duan","orcid":"0000-0002-1527-5934","position":4,"is_corresponding":false},{"id":292448,"name":"K. N. Houk","orcid":"0000-0002-8387-5261","position":5,"is_corresponding":false},{"id":1014029,"name":"Pengchen Ma","orcid":"0000-0002-4110-4696","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:02:54.415477Z","pmid":"38941192","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":[]}