{"doi":"10.1021/jacs.2c13289","title":"Catalytic Cross-Metathesis Reactions That Afford <i>E</i>- and <i>Z</i>-Trisubstituted Alkenyl Bromides: Scope, Applications, and Mechanistic Insights","abstract":"Stereochemically defined trisubstituted alkenes with a bromide and a methyl group at a terminus can be readily and stereoretentively derivatized through catalytic cross-coupling, affording unsaturated fragments found in many bioactive natural products. A direct method for generating such entities would be by stereocontrolled catalytic cross-metathesis (CM). Such methods are scarce however. Here, we present a stereoretentive strategy for CM between tri-, Z - or E -di, or monosubstituted olefins and Z - or E -2-bromo-2-butene, affording an assortment of E - or Z -trisubstituted alkenyl bromides. The majority of the transformations were catalyzed by two Mo monoaryloxide pyrrolide (MAP) complexes, one purchasable and the other accessible by well-established protocols. Substrates, such as feedstock trisubstituted olefins, can be purchased; the alkenyl bromide reagents are commercially available or can be prepared in two steps in a multigram scale. The catalytic process can be used to generate products that contain polar moieties, such as an amine or an alcohol, or sterically hindered alkenes that are α- or β-branched. The utility of the approach is highlighted by a brief and stereocontrolled synthesis of an unsaturated fragment of phomactin A and a concise total synthesis of ambrein. An unexpected outcome of these investigations was the discovery of a new role for the presence of a small-molecule alkene in an olefin metathesis reaction. DFT studies indicate that this additive swiftly reacts with a short-lived Mo alkylidene and probably helps circumvent the formation of catalytically inactive square pyramidal metallacyclobutanes, enhancing the efficiency of a transformation.","journal":"Journal of the American Chemical Society","year":2023,"id":335041,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9426,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1032149,"name":"Can Qin","orcid":"0000-0002-1565-1442","position":1,"is_corresponding":false},{"id":492205,"name":"Binh Khanh","orcid":"0000-0001-8487-1417","position":2,"is_corresponding":false},{"id":869840,"name":"Qinghe Liu","orcid":"0000-0003-3125-7135","position":3,"is_corresponding":false},{"id":869841,"name":"Yucheng Mu","orcid":"0000-0003-1493-2880","position":4,"is_corresponding":false},{"id":285942,"name":"Peng Liu","orcid":"0000-0002-8188-632X","position":5,"is_corresponding":false},{"id":308976,"name":"Amir H. Hoveyda","orcid":"0000-0002-1470-6456","position":6,"is_corresponding":false},{"id":869842,"name":"Tobias Koengeter","orcid":"0000-0001-6519-1758","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:09:53.742667Z","pmid":"36724200","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":[]}