{"doi":"10.1021/jacs.5c07856","title":"Radical Strategy to the Boron-to-Copper Transmetalation Problem: <i>N</i>-Alkylation with Alkylboronic Esters","abstract":"High Resolution Image Download MS PowerPoint Slide Organoboron compounds represent highly versatile reagents in organic synthesis, but their application to forge C(sp 3 )–heteroatom bonds, particularly C(sp 3 )–N coupling, remains underdeveloped. While the integration of alkylboron reagents with copper catalysis offers a promising approach, the inherently sluggish boron-to-copper transmetalation presents a significant challenge. Here, we develop a radical strategy to circumvent the two-electron transmetalation problem via an alkyl radical-capture mechanism, wherein the alkyl radical is generated through an aminyl radical-mediated boron abstraction. Leveraging a reductively activated boron-group transfer reagent, this mechanistically distinct approach enables a general N -alkylation using a diverse array of readily available N -nucleophiles and alkylboronic esters. This transformation differs fundamentally from previous approaches to provide a greater number of N -derivatives of complex small molecules with excellent regioselectivity. This method’s operational simplicity, broad functionality compatibility, and scalability enable streamlined access to N -alkylated architectures, addressing unmet needs in medicinal and process chemistry programs.","journal":"Journal of the American Chemical Society","year":2025,"id":510105,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"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":275686,"name":"Jason E. Gestwicki","orcid":"0000-0002-6125-3154","position":1,"is_corresponding":false},{"id":1365400,"name":"Ruocheng Sang","orcid":"0000-0003-2512-9479","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"40550745","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":[]}