DeCicco Ethan M, Tlapale-Lara Neively, Paradine Shauna M
Department of Chemistry, University of Rochester 120 Trustee Road Rochester NY 14627 USA
RSC Adv. 2024 Sep 10;14(39):28822-28826. doi: 10.1039/d4ra06178k. eCollection 2024 Sep 4.
Despite the maturity of alkene 1,2-difunctionalization reactions involving C-N bond formation, a key limitation across aminofunctionalization methods is incompatibility with substrates bearing medicinally relevant N-heterocycles. Using a cooperative ligand-substrate catalyst activation strategy, we have developed an aerobic, copper-catalyzed alkene aminooxygenation method that exhibits broad tolerance for β,γ-unsaturated carbamates bearing aromatic azaheterocycle substitution. The synthetic potential of this methodology was demonstrated by engaging a densely-functionalized vonoprazan analogue and elaborating an amino oxygenated product to synthesize a heteroarylated analogue precursor of the FDA-approved antibiotic chloramphenicol.
尽管涉及碳-氮键形成的烯烃1,2-双官能化反应已经成熟，但氨基官能化方法的一个关键限制是与带有具有药物相关性的氮杂环的底物不相容。通过一种配体-底物协同催化活化策略，我们开发了一种需氧的、铜催化的烯烃氨氧化方法，该方法对带有芳族氮杂环取代基的β,γ-不饱和氨基甲酸酯具有广泛的耐受性。通过使用一个高度官能化的沃克帕唑类似物，并将氨氧化产物进一步转化，合成了FDA批准的抗生素氯霉素的杂芳基化类似物前体，证明了该方法的合成潜力。
