TY - JOUR

T1 - Non-Friedländer Route to Diversely 3-Substituted Quinolines through Au(III)-Catalyzed Annulation Involving Electron-Deficient Alkynes

AU - Дубовцев, Алексей Юрьевич

AU - Кукушкин, Вадим Юрьевич

AU - Чикунова, Елена Игоревна

PY - 2023/11/28

Y1 - 2023/11/28

N2 - Gold(III)-catalyzed annulation of electron-deficient alkynes and 2-amino-arylcarbonyls provides general modular one-step access to a broad scope of quinoline products. This highly selective reaction is a useful alternative to the classic Friedländer synthesis, which requires harsh reaction conditions. In contrast, the developed method works under relatively mild PicAuCl2-catalyzed conditions and exhibits a high functional group tolerance (40 examples; yields of ≤96%). Another feature of the developed approach is a versatility toward other electron-deficient alkynes. Alkynylsulfones, alkynylcarbonyls, alkynylphosphonates, propiolonitriles, and trifluoromethylated alkynes can be used as the starting materials for the preparation of quinolines diversely substituted at position 3. On the basis of experimental data, we proposed a reaction mechanism in which gold(III) functions as a strong electrophilic activator of the C≡C bond and the carbonyl group. The synthetic potential of the presented method is additionally illustrated by practical postmodifications of the obtained compounds, including a two-step synthesis of interpirdine, a potent drug candidate.

AB - Gold(III)-catalyzed annulation of electron-deficient alkynes and 2-amino-arylcarbonyls provides general modular one-step access to a broad scope of quinoline products. This highly selective reaction is a useful alternative to the classic Friedländer synthesis, which requires harsh reaction conditions. In contrast, the developed method works under relatively mild PicAuCl2-catalyzed conditions and exhibits a high functional group tolerance (40 examples; yields of ≤96%). Another feature of the developed approach is a versatility toward other electron-deficient alkynes. Alkynylsulfones, alkynylcarbonyls, alkynylphosphonates, propiolonitriles, and trifluoromethylated alkynes can be used as the starting materials for the preparation of quinolines diversely substituted at position 3. On the basis of experimental data, we proposed a reaction mechanism in which gold(III) functions as a strong electrophilic activator of the C≡C bond and the carbonyl group. The synthetic potential of the presented method is additionally illustrated by practical postmodifications of the obtained compounds, including a two-step synthesis of interpirdine, a potent drug candidate.

UR - https://www.mendeley.com/catalogue/65d00ace-651d-3c5a-8523-8a00b84b5ff9/

U2 - 10.1021/acs.orglett.3c03775

DO - 10.1021/acs.orglett.3c03775

M3 - Article

VL - 25

SP - 8756

EP - 8760

JO - Organic Letters

JF - Organic Letters

SN - 1523-7060

IS - 48

ER -