Protecting Group-Controlled Regioselective Synthesis for Unsymmetrical 3,5-Disubstituted Pyridones
- 주제(키워드) 2-pyridone derivatives , Amrinone , Continuous flow chemistry , Milrinone , Regioselective Suzuki-Miyaura reaction , Selective halogen-lithium exchange
- 등재 SCIE, SCOPUS
- 발행기관 John Wiley and Sons Inc
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000191208
- 본문언어 영어
- Published As https://doi.org/10.1002/adsc.202101514
초록/요약
Protecting group-controlled regioselective functionalization of 3,5-dibromo-2-pyridones has been studied for preparation of unsymmetrical 3,5-disubstituted 2-pyridones. A bulky di-tert-butyl(isobutyl)silyl (BIBS) group was utilized for C5 regioselective arylation in Suzuki-Miyaura reactions. Meanwhile, the p-toluenesulfonyl (Ts) group was used to maximize C3 selective halogen-lithium exchange employing flow chemistry. Most of the reactions proceeded well, with yields of 76 to 95% and excellent regioselectivity. A one-pot synthesis of unsymmetrical 3,5-diaryl-2-pyridones starting from 3,5-dibromo-2-silyloxypyridine was conducted to demonstrate the practical convenience. Further functionalization onto the remaining bromine group, such as transition metal-catalyzed C−C and C−N bond-forming reactions and retro-Brook rearrangement for C−Si bond formation, was accomplished for synthesis of biologically relevant 3,5-disubstituted 2-pyridones. Finally, amrinone and milrinone, commonly used for congestive heart failure, were synthesized in three steps from 3,5-dibromo-2-pyridones in 41% and 56% overall yields, respectively. (Figure presented.). © 2022 Wiley-VCH GmbH.
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