Selective 1,4-syn-Addition to Cyclic 1,3-Dienes via Hybrid Palladium Catalysis.
ACS Cent Sci
; 10(6): 1191-1200, 2024 Jun 26.
Article
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| MEDLINE
| ID: mdl-38947211
ABSTRACT
1,4-cis-Disubstituted cyclic compounds play a pivotal role in pharmaceutical development, offering enhanced potency and bioavailability. However, their stereoselective and modular synthesis remains a long-standing challenge. Here, we report an innovative strategy for accessing these structures via mild conditions employing cyclic 1,3-dienes/alkyl(aryl)halides and amines. This procedure exhibits a wide substrate scope that tolerates various functional groups. The utility of this method is demonstrated in the efficient synthesis of a TRPV6 inhibitor, CFTR modulator, and other bioactive molecules. Combined experimental and computational studies suggest that the hybrid palladium-catalyzed radical-polar crossover mechanism is crucial for achieving exceptional 1,4-syn-addition selectivity (dr > 201).
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MEDLINE
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En
Revista:
ACS Cent Sci
Año:
2024
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Article
País de afiliación:
China