Catalytic stereodivergent allylic alkylation of 2-acylimidazoles for natural product synthesis

• Published in: Nature communications 2023-12, Vol.14 (1), p.8118-8118, Article 8118
• Main Authors: Lu, Ruimin, Zhang, Qinglin, Guo, Chang
• Format: Article
• Language: English
• Subjects: 140/131; 140/58; 639/638/403/933; 639/638/77/883; 639/638/77/888; Alkylation; Allyl compounds; Carbonyl compounds; Carbonyls; Catalysts; Chemical reactions; Chemical synthesis; Enantiomers; Humanities and Social Sciences; Iridium; multidisciplinary; Natural products; Nickel; Permutations; Science; Science (multidisciplinary); Stereoisomerism; Stereoisomers
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43986-6

The stereocontrolled allylic alkylation of carbonyl compounds with the goal of producing the full range of stereoisomers presents an effective approach for increasing the productivity of collective natural product synthesis and the creation of chiral molecule libraries for drug exploration. The simultaneous control of regio-, diastereo-, and enantioselectivity poses a significant synthetic challenge in contemporary organic synthesis. Herein, we describe a catalytic stereodivergent α-allylation protocol applicable to both aliphatic and aromatic 2-acylimidazoles, thereby providing a practical blueprint for the divergent synthesis of important chiral building blocks. Each of the six isomeric α-allylated compounds can be readily obtained with remarkable yields and exceptional stereoselectivities, by judiciously selecting the appropriate leaving group and permutations of enantiomers adapted from nickel and iridium catalysts. The versatility of this asymmetric allylic alkylation has been successfully utilized in the enantioselective synthesis of ( R )-arundic acid and ( S , S )-cinamomumolide, as well as in the stereodivergent total synthesis of tapentadol. The simultaneous control of regio-, diastereo-, and enantioselectivity poses a significant synthetic challenge in contemporary organic synthesis. Here, the authors describe a stereodivergent allylation of 2-acylimidazoles using nickel and iridium catalysts to provide completely isomeric allylated compounds.