Enantioselective Catalytic Aldehyde α‐Alkylation/Semipinacol Rearrangement: Construction of α‐Quaternary‐δ‐Carbonyl Cycloketones and Total Synthesis of (+)‐Cerapicol

• Published in: Angewandte Chemie International Edition Vol. 59; no. 22; pp. 8471 - 8475
• Main Authors: Yang, Jie, Zhang, Xiao‐Ming, Zhang, Fu‐Min, Wang, Shao‐Hua, Tu, Yong‐Qiang, Li, Zhen, Wang, Xi‐Chao, Wang, Hong
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 25.05.2020; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alcohols; Aldehydes; Alkylation; asymmetric catalysis; Carbonyl compounds; Carbonyls; Cascade chemical reactions; Catalysis; Chemistry; Chemistry, Multidisciplinary; Enantiomers; organocatalysis; Physical Sciences; quaternary carbon centers; Science & Technology; semipinacol rearrangement; tandem reactions; organocatalysis; ALCOHOLS; CORE; ALKYLATION; quaternary carbon centers; semipinacol rearrangement; asymmetric catalysis; CALYCIPHYLLINE; tandem reactions
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202001100

An enantioselective aldehyde α‐alkylation/semipinacol rearrangement was achieved through organo‐SOMO catalysis. The catalytically generated enamine radical cation serves as a carbon radical electrophile that can stereoselectively add to the alkene of an allylic alcohol and initiate ensuing ring‐expansion of cyclopropanol or cyclobutanol. This tandem reaction enables the production of a wide range of nonracemic functionalizable α‐quaternary‐δ‐carbonyl cycloketones in high yields and excellent enantioselectivity from simple aldehydes and allylic alcohols. As a key step, the intramolecular reaction was also successfully applied in the asymmetric total synthesis of (+)‐cerapicol. In tandem: An organocatalytic enantioselective aldehyde α‐alkylation/semipinacol rearrangement was developed with both inter‐ and intramolecular reaction variants. This tandem reaction provides efficient access to a wide range of enantioenriched α‐quaternary 1,5‐dicarbonyl compounds, the synthetic value is demonstrated by an asymmetric total synthesis of (+)‐cerapicol.