Development of bifunctional organocatalysts and application to asymmetric total synthesis of naucleofficine I and II.

Yuan, Yong-Hai; Han, Xue; Zhu, Fu-Ping; Tian, Jin-Miao; Zhang, Fu-Min; Zhang, Xiao-Ming; Tu, Yong-Qiang; Wang, Shao-Hua et al. · Nat Commun · 2019

basic_science · Level V

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Abstract

The proline-type organocatalysts has been efficiently employed to catalyze a wide range of asymmetric transformations; however, there are still many synthetically useful and challenging transformations that remain unachievable in an asymmetric fashion. Herein, a chiral bifunctional organocatalyst with a spirocyclic pyrrolidine backbone-derived containing fluoro-alkyl and aryl sulfonamide functionalities, are designed, prepared, and examined in the asymmetric Mannich/acylation/Wittig reaction sequence of 3,4-dihydro-β-carboline with acetaldehyde, acyl halides, and Wittig reagents. As a result, the spirocyclic pyrrolidine trifluoromethanesulfonamide catalyst can facilitate this versatile sequence as demonstrated by 18 examples displaying excellent enantioselectivity (up to 94% ee), as well as moderate to good yields (up to 54% over 3 steps). As a practical application, the asymmetric total synthesis of naucleofficine I (1a) and II (1b) in ten steps have been accomplished.