Enantioselective Total Synthesis of (+)-Corymine and (−)-Deformylcorymine

Abstract

We report herein the first enantioselective total synthesis of akuammiline alkaloids (+)-corymine and (−)-deformylcorymine. Starting from commercially available N-nosyltryptamine, the target molecules are both achieved in 11 steps. Key elements of the design include (a) a copper-catalyzed enantioselective addition of dimethyl malonate to a 3-bromooxindole to secure the C7 all-carbon quaternary stereocenter, (b) a one-step construction of cyclohexyl and pyrrolidinyl rings via intramolecular nucleophilic C-and N-addition, and (c) a nickel-promoted 7-endo cyclization of alkenyl bromide to furnish the azepanyl ring. The strategy is further extended to the synthesis of another three members of the akuammiline family, namely, (−)-10demethoxyvincorine, (−)-2(S)-cathafoline, and (−)-3-epi-dihydrocorymine 17-acetate.

Total Synthesis of (+)‐Alsmaphorazine C and Formal Synthesis of (+)‐Strictamine: A Photo‐Fries Approach

“…Over the past fifteen years, aims to address the synthetic challenges posed by these complex molecules have resulted in numerous innovations in methodologies toward the core structure [2] and stunning achievements in total synthesis [3] . However, despite these elegant advances, the concise and efficient cascade approaches for the direct assembly of 1 bearing a functional group (N or O) at C16, which is prevasive in a variety of akuammiline alkaloids such as aspidophylline A ( 3 ), corymine ( 4 ) and echitamine ( 5 ), remain limited and in urgent demand [2e, 3n,u] …”

α-C(sp3)-H Arylation of Cyclic Carbonyl Compounds

“…In view of the fact that the α-substituted cyclic carbonyl compounds can form chiral fixed all-carbon quaternary stereocenter by α-arylation, such as compounds 19a-19i, 26a-26g, and 29, which can effectively avoid the racemization of α-aryl compounds and subsequent reduce of optical purity. Moreover, the construction of chiral all-carbon quaternary stereocenter has always been attracted a majority of interests from the field of organic chemistry [52][53][54][55][56][57][58], so it is of great significance to design suitable substrates for such reactions. Hartwig et al initiated the asymmetric α-arylation of α-fluoroketone 34a under various catalytic systems.…”

Catalytic Function of Cu (I) and Cu (II) in Total Synthesis of Alkaloids

“…[34a] Corymine [34a] and deformylcorymine [242] were isolated from the leaves of this plant. Li and co-workers [243] in 2020 reported the fast, asymmetric total synthesis of akuammiline alkaloids (+)-corymine and (À )-deformylcorymine. Starting from market purchasable N-nosyltryptamine, the target molecules are both accomplished in 11 steps.…”