Organocatalytic, Asymmetric Total Synthesis of (-)-Haliclonin A
Lian-Dong Guo1, Xiong-Zhi Huang1, Shi-Peng Luo1
1Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, P.R. China.
Abstract:
The first total synthesis of the alkaloid (-)-haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3-alkenyl cyclohex-2-enone to set the stereochemistry of the all-carbon quaternary stereogenic center. The synthesis also features a Pd-promoted cyclization to form the 3-azabicyclo[3,3,1]nonane core, a SmI2 -mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.
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