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We describe the full details of our total synthesis of haliclonin A,a macrocyclic natural product suggest-ed to originate from a common biosynthetic intermediate as sarain A.Central to our synthetic route is the strategic employment of nitromethane for several purposes:(1)as an umpolung surrogate of an aminomethyl group;(2)as an ideal nucleophile for the highly enantioselective catalytic asymmetric conjugate addition to forge the challenging all-carbon quaternary stereogenic center that was used to induce the formations of all other chiral centers of the molecule;and(3)as a C1N1 building block to form the 3-azabicyclo[3.3.1]nonane framework.The realization of this strategy relied on the develop-ment of a novel organocatalytic asymmetric conjugate addition of nitromethane to 3-alkenyl cyclohex-2-enone,and the first Pd-promoted intramolecular coupling of a thiocarbamate moiety onto an electron-deficient alkene(enone)to form the 3-azabicyclo[3,3,1]nonane core.The synthesis also features a Sml2-mediated intermolecular reductive coupling of an enone with an aldehyde,ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocydes,and an unprecedented direct transformation of enol into enone.