of main observation and conclusion We describe the full details of our total synthesis of haliclonin A,a macrocyclic natural product suggested to originate from a common biosynthetic intermediate as sarain A.Central t...of main observation and conclusion We describe the full details of our total synthesis of haliclonin A,a macrocyclic natural product suggested 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 CiNi building block to form the 3-azabicyclo[3.3.1]nonane framework.The realization of this strategy relied on the development 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,l]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-macrocycles,and an unprecedented direct transformation of enol into enone.展开更多
基金The authors are grateful for financial support from the National Natural Science Foundation of China(Grant Nos.21672176,21931010,and 21472153)the National Basic Research Program(973 Program)of Lhina(Grant No.2010CB833200)and the Program for Changjiang Scholars and Innovative Research Team inllniversity(PCSIRT)of Ministry of Education,ChinaMs.Yanliao Gao is thanked for assisting in the submission of this manuscript.
文摘of main observation and conclusion We describe the full details of our total synthesis of haliclonin A,a macrocyclic natural product suggested 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 CiNi building block to form the 3-azabicyclo[3.3.1]nonane framework.The realization of this strategy relied on the development 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,l]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-macrocycles,and an unprecedented direct transformation of enol into enone.
