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Total Syntheses of Multiple Cladiellin Natural Products by Use of a Completely General Strategy

Clark, J. Stephen, Berger, Raphaëlle, Hayes, Stewart T., Senn, Hans Martin, Farrugia, Louis J., Thomas, Lynne H., Morrison, Angus J., Gobbi, Luca
Journal of organic chemistry 2013 v.78 no.2 pp. 673-696
alcohols, aldehydes, catalysts, chemical structure, copper, cycloaddition reactions, diazo compounds, enantioselectivity, iodides, organic chemistry, rhodium, samarium
The enantioselective total syntheses of 10 cladiellin natural products have been completed, starting from the known allylic alcohol (+)-14, which can be prepared in large quantities. The bridged tricyclic core of the cladiellins has been constructed via three ring-forming reactions: (i) an intramolecular reductive cyclization between an aldehyde and an unsaturated ester, mediated by samarium(II) iodide, to form a tetrahydropyranol; (ii) reaction of a metal carbenoid, generated from a diazo ketone, with an ether to produce an ylide-like intermediate that rearranges to produce E- or Z-oxabicyclo[6.2.1]-5-undecen-9-one; and (iii) a Diels–Alder cycloaddition reaction to construct the third ring found in the core structure of the cladiellins. The key ring-forming reaction, in which a diazo ketone is converted into a bridged bicyclic ether, can be tuned to give either of the isomeric oxabicyclo[6.2.1]-5-undecen-9-ones as the major product by switching from a copper to a rhodium catalyst and selecting the appropriate reaction conditions. The tricyclic products obtained from the three-step sequence involving the Diels–Alder cycloaddition reaction can be employed as advanced intermediates to prepare a wide range of cladiellin natural products.