PubAg

Main content area

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

Author:
Clark, J. Stephen, Berger, Raphaëlle, Hayes, Stewart T., Senn, Hans Martin, Farrugia, Louis J., Thomas, Lynne H., Morrison, Angus J., Gobbi, Luca
Source:
Journal of organic chemistry 2013 v.78 no.2 pp. 673-696
ISSN:
1520-6904
Subject:
alcohols, aldehydes, catalysts, chemical structure, copper, cycloaddition reactions, diazo compounds, enantioselectivity, iodides, organic chemistry, rhodium, samarium
Abstract:
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.
Agid:
5500560