A General and Enantioselective Approach to Pentoses: A Rapid Synthesis of PSI-6130, the Nucleoside Core of Sofosbuvir

An efficient route towards biologically relevant pentose derivatives is described. The <i>de novo</i> synthetic strategy features an enantioselective α-oxidation reaction enabled by a chiral amine in conjunction with copper­(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of <i>C</i>-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use

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

The enantioselective total syntheses of 10 cladiellin natural products have been completed, starting from the known allylic alcohol <b>(+)-14</b>, 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 <i>E</i>- or <i>Z</i>-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

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

The enantioselective total syntheses of 10 cladiellin natural products have been completed, starting from the known allylic alcohol <b>(+)-14</b>, 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 <i>E</i>- or <i>Z</i>-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