A highly regioselective gold(I)-catalyzed 6-endo-dig cyclization of 2,2-dimethyl-5-(alkynyl)-4H-benzo[d][1,3]dioxin-4-ones for the synthesis of 8-hydroxy-3-substituted isocoumarins is described. Key features of the reaction include the broad substrate scope, scalability, and tolerance for protecting groups. The synthetic utility of this novel method is demonstrated by the first total synthesis of exserolide F, an isocoumarin-containing polyol natural product.
A unified and concise first asymmetric total synthesis of (−)-citreoisocoumarin
(2), (−)-citreoisocoumarinol (3),
12-epi-citreoisocoumarinol (4), and
(−)-mucorisocoumarins A (5) and B (6) have been accomplished from the common intermediate (−)-6-O-methyl-citreoisocoumarin (1). Central to
the synthetic approach is a regioselective gold(I)-catalyzed 6-endo-dig cyclization strategy for the construction
of the isocoumarin skeleton. The other key steps in this approach
included Sonogashira coupling, Tsuji-Wacker oxidation, Evans-Saksena’s
1,3-anti-reduction, and Narasaka-Prasad’s
1,3-syn-reduction. The synthetic results unambiguously
confirmed the absolute configuration of the natural products mucorisocoumarins
A and B as (−)-(10R,12S)-5 and (+)-(10S,12S)-6, respectively.
An efficient and concise approach to the total syntheses of paecilomycins E (1) and F (2) is described. A protecting group directed intermolecular diastereoselective Nozaki–Hiyama–Kishi (NHK) reaction, a Julia–Kocienski olefination, a Sharpless asymmetric dihydroxylation, and De Brabander's lactonization protocol are used as the key steps.
A protocol for general diastereoselective tandem dihydroxylation followed by S N 2 cyclization was developed for the convenient and efficient synthesis of cis-and trans-2,6-disubstituted tetrahydropyrans from ζ-mesyloxy α,β-unsaturated esters. The application of this novel method was demonstrated through the concise formal synthesis of (+)-muconin, a nonclassical acetogenin, with sequential THP−THF ring formation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.