Total Synthesis of (-)-Citreoisocoumarin, (-)-Citreoisocoumarinol, (-)-12-epi-Citreoisocoumarinol, and (-)-Mucorisocoumarins A and B Using a Gold(I)-Catalyzed Cyclization Strategy

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.