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 (−)-(10 R,12 S )- 5 and (+)-(10 S,12 S )- 6, respectively.