Total Synthesis of a Few Naturally Occurring Isocoumarins and Dihydroisocoumarins: Successful Exploration of the Ag(I)-Mediated 6-Endo-Dig Cyclization and Asymmetric Hydrogenation Strategy

Abstract

We disclose the total synthesis of naturally occurring isocoumarins: (S)-fusarimarin B, (S)-diaporthin, (10S)-8-methoxydiaporthin, (S)-orthosporin, (S)-monarubin B, (S)-lunatinin, and isochromans aspergillumarin A, aspergillumarin B, and penicimarin B. The synthetic strategy highlights an efficient Ag(I)-mediated 6-endo-dig cyclization of properly substituted 2-alkynylated benzoates to yield the corresponding isocoumarins in excellent yields. The obtained isocoumarins, upon asymmetric hydrogenation with the Ru-BINAP catalyst, provided the corresponding isochromans with excellent yields and enantioselectivity. A Sonogashira cross-coupling reaction of properly functionalized terminal alkynes and substituted aryl bromides was employed to access 2-alkynylated benzoates. This report constitutes the first asymmetric synthesis of three naturally occurring isocoumarins: (S)-fusarimarin B, and (S)-monarubin B.