Catalytic Asymmetric Total Syntheses of (−)-Galanthamine and (−)-Lycoramine

Abstract

The catalytic asymmetric total syntheses of the biologically important and therapeutically valuable Amaryllidaceae alkaloids (−)-galanthamine and (−)-lycoramine have been divergently achieved from commercially available 3-butyn-1-ol. A newly developed spirocyclic pyrrolidine (SPD)-catalyzed enantioselective Robinson annulation rapidly constructs the key cishydrodibenzofuran core, which bears an all-carbon quaternary stereocenter of the target molecules with an excellent stereoselective control. Additionally, the current asymmetric synthetic strategy provides an alternative approach toward the syntheses of (−)-galanthamine and its analogues.

α-C(sp3)-H Arylation of Cyclic Carbonyl Compounds

“…In view of the fact that the α-substituted cyclic carbonyl compounds can form chiral fixed all-carbon quaternary stereocenter by α-arylation, such as compounds 19a-19i, 26a-26g, and 29, which can effectively avoid the racemization of α-aryl compounds and subsequent reduce of optical purity. Moreover, the construction of chiral all-carbon quaternary stereocenter has always been attracted a majority of interests from the field of organic chemistry [52][53][54][55][56][57][58], so it is of great significance to design suitable substrates for such reactions. Hartwig et al initiated the asymmetric α-arylation of α-fluoroketone 34a under various catalytic systems.…”

Palladium-catalyzed allylic etherification of phenols with vinyl ethylene carbonate

“…(Trost and Toste 1998;Cao et al, 2002;Tanaka et al, 2003;Trost et al, 2003;Sawayama et al, 2004;Trost 2004;Trost et al, 2004;Pochetti et al, 2010). Among the many different varieties, allylic aryl ethers have gotten a lot of interest because of their wide range of uses in academia and industry (Trost and Tang 2002;Parker and Fokas 2006;Varghese and Hudlicky 2014;Zhang et al, 2019a;Zhang et al, 2019b), and selective functionalization of the motif has acted as a foundation for the synthesis of novel bioactive compounds (Figure 1). The divergent synthesis of allylic aryl ethers from simple substrates, on the other hand, remains a difficult process that has yet to be fully explored.…”

Enantioselective Construction of 2-Aryl-2,3-dihydrobenzofuran Scaffolds Using Cu/SPDO-Catalyzed [3 + 2] Cycloaddition

“…Recently, an SPD-organocatalyst-catalyzed enantioselective one-pot intramolecular Robison cyclization to construct 2-alkyl-2,3-dihydrobenzofuran scaffolds, unfortunately not efficient for 2-aryl-2,3-dihydrobenzofuran scaffolds, have been developed by our group (Scheme b) . Subsequently, another asymmetric intermolecular oxidative cross-coupling of 3-methyloxy­carbonyl-2-naphthol with 2-naphthol for the preparation of C1 -symmetric BINOLs through our well designed Cu/SPDO catalysis system also has been explored, in which a proposed intermediate involving Cu/dioxygen of the quinone ester model plays a crucial role in the stereocontrol.…”