Galanthamine enantioselective synthesis

Trost, B.M., Tang, W., Toste, ED. (2005) Divergent Enantioselective Synthesis of (—)-Galanthamine and (—)-Morphine. Journal of the American Chemical Society, 127, 14785-14803. 

With such possibilities for regio-and stereocontrol, Pd-Ag-catalyzed Heck reactions have been and still are widely applied to total synthesis. However, just a few more examples are provided here. Brown et al. described a very convergent enantioselective synthesis of ( )-galanthamine (Scheme 10.35), an Amaryllidaceae... 

In contrast to less efficient allylation of alcohols, allylation of phenols proceeds much more smoothly. In the enantioselective synthesis of (—)-galanthamine by Trost, two Pd-catalyzed reactions were utilized. Asymmetric allylation of the bro-movanillin 191 with the cyclic allylic carbonate 192 gave the ether 193 by using ( ] -allyl-PdCl)2 and chiral Trost L-2. Subsequent Heck reaction of 194 afforded 195 in 91 % yield when DPPP was used as a ligand. DPPF and DPPE gave lower yield [74]. 

Palladium-catalyzed cross coupling of pyrone 252 with stannane 253 resulted in the intermediate 257, which underwent a Diels-Alder reaction to give cycloadducts 254 and 255 in a combined yield of 45%, favoring the endo product 255 (endo/exo = 2.5 1). In this reaction, the addition of Cul was cracial, as without Cul only traces of the cycloadducts were obtained. Further transformations of 255 resulted in racemic galanthamine (256). In 2000, the group of Trost [103] reported an enantioselective synthesis of this alkaloid applying a Pd-catalyzed asymmetric aUyUc alkylation and an intramolecular Heck reaction to assemble the... 

Another application of enantioselective allylic substitution is seen in the synthesis of (-)-galanthamine, the parent member of the galanthamine-type Ama-ryllidaceae alkaloids. Displacement of the carbonate group in the racemate with the phenol is accomplished by the Pd catalyst in the presence of the chiral ligand [84]. 

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