Allylation of Oxygen and Nitrogen Nucleophiles

Stereoselective formation of 3-methylenetetrahydrofuran such as 180 by intramolecular allylation of alcohol with allyl benzoate in 179 was utilized in synthetic studies of the core of amphidinolide [70]. Thus treatment of 179 with Pd(OAc)2 and PPh3 in the presence of Me3SnCl (1 equiv.) and NaH in THF afforded the cA-tetrahydrofuran 180 stereoselectively in 77 % yield. In this reaction, the less reactive hydroxy group was converted to the more reactive tin alkoxide by the reaction of Me3SnCl (1 equiv.) and NaH. 

Tetrahydrofuran formation proceeds with high stereocontrol. Cyclization of (E)-allylic ester 181 proceeded at room temperature with overall retention of configuration to give the 2,5-ci5 -tetrahydrofuran 182 using Pd(PPh3)4 in the presence of neocuprone (2,9-dimethyl-l,10-phenanthroline). On the other hand, overall inversion occurred in the reaction of (Z)-allylic ester 183 to afford the 2,5-trans-tetrahydrofuran 184 with ( )-alkene [71]. 

Formal total synthesis of uvaricin was achieved by applying double cyclization of vicinal diol bis(allylic acetate) to afford bis-THF core selectively using chiral ligand Trost L-1 as a key reaction [72], Thus the cyclization of 185 afforded the diene 186 with two new stereocenters in 97 % yield as a single diastereomer. 

The F-ring of the polyether macrolide halichondrin was constructed by Pd-catalyzed selective monocyclization of 187 and 189. No dicyclization took place due to steric reasons. Desymmetrization of the meso-Aio 187 gave the tetrahydro-fiiran 188 in high yield using Trost L-1 as a chiral ligand, and cyclization of the C2 symmetric diacetate 189 afforded the desired diastereoisomeric tetrahydrofuran 190 [73]. 

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]. 

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Scheme 192. Reaction of Alkenyl Epoxides and Aziridines Producing Heterocycles via Carbon-Heteroatom Bond Formation by (a) Intramolecular Allylation of Oxygen and Nitrogen Nucleophiles and (b) Intermolecular [3 + 2]-Cycloaddition with Heterocumulenes...

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