RESUMO
An intramolecular aza-Prins cyclization of aza-Achmatowicz rearrangement products was developed in which bismuth tribromide (BiBr3 ) plays a dual role as an efficient Lewis acid and source of the bromide nucleophile. This approach enables the facile construction of highly functionalized 9-azabicyclo[3.3.1]nonanes (9-ABNs), which are valuable synthetic building blocks and a powerful platform for the synthesis of a variety of alkaloid natural products and drug molecules. Suitable substrates for the aza-Prins cyclization include 1,1-disubstituted alkenes, 1,2-disubstituted alkenes, alkynes, and allenes, with good to excellent yields observed. Finally, we showcase the application of this new approach to the enantioselective total synthesis of six indole alkaloids: (-)-suaveoline (1), (-)-norsuaveoline (2), (-)-macrophylline (3), (+)-normacusine B (4), (+)-Na -methyl-16-epipericyclivine (5) and (+)-affinisine (6) in a total of 9-14â steps. This study significantly expands the synthetic utility of the aza-Achmatowicz rearrangement, and the strategy (aza-Achmatowicz/aza-Prins) is expected to be applicable to the total synthesis of other members of the big family of macroline and sarpagine indole alkaloids.
RESUMO
The first Pd-catalyzed arylation of Achmatowicz rearrangement products with arylboronic acids under mild conditions (rt) to provide the synthetically versatile C-aryl dihydropyranones is reported. It is found that the 4-keto group of Achmatowicz products is essential to increase the reactivity of the Pd-π-allyl complex toward arylboronic acids and that phosphine as the palladium ligand would be destructive to the reaction. This new coupling method addresses the major limitations of previous Pd-catalyzed allyl-aryl couplings of 2,3-unsaturated glycosides with an aryl Grignard or aryl zinc reagent.
