Asymmetric Total Syntheses of Naphthylisoquinoline Alkaloids via Atroposelective Coupling Reaction Using Central Chirality as Atroposelectivity-Controlling Group

Abstract

We describe the asymmetric total syntheses of naphthylisoquinoline alkaloids. Atroposelective biaryl coupling reaction between naphthyl pinacol boronate and an aryl iodide, bearing (S)-2-aminopropyl group at the ortho-position using the existing central chirality as an atroposelectivity-controlling group, provided the desired biaryl product with high atroposelectivity, without the use of an external chiral source. From the resulting biaryl product, several naphthylisoquinoline alkaloids were prepared via the stereoselective formation of the isoquinoline framework with the appropriate oxidation state and stereochemistry.

Atroposelective Total Syntheses of Naphthylisoquinoline Alkaloids with (P)-Configuration

“…First, we attempted to synthesize ancistroealaine A ( 1 ), the atropodiastereomer of ancistrotanzanine B ( 4 ), via a route similar to that for ancistrotanzanine B from its ( M )-isomer . Unexpectedly, the axial chirality in biaryl compound 9 displayed a considerably different reactivity in the following transformations.…”

“…Our group has initiated a research program toward the atroposelective total synthesis of naphthylisoquinoline alkaloids by exploiting the central chirality in the isoquinoline ring as the atroposelectivity-controlling group. , Along this line, our group recently developed an ( M )-atroposelective Suzuki–Miyaura coupling reaction of naphthyl pinacol boronate 7 and chiral aryl iodide 8 bearing an ( S )-2-( N -acetylamino)­propyl group at the ortho -position using the central chirality in the 2-( N -acetylamino)­propyl group as the atroposelectivity-controlling group, without the need for external chiral ligands and/or chiral auxiliaries. With a combination of a palladium catalyst and t -BuXPhos, an axially chiral biaryl compound ( M )- 9 was obtained in high yield with excellent atroposelectivity (>13:1) (Scheme a) .…”

“…Our investigation into the parameters pertaining to the above-mentioned atroposelective Suzuki–Miyaura coupling reaction revealed that the atroposelectivity of the coupling product 9 was strongly dependent on the type of ligand (Scheme ). For instance, the Suzuki–Miyaura reaction with P­( o -tol) 3 afforded ( M )- 9 as the major product; in contrast, ( P )- 9 was obtained as the major product from the reaction with PPh 3 , although the atroposelectivity was not as good as the ( M )-isomer.…”

“…The treatment of trans - 12 with LiAlH 4 completed the total synthesis of 6- O -methylancistrobertsonine A (6-Me- 3 ), the atropodiastereomer of N -methyl-ancistrotectoriline A, in 91% yield. Our current and previous reports on the asymmetric total synthesis of naphthylisoquinoline alkaloids indicate that both atropisomers can be prepared from the same building blocks via an atropodiastereoselective coupling reaction by choosing the appropriate catalytic system without the use of external or internal chiral sources.…”

Synthesis of ortho-Diamino-Functionalized 1-Arylnaphthalenes through Nickel-Catalyzed Cyclization of Ynamide-Benzylnitriles with Organoboronic Acids

“…As a result, much effort has been devoted toward the synthesis of 1-arylnaphthalenes, which include aryl–aryl cross-coupling reactions, metal catalyzed cyclizations or benzannulations, [2 + 2 + 2] cycloadditions, Diels–Alder reactions, ring expansion of benzocyclo­butenones, etc. Despite the outstanding progress that has been achieved, the construction of 1-arylnaphthalenes bearing ortho -functional groups such as diamino groups on the naphthyl ring is quite rare and remained a challenging task.…”