Enantioselective Formal Synthesis of (−)-Podophyllotoxin from (2<i>S</i>,3<i>R</i>)‑3-Arylaziridine-2-carboxylate

Meyers’ 4-aryl-1-tetralone-lactone and <i>ent</i>-Zhang’s 2-diarylmethyl-4-oxobutanoate were synthesized in the formal synthesis of (−)-podophyllotoxin from (2<i>S</i>,3<i>R</i>)-3-arylaziridine-2-carboxylate, via 3,3-diarylpropanoate as a common intermediate, in an overall 42% yield through 10 steps and 31% yield through 6 steps, respectively. The key steps in the synthesis were regio- and diastereoselective ring opening with an aromatic nucleophile, samarium iodide promoted reductive C–N bond cleavage, and Stille coupling for introducing the vinyl functionality. The starting aziridine was enantioselectively prepared from 3,4,5-trimethoxybenzaldehyde by guanidinium ylide mediated asymmetric aziridination. All nitrogen components used in the reaction sequence are reusable as the starting guanidinium source

Enantioselective Construction of a Polyhydroxylated Pyrrolidine Skeleton from 3‑Vinylaziridine-2-carboxylates: Synthesis of (+)-DMDP and a Potential Common Intermediate for (+)-Hyacinthacine A₁ and (+)-1-<i>epi</i>-Australine

We report an enantioselective synthesis of the polyhydroxylated pyrrolidine alkaloid (+)-DMDP. The key steps in the synthesis were guanidinium ylide mediated asymmetric aziridination, stereospecific ring opening of <i>trans</i>-3-vinylaziridine-2-carboxylate with an oxygen nucleophile, iodine-mediated 5<i>-endo-trig</i> amino cyclization, and Prévost displacement. In addition, a potential common intermediate for the polyhydroxylated pyrrolizidine alkaloids (+)-hyacinthacine A₁ and (+)-1-<i>epi</i>-australine was synthesized from a diastereoisomeric <i>cis</i>-aziridine coformed in the asymmetric aziridination using the same strategy. A rationale for the diastereoselectivity observed for the iodine-mediated amino cyclization reactions is proposed on the basis of the heats of formation of the products

Enantioselective Construction of a Polyhydroxylated Pyrrolidine Skeleton from 3‑Vinylaziridine-2-carboxylates: Synthesis of (+)-DMDP and a Potential Common Intermediate for (+)-Hyacinthacine A₁ and (+)-1-<i>epi</i>-Australine

We report an enantioselective synthesis of the polyhydroxylated pyrrolidine alkaloid (+)-DMDP. The key steps in the synthesis were guanidinium ylide mediated asymmetric aziridination, stereospecific ring opening of <i>trans</i>-3-vinylaziridine-2-carboxylate with an oxygen nucleophile, iodine-mediated 5<i>-endo-trig</i> amino cyclization, and Prévost displacement. In addition, a potential common intermediate for the polyhydroxylated pyrrolizidine alkaloids (+)-hyacinthacine A₁ and (+)-1-<i>epi</i>-australine was synthesized from a diastereoisomeric <i>cis</i>-aziridine coformed in the asymmetric aziridination using the same strategy. A rationale for the diastereoselectivity observed for the iodine-mediated amino cyclization reactions is proposed on the basis of the heats of formation of the products

Unprecedented 8,9′-Neolignans: Enantioselective Synthesis of Possible Stereoisomers for Structural Determination

(+)-Wutaienin (<b>3</b>) and its C-7 methyl ether (<b>4</b>), isolated from <i>Zanthoxylum wutaiense</i>, were found to be unprecedented 8,9′-neolignans containing an (<i>S</i>)-2-(1,1-dimethyl-1-hydroxymethyl)-7-methoxydihydro­benzofuran skeleton. Wutaienin (<b>3</b>) was present in the plant as an inseparable 1:1 mixture of the (7,8)-<i>syn</i>-diastereoisomers. The diastereoisomeric mixture was characterized by comparison with four possible diastereoisomers, which were enantioselectively synthesized from (<i>S</i>)-5-bromo-(1,1-dimethyl-1-hydroxymethyl)-7-methoxydihydro­benzofuran using Evans’ oxazolidinone-assisted asymmetric aldol condensation to install the chiral centers at the C-7 and C-8 positions