Regioselective Pd-Catalyzed Aerobic Aza-Wacker Cyclization for Preparation of Isoindolinones and Isoquinolin-1(2<i>H</i>)-ones

A switchable regioselective intramolecular aerobic aza-Wacker cyclization catalyzed by palladium is presented. Isoindolinones or isoquinolin-1(2<i>H</i>)-ones could be prepared selectively from the same substrates using different catalysts. The type and steric hindrance of the ligands may be the variables most significant for regiocontrol

Asymmetric Aza-Wacker-Type Cyclization of <i>N</i>‑Ts Hydrazine-Tethered Tetrasubstituted Olefins: Synthesis of Pyrazolines Bearing One Quaternary or Two Vicinal Stereocenters

We have developed an asymmetric aza-Wacker-type cyclization of <i>N</i>-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the CC double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a <i>syn</i>-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is <i>cis</i> to the intranucleophilic group participates more readily in β-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, β-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps

Iridium-Catalyzed Asymmetric Hydrogenation of 2<i>H</i>‑Chromenes: A Highly Enantioselective Approach to Isoflavan Derivatives

A highly efficient (a<i>S</i>)-Ir/In-BiphPHOX-catalyzed asymmetric hydrogenation of substituted 2<i>H</i>-chromenes and substituted benzo­[<i>e</i>]­[1,2]­oxathiine 2,2-dioxides is described. A series of 2<i>H</i>-chromenes and benzo­[<i>e</i>]­[1,2]­oxathiine 2,2-dioxides were hydrogenated to give the target products in high yields (92–99%) with excellent enantioselectivities (up to 99.7% ee) using our catalytic system. This reaction provides a direct and efficient method for the construction of chiral benzo six-membered oxygen-containing compounds

Asymmetric Aza-Wacker-Type Cyclization of <i>N</i>‑Ts Hydrazine-Tethered Tetrasubstituted Olefins: Synthesis of Pyrazolines Bearing One Quaternary or Two Vicinal Stereocenters

We have developed an asymmetric aza-Wacker-type cyclization of <i>N</i>-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the CC double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a <i>syn</i>-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is <i>cis</i> to the intranucleophilic group participates more readily in β-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, β-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps

Asymmetric Aza-Wacker-Type Cyclization of <i>N</i>‑Ts Hydrazine-Tethered Tetrasubstituted Olefins: Synthesis of Pyrazolines Bearing One Quaternary or Two Vicinal Stereocenters

We have developed an asymmetric aza-Wacker-type cyclization of <i>N</i>-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the CC double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a <i>syn</i>-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is <i>cis</i> to the intranucleophilic group participates more readily in β-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, β-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps

Iridium-Catalyzed Asymmetric Hydrogenation of 2<i>H</i>‑Chromenes: A Highly Enantioselective Approach to Isoflavan Derivatives

A highly efficient (a<i>S</i>)-Ir/In-BiphPHOX-catalyzed asymmetric hydrogenation of substituted 2<i>H</i>-chromenes and substituted benzo­[<i>e</i>]­[1,2]­oxathiine 2,2-dioxides is described. A series of 2<i>H</i>-chromenes and benzo­[<i>e</i>]­[1,2]­oxathiine 2,2-dioxides were hydrogenated to give the target products in high yields (92–99%) with excellent enantioselectivities (up to 99.7% ee) using our catalytic system. This reaction provides a direct and efficient method for the construction of chiral benzo six-membered oxygen-containing compounds

Asymmetric Aza-Wacker-Type Cyclization of <i>N</i>‑Ts Hydrazine-Tethered Tetrasubstituted Olefins: Synthesis of Pyrazolines Bearing One Quaternary or Two Vicinal Stereocenters

We have developed an asymmetric aza-Wacker-type cyclization of <i>N</i>-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the CC double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a <i>syn</i>-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is <i>cis</i> to the intranucleophilic group participates more readily in β-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, β-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps

Pd(II)-Catalyzed Asymmetric Addition of Arylboronic Acids to Isatin-Derived Ketimines

A Pd­(II)/Pyrox-catalyzed enantioselecitve addition of arylboronic acids to 3-ketimino oxindoles was developed, providing chiral 3-amino-2-oxindoles with a quaternary stereocenter in high yields and with good enantioselectivities. A variety of functionalized 3-ketimino oxindoles can be used, and the method tolerates some variation in arylboronic acid scope. This asymmetric arylation provides an alternative efficient catalytic method for the preparation of chiral 3-aryl-3-amino-2-oxindoles, which also represents the first example of a Pd­(II)-catalyzed addition of arylborons to exocyclic ketimines

Stereoselective and Site-Specific Allylic Alkylation of Amino Acids and Small Peptides via a Pd/Cu Dual Catalysis

We report a stereo­selective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were easily synthesized in high yields and with excellent enantio­selectivities (up to >99% ee). Furthermore, a direct and highly stereo­selective synthesis of small peptides with enantio­pure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system

Tetrathiafulvalene Terminal-Decorated PAMAM Dendrimers for Triggered Release Synergistically Stimulated by Redox and CB[7]

A series of polyamidoamine (PAMAM) dendrimers with tetrathiafulvalene (TTF) at the periphery (G<i>n</i>-PAMAM-TTF), generation 0–2, were synthesized. These functionalized dendrimers exist as nanospheres with diameters around 80–100 nm in aqueous phase, which can encapsulate hydrophobic molecules. The terminal TTF groups can go through a reversible redox process upon addition of the oxidizing and reducing agents. Each terminal TTF^+• group of the oxidized G<i>n</i>-PAMAM-TTF assembled with cucurbit[7]­uril (CB[7]) forming a 1:1 inclusion complex with association constants of (3.14 ± 0.36) × 10⁵, (1.29 ± 0.12) × 10⁶, and (1.79 ± 0.24) × 10⁶ M^–1 for generation 0–2, respectively, even at the aggregate state. The formation of the inclusion complex loosened the structure of the nanospheres and initiated the release of cargo, and the release mechanism was validated by dynamic light scattering (DLS), cryo-transmission electron microscopy (TEM), and electron paramagnetic resonance (EPR) experiments. This study provides a potential strategy for the development of drug delivery systems synergistically triggered by redox and supramolecular assembly