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

Iridium-Catalyzed Asymmetric Hydrogenation of β,γ-Unsaturated γ‑Lactams: Scope and Mechanistic Studies

An efficient asymmetric hydrogenation of β,γ-unsaturated γ-lactams using an iridium–phosphoramidite complex is reported. The chiral γ-lactams were obtained in excellent yields and enantioselectivities (up to 99% yield and 99% ee). The mechanistic studies indicated that the reduced products were obtained via the hydrogenation of the <i>N</i>-acyliminium cations, generated from β,γ-unsaturated γ-lactams, which was verified by ¹H NMR analysis. The reaction was carried out at a reduced catalyst loading of 0.1 mol %, and the reduced products can be transformed to two potential bioactive compounds. A new route is provided for the synthesis of chiral γ-lactams

Synthesis of Chiral γ‑Lactams via in Situ Elimination/Iridium-Catalyzed Asymmetric Hydrogenation of Racemic γ‑Hydroxy γ‑Lactams

Chiral γ-lactams have been synthesized in excellent yields and enantioselectivities (up to 99% yield and 96% ee) from easily accessible racemic γ-hydroxy γ-lactams via an iridium-phosphoramidite catalyzed asymmetric hydrogenation. The reaction was designed based on insight into the reaction mechanism demonstrated in previous work and can be carried out at a reduced catalyst loading of 0.1 mol % on a gram scale. Several potential bioactive compounds can be synthesized from the reduced products. Mechanistic studies indicated that the reduced products were obtained via the hydrogenation of the <i>N</i>-acyliminium cations, generated from γ-hydroxy γ-lactams

Pd(II)-Catalyzed Aerobic Intermolecular 1,2-Diamination of Conjugated Dienes: A Regio- and Chemoselective [4 + 2] Annulation for the Synthesis of Tetrahydro­quinoxalines

A Pd­(II)-catalyzed aerobic intermolecular 1,2-diamination of conjugated dienes was developed for the regio- and chemoselective preparation of a variety of functionalized tetrahydro­quinoxalines, using simple sulfonyl protected <i>o</i>-phenylendiamines as a nitrogen source. This methodology provides a direct and efficient synthesis of tetrahydro­quinoxalines. O₂ was used as the stoichiometric oxidant, and reaction conditions were applied to a series of <i>o</i>-phenylendiamines and conjugated dienes. 35 examples are described, and good yields and selectivities are obtained for the majority of the products

Pd(II)-Catalyzed Aerobic Intermolecular 1,2-Diamination of Conjugated Dienes: A Regio- and Chemoselective [4 + 2] Annulation for the Synthesis of Tetrahydro­quinoxalines

A Pd­(II)-catalyzed aerobic intermolecular 1,2-diamination of conjugated dienes was developed for the regio- and chemoselective preparation of a variety of functionalized tetrahydro­quinoxalines, using simple sulfonyl protected <i>o</i>-phenylendiamines as a nitrogen source. This methodology provides a direct and efficient synthesis of tetrahydro­quinoxalines. O₂ was used as the stoichiometric oxidant, and reaction conditions were applied to a series of <i>o</i>-phenylendiamines and conjugated dienes. 35 examples are described, and good yields and selectivities are obtained for the majority of the products

Pd(II)-Catalyzed Aerobic Intermolecular 1,2-Diamination of Conjugated Dienes: A Regio- and Chemoselective [4 + 2] Annulation for the Synthesis of Tetrahydro­quinoxalines

A Pd­(II)-catalyzed aerobic intermolecular 1,2-diamination of conjugated dienes was developed for the regio- and chemoselective preparation of a variety of functionalized tetrahydro­quinoxalines, using simple sulfonyl protected <i>o</i>-phenylendiamines as a nitrogen source. This methodology provides a direct and efficient synthesis of tetrahydro­quinoxalines. O₂ was used as the stoichiometric oxidant, and reaction conditions were applied to a series of <i>o</i>-phenylendiamines and conjugated dienes. 35 examples are described, and good yields and selectivities are obtained for the majority of the products

An Ir/Zn Dual Catalysis for Enantio- and Diastereodivergent α‑Allylation of α‑Hydroxyketones

An Ir/Zn dual catalysis has been developed for the enantio- and diastereodivergent α-allylation of unprotected α-hydroxyketones under mild conditions, in the absence of any additional base. The cooperative action of a chiral iridium complex derived from phosphoramidites and a chiral Zn-ProPhenol complex is most likely responsible for its high reactivity, excellent enantioselectivity (up to >99% ee), and good diastereoselectivity (up to >20:1 dr). All four product stereoisomers could be prepared from the same set of starting materials and under identical conditions by simple selection of appropriate catalyst combinations

An Ir/Zn Dual Catalysis for Enantio- and Diastereodivergent α‑Allylation of α‑Hydroxyketones

An Ir/Zn dual catalysis has been developed for the enantio- and diastereodivergent α-allylation of unprotected α-hydroxyketones under mild conditions, in the absence of any additional base. The cooperative action of a chiral iridium complex derived from phosphoramidites and a chiral Zn-ProPhenol complex is most likely responsible for its high reactivity, excellent enantioselectivity (up to >99% ee), and good diastereoselectivity (up to >20:1 dr). All four product stereoisomers could be prepared from the same set of starting materials and under identical conditions by simple selection of appropriate catalyst combinations

Synthesis of Chiral α,β-Unsaturated γ‑Amino Esters via Pd-Catalyzed Asymmetric Allylic Amination

A Pd-catalyzed asymmetric allylic amination of 4-substituted 2-acetoxybut-3-enoates with amines has been developed for the regiospecific synthesis of chiral α,β-unsaturated γ-amino esters. The desired chiral aminated products can be obtained in up to 98% yield, and 99% ee and can be conveniently transformed to chiral γ-amino acid/alcohol derivatives and chiral γ-lactams, which can then be subjected to the synthesis of several types of chiral drugs and drug candidates. The preferential formation of chiral γ-amino esters may be attributed to the bulky substituents on the right side of the allyl substrates. This work provides an efficient strategy for the synthesis of chiral α,β-unsaturated γ-amino esters and their derivatives

Synthesis of Chiral α,β-Unsaturated γ‑Amino Esters via Pd-Catalyzed Asymmetric Allylic Amination

A Pd-catalyzed asymmetric allylic amination of 4-substituted 2-acetoxybut-3-enoates with amines has been developed for the regiospecific synthesis of chiral α,β-unsaturated γ-amino esters. The desired chiral aminated products can be obtained in up to 98% yield, and 99% ee and can be conveniently transformed to chiral γ-amino acid/alcohol derivatives and chiral γ-lactams, which can then be subjected to the synthesis of several types of chiral drugs and drug candidates. The preferential formation of chiral γ-amino esters may be attributed to the bulky substituents on the right side of the allyl substrates. This work provides an efficient strategy for the synthesis of chiral α,β-unsaturated γ-amino esters and their derivatives