Palladium-Catalyzed Regiodivergent Three-Component Alkenylamination of 1,3-Dienes with Alkyl and Aryl Amines

We report a palladium-catalyzed method for 4,3- or 4,1-selective alkenylamination of terminal dienes. Three-component couplings proceed with alkenyl triflates and several amines, giving vicinal carboamination with a Xantphos-supported catalyst and distal difunctionalization with a phosphoramidite ligand. A number of constitutionally different disubstituted dienes also participate in regiodivergent carboaminations. Experimental evidence indicates that selectivity in the Xantphos reactions is largely influenced by the substrate, whereas the phosphoramidite-promoted process is catalyst controlled, orchestrated by a key π-stacking interaction among the ligand, solvent, and substrate

A Diastereodivergent and Enantioselective Approach to <i>syn</i>- and <i>anti</i>-Diamines: Development of 2‑Azatrienes for Cu-Catalyzed Reductive Couplings with Imines That Furnish Allylic Amines

We introduce a new reagent class, 2-azatrienes, as a platform for catalytic enantioselective synthesis of allylic amines. Herein, we demonstrate their promise by a diastereodivergent synthesis of syn- and anti-1,2-diamines through their Cu–bis­(phosphine)-catalyzed reductive couplings with imines. With Ph-BPE as the supporting ligand, anti-diamines are obtained (up to 91% yield, >20:1 dr, and >99:1 er), and with the rarely utilized t-Bu-BDPP, syn-diamines are generated (up to 76% yield, 1:>20 dr, and 97:3 er)

Preparation of Chiral Allenes through Pd-Catalyzed Intermolecular Hydroamination of Conjugated Enynes: Enantioselective Synthesis Enabled by Catalyst Design

In this study, we establish that conjugated enynes undergo selective 1,4-hydroamination under Pd catalysis to deliver chiral allenes with pendant allylic amines. Several primary and secondary aliphatic and aryl-substituted amines couple with a wide range of mono- and disubstituted enynes in a nonenantioselective reaction where DPEphos serves as the ligand for Pd. Benzophenone imine acts as an ammonia surrogate to afford primary amines in a two-step/one-pot process. Examination of chiral catalysts revealed a high degree of reversibility in the C–N bond formation that negatively impacted enantioselectivity. Consequently, an electron-poor ferrocenyl-PHOX ligand was developed to enable efficient and enantioselective enyne hydroamination

Enantioselective Synthesis of <i>anti</i>-1,2-Diamines by Cu-Catalyzed Reductive Couplings of Azadienes with Aldimines and Ketimines

Here we report highly efficient and chemoselective azadiene–imine reductive couplings catalyzed by (Ph-BPE)­Cu–H that afford <i>anti</i>-1,2-diamines. In all cases, reactions take place with either aldimine or ketimine electrophiles to deliver a single diastereomer of product in >95:5 er. The products’ diamines are easily differentiable, facilitating downstream synthesis

Enantioselective Synthesis of <i>anti</i>-1,2-Diamines by Cu-Catalyzed Reductive Couplings of Azadienes with Aldimines and Ketimines

Here we report highly efficient and chemoselective azadiene–imine reductive couplings catalyzed by (Ph-BPE)­Cu–H that afford <i>anti</i>-1,2-diamines. In all cases, reactions take place with either aldimine or ketimine electrophiles to deliver a single diastereomer of product in >95:5 er. The products’ diamines are easily differentiable, facilitating downstream synthesis

Enantioselective Synthesis of <i>anti</i>-1,2-Diamines by Cu-Catalyzed Reductive Couplings of Azadienes with Aldimines and Ketimines

Here we report highly efficient and chemoselective azadiene–imine reductive couplings catalyzed by (Ph-BPE)­Cu–H that afford <i>anti</i>-1,2-diamines. In all cases, reactions take place with either aldimine or ketimine electrophiles to deliver a single diastereomer of product in >95:5 er. The products’ diamines are easily differentiable, facilitating downstream synthesis

Enantio- and Diastereoselective Synthesis of Homoallylic α‑Trifluoromethyl Amines by Catalytic Hydroalkylation of Dienes

We describe a strategy for the enantio- and diastereoselective synthesis of homoallylic α-trifluoromethyl amines by the catalytic hydroalkylation of terminal dienes. Trifluoromethyl-substituted isatin-derived azadienolate nucleophiles undergo γ-selective alkylation with a Pd–DTBM-SEGPHOS catalyst, which additionally promotes regioselective addition to the diene and delivers products in up to 86% yield, 10:1 dr, and 97.5:2.5 er

Enantioselective Intermolecular Pd-Catalyzed Hydroalkylation of Acyclic 1,3-Dienes with Activated Pronucleophiles

We report a highly enantioselective Pd–PHOX-catalyzed intermolecular hydroalkylation of acyclic 1,3-dienes. Meldrum’s acid derivatives and other activated C-pronucleophiles, such as β-diketones and malononitriles, react with a variety of aryl- and alkyl-substituted dienes in ≤20 h at room temperature. The coupled products, obtained in up to 96% yield and 97.5:2.5 er, are easily transformed into useful chemical building blocks for downstream synthesis