One Amine-3†Tasks: Reductive Coupling of Imines with Olefins in Batch and Flow.

Owing to their wide range of biological properties, γ-aminobutyric acid derivatives (GABA) have been extensively studied and found noteworthy industrial applications. However, atom-economical and efficient processes for their production are scarce and would greatly benefit from further investigations. Herein, we demonstrate that an iridium-based photocatalyst promotes the direct reductive cross-coupling of imines with olefins upon irradiation with visible light to give GABA derivatives in good yields and selectivities. We also stress the enabling triple role of tributylamine additive in this process, discuss the advantages of strategies based on proton-coupled electron transfer (PCET) and demonstrate the scale-up of this reaction in continuous flow.

Visible-Light Photoredox-Catalyzed Giese Reaction: Decarboxylative Addition of Amino Acid Derived α-Amino Radicals to Electron-Deficient Olefins.

A tin- and halide-free, visible-light photoredox-catalyzed Giese reaction was developed. Primary and secondary α-amino radicals were generated readily from amino acids in the presence of catalytic amounts of an iridium photocatalyst. The reactivity of the α-amino radicals has been evaluated for the functionalization of a variety of activated olefins.

Reductive Umpolung of Carbonyl Derivatives with Visible-Light Photoredox Catalysis: Direct Access to Vicinal Diamines and Amino Alcohols via α-Amino Radicals and Ketyl Radicals.

Visible-light-mediated photoredox-catalyzed aldimine-aniline and aldehyde-aniline couplings have been realized. The reductive single electron transfer (SET) umpolung of various carbonyl derivatives enabled the generation of intermediary ketyl and α-amino radical anions, which were utilized for the synthesis of unsymmetrically substituted 1,2-diamines and amino alcohols.

Synthesis of Strained γ-Lactams by Palladium(0)-Catalyzed C(sp(3) )-H Alkenylation and Application to Alkaloid Synthesis.

A variety of strained α-alkylidene-γ-lactams were synthesized by palladium(0)-catalyzed intramolecular C(sp(3) )-H alkenylation from easily accessible acyclic and monocyclic bromoalkene precursors. These lactams are valuable intermediates for accessing various classes of mono- and bicylic alkaloids containing a pyrrolidine ring, as illustrated with the synthesis of an advanced model of the marine natural product plakoridine A and of the indolizidine alkaloid δ-coniceine.

Palladium-catalyzed γ-selective arylation of zincated Boc-allylamines.

The regio- and diastereoselective arylation of Boc-protected allylamines was performed via a one-pot lithiation/transmetalation to zinc/cross-coupling sequence, through an appropriate choice of a phosphine ligand. A variety of γ-arylated products were obtained in moderate to good yield, and the products could be directly transformed into valuable γ-arylamines and ß-aryl aldehydes.

Ligand-controlled α- and ß-arylation of acyclic N-Boc amines.

The palladium-catalyzed ligand-controlled arylation of α-zincated acyclic amines, obtained by directed α-lithiation and transmetalation, is described. Whereas PtBu3 gave rise to α-arylated Boc-protected amines, more flexible N-phenylazole-based phosphine ligands induced major ß-arylation through migrative cross-coupling.

Room-temperature Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to maleimides and enones in the presence of CF3-substituted MeOBIPHEP analogues.

A Rh-based catalytic system implying electron-poor MeOBIPHEP analogues has been developed for the 1,4-addition of boronic acids to maleimides and enones under mild conditions at room temperature and led to succinimide derivatives and arylated cyclic ketones in good to excellent yields and ee. We uncovered the crucial role of the electronic and steric properties of diphosphine ligand and observed a strong boronic acid/ligand dependency in the case of maleimide derivatives and substrate/ligand matching in the case of cyclic enones.