Palladium-Catalyzed Intramolecular Asymmetric Hydroamination of Alkynes

Abstract

The Pd-catalyzed reaction of internal alkynes with tethered amino groups in the presence of PhCO2H and RENORPHOS as chiral phosphine ligand is reported. Various five- and six-membered nitrogen-containing heterocycles were obtained in good to high yield with moderate to high ee.

Enantioselective Rhodium‐Catalyzed Synthesis of Branched Allylic Amines by Intermolecular Hydroamination of Terminal Allenes

“…[4] Despite extensive effort, efficient methods for catalytic enantioselective intermolecular hydroamination are rare. [5] Although the enantioselective intermolecular hydroamination of allenes would be an efficient method for the synthesis of a-chiral allylic amines, [6,7] only one example has been reported, which requires internal allenes, has a limited scope, and provides only moderate levels of enantioselectivity (Scheme 1 a). [8,9] To date, the enantioselective intermolecular hydroamination of mono-substituted allenes has not been reported, owing to the propensity of many hydroamination catalysts to form achiral products (either imines or linear allylic amines) from such substrates (Scheme 1 b).…”

Synthesis of Saturated Heterocycles via Metal-Catalyzed Alkene Hydroamination or Hydroalkoxylation Reactions

“…This suggests that the enantiodetermining step is due to an irreversible and selective nucleophilic attack of the amine onto the gold-π-complex, with matched or mismatched reactivity depending on the stereochemistry of the substrate and catalyst, and not as a result of selective formation of the gold allene π complex. Yamamoto developed an asymmetric palladium-catalyzed alkyne isomerization/ hydroamination by utilizing a chiral bisphosphine ligand (R,R)-RENORPHOS in combination with catalytic Pd 2 (dba) 3 to afford enantioenriched 2-alkenylpyrrolidines 135 and -piperidines 137 in moderate to excellent enantioselectivities (Scheme 56) [90,108,109]. Although the triflate protecting group was suitable, the use of the nonafluorobutanesulfonyl (Nf) group gave better results by allowing for reduced catalyst loadings.…”

Transition Metal‐Catalyzed Asymmetric Hydroamination of Alkenes (AHA)

“…However, Yamamoto recently reported the asymmetric hydroamination of N-protected aminoalkynes yielding vinylpyrrolidines and vinylpiperidines using a chiral palladium catalyst and benzoic acid as cocatalyst (Table 16). [60] A survey over different mono-and bidentate phosphine ligands and different N-protecting groups revealed that RE-NORPHOS is the optimal ligand and nonafluorobutanesulfonyl (Nf) the best protecting group. …”

“…[60] Hydropalladation of the alkyne is thought to generate a vinylpalladium intermediate, which rearranges to a p-allylpalladium species via a consecutive b-H-elimination/hydropalladation process. Nucleophilic attack of the amine on this p-allylpalladium species releases the heterocyclic product and regenerates the hydridopalladium catalyst.…”