Enantioselective Pd-catalyzed allylic amination with self-assembling and non-assembling monodentate phosphine ligands

New chiral phospholanes were prepared by coupling of bromo-substituted heterocycles with the enantiopure, building block (2R,5R)-2,5-dimethyl-1-chlorophospholane. Some of the new phosphine ligands have the potential for self-assembling via hydrogen bondings in a metal complex. By application of these and related ligands in the palladium catalyzed allylic amination reaction, high enantioselectivities (up to 99%) were achieved. The influence of the construction of the cyclic phosphine ligands on the enantioselectivity is analyzed.

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(2R,5R)-2,5-Dimethyl-1-(2-pivaloylamino-pyrid-6-yl)-phospholaneC14H23N2OP[α]D19=-74 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(2R,5R)-2,5-Dimethyl-1-(3-pivaloylamino-thiazol-4-yl)-phospholaneC16H25N2OP[α]D19=-61 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(2R,5R)-2,5-Dimethyl-1-(1-tert-butoxy-isoquinolin-3-yl)-phospholaneC19H26NOP[α]D19=-97 (c 0.65, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(2R,5R)-2,5-Dimethyl-1-(1-oxo-1,2-dihydro-isoquinolin-3-yl)-phospholaneC15H18NOP[α]D19=-129 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)