Phenylalanine‐Derived Imidazolines Bearing Heteroaromatic Pendants: Synthesis, Characterization, and Application in the Asymmetric Henry Reaction

Abstract

Starting from L‐phenylalanine, (2S)‐3‐phenylpropane‐1,2‐diamine has been prepared and used as building block for the construction of the imidazoline ring. Four new optically pure NH‐imidazolines bearing different six‐membered heteroaromatic substituents on the C(2) position have been prepared and subsequently N‐modified. N‐Substitution afforded two regioisomers that were separated. Some of them proved to be instable and hydrolyzed to diamides. The molecular structures of NH‐imidazolines, both N‐substituted regioisomers, as well as diamides, were unambiguously confirmed by X‐ray‐analysis and NMR spectra. The successfully prepared imidazolines, as well as diamides, were applied as catalysts in a Cu(II)‐catalyzed Henry reaction achieving 26–98% chemical yields and enantiomeric excesses of 3–42%.

Chiral Imidazoline Ligands and Their Applications in Metal‐Catalyzed Asymmetric Synthesis†

“…In addition to PyIM ligands, some structurally related heterocycles such as pyrimidine, isoquinoline, and pyrazine were also employed to replace the pyridine ring, but they also could not give better results. [ 38‐39 ]…”

Synthesis of C2-Symmetric Bisphosphines and Their Application in Enantioselective Transition Metal Catalysis

“…[1][2][3][4][5][6][7] In this context, there is a remarkable attention in this type of synthesis and over the past few years, extensive researches have been carried out in order to develop efficient chiral ligands. [8][9][10][11][12][13][14][15][16][17][18][19] The first known palladium-catalyzed enantioselective allylic alkylation was introduced by Trost and Strege with moderate enantioselectivities in the presence of chiral 2,3-Oisoproylidene-2,3dihydroxy-1,4-bis(diphenylphosphino)butane (DIOP). [20] Since the initial report, it took many years to develop efficient enantioselective catalysts due to the complex enantiocontrol in allylic substitutions.…”