A library of chiral imidazoline-aminophenol ligands: discovery of an efficient reaction sphere.
A library of imidazoline-aminophenol ligands was synthesized on solid supports. After immobilization of chiral chloromethylimidazolines 1 and 2 onto the polystyrylsulfonyl chloride, nucleophilic substitution with (R)- or (S)-phenylethylamine (3 and 4) provided four combinations of polymer-supported imidazoline-amine ligands. Further reductive alkylation using salicylaldehydes 7-10 provided a series of imidazoline-aminophenol ligands (L9-L24). Analysis by solid-phase catalysis/circular dichroism high-throughput screening of a copper-catalyzed Henry reaction revealed that ligand L25, comprising a (S,S)-diphenylethylenediamine-derived imidazoline, (S)-phenylethylamine, and dibromophenol, was highly efficient, thus providing the adduct of nitromethane and benzaldehyde in 95 % ee. The combination of stereogenic centers was crucial in promoting the highly stereoselective reactions. The unique reaction sphere of L25 was also examined in a Friedel-Crafts alkylation of indole and nitroalkene to give the adduct in up to 83 % ee.
Arai
Takayoshi
T
Department of Chemistry, Graduate School of Science, Chiba University, Inage, Chiba 263-8522, Japan. tarai@faculty.chiba-u.jp
Yokoyama
Naota
N
Yanagisawa
Akira
A
D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry; D000627:Aminophenols / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003300:Copper / Q000737:chemistry; D048288:Imidazolines / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry; D008024:Ligands; D008968:Molecular Conformation; D009573:Nitrites / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D000627:Aminophenols; D048288:Imidazolines; D007211:Indoles; D008024:Ligands; D009573:Nitrites; D054852:Small Molecule Libraries; D003300:Copper