A library of chiral imidazoline-aminophenol ligands: Discovery of an efficient reaction sphere

作者：Arai Takayoshi^*; Yokoyama Naota; Yanagisawa Akira

来源：Chemistry - A European Journal, 2008, 14(7): 2052-2059.

DOI：10.1002/chem.200701439

• asymmetric catalysis
• circular dichroism
• combinatorial chemistry
• high-throughput screening
• solid-phase synthesis

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)-phenyle-thylamine, 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 FriedelCrafts alkylation of indole and nitroalkene to give the adduct in up to 83% ee.

• 出版日期2008