The Synthesis of a New Class of Chiral Pincer Ligands and Their Applications in Enantioselective Catalytic Fluorinations and the Nozaki-Hiyama-Kishi Reaction

• Published in: Chemistry : a European journal 2011-12, Vol.17 (52), p.14922-14928
• Main Authors: Deng, Qing-Hai, Wadepohl, Hubert, Gade, Lutz H.
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohols; Aldehydes; asymmetric catalysis; Chemical reactions; Chemistry; Fluorination; ligand design; Ligands; Modular; nickel; Nozaki-Hiyama-Kishi reaction; Optimization; Phthalimides
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201102375

A new class of chiral tridentate N‐donor pincer ligands, bis(oxazolinylmethylidene)isoindolines (boxmi), was synthesized in three steps starting from readily available phthalimides. Their reaction with ethyl (triphenylphosphoranylidene)acetate by means of a key‐step Wittig reaction gave the ligand backbones, which were condensed with amino alcohols and then cyclized to obtain the corresponding ligands. These ligands were subsequently applied in the nickel(II)‐catalyzed enantioselective fluorination of oxindoles and β‐ketoesters to obtain the corresponding products with enantioselectivities of up to >99 % ee and high yields. Application of the chiral pincer ligands in the chromium‐catalyzed enantioselective Nozaki–Hiyama–Kishi reaction of aldehydes gave the corresponding alcohols with an optimal enantioselectivity of 93 %. A pincer with a twist: A Wittig coupling is the key step in the modular synthesis of chiral pincer ligands 1 (boxmi). Their NiII complexes catalyze the enantioselective fluorination of oxindoles and cyclic β‐ketoesters with extremely high enantioselectivity, whereas their use in Cr‐catalyzed enantioselective Nozaki–Hiyama–Kishi reactions of aldehydes gave the corresponding alcohols.