Design and Synthesis of Chiral Imidazolidine-Pyridine Ligands

Abstract

Condensation of chiral diamines and aldehydes gave a series of chiral imidazolidine-pyridine compounds with high diastereoselectivities. The ability of these compounds to act as chiral ligands was examined in the catalytic Henry reaction.The synthesis of chiral molecules in a catalytic asymmetric manner is essential for supplying fundamentally valuable organic compounds. 1 Because the creation of a wellorganized reaction sphere using highly functionalized chiral ligands is the key to controlling stereoselective metal catalysis, the design and development of new chiral ligands is at the forefront of research on catalytic asymmetric synthesis. In this communication, the quick and efficient stereoselective synthesis of imidazolidine compounds is reported, and their ability to act as chiral ligands is examined in the Cu(OAc) 2 -catalyzed Henry reaction. 2,3As part of our research program for exploring efficient asymmetric catalysts, we have succeeded in developing imidazoline-containing chiral ligands for metal-catalyzed reactions. 4,5 For example, imidazoline-aminophenol (L0)-Cu complexes have been realized as efficient catalysts for the Henry reaction, 4d the Friedel-Crafts reaction, 4d,e and the tandem Friedel-Crafts-Henry reaction. 4fAlthough the unique asymmetric reaction sphere produced by the imidazoline-aminophenol (L0)-metal complex has potential for successful application to other various asymmetric reactions, the simple imidazolinepyridine analogues (L1) were not effective for the Cu(OAc) 2 -catalyzed Henry reaction (Table 1, entries 2-5). We assumed that the relatively flat structure around the Cu center in the square-planar L1-Cu(II) complex was not sufficient to promote the stereoselective reactions [see Figure 1, L1 and Figure 4, L1b-Cu(OAc) 2 ]. To produce more stereochemical complexity, we focused on the imidazolidine ring, in which the sp 2 -carbon of the imidazoline ring is replaced by a sp 3 -carbon [Figure 1, L2 and Figure 4, L2a-Cu(OAc) 2 ].Relatives of the imidazolidines, chiral imidazolidinones are widely employed as organocatalysts for asymmetric reactions, as pioneered by MacMillan. 6 Furthermore, Uozumi reported elegant work on the stereoselective synthesis of an imidazoindole ligand for asymmetric palladium catalyses. 7 Despite the prevailing applications as organocatalysts, 8 however, the challenges on the ligand for the metal catalysts are rather limited. 9,10 Figure 1 Structurally simplified analogues (L1 and L2) of L0Although the newly formed sp 3 -carbon is a stereogenic center, we envisioned that the configuration of the product would be controlled by the steric repulsion relayed from the substituents of the chiral diamine. A DFT calculation at the level of B3LYP/6-31G* suggested that L2 depicted in Figure 2 is more stable than the epimer at the newly formed asymmetric sp 3 -carbon by 5.7 kcal/mol.The synthesis of imidazolidine-pyridine ligands was readily achieved by a simple condensation of monoalkyl chiral diamines and aldehydes using acetic acid Table 1 Henry Reaction Catalyzed b...

Modular Urea‐Based Catalytic Platforms Bearing Flexible Pyridylmethylamine and Rigid Pyridyl‐Imidazolidine Fragments

“…The relative as well as absolute configurations of these compounds were unequivocally assigned by X‐ray diffraction analysis of the platform 2b (Scheme ) and the corresponding Pd complex (see the Supporting Information). X‐ray diffraction analysis confirmed the selective installation of the urea motif, in full agreement with Arai and Suzuki's recent observations on the mono‐ N ‐alkylated pyridyl‐imidazolidine series …”

“…X-ray diffraction analysis confirmed the selective installation of the urea motif, in full agreement with Arai and Suzuki's recent observations on the mono-N-alkylated pyridyl-imidazolidine series. [23] Our next objective was to evaluate the catalytic properties of platforms 1 and 2 in two model reactions: the organocatalysed Michael addition of isobutyraldehyde to N-phenylmaleimide and the copper-promoted nitroaldol reaction.…”

Alternating Copolymerization of CO2 and Cyclohexene Oxide by New Pyridylamidozinc(II) Catalysts

“…The pyridylamino proligands L x H ( x = 1–5) were synthesized following previously reported procedures (see the Supporting Information). ,− Complexes 1 – 4 were cleanly obtained in yields ranging between 90% and 95%, following a typical synthetic approach, i.e., the reaction of L x H and Zn­[(NSiMe 3 ) 2 ] 2 in 1:1 ratio (Scheme ) in toluene, at 25 °C for complex 1 and at 80 °C for complexes 2 – 4 . Complexes 1 – 4 were characterized by multinuclear NMR spectroscopy, confirming heteroleptic monomeric structures (see the Supporting Information).…”

Asymmetric Benzoylation of meso‐Hydrobenzoin Using a Reusable Tripodal Imidazoline–Pyridine–Cu Catalyst

“…[5b] We have also studied imidazoline-pyridine L2 [6] as a simple analogue of imidazoline-pletion of the asymmetric benzoylation reaction, the self-supported tripodal imidazoline-pyridine-Cu catalyst could be easily recovered as a precipitate by adding hexane, and the recovered catalyst could be reused several times while maintaining the catalyst activity and selectivity. aminophenol L3, [7] which was effective for the Cu-catalyzed asymmetric Henry reaction.…”

“…[5] Although the L1-CuCl catalyst was originally discovered by using a polystyrene-supported catalyst system, once it was immobilized onto a conventional polymer backbone it showed lower activity than that of homogeneous unimolecular catalyst L1-CuCl; moreover, the heterogeneous catalyst was difficult to recycle. [5b] We have also studied imidazoline-pyridine L2 [6] as a simple analogue of imidazoline-pletion of the asymmetric benzoylation reaction, the self-supported tripodal imidazoline-pyridine-Cu catalyst could be easily recovered as a precipitate by adding hexane, and the recovered catalyst could be reused several times while maintaining the catalyst activity and selectivity. aminophenol L3, [7] which was effective for the Cu-catalyzed asymmetric Henry reaction.…”