N-Heterocyclic carbenes (NHCs) and their palladium complexes have been developed to facilitate the formation of carbon-carbon and carbon-heteroatom bonds.[1] NHC complexes exhibit unique chemical properties such as strong Pd-NHC s bonding, which enhances the stabilities of active organometallic compounds relative to conventional phosphane complexes.[2] Moreover, chiral NHC ligands have been synthesized to promote asymmetric catalysis. [3] Most of the chiral NHC ligands that have been utilized for asymmetric Pd II catalysis are monodentate, as Lee and Hartwig demonstrated moderate enantioselectivities (71-76 % ee) in a-arylation.[4] However, monodentate ligands caused practical difficulties including concomitant formation of inactive palladium-ligand complexes, such as those with a trans conformation. Bidentate NHC ligands exhibited better stabilities and selectivities: Douthwaite reported better enantioselectivities (up to 92 % ee) for asymmetric allylic alkylation [5a, b] than reactions employing the corresponding monodentate ligand.[5c]We envisioned tridentate NHCs would enhance the stabilities of Pd II complexes and enantioselectivities of various asymmetric reactions. As depicted in Figure 1, we sought a "chiral {Pd(OAc) 2 } complex" and designed and synthesized novel chiral tridentate NHC-Pd II complexes (II). Notably, ligand systems with NHCs, amidates, and oxygen functionalities (a C,N,O triad) could exert high electron densities and strong coordination on the Pd II complexes to increase stabilities even in nucleophilic solvents such as water and alcohols. Therefore, labile ligands such as water, alcohols, and acetonitrile are likely to be removed easily and thus enhance the reactivities and efficiencies of NHC-Pd catalysts.We report herein the synthesis of chiral tridentate NHC-Pd II complexes and their applications in an asymmetric oxidative Heck-type reaction as a proof of concept.The preparation of chiral ligands 4 is shown in Scheme 1. Hydroxyamide compounds 2 were prepared by reduction of amino acids 1 and subsequent N-alkylation with bromoacetyl bromide. Treatment of 2 with benzimidazole in the presence of KOH in DMF provided compounds 3, which were subjected to methylation to yield the amido alcohol substituted benzimidazolium salts 4. The structure was confirmed by 1 H NMR spectroscopic analysis; new peaks assigned to the NCH 3 appeared at d = 4.18 (4 a) and 4.15 ppm (4 b). Also, the imidazole H resonances shifted significantly as expected for iodine salts, appearing at d = 9.55 (4 a) and 9.50 ppm (4 b).Because direct coordination of ligands 4 to palladium was not efficient under numerous conditions, the ligands were transferred to palladium via silver NHC complexes.[6] As described in Scheme 2, compounds 4 a and 4 b were treated with Ag 2 O in CH 2 Cl 2 to give silver NHC complexes.
Herein, we report an asymmetric intermolecular Heck-type reaction of acyclic alkenes by using a palladium-pyridinyl oxazoline diacetate complex under oxidative palladium(II) catalysis conditions. A premade palladium-ligand complex afforded higher enantioselectivities than a corresponding premixed palladium-ligand system, while offering enhanced asymmetric induction when compared to known intermolecular Heck-type protocols.
Chiral dimeric tridentate NHC-amidate-alkoxide palladium(II) complexes, 3a and 3b, effected oxidative boron Heck-type reactions of aryl boronic acids with both acyclic and cyclic alkenes at room temperature to afford the corresponding coupling products with high enantioselectivities. The high degree of enantioselection, far superior to existing methods, stems from differences in the nonbonding interactions in the proposed transition states, due to the influence from bulky substituents of the alkene substrates and the "counter axial groups" of the palladium (II) catalysts.
KeywordsN-heterocyclic carbene ligand; amidate ligand; oxidative palladium(II) catalysis; boron-Heck; asymmetric catalysis; carbon-carbon bond formation
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