Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes Deepankar Das1, Rudrajit Mal1, Nisha Mittal1, Zhengbo Zhu2, Thomas J. Emge1 and Daniel Seidel*1,2 Full Research Paper Address: 1Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA and 2Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, Florida 32611, USA Email: Daniel Seidel* - * Corresponding author Open Access Beilstein J. Org. Chem. 2018, 14, 2002–2011. doi:10.3762/bjoc.14.175 Received: 28 May 2018 Accepted: 12 July 2018 Published: 01 August 2018 Associate Editor: L. Ackermann © 2018 Das et al.; licensee Beilstein-Institut. License and terms: see end of document. Keywords: bimetallic complexes; bisoxazolines; chiral ligands; heterocycles Abstract Chiral bisoxazoline ligands containing naphthyridine, pyridazine, pyrazole, and phenol bridging units were prepared and shown to form bimetallic complexes with various metal salts. X-ray crystal structures of bis-nickel naphthyridine-bridged, bis-zinc pyridazine-bridged, and bis-nickel as well as bis-palladium pyrazole-bridged complexes were obtained. Introduction Metal-centered asymmetric catalysis most commonly relies on monometallic complexes of various chiral ligands, among which chiral bisoxazolines have been highly successful in facilitating various Lewis acid-catalyzed asymmetric transformations [1-3]. In addition to monometallic catalysis, it has long been recognized that catalysts possessing two or more metal centers in close proximity can be uniquely effective in catalyzing certain types of reactions [4-6]. Serving as a main source of inspiration in the design of chiral small-molecule systems, nature utilizes a variety of bimetallic and multimetallic protein complexes to perform a host of biological functions [7]. Urease [8], hemerythrin [9], methane monooxygenase [10], ribonucleotide reductase [11], catechol oxidase [12], and arginase [13], are prominent examples of such bimetallic enzymes. A range of bi- and multi-metallic complexes have been utilized in asymmetric catalysis (Figure 1) [6]. For instance, Shibasaki and co-workers introduced a number of chiral multi-metallic complexes such as the hetero-bimetallic complex 1, in which the two different metals play distinct roles [14,15]. Jacobsen and co-workers reported dimeric salen complexes 2 which show cooperative reactivity between the two metal centers in the asymmetric ring opening of meso-epoxides [16]. Trost et al. disclosed the synthesis of dinuclear zinc complexes 3 and their application to enantioselective Aldol reactions [17,18] and a 2002 Beilstein J. Org. Chem. 2018, 14, 2002–2011. host of other asymmetric transformations [18]. Other notable contributions in this area were provided by the groups of Martell [19,20], Maruoka [21,22], Wuest [4,23-25], and others [26-46]. In the majority of cases where bimetallic complexes are used as the catalytically active species, the two metal centers perform different functions [47,48]. bis-copper complex with two equivalents of CuCl2 (Cu∙∙∙Cu distance = 4.291 Å) [53]. Tetraoxazoline ligand 13 undergoes formation of dinuclear complexes upon treatment with two equivalents of either ZnCl2, Ni(PPh3)2Br2, or Cu(OAc)2 (metal distances: Zn∙∙∙Zn = 8.963 Å; Ni∙∙∙Ni = 11.341 Å; Cu∙∙∙Cu = 9.432 Å) [54]. Efforts toward synthesizing bisoxazoline ligands capable of concurrently binding to two metal centers have been rather limited. Previous work by Pfaltz, Fahrni, Tsukada, BelleminLaponnaz and our group resulted in the synthesis of bisoxazoline containing ligands 6–13 that can simultaneously bind to two metals (Figure 2). For instance, treatment of 6 with two equivalents of copper perchlorate hexahydrate led to the formation of a bis-copper complex [49,50]. The two Cu(ΙΙ) ions, which have a Cu∙∙∙Cu distance of 2.947 Å, are coordinated to the pentadentate bisoxazoline-imidazole moiety and are bridged by the central phenoxy group in addition to a hydroxide ligand. Ligand 7 forms complex binuclear complexes with ZnCl2 and NiCl2 involving two metal centers and three ligand units. The 2:3 ZnCl2/7 complex crystal structure exhibits a Zn∙∙∙Zn distance of 3.056 Å. Compound 8a forms 2:2 complexes with ZnCl2 and NiCl2, whereas 8b was reported to form a bis-palladium complex with one equivalent of [(η3-C3H3)PdCl]2 [51]. Little is known about the complexing abilities of compounds 9 and 11 [49,52]. The naphthyridine-based ligand 10 forms a dinuclear complex with nickel(ΙΙ) acetate (Ni∙∙∙Ni distance = 3.132 Å). Compound 12, possessing an urea backbone, forms a Results and Discussion A number of bisoxazoline ligands with different bridging units were designed. We rationalized that the presence of three binding sites per metal center would be ideal in order to achieve the desired 1:2 ligand to metal ratio, and to prevent the potential formation of 2:2 or other higher order complexes. Variation of the bridging moiety should allow for modulation of the distance between the metal centers. An important criterion for selecting bridging units was their known ability to engage in metal-binding, along with being readily available. This led to the selection of naphthyridine, pyridazine, pyrazole, and phenol building blocks. We opted to connect these linkers to oxazolines via amide bonds. The reasoning for this was twofold. Firstly, this should provide ligands with significantly improved stabilities over for instance imine linkers. In addition, each amide moiety, upon deprotonation (a requirement for complex formation), would provide a formal negative charge on the ligand, thus resulting in increased complex stability while reducing the number of spectator anions associated with the two metals. Different combinations of five- and six-membered chelate rings were considered, as those allow for further modu- Figure 1: Examples of chiral bimetallic complexes utilized in asymmetric catalysis. 2003 Beilstein J. Org. Chem. 2018, 14, 2002–2011. Figure 2: Previously reported bisoxazoline ligands capable of stabilizing bimetallic complexes. lation of metal–metal distances. Convenient synthetic sequences were developed for six different ligands. Naphthyridine-bridged bisoxazoline ligands. The synthesis of naphthyridine bridged bisoxazoline ligand 16-H2 is outlined in Scheme 1. 1,8-Naphthyridine-2,7-diacyl chloride 14, obtained via a known procedure from the corresponding diacid [49], was allowed to react with aminoindanol-derived aminophenyloxazo- line 15 [55] to provide bisoxazoline ligand 16-H2 in 65% yield. Upon deprotonation, 16-H2 provides a dianionic ligand with three nitrogen donor atoms per metal center. Ligand 16-H2 was found to undergo complex formation with various copper, zinc, palladium and nickel salts. Figure 3 shows the X-ray crystal structure of 16·Ni2(OAc)2, obtained from ligand 16-H 2 and two equivalents of nickel(ΙΙ) Scheme 1: Synthesis of naph (...truncated)