b School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China;
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
Design and synthesis of axially chiral ligands have played a significant role in the development of asymmetric catalysis, and have attracted a great deal of attention from both academia and industry [1, 2, 3, 4]. Although many successful examples using axially chiral ligands with a biaryl framework [5, 6] have been disclosed, there are still a considerable amount of reactions in which these ligands are not efficient. The search for new well-designed axially chiral ligands is therefore still a remarkably challenging subject in the field of asymmetric catalysis [7, 8, 9, 10, 11].
Recently, we reported a novel type of axially chiral ligand [12, 13, 14] with an N-naphthyl framework (Fig. 1) instead of traditional binaphthyl framework and their coordination behavior with transition metals. When coordinated with Pd(OAc)2, only the Pd(Ⅱ)-complexes, (aS, S)-2, were obtained, while Pd(Ⅱ)-complexes (aR, S)-2 with R-geometry of the chiral N-naphthyl axis could not be prepared from (aR, S)-1 due to the steric repulsion between the substituents on the oxazoline ring and Pd salt . It means that ligands (aR, S)-1 were not the desired ligands. Moreover, the preparation of these axis-fixed oxazoline ligands requires inconvenient diastereomeric separation in their synthetic processes . However, tropos ligands bearing a chiral oxazoline coordination group delivered a practical way to furnish their axially chiral transition metal complexes based on seminal contributions from the laboratories of Zhang [17, 18, 19, 20], not only in view of atom economy, but also in view of separation process. Therefore, in pursuit of the development of novel axially chiral transition metal complexes with a N-Ar framework, herein, we wish to report the synthesis of a series of tropos ligands bearing N-heterocyclic carbene and chiral oxazoline coordination group with N-phenyl framework and their palladium complexes (Scheme 1).
|Fig. 1.Axially chiral ligands and palladium complexes with a N–Ar framework.|
|Scheme 1.Synthesis of axially chiral palladium complexes with a N–Ph framework.|
A mixture of imidazole 4 (1.5 mmol) and 2-iodophenyl substrates 3 (1.0 mmol) was stirred at 60 ℃ for 16 h in the presence of CuI (20 mol%) and tBuOK (1.5 equiv.) under Ar. The reaction mixture was concentrated and the residue with the addition of CH2Cl2 (50 mL) was washed by concentrated ammonia and saturated brine. The volatiles were then removed under reduced pressure and the residue was purified by column chromatography (silica gel, hexane/AcOEt) to afford addition products 5.2.2. General procedure for the synthesis of compounds 6
The compound 5 (2.0 mmol) and MeI or BnBr (15 mmol) in CH3CN (10 mL) were stirred under reflux until the compound 5 was consumed. After cooling to room temperature, volatiles were removed under reduced pressure to obtain the corresponding crude benzimidazolium salt. Benzimidazolium salt (1.0 mmol), Pd(OAc)2 (1.0 mmol), NaOAc (1.5 mmol) and KI (10.0 mmol) were refluxed in THF (25 mL) for 8 h. The volatiles were then removed under reduced pressure and the residue was purified by a silica gel flash column chromatography (dichloromethane/petroleum ether = 6/1-1/0) to give (aS, S)-6 as earth yellow solid.
The data and spectra of all target compounds are deposited in Supporting information.3. Results and discussion
To achieve the copper catalyzed cross-coupling of N-C bond, the reaction condition of compound 3a with 1H-benzo[d]imidazole 4a in the presence of CuI (x mol%) and tBuOK (1.5 equiv.) was optimized. To our delight, the product 5aa was obtained, and the results were shown in Table 1. Increasing the employed amount of CuI to 20 mol% from 10 mol%, the yield of product 5aa was increased to 51% (entry 2). However, further increasing the amount of CuI, the yield did not change so much. From the screen of reaction temperature (entries 2 and 3-6), it was found that 60 ℃ gave the best yield and product 5aa was obtained in 85% isolated yield. Further optimization of reaction solvent (entries 7 and 8), DMSO and DMF gave a little lower yield of product 5aa than that of CH3CN.
In order to evaluate the substrate scope of this CuI-catalysed cross-coupling, a series of imidazoles 4 and 2-iodophenyl substrates 3 were tested under the optimized reaction conditions, and the results were shown in Table 2. Various substituted imidazoles 4b-d (entries 1-3) were first used to react with 2- iodophenyl substrate 3a, affording the corresponding products 5 in moderate to good yields. It is worth noting that 4, 5-diphenyl-1Himidazole 4d delivered the low yield of product 5ad (entry 3), maybe due to its highly steric hindrance. Subsequently, the crosscoupling of other 2-iodophenyl substrates 3b and 3c with imidazoles 4 were also performed. All the reactions conducted smoothly, giving the desired products 5 in moderate to good yields (entries 4-9).
With coupling products 5 in hand, we paid our attention to the coordination behavior of their imidazole salts which are classical precursors for N-heterocyclic carbene (NHC) ligands . Compounds 5 were refluxed in CH3CN under the presence of alkyl halide for 24 h to give their corresponding salts 7. Subsequently, the study of these salts 7 coordinated with Pd(OAc)2 was carried out. As expected, only these palladium complexes (aS, S)-6 with Sgeometry of the chiral N-phenyl axis were prepared in 52%-75% yields (Table 3). The high yield of (aS, S)-6 suggests that salts (aR, S)- 7 were easily rotated to salts (aS, S)-7 further giving their Pd(Ⅱ)- complexes. This also means that salts 7 can be directly used to prepare their Pd(Ⅱ)-complexes without waste, unlike these axisfixed oxazoline ligands coordinated with transition metal have a configurational mismatching effect. Moreover, the structure of (aS, S)-6aa-Me was further confirmed by single-crystal X-ray diffraction (Fig. 2).
In summary, we have synthesized a series of tropos ligands with a N-phenyl framework by a copper-catalyzed C-N cross coupling of 2-iodophenyl substrates with imidazoles. Some of these coupling products were subsequently reacted with alkyl halide to afford corresponding imidazole salts which were further used to coordinate with Pd(OAc)2 affording desired axially chiral palladium complexes bearing a N-heterocyclic carbene and a chiral oxazoline coordination group with S-geometry of the chiral N-phenyl axis in moderate yields.Acknowledgment
The authors acknowledge the National Natural Science Foundation of China for financial support (Nos. 21372075 and 61376003).Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.cclet.2016.01.047.
|||J.D. Morrison, Asymmetric Synthesis, Academic Press, New York, 1985, p. 5.|
|||R. Noyori, Asymmetric Catalysis in Organic Synthesis, John Wiley & Sons, New York, 1994.|
|||E.N. Jacobsen, A. Pfaltz, H. Yamamoto, Comprehensive Asymmetric Catalysis, Ⅰ-Ⅲ, Springer, Berlin, 1999.|
|||I. Ojima, Catalytic Asymmetric Synthesis, 2nd ed., Wiley-VCH, New York, 2000.|
|||A. Miyashita, A. Yasuda, H. Takaya, et al., Synthesis of 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), an atropisomeric chiral bis(triaryl)phosphine, and its use in the rhodium(I)-catalyzed asymmetric hydrogenation of α-(acylamino) acrylic acids, J. Am. Chem. Soc. 102(1980) 7932-7934.|
|||R. Noyori, Asymmetric catalysis:science and opportunities, Angew. Chem. Int. Ed. 41(2002) 2008-2022.|
|||F. Wang, Y.J. Zhang, H. Wei, J. Zhang, W. Zhang, Atropisomeric bisoxazoline ligands with a bridge across the 5,5'-position of biphenyl for asymmetric catalysis, Tetrahedron Lett. 48(2007) 4083-4086.|
|||H. Wei, Y.J. Zhang, F. Wang, W. Zhang, Novel atropisomeric bisphosphine ligands with a bridge across the 5,5'-position of biphenyl for asymmetric catalysis, Tetrahedron:Asymmetry 19(2008) 482-488.|
|||Y.J. Zhang, F. Wang, W. Zhang, Chelation-induced axially chiral palladium complex system with tetraoxazoline ligands for highly enantioselective Wacker-type cyclization, J. Org. Chem. 72(2007) 9208-9213.|
|||H. Yu, F. Xie, Z. Ma, Y. Liu, W. Zhang, Switchable stereoselectivity:the effects of substituents on the D2-symmetric biphenyl backbone of phosphoramidites in copper-catalyzed asymmetric conjugate addition reactions with triethylaluminium, Adv. Synth. Catal. 354(2012) 1941-1947.|
|||J. Chen, D. Liu, N. Butt, et al., Palladium-catalyzed asymmetric hydrogenation of aacyloxy-1-aryletheanones, Angew. Chem. Int. Ed. 52(2013) 11632-11636.|
|||F. Wang, S. Li, M. Qu, et al., A highly efficient kinetic resolution of Morita-Baylis-Hillman adducts achieved by N-Ar axially chiral Pd-complexes catalyzed asymmetric allylation, Chem. Commun. 47(2011) 12813-12815.|
|||F. Wang, S. Li, M. Qu, et al., Synthesis of axially chiral oxazoline-carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe2, Beilstein J. Org. Chem. 8(2012) 726-731.|
|||Q. Xu, P. Gu, F. Wang, M. Shi, Selectfluor promoted NHC-oxazoline gold(I) complex catalyzed cycloaddition/oxidation reaction of enynones with alkenes, Org. Chem. Front. 2(2015) 1475-1484.|
|||Y. Imai, W. Zhang, T. Kida, Y. Nakatsuji, I. Ikeda, Novel axial chiral catalyst derived from biphenyl ligands bearing only two ortho-substituents, Tetrahedron Lett. 38(1997) 2681-2684.|
|||H.A. McManus, P.J. Guiry, Recent developments in the application of oxazolinecontaining ligands in asymmetric catalysis, Chem. Rev. 104(2004) 4151.|
|||F. Tian, D. Yao, Y. Liu, F. Xie, W. Zhang, Iridium-catalyzed highly enantioselective hydrogenation of exocyclic α,β-unsaturated carbonyl compounds, Adv. Synth. Catal. 352(2010) 1841-1845.|
|||Y. Imai, W. Zhang, T. Kida, Y. Nakatsuji, I. Ikeda, Novel chiral bisoxazoline ligands with a biphenyl backbone:preparation, complexation, and application in asymmetric catalytic reactions, J. Org. Chem. 65(2000) 3326-3333.|
|||W. Zhang, F. Xie, S. Matsuo, et al., Bisoxazoline ligands with an axial-unfixed biaryl backbone:the effects of the biaryl backbone and the substituent at oxazoline ring on Cu-catalyzed asymmetric cyclopropanation, Tetrahedron:Asymmetry 17(2006) 767-777.|
|||F. Wang, Y.J. Zhang, G. Yang, W. Zhang, Pd(Ⅱ)-catalyzed Wacker-type cyclization of 2-allylphenols by use of bisoxazoline ligands with axial-unfixed biphenyl, Tetrahedron Lett. 48(2007) 4179-4182.|
|||F. Wang, L.J. Liu, W. Wang, S. Li, M. Shi, Chiral NHC-metal-based asymmetric catalysis, Coord. Chem. Rev. 256(2012) 804-853.|