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Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones
G Model
CCLET-3717; No. of Pages 4 Chinese Chemical Letters xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters journal homepage: www.elsevier.com/locate/cclet
Original article
Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones Meng Tao, Fang Wu, Teng Li, Yan-Yun Li *, Jing-Xing Gao College of Chemistry and Chemical Engineering, and National Engineering Laboratory for Green Chemical Production of Alcohols-Ethers-Esters, Xiamen University, Xiamen 361005, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 11 April 2016 Received in revised form 17 May 2016 Accepted 19 May 2016 Available online xxx
Novel chiral multidentate P3N4-type ligand has been synthesized and characterized by NMR and HRMS. Using i-PrOH as solvent and hydrogen source, asymmetric transfer hydrogenation of various ketones was investigated. The catalyst generated in situ from chiral multidentate aminophosphine ligand (R,R,R,R)-3 and IrCl(CO)(PPh3)2 exhibited highly catalytic activity and excellent enantioselectivity under mild conditions, achieving the corresponding chiral alcohols with up to 99% yield and 99% ee. ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Keywords: Chiral aminophosphine ligand Asymmetric catalysis Asymmetric transfer hydrogenation Chiral alcohols Aromatic ketones
1. Introduction The design of chiral ligands plays a key role in the development of asymmetric catalytic reactions. To date, a large number of chiral ligands have been prepared and their application for asymmetric reactions has been investigated. Among of them, chiral PxNy-type ligands possessing a combination of hard and soft donor atoms have attracted considerable attention [1–5]. The advantage of this combination is to stabilize metal center and provide unique chiral coordination environments during a catalytic reaction. Although many encouraging advances had been achieved in the design and synthesis of chiral ligands, it is still an attractive goal to develop more new chiral ligands with both high activity as well as excellent enantioselectivity for different kinds of asymmetric catalytic reactions. The enantioselective reduction of prochiral ketones catalyzed by transition metal complexes is a powerful method to obtain optically active alcohols, which are important intermediates in pharmaceuticals, agrochemicals, and fragrances industries. Especially, the asymmetric transfer hydrogenation (ATH) of ketones, which used a hydrogen donor rather than hydrogen gas, has become an efficient and practical method
* Corresponding author. E-mail address: [email protected] (Y.-Y. Li).
due to its operational simplicity and versatility [6–17]. For these years, we have devoted ourselves to the development of novel chiral PxNy-type ligands, including bidentate, tridentate, tetradentate, multidentate, and macrocycle aminophosphine ligands, further studied their application in asymmetric catalysis [18–28]. As continuation of our study, herein we firstly reported the synthesis of novel chiral P3N4-type multidentate ligands, which displayed highly catalytic activity and enantioselectivity for the ATH of various aromatic ketones under mild conditions. 2. Experimental All reactions were carried out under a N2 atmosphere using Schlenk glassware. Solvents were dried according to standard procedures. Chiral ligand (R,R,R,R)-1 was prepared as our previous procedure [26]. NMR spectra were recorded on Bruker AV 400 spectrometer with TMS as the internal standard. Melting point was measured in sealed tubes and was not corrected. Mass spectra were obtained on Bruker En Apex ultra 7.0T FT-MS. Optical rotation values were measured on Perkin-Elmer 341 polarimeter. The yield and ee values were determined by a GC-950 instrument with an FID detector and a CP-Chiralsil-Dex CB column. The NMR spectra and HRMS spectra of chiral multidentate ligand (R,R,R,R)-3 and GC traces of ATH products are given in the Supporting information.
http://dx.doi.org/10.1016/j.cclet.2016.05.028 1001-8417/ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: M. Tao, et al., Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.05.028
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CCLET-3717; No. of Pages 4 M. Tao et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
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Scheme 1. Synthesis of chiral multidentate P3N4-type ligand.
2.1. Synthesis of chiral multidentate P3N4-type ligand Chiral multidentate P3N4-type ligand (R,R,R,R)-3 was synthesized as Scheme 1. A mixture of o-(diphenylphosphine)benzaldehyde (0.61 g, 2.1 mmol), (R,R,R,R)-1 (0.5 g, 0.97 mmol) and anhydrous Na2SO4 (5.0 g) in CH2Cl2 (50 mL) was stirred at room temperature for 2 days. The resulting yellow solution was filtered and the solvent was removed under reduced pressure to give a pale yellow solid (R,R,R,R)-2 (1.0 g, 97% yield). A solution of (R,R,R,R)-2 (1.0 g, 0.94 mmol) and NaBH4 (2.5 g, 66.0 mmol) in absolute ethanol (120 mL) was refluxed with stirring for 42 h. The solution was cooled to room temperature and H2O (30 mL) was added to decompose excess NaBH4. The mixture solution was extracted with CH2Cl2 (50 mL). Then, the combined extracts were washed with saturated NH4Cl solution, H2O and saturated brine solution, successively. The organic layers were combined and dried over anhydrous Na2SO4, filtered. The solvent was removed under reduced pressure to afford (R,R,R,R)-3 as a white solid in 90% yield (0.9 g). Mp 113–116 8C. 1H NMR (400 MHz, CDCl3): d 0.74 (d, 4H, J = 8.7 Hz), 1.00 (d, 4H, J = 29.8 Hz), 1.48 (s, 4H), 1.85 (m, 8H), 2.01 (s, 4H), 3.63–3.82 (m, 4H), 3.83–4.00 (m, 4H), 6.61–6.80 (m, 4H), 6.93–7.32 (m, 31H), 7.49 (ddd, 6H, J = 28.2, 14.1, 7.0 Hz); 13C NMR (100 MHz, CDCl3): d 24.86, 31.02, 48.82, 60.47, 60.85 (d, J = 6.13 Hz), 62.81, 63.05, 127.36, 128.68, 129.15 (d, J = 7.01 Hz), 132.28 (d, J = 26.97 Hz), 133.57, 134.22, 135.01, 135.63, 136.21 (d, J = 9.48 Hz), 136.71 (dd, J = 4.03, 10.23 Hz), 144.40, 144.64, 145.43, 145.66; 31P NMR (162 MHz, CDCl3): d 15.84, 15.86, 25.81. HRMS (ESI) Calcd. for [M+H]+: 1063.5126, Found: 1063.5117. ½a20 D 20.9 (c 0.2, CHCl3). 2.2. Typical procedure for ATH Under nitrogen atmosphere, the catalyst precursor IrCl(CO)(PPh3)2 (3.9 mg, 0.005 mmol) and (R,R,R,R)-3 (5.3 mg, 0.005 mmol) were placed in a tube equipped with a Teflon-coated magnetic stirring bar. i-PrOH was then added and the mixture was stirred at 40 8C for 20 min. An appropriate amount of KOH/i-PrOH solution was then added, and the mixture was continually stirred for another 20 min. Next, ketone (0.5 mmol) was introduced and the mixture was stirred at 40 8C for the required reaction time. At the end of the reaction, the product was analyzed by GC using a chiral CP-Chirasil-Dex CB column. 3. Results and discussion The condensation of chiral aminophosphine ligand (R,R,R,R)-1 and o-(diphenylphosphine)benzaldehyde proceeded in CH2Cl2 for 48 h, obtaining a pale yellow solid (R,R,R,R)-2 in 97% yield. Reduction of (R,R,R,R)-2 with excess NaBH4 was carried out in refluxing ethanol, giving the corresponding P3N4-type amine
ligand (R,R,R,R)-3 as a white solid in 90% yield, which features the HRMS signals at 1063.5117 (M+H). The 31P NMR spectrum of (R,R,R,R)-3 in CDCl3 solution exhibited three singlets at d 15.84 (– PPh2), 15.86 (–PPh2), and 25.81 (–PPh). Compound (R,R,R,R)-3 contains four chiral carbon atoms and seven possible coordination sites, which is hopeful to exhibit unique performance in both coordination chemistry and asymmetric catalysis. Next, we are interested in the asymmetric catalytic behavior of this novel chiral multidentate ligand (R,R,R,R)-3. Using i-PrOH as hydrogen donor, we examined the ATH of propiophenone catalyzed by combining (R,R,R,R)-3 with various iridium compounds (Table 1). It can be seen that the ATH of propiophenone proceeded smoothly to yield (S)-1-phenylpropanol under mild conditions. Notably, the catalyst system generated in situ from IrCl(CO)(PPh3)2 and (R,R,R,R)-3 gave 92% yield with 93% ee in just half an hour at 40 8C (Table 1, entry 5), surpassing those previously reported chiral PN4-type ligand (R,R,R,R)-1 [26]. Furthermore, we performed the reaction at lower catalyst loading (0.02 mol%), obtaining 61% yield with 90% ee (Table 1, entry 6). These results showed that the chiral multidentate ligand (R,R,R,R)-3 is highly effective for Ir-catalyzed enantioselective reduction of propiophenone. As we reported previously, adding an appropriate base is important for the reaction of ATH in terms of both reactivity and enantioselectivity [18]. Therefore, we examined the effect of the amount of KOH on ATH of propiophenone with IrCl(CO)(PPh3)2/ (R,R,R,R)-3. It showed that no reaction carried out if the base was absent or at low concentration. As the base concentration was increased, both the reaction rate and ee increased greatly. However, excess base decreased slightly the enantioselectivity although the conversion increased (For more details, see the Supporting information).
Table 1 Screening of catalysts for ATH of propiophenone.a
Entry
Iridium complex
Time (h)
Yield (%)b
ee (%)b
1 2 3 4 5 6c
[IrCl(COD)]2 [IrHCl(COD)]2 [Cp*IrCl2]2 IrH(CO)(PPh3)3 IrCl(CO)(PPh3)2 IrCl(CO)(PPh3)2
0.5 0.5 0.5 0.5 0.5 5
98 97 95 20 92 61
35 59 85 92 93 90
a Reaction conditions: propiophenone (1 mmol), iridium complex (0.005 mmol), (R,R,R,R)-3 (0.005 mmol), KOH (0.06 mmol), i-PrOH (10 mL), 40 8C. b Yield and ee were determined by GC analysis with a chiral CP-Chirasil-Dex CB column. c Propiophenone (25 mmol), IrCl(CO)(PPh3)2 (0.005 mmol), (R,R,R,R)-3 (0.005 mmol), KOH (0.25 mmol).
Please cite this article in press as: M. Tao, et al., Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.05.028
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Table 2 ATH of a broad scope of ketones catalyzed by IrCl(CO)(PPh3)2/(R,R,R,R)-3.a
R1
R2
1 2 3 4d 5 6d
C6H5 C6H5 4-Me-C6H4 C6H5 C6H5 C6H5
CH3 C2H5 C2H5 n-Bu (CH3)2CH
7 8 9 10 11
3-OMe-C6H4 2-Me-C6H4 4-Me-C6H4 4-Et-C6H4
CH3 CH3 CH3 CH3 CH3 CH3
Entry
12d
a b c d
Yield (%)b
ee (%)b
Config.c
98 96 95 94 99 99
81 94 91 96 97 99
S S S R S R
0.5 10 3 1 0.5
98 87 93 95 97
86 81 77 81 79
S S S S S
0.5
99
99
R
Time (h) 0.5 0.25 0.5 2 0.5 0.5
Reaction conditions: ketone (0.5 mmol), IrCl(CO)(PPh3)2 (0.005 mmol), (R,R,R,R)-3 (0.005 mmol), KOH (0.04 mmol), i-PrOH (10 mL), 40 8C. Yield and enantiomeric excesses were determined by GC analysis using a CP-Chiralsil-Dex CB column, 25 m 0.25 mm. The configurations were determined by comparison of the retention times of the enantiomers on the GC traces with literature values. Chiral ligand (S,S,S,S)-3 was used.
With the optimized conditions in hand, we further investigated the ATH of a broad scope of aromatic ketones using the catalytic system formed in situ from of IrCl(CO)(PPh3)2 and chiral ligand (R,R,R,R)-3 (Table 2). For the ATH of acetophenone, the catalyst exhibited high activity and good enantioselectivity (98% yield, 81% ee, Table 2, entry 1). To our delight, the ATH of various asubstituted aromatic ketones proceeded smoothly, affording the corresponding chiral alcohols with high yields and excellent enantioselectivities (up to 99% ee, Table 2, entries 2–6). When aryl methyl ketones were used as substrates, high yields and ee were obtained (Table 2, entries 7–12). An exception is found in the ATH of 2-methylacetophenone, which gave low activity (10 h, 87% yield, Table 2, entry 8). This result hints that the steric hindrance of substituent on the phenyl ring may hamper the reaction. Interestingly, more hindered ketone, 1,10 -diphenylpropan-2-one, could be reduced with high yield as well as excellent enantioselectivity (99% ee, Table 2, entry 12).
4. Conclusion In summary, we demonstrated novel chiral multidentate P3N4type ligand (R,R,R,R)-3, which displayed highly catalytic activity and enantioselectivity for the ATH of aromatic ketones under mild conditions. Using i-PrOH as hydrogen source, various aromatic ketones could be enantioselectively reduced by IrCl(CO)(PPh3)2/ (R,R,R,R)-3 to the corresponding chiral alcohols with up to 99% ee. Compared with the chiral PxNy-type ligands traditionally used in the ATH reactions, this novel ligand is multidentate aminophosphine ligand. This unique structure would afford more coordination sites, which maybe result in excellent catalytic performance in asymmetric reaction. Considering its highly catalytic activity and enantioselectivity, the chiral multidentate ligand represents an interesting direction for design and synthesis of novel chiral ligands. Further study of these chiral aminophosphine ligands is in progress to develop more efficient chiral ligands for asymmetric catalysis. Acknowledgments We are grateful to the National Natural Science Foundation of China (No. 21173176), the Program for Innovative Research Team
in Chinese Universities (No. IRT_14R31), the Fundamental Research Funds for the Central Universities (No. 20720150040) and NFFTBS (No. J1310024) for financial support.
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.2016.05. 028. References [1] A. Mezzetti, Ruthenium complexes with chiral tetradentate PNNP ligands: asymmetric catalysis from the viewpoint of inorganic chemistry, Dalton Trans. 39 (2010) 7851–7869. [2] D.K. Ioannis, Recent advances on P,N-containing ligands for transition-metal homogeneous catalysis, Curr. Org. Synth. 5 (2008) 227–249. [3] G. Chelucci, G. Orru, G.A. Pinna, Chiral P,N-ligands with pyridine–nitrogen and phosphorus donor atoms. Syntheses and applications in asymmetric catalysis, Tetrahedron 59 (2003) 9471–9515. [4] G. Helmchen, A. Pfaltz, Phosphinooxazolines: a new class of versatile, modular P,N-ligands for asymmetric catalysis, Acc. Chem. Res. 33 (2000) 336–345. [5] P. Espinet, K. Soulantica, Phosphine-pyridyl and related ligands in synthesis and catalysis, Coord. Chem. Rev. 193–195 (1999) 499–556. [6] R. Malacea, R. Poli, E. Manoury, Asymmetric hydrosilylation, transfer hydrogenation and hydrogenation of ketones catalyzed by iridium complexes, Coord. Chem. Rev. 254 (2010) 729–752. [7] R.H. Morris, Asymmetric hydrogenation, transfer hydrogenation and hydrosilylation of ketones catalyzed by iron complexes, Chem. Soc. Rev. 38 (2009) 2282– 2291. [8] C. Wang, X.F. Wu, J.L. Xiao, Broader, greener, and more efficient: recent advances in asymmetric transfer hydrogenation, Chem. Asian J. 3 (2008) 1750–1770. [9] T. Ikariya, A.J. Blacker, Asymmetric transfer hydrogenation of ketones with bifunctional transition metal-based molecular, Acc. Chem. Res. 40 (2007) 1300–1308. [10] R. Noyori, S. Hashiguchi, Asymmetric transfer hydrogenation catalyzed by chiral ruthenium complexes, Acc. Chem. Res. 30 (1997) 97–102. [11] T. Hamada, T. Torii, T. Onishi, et al., Asymmetric transfer hydrogenation of aaminoalkyl a0 -chloromethyl ketones with chiral Rh complexes, J. Org. Chem. 69 (2004) 7391–7394. [12] N. Debono, M. Besson, C. Pinel, et al., New chiral bis(oxazoline) Rh(I)-, Ir(I)- and Ru(II)-complexes for asymmetric transfer hydrogenations of ketones, Tetrahedron Lett. 45 (2004) 2235–2238. [13] D.S. Matharu, D.J. Morris, A.M. Kawamoto, et al., A stereochemically well-defined rhodium(III) catalyst for asymmetric transfer hydrogenation of ketones, Org. Lett. 7 (2005) 5489–5491. [14] P. Paredes, J. Diez, M.P. Gamasa, Synthesis of enantiopure iridium(I) and iridium(III) pybox complexes and their application in the asymmetric transfer hydrogenation of ketones, Organometallics 27 (2008) 2597–2607.
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[15] V.H. Vazquez, S. Reber, M.A. Ariger, et al., Iridium diamine catalyst for the asymmetric transfer hydrogenation of ketones, Angew. Chem. Int. Ed. 50 (2011) 8979–8981. [16] W.W. Zuo, A.J. Lough, Y.F. Li, R.H. Morris, Amine(imine)diphosphine iron catalysts for asymmetric transfer hydrogenation of ketones and imines, Science 342 (2013) 1080–1083. [17] R. Bigler, R. Huber, A. Mezzetti, Highly enantioselective transfer hydrogenation of ketones with chiral (NH)2P2 macrocyclic iron(II) complexes, Angew. Chem. Int. Ed. 54 (2015) 5171–5174. [18] Y.Y. Li, S.L. Yu, W.Y. Shen, J.X. Gao, Iron-, cobalt-, and nickel-catalyzed asymmetric transfer hydrogenation and asymmetric hydrogenation of ketones, Acc. Chem. Res. 48 (2015) 2587–2598. [19] J.X. Gao, T. Ikariya, R. Noyori, A ruthenium(II) complex with a C2-symmetric diphosphine/diamine tetradentate ligand for asymmetric transfer hydrogenation of aromatic ketones, Organometallics 15 (1996) 1087–1089. [20] H. Zhang, C.B. Yang, Y.Y. Li, et al., Highly efficient chiral metal cluster systems derived from Ru3(CO)12 and chiral diiminodiphosphines for the asymmetric transfer hydrogenation of ketones, Chem. Commun. 1 (2003) 142–143. [21] Z.R. Dong, Y.Y. Li, J.S. Chen, et al., Highly efficient iridium catalyst for asymmetric transfer hydrogenation of aromatic ketones under base-free conditions, Org. Lett. 7 (2005) 1043–1045.
[22] Y.Y. Li, X.Q. Zhang, Z.R. Dong, et al., Kinetic resolution of racemic secondary alcohols catalyzed by chiral diaminodiphosphine-Ir(I) complexes, Org. Lett. 8 (2006) 5565–5567. [23] S.L. Yu, Y.Y. Li, Z.R. Dong, et al., Synthesis of novel chiral N,P-containing multidentate ligands and their applications in asymmetric transfer hydrogenation, Chin. Chem. Lett. 22 (2011) 1269–1272. [24] J.N. Zhang, X.R. Yang, H. Zhou, et al., Oxidative kinetic resolution of racemic secondary alcohols in water with chiral PNNP/Ir catalyst, Green Chem. 14 (2012) 1289–1292. [25] S.L. Yu, W.Y. Shen, Y.Y. Li, et al., Iron-catalyzed highly enantioselective reduction of aromatic ketones with chiral P2N4-type macrocycles, Adv. Synth. Catal. 354 (2012) 818–822. [26] Y.Q. Xu, S.L. Yu, Y.Y. Li, Z.R. Dong, J.X. Gao, Novel chiral C2-symmetric multidentate aminophosphine ligands for use in catalytic asymmetric reduction of ketones, Chin. Chem. Lett. 24 (2013) 527–530. [27] Y.Y. Li, S.L. Yu, X.F. Wu, et al., Iron catalyzed asymmetric hydrogenation of ketones, J. Am. Chem. Soc. 136 (2014) 4031–4039. [28] L. Zeng, F. Wu, Y.Y. Li, Z.R. Dong, J.X. Gao, Synthesis and characterization of novel chiral bidentate P,N-containing ligands and ruthenium(II) complex. The application in asymmetric transfer hydrogenation of ketones, J. Organomet. Chem. 762 (2014) 34–39.
Please cite this article in press as: M. Tao, et al., Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.05.028
CCLET-3717; No. of Pages 4 Chinese Chemical Letters xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters journal homepage: www.elsevier.com/locate/cclet
Original article
Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones Meng Tao, Fang Wu, Teng Li, Yan-Yun Li *, Jing-Xing Gao College of Chemistry and Chemical Engineering, and National Engineering Laboratory for Green Chemical Production of Alcohols-Ethers-Esters, Xiamen University, Xiamen 361005, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 11 April 2016 Received in revised form 17 May 2016 Accepted 19 May 2016 Available online xxx
Novel chiral multidentate P3N4-type ligand has been synthesized and characterized by NMR and HRMS. Using i-PrOH as solvent and hydrogen source, asymmetric transfer hydrogenation of various ketones was investigated. The catalyst generated in situ from chiral multidentate aminophosphine ligand (R,R,R,R)-3 and IrCl(CO)(PPh3)2 exhibited highly catalytic activity and excellent enantioselectivity under mild conditions, achieving the corresponding chiral alcohols with up to 99% yield and 99% ee. ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Keywords: Chiral aminophosphine ligand Asymmetric catalysis Asymmetric transfer hydrogenation Chiral alcohols Aromatic ketones
1. Introduction The design of chiral ligands plays a key role in the development of asymmetric catalytic reactions. To date, a large number of chiral ligands have been prepared and their application for asymmetric reactions has been investigated. Among of them, chiral PxNy-type ligands possessing a combination of hard and soft donor atoms have attracted considerable attention [1–5]. The advantage of this combination is to stabilize metal center and provide unique chiral coordination environments during a catalytic reaction. Although many encouraging advances had been achieved in the design and synthesis of chiral ligands, it is still an attractive goal to develop more new chiral ligands with both high activity as well as excellent enantioselectivity for different kinds of asymmetric catalytic reactions. The enantioselective reduction of prochiral ketones catalyzed by transition metal complexes is a powerful method to obtain optically active alcohols, which are important intermediates in pharmaceuticals, agrochemicals, and fragrances industries. Especially, the asymmetric transfer hydrogenation (ATH) of ketones, which used a hydrogen donor rather than hydrogen gas, has become an efficient and practical method
* Corresponding author. E-mail address: [email protected] (Y.-Y. Li).
due to its operational simplicity and versatility [6–17]. For these years, we have devoted ourselves to the development of novel chiral PxNy-type ligands, including bidentate, tridentate, tetradentate, multidentate, and macrocycle aminophosphine ligands, further studied their application in asymmetric catalysis [18–28]. As continuation of our study, herein we firstly reported the synthesis of novel chiral P3N4-type multidentate ligands, which displayed highly catalytic activity and enantioselectivity for the ATH of various aromatic ketones under mild conditions. 2. Experimental All reactions were carried out under a N2 atmosphere using Schlenk glassware. Solvents were dried according to standard procedures. Chiral ligand (R,R,R,R)-1 was prepared as our previous procedure [26]. NMR spectra were recorded on Bruker AV 400 spectrometer with TMS as the internal standard. Melting point was measured in sealed tubes and was not corrected. Mass spectra were obtained on Bruker En Apex ultra 7.0T FT-MS. Optical rotation values were measured on Perkin-Elmer 341 polarimeter. The yield and ee values were determined by a GC-950 instrument with an FID detector and a CP-Chiralsil-Dex CB column. The NMR spectra and HRMS spectra of chiral multidentate ligand (R,R,R,R)-3 and GC traces of ATH products are given in the Supporting information.
http://dx.doi.org/10.1016/j.cclet.2016.05.028 1001-8417/ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: M. Tao, et al., Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.05.028
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CCLET-3717; No. of Pages 4 M. Tao et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
2
Scheme 1. Synthesis of chiral multidentate P3N4-type ligand.
2.1. Synthesis of chiral multidentate P3N4-type ligand Chiral multidentate P3N4-type ligand (R,R,R,R)-3 was synthesized as Scheme 1. A mixture of o-(diphenylphosphine)benzaldehyde (0.61 g, 2.1 mmol), (R,R,R,R)-1 (0.5 g, 0.97 mmol) and anhydrous Na2SO4 (5.0 g) in CH2Cl2 (50 mL) was stirred at room temperature for 2 days. The resulting yellow solution was filtered and the solvent was removed under reduced pressure to give a pale yellow solid (R,R,R,R)-2 (1.0 g, 97% yield). A solution of (R,R,R,R)-2 (1.0 g, 0.94 mmol) and NaBH4 (2.5 g, 66.0 mmol) in absolute ethanol (120 mL) was refluxed with stirring for 42 h. The solution was cooled to room temperature and H2O (30 mL) was added to decompose excess NaBH4. The mixture solution was extracted with CH2Cl2 (50 mL). Then, the combined extracts were washed with saturated NH4Cl solution, H2O and saturated brine solution, successively. The organic layers were combined and dried over anhydrous Na2SO4, filtered. The solvent was removed under reduced pressure to afford (R,R,R,R)-3 as a white solid in 90% yield (0.9 g). Mp 113–116 8C. 1H NMR (400 MHz, CDCl3): d 0.74 (d, 4H, J = 8.7 Hz), 1.00 (d, 4H, J = 29.8 Hz), 1.48 (s, 4H), 1.85 (m, 8H), 2.01 (s, 4H), 3.63–3.82 (m, 4H), 3.83–4.00 (m, 4H), 6.61–6.80 (m, 4H), 6.93–7.32 (m, 31H), 7.49 (ddd, 6H, J = 28.2, 14.1, 7.0 Hz); 13C NMR (100 MHz, CDCl3): d 24.86, 31.02, 48.82, 60.47, 60.85 (d, J = 6.13 Hz), 62.81, 63.05, 127.36, 128.68, 129.15 (d, J = 7.01 Hz), 132.28 (d, J = 26.97 Hz), 133.57, 134.22, 135.01, 135.63, 136.21 (d, J = 9.48 Hz), 136.71 (dd, J = 4.03, 10.23 Hz), 144.40, 144.64, 145.43, 145.66; 31P NMR (162 MHz, CDCl3): d 15.84, 15.86, 25.81. HRMS (ESI) Calcd. for [M+H]+: 1063.5126, Found: 1063.5117. ½a20 D 20.9 (c 0.2, CHCl3). 2.2. Typical procedure for ATH Under nitrogen atmosphere, the catalyst precursor IrCl(CO)(PPh3)2 (3.9 mg, 0.005 mmol) and (R,R,R,R)-3 (5.3 mg, 0.005 mmol) were placed in a tube equipped with a Teflon-coated magnetic stirring bar. i-PrOH was then added and the mixture was stirred at 40 8C for 20 min. An appropriate amount of KOH/i-PrOH solution was then added, and the mixture was continually stirred for another 20 min. Next, ketone (0.5 mmol) was introduced and the mixture was stirred at 40 8C for the required reaction time. At the end of the reaction, the product was analyzed by GC using a chiral CP-Chirasil-Dex CB column. 3. Results and discussion The condensation of chiral aminophosphine ligand (R,R,R,R)-1 and o-(diphenylphosphine)benzaldehyde proceeded in CH2Cl2 for 48 h, obtaining a pale yellow solid (R,R,R,R)-2 in 97% yield. Reduction of (R,R,R,R)-2 with excess NaBH4 was carried out in refluxing ethanol, giving the corresponding P3N4-type amine
ligand (R,R,R,R)-3 as a white solid in 90% yield, which features the HRMS signals at 1063.5117 (M+H). The 31P NMR spectrum of (R,R,R,R)-3 in CDCl3 solution exhibited three singlets at d 15.84 (– PPh2), 15.86 (–PPh2), and 25.81 (–PPh). Compound (R,R,R,R)-3 contains four chiral carbon atoms and seven possible coordination sites, which is hopeful to exhibit unique performance in both coordination chemistry and asymmetric catalysis. Next, we are interested in the asymmetric catalytic behavior of this novel chiral multidentate ligand (R,R,R,R)-3. Using i-PrOH as hydrogen donor, we examined the ATH of propiophenone catalyzed by combining (R,R,R,R)-3 with various iridium compounds (Table 1). It can be seen that the ATH of propiophenone proceeded smoothly to yield (S)-1-phenylpropanol under mild conditions. Notably, the catalyst system generated in situ from IrCl(CO)(PPh3)2 and (R,R,R,R)-3 gave 92% yield with 93% ee in just half an hour at 40 8C (Table 1, entry 5), surpassing those previously reported chiral PN4-type ligand (R,R,R,R)-1 [26]. Furthermore, we performed the reaction at lower catalyst loading (0.02 mol%), obtaining 61% yield with 90% ee (Table 1, entry 6). These results showed that the chiral multidentate ligand (R,R,R,R)-3 is highly effective for Ir-catalyzed enantioselective reduction of propiophenone. As we reported previously, adding an appropriate base is important for the reaction of ATH in terms of both reactivity and enantioselectivity [18]. Therefore, we examined the effect of the amount of KOH on ATH of propiophenone with IrCl(CO)(PPh3)2/ (R,R,R,R)-3. It showed that no reaction carried out if the base was absent or at low concentration. As the base concentration was increased, both the reaction rate and ee increased greatly. However, excess base decreased slightly the enantioselectivity although the conversion increased (For more details, see the Supporting information).
Table 1 Screening of catalysts for ATH of propiophenone.a
Entry
Iridium complex
Time (h)
Yield (%)b
ee (%)b
1 2 3 4 5 6c
[IrCl(COD)]2 [IrHCl(COD)]2 [Cp*IrCl2]2 IrH(CO)(PPh3)3 IrCl(CO)(PPh3)2 IrCl(CO)(PPh3)2
0.5 0.5 0.5 0.5 0.5 5
98 97 95 20 92 61
35 59 85 92 93 90
a Reaction conditions: propiophenone (1 mmol), iridium complex (0.005 mmol), (R,R,R,R)-3 (0.005 mmol), KOH (0.06 mmol), i-PrOH (10 mL), 40 8C. b Yield and ee were determined by GC analysis with a chiral CP-Chirasil-Dex CB column. c Propiophenone (25 mmol), IrCl(CO)(PPh3)2 (0.005 mmol), (R,R,R,R)-3 (0.005 mmol), KOH (0.25 mmol).
Please cite this article in press as: M. Tao, et al., Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.05.028
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3
Table 2 ATH of a broad scope of ketones catalyzed by IrCl(CO)(PPh3)2/(R,R,R,R)-3.a
R1
R2
1 2 3 4d 5 6d
C6H5 C6H5 4-Me-C6H4 C6H5 C6H5 C6H5
CH3 C2H5 C2H5 n-Bu (CH3)2CH
7 8 9 10 11
3-OMe-C6H4 2-Me-C6H4 4-Me-C6H4 4-Et-C6H4
CH3 CH3 CH3 CH3 CH3 CH3
Entry
12d
a b c d
Yield (%)b
ee (%)b
Config.c
98 96 95 94 99 99
81 94 91 96 97 99
S S S R S R
0.5 10 3 1 0.5
98 87 93 95 97
86 81 77 81 79
S S S S S
0.5
99
99
R
Time (h) 0.5 0.25 0.5 2 0.5 0.5
Reaction conditions: ketone (0.5 mmol), IrCl(CO)(PPh3)2 (0.005 mmol), (R,R,R,R)-3 (0.005 mmol), KOH (0.04 mmol), i-PrOH (10 mL), 40 8C. Yield and enantiomeric excesses were determined by GC analysis using a CP-Chiralsil-Dex CB column, 25 m 0.25 mm. The configurations were determined by comparison of the retention times of the enantiomers on the GC traces with literature values. Chiral ligand (S,S,S,S)-3 was used.
With the optimized conditions in hand, we further investigated the ATH of a broad scope of aromatic ketones using the catalytic system formed in situ from of IrCl(CO)(PPh3)2 and chiral ligand (R,R,R,R)-3 (Table 2). For the ATH of acetophenone, the catalyst exhibited high activity and good enantioselectivity (98% yield, 81% ee, Table 2, entry 1). To our delight, the ATH of various asubstituted aromatic ketones proceeded smoothly, affording the corresponding chiral alcohols with high yields and excellent enantioselectivities (up to 99% ee, Table 2, entries 2–6). When aryl methyl ketones were used as substrates, high yields and ee were obtained (Table 2, entries 7–12). An exception is found in the ATH of 2-methylacetophenone, which gave low activity (10 h, 87% yield, Table 2, entry 8). This result hints that the steric hindrance of substituent on the phenyl ring may hamper the reaction. Interestingly, more hindered ketone, 1,10 -diphenylpropan-2-one, could be reduced with high yield as well as excellent enantioselectivity (99% ee, Table 2, entry 12).
4. Conclusion In summary, we demonstrated novel chiral multidentate P3N4type ligand (R,R,R,R)-3, which displayed highly catalytic activity and enantioselectivity for the ATH of aromatic ketones under mild conditions. Using i-PrOH as hydrogen source, various aromatic ketones could be enantioselectively reduced by IrCl(CO)(PPh3)2/ (R,R,R,R)-3 to the corresponding chiral alcohols with up to 99% ee. Compared with the chiral PxNy-type ligands traditionally used in the ATH reactions, this novel ligand is multidentate aminophosphine ligand. This unique structure would afford more coordination sites, which maybe result in excellent catalytic performance in asymmetric reaction. Considering its highly catalytic activity and enantioselectivity, the chiral multidentate ligand represents an interesting direction for design and synthesis of novel chiral ligands. Further study of these chiral aminophosphine ligands is in progress to develop more efficient chiral ligands for asymmetric catalysis. Acknowledgments We are grateful to the National Natural Science Foundation of China (No. 21173176), the Program for Innovative Research Team
in Chinese Universities (No. IRT_14R31), the Fundamental Research Funds for the Central Universities (No. 20720150040) and NFFTBS (No. J1310024) for financial support.
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Please cite this article in press as: M. Tao, et al., Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.05.028