Chromium(II)-catalyzed enantioselective arylation of ketones

  1. Gang Wang1,2,
  2. Shutao Sun2,
  3. Ying Mao2,
  4. Zhiyu Xie2 and
  5. Lei Liu1,2,3

1Shenzhen Research Institute of Shandong University, Shenzhen 518057, China
2School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
3School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China

  1. Corresponding author email

This article is part of the Thematic Series "Strategies in asymmetric catalysis".

Guest Editor: T. P. Yoon
Beilstein J. Org. Chem. 2016, 12, 2771–2775. https://doi.org/10.3762/bjoc.12.275
Received 17 Oct 2016, Accepted 06 Dec 2016, Published 19 Dec 2016

  • Full Research Paper

Abstract

The chromium-catalyzed enantioselective addition of carbo halides to carbonyl compounds is an important transformation in organic synthesis. However, the corresponding catalytic enantioselective arylation of ketones has not been reported to date. Herein, we report the first Cr-catalyzed enantioselective addition of aryl halides to both arylaliphatic and aliphatic ketones with high enantioselectivity in an intramolecular version, providing facile access to enantiopure tetrahydronaphthalen-1-ols and 2,3-dihydro-1H-inden-1-ols containing a tertiary alcohol.

Keywords: arylation; asymmetric catalysis; chromium; ketone; tertiary alcohol

Introduction

Catalytic enantioselective carbon–carbon bond formation reactions have achieved enormous development during the last few decades as a consequence of the growing demand for enantiopure compounds in modern industry, especially the pharmaceutical industry. The chromium (Cr)-catalyzed enantioselective addition of carbo halides to carbonyl compounds is one of the most reliable methods in organic chemistry for chemoselective and structurally diverse synthesis [1-9]. To date, the Cr-catalyzed enantioselective carbonyl addition reactions mainly focused on allylation, propargylation, alkenylation and alkylation of aldehydes [10,11]. Since the first example of enantioselective allylation of aldehydes catalyzed by a Cr(II)–salen complex in 1999 by Cozzi and co-workers [12], several elegant catalytic enantioselective allylation and propargylation reactions have been developed by the groups of Nakada [13,14], Berkessel [15], Kishi [16], Sigman [17], Yamamoto [18], Guiry [19], Chen [20], Gade [21], White [22], and Zhang [23-25], respectively. The alkenylation and alkylation reactions were mainly explored by the Kishi group [26-30], and they established a toolbox approach to search for the specific ligand with a given substrate in the Cr-catalyzed process [28]. They successfully applied the method to the natural product total synthesis like halichondrin B and norhalichondrin B, and in the subsequent pharmaceutical study, finally leading to the discovery of the anticancer drug Eribulin [31-35]. However, to our knowledge, the Cr-catalyzed enantioselective arylation of carbonyl compounds has rarely been explored. On the other hand, most of the reactions focused on aldehyde components, while asymmetric addition to ketones remains a big challenge probably due to the decreased reactivity and selectivity [36,37]. A breakthrough was made by the Sigman group who reported the catalytic enantioselective addition of allylic bromides and propargyl halides to arylaliphatic ketones using oxazoline ligands with high enantioselectivity (up to 95% ee) [38-41]. After that, the Chen group also disclosed enantioselective allylation of ketones using spirocyclic chiral borate and chiral bipyridyl alcohol ligands with the ee value ranging from 27% to 97% [42,43]. However, as far as we know, a Cr-catalyzed enantioselective arylation of ketones has never been reported to date [44]. Tetrahydronaphthalen-1-ol bears a chiral tertiary alcohol center and is a common structural motif in numerous biologically active natural products and clinical drugs [45]. The method to prepare these compounds through intramolecular arylation of ketones would be highly desired. Herein, we report the first Cr-catalyzed enantioselective arylation of ketones in an intramolecular version.

Results and Discussion

Initially, the Cr-catalyzed asymmetric intramolecular arylation of arylaliphatic ketone 5-(2-iodophenyl)pentan-2-one (1a) was selected as the model reaction for optimization employing Kishi’s oxazoline/sulfonamides as the chiral ligands. A series of oxazoline/sulfonamide ligands (L1–L8) were tested and the results were summarized in Table 1. Four subgroups of R1 were studied (entries 1–4, Table 1) and isopropyl substituted oxazoline proved to be the best ligand with a 42% ee. Afterwards, R2 (Table 1, entries 2, 5 and 6) and R3 (Table 1, entries 6–8) substituents were also examined, and L8 bearing a methyl group in both R2 and R3 gave the best enantiocontrol. The solvent effect was then investigated, and 1,2-dimethoxyethane (DME) was identified to be the best choice (Table 1, entries 8–10). Lowering the reaction temperature was found to be beneficial for improving the enantioselectivity, and when the reaction was performed at −20 °C, expected 2a was isolated in 81% yield with 97% ee (Table 1, entries 10–13). Aryl bromide proved to be an inferior coupling component, providing 2a in 35% yield and 70% ee (Table 1, entry 14).

Table 1: Screening conditions of the catalytic enantioselective Cr-mediated arylation of ketone.a

[Graphic 1]
entry L R1 R2 R3 Solvent Yield (%)a eeb
1 L1 Me Ph H MeCN 43 28
2 L2 iPr Ph H MeCN 50 42
3 L3 t-Bu Ph H MeCN 47 25
4 L4 Ph Ph H MeCN 51 21
5 L5 iPr Bn H MeCN 12 37
6 L6 iPr Me H MeCN 49 56
7 L7 iPr Me OMe MeCN 75 75
8 L8 iPr Me Me MeCN 85 82
9 L8 iPr Me Me THF 93 81
10 L8 iPr Me Me DME 90 86
11c L8 iPr Me Me DME 86 92
12d L8 iPr Me Me DME 81 97
13e L8 iPr Me Me DME 51 83
14d,f L8 iPr Me Me DME 35 70

aYield of isolated product. bDetermined by HPLC analysis on a chiral column. cReaction at 0 °C for 24 h. dReaction at −20 °C for 24 h. eReaction at −40 °C for 24 h. fAryl bromide used instead of aryl iodide.

With the optimized conditions in hand, the scope of the ketone component was first explored (Scheme 1). Aliphatic ketones with (longer) alkyl chain such as ethyl (1b) and n-hexyl ketones (1c), were also tolerated albeit with slightly decreased yield and selectivity. The asymmetric arylation of various arylaliphatic ketones also went smoothly (1d–h). Phenyl ketone 1d and ketones with electron-withdrawing groups in different substituent patterns gave the expected products with good enantiocontrol, while the enantioselectivity for ketone 1e bearing an electron-donating group decreased. The mild process exhibited excellent functional group tolerance, with chloride (2f), fluoride (2g), and CF3 moieties (2h) well tolerated for further manipulation [46,47]. Heteroaryl ketones such as furan-substituted ketone (1i) were also suitable substrate, giving product 2i in 78% ee. The scope of the aryl halide component was next explored (1j–l). Aryl halides bearing different substituent patterns were tolerated giving the tetrahydronaphthalen-1-ols with good ee values. When 4-(2-iodophenyl)butan-2-one (1m) was used, enantiopure indan-1-ol was obtained in 70% yield and 82% ee.

[1860-5397-12-275-i1]

Scheme 1: Scope of the catalytic enantioselective Cr-mediated arylation of ketones.

Conclusion

In summary, we have developed the first Cr-catalyzed enantioselective arylation of ketones in an intramolecular version using oxazoline/sulfonamide L8 as the catalyst. Both aliphatic and arylaliphatic ketones proceeded smoothly, providing corresponding tetrahydronaphthalen-1-ols bearing a tertiary alcohol center with good enantioselectivities (up to 97% ee).

Experimental

General procedure for the chromium(II) catalyzed enantioselective arylation of ketones: The solution of L8 (0.25 equiv, 0.025 mmol), proton sponge (0.25 equiv, 0.025 mmol) and CrCl2 (0.23 equiv, 0.023 mmol) in DME (1.0 mL) was stirred at room temperature in a glove-box for 1 h. Then the substrate 1 (1.0 equiv, 0.1 mmol), LiCl (2.0 equiv, 0.2 mmol), Mn powder (3.0 equiv, 0.3 mmol), NiCl2·DMP (0.12 equiv, 0.012 mmol) and Zr(CP)2Cl2 (2.0 equiv, 0.2 mmol) were added successively and the mixture was stirred at indicated temperature for 24 h. After that, the mixture was filtered through a short pad of celite and purified by flash chromatography using silica gel or alumina (200–300 mesh) to give the product 2.

Supporting Information

Supporting Information File 1: Experimental procedures, analytical data for products, copies of NMR spectra and HPLC chromatograms.
Format: PDF Size: 1.0 MB Download

Acknowledgements

We thank the National Science Foundation of China (21472112), Fok Ying Tung Education Foundation (151035), the Program for New Century Excellent Talents in University (NCET-13-0346), Shenzhen Strategic Emerging Industry Development Special Funds (JCYJ20150430160921949), the Shandong Science Fund for Distinguished Young Scholars (JQ201404), and the Fundamental Research Funds of Shandong University (2015JC035) for financial support.

References

  1. Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J. Am. Chem. Soc. 1977, 99, 3179–3181. doi:10.1021/ja00451a061
    Return to citation in text: [1]
  2. Okude, Y.; Hiyama, T.; Nozaki, H. Tetrahedron Lett. 1977, 18, 3829–3830. doi:10.1016/S0040-4039(01)83365-7
    Return to citation in text: [1]
  3. Fürstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 2533–2534. doi:10.1021/ja9537538
    Return to citation in text: [1]
  4. Fürstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 12349–12357. doi:10.1021/ja9625236
    Return to citation in text: [1]
  5. Avalos, M.; Babiano, R.; Cintas, P.; Jiménez, J. L.; Palacios, J. C. Chem. Soc. Rev. 1999, 28, 169–177. doi:10.1039/a806117c
    Return to citation in text: [1]
  6. Takai, K.; Nozaki, H. Proc. Jpn. Acad., Ser. B 2000, 76, 123–131. doi:10.2183/pjab.76.123
    Return to citation in text: [1]
  7. Fürstner, A. Chem. Rev. 1999, 99, 991–1046. doi:10.1021/cr9703360
    Return to citation in text: [1]
  8. Hargaden, G. C.; Guiry, P. J. Adv. Synth. Catal. 2007, 349, 2407–2424. doi:10.1002/adsc.200700324
    Return to citation in text: [1]
  9. Tian, Q.; Zhang, G. Synthesis 2016, 48, 4038–4049. doi:10.1055/s-0036-1589457
    Return to citation in text: [1]
  10. Choi, H.-w.; Nakajima, K.; Demeke, D.; Kang, F.-A.; Jun, H.-S.; Wan, Z.-K.; Kishi, Y. Org. Lett. 2002, 4, 4435–4438. doi:10.1021/ol026981x
    Return to citation in text: [1]
  11. Namba, K.; Kishi, Y. Org. Lett. 2004, 6, 5031–5033. doi:10.1021/ol047661b
    Return to citation in text: [1]
  12. Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. Angew. Chem. 1999, 111, 3558–3561. doi:10.1002/(SICI)1521-3757(19991115)111:22<3558::AID-ANGE3558>3.0.CO;2-6
    Angew. Chem. Int. Ed. 1999, 38, 3357-3359. doi:10.1002/(SICI)1521-3773(19991115)38:22<3357::AID-ANIE3357>3.0.CO;2-W
    Return to citation in text: [1]
  13. Inoue, M.; Suzuki, T.; Nakada, M. J. Am. Chem. Soc. 2003, 125, 1140–1141. doi:10.1021/ja021243p
    Return to citation in text: [1]
  14. Inoue, M.; Nakada, M. Org. Lett. 2004, 6, 2977–2980. doi:10.1021/ol048826j
    Return to citation in text: [1]
  15. Berkessel, A.; Menche, D.; Sklorz, C. A.; Schröder, M.; Paterson, I. Angew. Chem. 2003, 115, 1062–1065. doi:10.1002/ange.200390240
    Angew. Chem., Int. Ed. 2003, 42, 1032–1035. doi:10.1002/anie.200390265
    Return to citation in text: [1]
  16. Kurosu, M.; Lin, M.-H.; Kishi, Y. J. Am. Chem. Soc. 2004, 126, 12248–12249. doi:10.1021/ja045557j
    Return to citation in text: [1]
  17. Lee, J.-Y.; Miller, J. J.; Hamilton, S. S.; Sigman, M. S. Org. Lett. 2005, 7, 1837–1839. doi:10.1021/ol050528e
    Return to citation in text: [1]
  18. Xia, G.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 2554–2555. doi:10.1021/ja058454p
    Return to citation in text: [1]
  19. McManus, H. A.; Cozzi, P. G.; Guiry, P. J. Adv. Synth. Catal. 2006, 348, 551–558. doi:10.1002/adsc.200505332
    Return to citation in text: [1]
  20. Huang, X.-R.; Pan, X.-H.; Lee, G.-H.; Chen, C. Adv. Synth. Catal. 2011, 353, 1949–1954. doi:10.1002/adsc.201100023
    Return to citation in text: [1]
  21. Deng, Q.-H.; Wadepohl, H.; Gade, L. H. Chem. – Eur. J. 2011, 17, 14922–14928. doi:10.1002/chem.201102375
    Return to citation in text: [1]
  22. White, J. D.; Shaw, S. Org. Lett. 2011, 13, 2488–2491. doi:10.1021/ol2007378
    Return to citation in text: [1]
  23. Chen, W.; Yang, Q.; Zhou, T.; Tian, Q.; Zhang, G. Org. Lett. 2015, 17, 5236–5239. doi:10.1021/acs.orglett.5b02597
    Return to citation in text: [1]
  24. Xiong, Y.; Zhang, G. Org. Lett. 2016, 18, 5094–5097. doi:10.1021/acs.orglett.6b02540
    Return to citation in text: [1]
  25. Tian, Q.; Bai, J.; Chen, B.; Zhang, G. Org. Lett. 2016, 18, 1828–1831. doi:10.1021/acs.orglett.6b00559
    Return to citation in text: [1]
  26. Namba, K.; Cui, S.; Wang, J.; Kishi, Y. Org. Lett. 2005, 7, 5417–5419. doi:10.1021/ol052084s
    Return to citation in text: [1]
  27. Namba, K.; Cui, S.; Wang, J.; Kishi, Y. Org. Lett. 2005, 7, 5421–5424. doi:10.1021/ol052085k
    Return to citation in text: [1]
  28. Guo, H.; Dong, C.-G.; Kim, D.-S.; Urabe, D.; Wang, J.; Kim, J. T.; Liu, X.; Sasaki, T.; Kishi, Y. J. Am. Chem. Soc. 2009, 131, 15387–15393. doi:10.1021/ja905843e
    Return to citation in text: [1] [2]
  29. Liu, X.; Li, X.; Chen, Y.; Hu, Y.; Kishi, Y. J. Am. Chem. Soc. 2012, 134, 6136–6139. doi:10.1021/ja302177z
    Return to citation in text: [1]
  30. Peng, J.; Kishi, Y. Org. Lett. 2012, 14, 86–89. doi:10.1021/ol202878v
    Return to citation in text: [1]
  31. Aicher, T. D.; Buszek, K. R.; Fang, F. G.; Forsyth, C. J.; Jung, S. H.; Kishi, Y.; Matelich, M. C.; Scola, P. M.; Spero, D. M.; Yoon, S. K. J. Am. Chem. Soc. 1992, 114, 3162–3164. doi:10.1021/ja00034a086
    Return to citation in text: [1]
  32. Namba, K.; Kishi, Y. J. Am. Chem. Soc. 2005, 127, 15382–15383. doi:10.1021/ja055966v
    Return to citation in text: [1]
  33. Kim, D.-S.; Dong, C.-G.; Kim, J. T.; Guo, H.; Huang, J.; Tiseni, P. S.; Kishi, Y. J. Am. Chem. Soc. 2009, 131, 15636–15641. doi:10.1021/ja9058475
    Return to citation in text: [1]
  34. Dong, C.-G.; Henderson, J. A.; Kaburagi, Y.; Sasaki, T.; Kim, D.-S.; Kim, J. T.; Urabe, D.; Guo, H.; Kishi, Y. J. Am. Chem. Soc. 2009, 131, 15642–15646. doi:10.1021/ja9058487
    Return to citation in text: [1]
  35. Liu, X.; Henderson, J. A.; Sasaki, T.; Kishi, Y. J. Am. Chem. Soc. 2009, 131, 16678–16680. doi:10.1021/ja9079308
    Return to citation in text: [1]
  36. Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J. Am. Chem. Soc. 1977, 99, 3179–3181. doi:10.1021/ja00451a061
    Return to citation in text: [1]
  37. Chen, C.; Tagami, K.; Kishi, Y. J. Org. Chem. 1995, 60, 5386–5387. doi:10.1021/jo00122a011
    Return to citation in text: [1]
  38. Miller, J. J.; Sigman, M. S. J. Am. Chem. Soc. 2007, 129, 2752–2753. doi:10.1021/ja068915m
    Return to citation in text: [1]
  39. Miller, J. J.; Sigman, M. S. Angew. Chem., Int. Ed. 2008, 47, 771–774. doi:10.1002/anie.200704257
    Return to citation in text: [1]
  40. Harper, K. C.; Sigman, M. S. Science 2011, 333, 1875–1878. doi:10.1126/science.1206997
    Return to citation in text: [1]
  41. Harper, K. C.; Vilardi, S. C.; Sigman, M. S. J. Am. Chem. Soc. 2013, 135, 2482–2485. doi:10.1021/ja4001807
    Return to citation in text: [1]
  42. Huang, X.-R.; Chen, C.; Lee, G.-H.; Peng, S.-M. Adv. Synth. Catal. 2009, 351, 3089–3095. doi:10.1002/adsc.200900595
    Return to citation in text: [1]
  43. Chen, R.-Y.; Dhondge, A. P.; Lee, G.-H.; Chen, C. Adv. Synth. Catal. 2015, 357, 961–966. doi:10.1002/adsc.201400945
    Return to citation in text: [1]
  44. Chen, C. Synlett 1998, 1311–1312. doi:10.1055/s-1998-1984
    Return to citation in text: [1]
  45. Chopra, I.; Roberts, M. Microbiol. Mol. Biol. Rev. 2001, 65, 232–260. doi:10.1128/MMBR.65.2.232-260.2001
    Return to citation in text: [1]
  46. Xu, T.; Mu, X.; Peng, H.; Liu, G. Angew. Chem., Int. Ed. 2011, 50, 8176–8179. doi:10.1002/anie.201103225
    Return to citation in text: [1]
  47. Wang, F.; Qi, X.; Liang, Z.; Chen, P.; Liu, G. Angew. Chem., Int. Ed. 2014, 53, 1881–1886. doi:10.1002/anie.201309991
    Return to citation in text: [1]

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