Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

  1. Akihiro Yuasa,
  2. Kazunori Nagao and
  3. Hirohisa OhmiyaORCID Logo

Division of Pharmaceutical Sciences, Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan

  1. Corresponding author email

This article is part of the thematic issue "Copper-catalyzed reactions for organic synthesis".

Guest Editor: O. Riant
Beilstein J. Org. Chem. 2020, 16, 185–189. doi:10.3762/bjoc.16.21
Received 15 Oct 2019, Accepted 03 Feb 2020, Published 07 Feb 2020

Abstract

The allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions is described. The synergistic palladium/copper-catalyzed reaction of aromatic aldehydes, allylic carbonates, and a silylboronate produces the corresponding homoallylic alcohol derivatives. This process involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(I) species and the subsequent palladium-catalyzed allylic substitution.

Keywords: aldehyde; copper; copper catalysis; cross-coupling; palladium; synthetic method

Introduction

α-Alkoxy-substituted carbanions (α-alkoxyalkyl anions) are useful C(sp3) nucleophiles for the construction of alcohol units found in a majority of pharmaceuticals, agrochemicals and bioactive natural products. Generally, α-alkoxyalkyl anions are presynthesized as stoichiometric organometallic reagents such as organolithium, organozinc, organocuprate, organostannane, organosilane and organoboron compounds [1-6]. Alternatively, we showed that easily available aromatic aldehydes can be used as α-alkoxyalkyl anions for catalytic carbon–carbon bond formations [7-9]. For example, a nucleophilic α-silyloxybenzylcopper(I) species can be generated catalytically from aromatic aldehydes through the 1,2-addition of a silylcopper(I) species followed by [1,2]-Brook rearrangement and then successfully trapped with aryl bromides under palladium catalysis (Scheme 1). This system was extended to an asymmetric version using the chiral α-silyloxybenzylcopper(I) species having a chiral NHC ligand. In the asymmetric system, one example of allylic carbonate was used as the carbon electrophile [8,10,11]. This paper describes in full detail the racemic system using allylic carbonates. The allylic cross-coupling of aromatic aldehydes and allylic carbonates with a silylboronate by the merging of a copper–N-heterocyclic carbene catalyst and a palladium–bisphosphine catalyst produced homoallylic alcohol derivatives [12-14].

[1860-5397-16-21-i1]

Scheme 1: Our strategy.

Results and Discussion

Specifically, the three-component allylic cross-coupling reaction of benzaldehyde (1a, 0.4 mmol), tert-butyl cinnamyl carbonate (2a, 0.2 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester [PhMe2SiB(pin)] (0.4 mmol) occurred in the presence of catalytic amounts of Pd(OCOCF3)2 (3 mol %), DPPF (3 mol %), (SIPr)CuCl (15 mol %) and KOt-Bu (25 mol %) in toluene at 80 °C to afford homoallylic alcohol derivative 3aa in 64% yield (based on 2a) (Scheme 2). The reaction yielded small amounts of side products such as cinnamylsilane and benzyl silyl ether, which are derived from the Pd-catalyzed allylic silylation of 2a and the Cu-catalyzed silylation of 1a and the subsequent [1,2]-Brook rearrangement, respectively. In this coupling reaction, (SIPr)CuCl was a slightly better copper complex than (IPr)CuCl (62%), (SIMes)CuCl (60%) and (IMes)CuCl (53%) in terms of the chemical yield. Notably, the allylic cross-coupling reaction did not occur at all without Pd(OCOCF3)2–DPPF or (SIPr)CuCl, and thus the palladium and copper catalysts cooperatively acted in the allylic cross-coupling.

[1860-5397-16-21-i2]

Scheme 2: Allylic cross-coupling using aldehydes as α-alkoxyalkyl anions.

Scheme 3 shows the substrate range of aromatic aldehydes 1 and allylic carbonates 2. Methyl, tert-butyl and fluoro substituents were tolerated at the ortho- or para-positions of the aromatic aldehyde (3bada). 2,6-Dimethylphenyl- or 1-naphthyl moieties as the γ-substituent of the primary allylic carbonate were tolerated in the reaction (3ab and 3ac). Cinnamyl carbonates having a fluoro or acetal substituent were also suitable coupling partners (3ad and 3ae).

[1860-5397-16-21-i3]

Scheme 3: Substrate scope and reaction conditions. a) reactions were carried out with 1 (0.4 mmol), 2 (0.2 mmol), PhMe2SiBpin (0.4 mmol), Pd(OCOCF3)2 (3 mol %), DPPF (3 mol %), (SIPr)CuCl (15 mol %), KOt-Bu (25 mol %) in toluene (2 mL) at 100 °C for 12 h. b) Pd(OCOCF3)2/DPPF (3 mol %), (SIPr)CuCl (25 mol %) and KOt-Bu (35 mol %) were used and the reaction temperature was decreased to 80 °C. c) Pd(OCOCF3)2/DPPF (3 mol %), (SIPr)CuCl (25 mol %) and KOt-Bu (35 mol %) were used. d) The reaction temperature was decreased to 80 °C. e) Pd(OCOCF3)2/DPPF (5 mol %), (SIPr)CuCl (25 mol %) and KOt-Bu (35 mol %) were used.

The synergistic palladium/copper catalysis was used for the reaction of a secondary allylic carbonate. For example, the allylic cross-coupling of 2a’, a constitutional isomer of 2a, with benzaldehyde (1a) afforded the linear allylation product 3aa with complete regioselectivity. The symmetric secondary allylic carbonate was converted to the corresponding homoallylic alcohol derivative in 50% yield (3af).

To gain understanding into the mechanism of this synergistic palladium/copper-catalyzed allylic cross-coupling, a stoichiometric experiment was conducted (Scheme 4). The reaction of the SIPr-ligated α-silyloxybenzylcopper 4 with the cinnamyl–palladium complex 5, which was prepared in situ from [(cinnamyl)PdCl]2 and DPPF, gave the corresponding homoallylic alcohol derivative 3aa.

[1860-5397-16-21-i4]

Scheme 4: Stoichiometric reaction.

Based on previous reports and the outcome obtained by the stoichiometric experiment in Scheme 4, a possible reaction pathway involving a cooperative action of palladium and copper catalysis can be proposed as illustrated in Scheme 5. The reaction of SIPr-ligated CuCl (A), KOt-Bu and a silylboronate produces a silylcopper(I) species B. The 1,2-addition of silylcopper(I) B to the aromatic aldehyde 1 [15-19] and the subsequent [1,2]-Brook rearrangement from the obtained α-silyl-substituted copper(I) alkoxide C forms the key intermediate, an α-silyloxybenzylcopper(I) species D. The transmetallation between D and an allylpalladium(II) species F that is generated through the oxidative addition of an allylic carbonate 2 across a palladium(0)–DPPF complex E, followed by reductive elimination from G produces the homoallylic alcohol 3 and then regenerate A and E for the next catalytic cycle [20-23].

[1860-5397-16-21-i5]

Scheme 5: Possible pathway.

Conclusion

In summary, we developed an umpolung strategy for catalytically formed α-alkoxyalkyl anions from aromatic aldehydes for the use in allylic cross-coupling reactions. The synergistic palladium/copper-catalyzed reaction of aromatic aldehydes, allylic carbonates, and a silylboronate delivered the homoallylic alcohol derivatives. This process involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(I) species and the subsequent palladium-catalyzed allylic substitution.

Experimental

SIPrCuCl (14.7 mg, 0.03 mmol), and KOt-Bu (4.5 mg, 0.04 mmol) were placed in a vial containing a magnetic stirring bar. The vial was sealed with a Teflon®-coated silicon rubber septum, and then the vial was evacuated and filled with nitrogen. Toluene (0.6 mL) was added to the vial, and then the mixture was stirred at 25 °C for 10 min. Next, PhMe2SiB(pin) (104.9 mg, 0.4 mmol) and benzaldehyde (1a, 42.4 mg, 0.4 mmol) were added, and the mixture (mixture A) was stirred at 25 °C for 10 min. Meanwhile, Pd(OCOCF3)2 (2.0 mg, 0.006 mmol) and DPPF (3.3 mg, 0.006 mmol) were placed in another vial. This vial was sealed with a Teflon®-coated silicon rubber septum and then evacuated and filled with nitrogen. After toluene (0.8 mL) was added to the vial, the mixture was stirred at 25 °C for 10 min. Next, KOt-Bu (1.1 mg, 0.01 mmol) and allylic carbonate 2a (46.9 mg, 0.2 mmol) were added to the vial, and the mixture (mixture B) was stirred at 25 °C for 10 min. Finally, the palladium solution (mixture B) was transferred to the vial (mixture A) containing the copper complex with toluene (0.6 mL). After 12 h stirring at 80 °C, the reaction mixture was diluted with diethyl ether (1 mL). The reaction mixture was filtered through a short plug of aluminum oxide (1 g) with diethyl ether as an eluent. After volatiles were removed under reduced pressure, GPC (EtOAc) followed by flash chromatography on silica gel (0–1% EtOAc/hexane) gave product 3aa in 64% isolated yield (45.7 mg, 0.13 mmol).

Supporting Information

Supporting Information File 1: Experimental procedures, spectroscopic and analytical data, and copies of NMR spectra for newly synthesized compounds.
Format: PDF Size: 9.9 MB Download

Funding

This work was supported by JSPS KAKENHI Grant Number JP18H01971 to Scientific Research (B), JSPS KAKENHI Grant Number JP17H06449 (Hybrid Catalysis), and Kanazawa University SAKIGAKE project 2018 (to H.O.).

References

  1. Hoppe, D.; Hense, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 2282–2316. doi:10.1002/anie.199722821
    Return to citation in text: [1]
  2. Still, W. C. J. Am. Chem. Soc. 1978, 100, 1481–1487. doi:10.1021/ja00473a025
    Return to citation in text: [1]
  3. Papillon, J. P. N.; Taylor, R. J. K. Org. Lett. 2002, 4, 119–122. doi:10.1021/ol016986e
    Return to citation in text: [1]
  4. Linderman, R. J.; Godfrey, A.; Horne, K. Tetrahedron Lett. 1987, 28, 3911–3914. doi:10.1016/s0040-4039(00)96418-9
    Return to citation in text: [1]
  5. Arai, N.; Suzuki, K.; Sugizaki, S.; Sorimachi, H.; Ohkuma, T. Angew. Chem., Int. Ed. 2008, 47, 1770–1773. doi:10.1002/anie.200704696
    Return to citation in text: [1]
  6. Laitar, D. S.; Tsui, E. Y.; Sadighi, J. P. J. Am. Chem. Soc. 2006, 128, 11036–11037. doi:10.1021/ja064019z
    Return to citation in text: [1]
  7. Takeda, M.; Yabushita, K.; Yasuda, S.; Ohmiya, H. Chem. Commun. 2018, 54, 6776–6779. doi:10.1039/c8cc01055b
    Return to citation in text: [1]
  8. Yabushita, K.; Yuasa, A.; Nagao, K.; Ohmiya, H. J. Am. Chem. Soc. 2019, 141, 113–117. doi:10.1021/jacs.8b11495
    Return to citation in text: [1] [2]
  9. Takeda, M.; Mitsui, A.; Nagao, K.; Ohmiya, H. J. Am. Chem. Soc. 2019, 141, 3664–3669. doi:10.1021/jacs.8b13309
    Return to citation in text: [1]
  10. Nahra, F.; Macé, Y.; Lambin, D.; Riant, O. Angew. Chem., Int. Ed. 2013, 52, 3208–3212. doi:10.1002/anie.201208612
    Return to citation in text: [1]
  11. Jia, T.; Cao, P.; Wang, B.; Lou, Y.; Yin, X.; Wang, M.; Liao, J. J. Am. Chem. Soc. 2015, 137, 13760–13763. doi:10.1021/jacs.5b09146
    Return to citation in text: [1]
  12. Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 6340–6341. doi:10.1021/ja802001b
    Return to citation in text: [1]
  13. Ketcham, J. M.; Shin, I.; Montgomery, T. P.; Krische, M. J. Angew. Chem., Int. Ed. 2014, 53, 9142–9150. doi:10.1002/anie.201403873
    Return to citation in text: [1]
  14. Denmark, S. E.; Matesich, Z. D. J. Org. Chem. 2014, 79, 5970–5986. doi:10.1021/jo501004j
    Return to citation in text: [1]
  15. Kleeberg, C.; Feldmann, E.; Hartmann, E.; Vyas, D. J.; Oestreich, M. Chem. – Eur. J. 2011, 17, 13538–13543. doi:10.1002/chem.201102367
    Return to citation in text: [1]
  16. Cirriez, V.; Rasson, C.; Hermant, T.; Petrignet, J.; Díaz Álvarez, J.; Robeyns, K.; Riant, O. Angew. Chem., Int. Ed. 2013, 52, 1785–1788. doi:10.1002/anie.201209020
    Return to citation in text: [1]
  17. Delvos, L. B.; Hensel, A.; Oestreich, M. Synthesis 2014, 46, 2957–2964. doi:10.1055/s-0034-1378542
    Return to citation in text: [1]
  18. Oestreich, M.; Hartmann, E.; Mewald, M. Chem. Rev. 2013, 113, 402–441. doi:10.1021/cr3003517
    Return to citation in text: [1]
  19. Hensel, A.; Oestreich, M. Asymmetric Addition of Boron and Silicon Nucleophiles. In Progress in Enantioselective Cu(I)-catalyzed Formation of Stereogenic Centers; Harutyunyan, S., Ed.; Top. Organomet. Chem., Vol. 58; Springer: Cham, Switzerland, 2016; pp 135–167. doi:10.1007/3418_2015_156
    Return to citation in text: [1]
  20. Pye, D. R.; Mankad, N. P. Chem. Sci. 2017, 8, 1705–1718. doi:10.1039/c6sc05556g
    Return to citation in text: [1]
  21. Semba, K.; Nakao, Y. J. Am. Chem. Soc. 2014, 136, 7567–7570. doi:10.1021/ja5029556
    Return to citation in text: [1]
  22. Smith, K. B.; Logan, K. M.; You, W.; Brown, M. K. Chem. – Eur. J. 2014, 20, 12032–12036. doi:10.1002/chem.201404310
    Return to citation in text: [1]
  23. Friis, S. D.; Pirnot, M. T.; Buchwald, S. L. J. Am. Chem. Soc. 2016, 138, 8372–8375. doi:10.1021/jacs.6b04566
    Return to citation in text: [1]

© 2020 Yuasa et al.; licensee Beilstein-Institut.
This is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the authors and source are credited.
The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc)

 
Back to Article List