Nickel-catalysed cross-coupling reaction of aryl(trialkyl)silanes with aryl chlorides and tosylates

Abstract

Using highly stable, readily accessible, and recyclable 2-(2-hydroxyprop-2-yl)cyclohexyl-substituted arylsilanes activated by a mild carbonate base, nickel-catalysed silicon-based aryl–aryl cross-coupling reaction proceeds for the first time with inexpensive aryl chlorides and tosylates in a highly chemoselective manner.

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Biaryls play key roles in many functional organic molecules from pharmaceuticals to optoelectronic materials. Metal-catalysed cross-coupling reactions have innovated synthetic processes to access these structural motifs.¹ While a number of protocols have been developed using a range of aryl nucleophiles, increasing demands for chemoselectivity, availability, stability, and non-toxicity have made arylsilanes an attractive alternative to conventionally employed arylmagnesium, -zinc, -tin, and -boron reagents.² On the other hand, use of inexpensive and abundant metal complexes such as iron and nickel instead of palladium for the cross-coupling reactions has also gained much attention in this field. Nevertheless, such protocols have rarely met with success in the silicon-based cross-coupling reactions except for those with alkyl electrophiles by nickel catalysis.³ With these background in mind, we examined a silicon-based aryl–aryl cross-coupling reaction using a nickel catalyst. We have recently developed novel tetraorganosilicon reagents that participate in a variety of transition metal-catalysed transformations including cross-coupling and carbonyl addition reactions through transmetallation to palladium, copper, and rhodium.⁴ Formation of pentacoordinate silicates and/or metal alkoxides is likely responsible for the transmetallation under mild conditions with carbonate salts as a mild activator. The new protocol achieves highly chemoselective C–C bond forming reactions using highly robust tetraorganosilicon reagents. Herein, we report that such a reagent design also allows nickel-catalysed aryl–aryl cross-coupling using arylsilanes with inexpensive aryl chlorides⁵ and tosylates.⁶ We have found that newly developed 2-(2-hydroxyprop-2-yl)cyclohexyl-substituted arylsilanes (1, Scheme 1) serve as an excellent arylating agent over originally developed 2-(hydroxymethyl)phenyl-substituted ones 2.

Scheme 1 Synthesis of tetraorganosilicon reagents 1a and 1′a.

We have experienced that the original 2-(hydroxymethyl)phenyl-substituted arylsilanes 2 sometimes suffer from cleavage of the substituted phenyl–Si bond depending on reaction conditions.⁴ We hypothesised that more robust but reactive silicon reagents could be available by making the phenyl group saturated based on the fact that C(sp³)–Si bonds are generally much more stable than C(sp²)–Si bonds. The preparation of 2-(2-hydroxyprop-2-yl)cyclohexyl-(dimethyl)phenylsilane 1a and 2-hydroxymethyl analog 1′a is shown in Scheme 1. O-Silylation of 1-(2-hydroxyalk-2-yl)cyclohexene was performed with HN(SiMe₂H)₂, and the resulting silyl ethers were subjected to platinum-catalysed intramolecular hydrosilylation⁷ to give cyclic silyl ethers that underwent ring-opening reactions upon treatment with phenyl Grignard reagent.⁸ Thus, the new tetraorganosilicon reagents are conveniently prepared in one-pot from readily available cyclohexenylmethanols. The trans geometry of the silicon reagents thus obtained was unambiguously confirmed by X-ray crystallography of 3,5-dinitrobenzoate derived from 1′a (Fig. 1).†

Fig. 1 ORTEP drawing for 3,5-dinitrobenzoate of 1′a.

We then examined the nickel-catalysed reaction of the arylsilanes with 4-chloroanisole (3a) (eqn (1)). After screening various parameters, the reaction of 1a (1.3 mmol) with 3a (1.0 mmol) in the presence of NiCl₂·dme (5 mol%), Zn [a reducing agent for nickel(II), 10 mol%], dppf (5 mol%), PCy₃ (5 mol%), and Cs₂CO₃ (2.0 mmol) in DME–DMF (2 ∶ 1) at 60 °C for 30 h gave 4-phenylanisole (4aa) in 62% yield after isolation by silica gel chromatography. We also observed quantitative recovery of a cyclic silyl ether 5 by GC. The use of two different phosphorus ligands was critical to achieve a good conversion of 3a: either dppf or PCy₃ alone resulted in less than 50% conversion. While rationale for this mixed ligand system is under investigation, similar protocols for nickel-catalysed Suzuki–Miyaura cross-coupling reactions with aryl halides, tosylates, and mesylates have been reported.⁹ Inexpensive bases such as K₂CO₃ and K₃PO₄ were also examined, but gave 4aa in modest yields (∼50%). The cross-coupling reaction using 1′a resulted in a poor yield (<10%) due to competitive oxidation of the hydroxymethyl group.^4d The yield obtained with modified original phenylsilane 2 was modest in spite of complete conversion of the silicon reagent, whereas 2′ suffered from the oxidation of the hydroxymethyl group.

The scope of the present aryl–aryl cross-coupling is shown in Table 1. A range of substrates including aniline, ester, aldehyde, enolisable ketone, and nitrile derivatives participated in the reaction to give respective biaryls in modest to good yields (entries 1–13). The reaction can be performed on a 10 mmol-scale in good yield, allowing recovery of 5 in 93% yield by distillation of a crude mixture (entry 5). The reaction conditions employing the mild carbonate base allows silyl ethers to be tolerated in contrast to the conventional fluoride-activation which results in desilylation (entries 2 and 10). Heteroaryl chlorides also gave phenylated heteroarenes (entries 14–16). Substituted phenylsilanes 1b–1d as well as heteroarylsilanes 1e–1g were prepared similarly from the corresponding aryl Grignard reagents and reacted with aryl chlorides in good yields irrespective of electronic and steric characters of the substituents (entries 17–22).

Table 1 Nickel-catalysed cross-coupling of 1 with aryl chlorides

Entry	1	Cl–Ar^2	Temp/°C	Time/h	Yield of 4^a (%)
a Isolated yield. b Run with acetone–DMF (2 ∶ 1) as a solvent. c Run on a 10 mmol-scale. d 5 was also isolated in 93% yield by distillation. e Run in the absence of PCy3.
1	1a	Me (3b)	60	36	78 (4ab)
2	1a	CH2OSiMe2t-Bu (3c)	60	30	70 (4ac)
3^b	1a	NH2 (3d)	60	24	51 (4ad)
4	1a	F (3e)	75	24	82 (4ae)
5^c	1a	CO2Et (3f)	75	30	82 (4af)^d
6^e	1a	CHO (3g)	75	24	52 (4ag)
7	1a	Ac (3h)	75	24	85 (4ah)
8^b	1a	CN (3i)	75	20	71 (4ai)
9	1a	CF3 (3j)	75	24	83 (4aj)
10	1a		60	30	72 (4ak)
11	1a		60	30	73 (4al)
12^b	1h		60	30	77 (4am)
13^e	1a		60	30	50 (4an)
14	1a		60	36	67 (4ao)
15^b	1a		60	24	48 (4ap)
16^b	1a		60	24	65 (4aq)
17	1b	3f	75	24	77 (4bf)
18	1c	3f	75	24	84 (4cf)
19	1d	3f	75	24	75 (4df)
20	1e	3b	60	36	63 (4eb)
21	1f	3b	60	24	75 (4fb)
22	1g	3b	75	24	56 (4gb)

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Having had succeeded in the biaryl synthesis from aryl chlorides, we turned our attention to that with aryl tosylates. Because of their ready availability from various inexpensive phenol derivatives, the cross-coupling reaction with aryl tosylates and mesylates has gained much importance.¹⁰ While the silicon-based cross-coupling with these aryl electrophiles would be of great synthetic potential, only limited examples have been reported using trialkoxy(aryl)silanes and palladium catalysts in the presence of an excess amount of highly nucleophilic and expensive TBAF as a fluoride activator.⁶ After brief tuning of the reaction conditions, we found that the reaction of 1a (1.3 mmol) with unactivated 4-methoxyphenyl tosylate (6a, 1.0 mmol) proceeded smoothly in the presence of Ni(PPh₃)₂Cl₂ (5 mol%), Zn (10 mol%), extra PPh₃ (5 mol%), PCy₃ (15 mol%), and Cs₂CO₃ (2.0 mmol) in acetone–DMF (2 ∶ 1) at 80 °C for 24 h to give 4aa in 72% yield (entry 1 of Table 2). A range of functionalised aryl tosylates reacted with 1a to give the corresponding biaryls (entries 2–8). An aryl mesylate also participated in the reaction to give biaryl 4ab in comparable yield (entry 3).

Table 2 Nickel-catalysed cross-coupling of 1a with aryl tosylates

Entry	TsO–Ar	Time/h	Yield of 3^a (%)
a Isolated yields. b Run with p-tolyl methanesulfonate. c Run with Ni(PPh2Me)2Cl2 (5 mol%) and PPh2Me (5 mol%) instead of Ni(PPh3)2Cl2 (5 mol%) and PPh3 (5 mol%).
1	OMe (6a)	24	72 (4aa)
2	Me (6b)	24	73 (4ab)
3	Me (6′b)^b	24	71 (4ab)
4^c	F (6c)	20	73 (4ae)
5^c	CO2Me (6d)	20	83 (4ar)
6^c	Ac (6e)	20	73 (4ah)
7^c	CN (6f)	20	64 (4ai)
8		24	62 (4ak)

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In summary, we have demonstrated that newly developed arylsilane reagents 1 effect the nickel-catalysed silicon-based aryl–aryl cross-coupling reaction for the first time. Use of highly stable, readily accessible, and recyclable aryl(trialkyl)silanes activated by a mild carbonate base in the presence of a nickel catalyst prepared in situ from inexpensive nickel(II) salts would merit synthetic organic chemists both in academia and industry to perform chemoselective biaryl synthesis.

The authors are grateful to Professor Masaki Shimizu for X-ray crystallographic analysis. This work has been supported financially by a Grant-in-Aid for Priority Areas “Synergy of Elements” from MEXT. S.T. acknowledges the JSPS for a postdoctoral fellowship.

Notes and references

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6. For palladium-catalysed silicon-based aryl–aryl cross-coupling with aryl tosylates and mesylates, see: (a) L. Zhang and J. Wu, J. Am. Chem. Soc., 2008, 130, 12250; (b) L. Zhang, J. Qing, P. Yang and J. Wu, Org. Lett., 2008, 10, 4971; (c) C. M. So, H. W. Lee, C. P. Lau and F. Y. Kwong, Org. Lett., 2009, 11, 317.
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8. See ESI† for details.
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10. For a review, see: A. Littke, in Modern Arylation Methods, ed. L. Ackermann,Wiley-VCH, Weinheim, 2009, pp. 25–67.

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Footnotes

† Electronic supplementary information (ESI) available: General experimental information, spectral data and crystallographic data (excluding structure factors) for the structure of 3,5-dinitrobenzoate of 1′a. CCDC 779621. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c0cc02173c

‡ Present address: Research & Development Initiative, Chuo University, Bunkyo-ku, Tokyo 112-8551, Japan.

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