A convenient nickel-catalysed hydrosilylation of carbonyl derivatives

Abstract

Hydrosilylation of aldehydes and ketones catalysed by nickel acetate and tricyclohexylphosphine as the catalytic system was demonstrated using polymethylhydrosiloxane as a cheap reducing reagent.

---

The research on alternatives to precious metal catalysts has grown rapidly over the last few years, essentially correlated with the increasing cost of raw materials.¹ In the field of the hydrosilylation of unsaturated carbon–heteroatom bonds, rhodium, platinum and titanium were traditionally the metals of choice to catalyse this reaction.² However, some limitations related to the price or the accessibility to these catalysts and to the price and/or stability of molecular hydrosilanes have led to the development of alternative systems based on earth abundant metals combined with stable inexpensive silanes.^2c Among the commercially available silanes, the polymethylhydrosiloxane³ (PMHS) is the most inexpensive and abundant hydrosilane source arising from the silicone industry, which besides has the advantage to be stable to air and water, soluble in most organic solvents, which makes the hydrosilylation reaction a viable alternative to hydrogenation.⁴ Several earth abundant metals have been recently used as catalysts for hydrosilylation reactions, such as copper,^5,6 zinc^2c,d,7 and lately iron,^8,9 especially with PMHS; however nickel, which is also a cheap and abundant metal, has been far less studied.^10–13 In this area, for example, in 2006, the reduction of ketones with Ph₂SiH₂ has been reported by Kempe et al., using the combination of [Ni(0)(COD)]₂ and chiral bidentate phosphines as the catalytic system.^10b Recently, Guan et al.^10d and Jones et al.^10f have shown, respectively, that nickel PCP and PNP-pincer hydride complexes could efficiently catalyse the reduction of aldehydes in the presence of PhSiH₃ under mild conditions with low catalyst loading (down to 0.2 mol%). Lately, we have developed a NHC–nickel-hydride catalyst for the reduction of carbonyl derivatives at room temperature, using Ph₂SiH₂ as the reducing agent.¹⁴ Thus, we decided to investigate simple catalytic systems based on air-stable nickel(II) salts using PMHS as the hydrogen source (Scheme 1 and Table 1). Interestingly, Ananikov and Beletskaya et al. have shown that the combination of Ni(acac)₂ and phosphines is an excellent precursor of nickel(0) for the catalytic system.¹⁵ In the light of these results, initial studies focused on the reduction of benzaldehyde with 3 equiv. of PMHS in the presence of catalytic amounts of nickel(II) salts under various conditions to optimize the reaction parameters. (Table 1) Using 5 mol% of Ni(acac)₂ and 10 mol% of PCy₃ as the ligand in THF at 70 °C, a full conversion was observed. (Table 1, entry 1).

Scheme 1 Nickel-catalysed hydrosilylation of benzaldehyde.

Table 1 Optimization of the reaction conditions for the reduction of the benzaldehyde with PMHS

Entry^a	Nickel salt	Ligand	Time (h)	Conversion^b (%)
a Typical procedure: the nickel salts (5 mol%), THF (1 mL), the ligand (10 mol%), the aldehyde (0.5 mmol) and PMHS (1.5 mmol) are added in this order and the reaction was stirred in a preheated oil bath at 70 °C.b Conversions determined by GC after methanolysis (MeOH, 2 M NaOH) and extraction with Et2O.c Reaction performed at 50 °C.d 2 mL of solvent.e Mes2NHC·HCl (5.5 mol%) deprotonated by n-BuLi (11 mol%).f Toluene as the solvent.g Ni(OAc)2·4H2O 1 mol%, PCy3 2 mol%, reaction run on the 2.5 mmol scale.h Ni(OAc)2·4H2O 0.1 mol%, PCy3 0.2 mol%, reaction run on the 12.5 mmol scale.
1	Ni(acac)2	PCy3	24	98
2	Ni(OAc)2·4H2O	PCy3	16	97
3	Ni(OAc)2	PCy3	24	98
4	NiBr2	PCy3	16	0
5	NiCl2	PCy3	16	3
6^c	Ni(OAc)2·4H2O	PCy3	22	52
7	Ni(OAc)2·4H2O	PPh3	16	2
8	Ni(OAc)2·4H2O	P(o-tolyl)3	16	0
9	Ni(OAc)2·4H2O	dppe	16	6
10	Ni(OAc)2·4H2O	PMe2Ph	16	98
11^d^,^e	Ni(OAc)2·4H2O	Mes2NHC	16	40
12^f	Ni(OAc)2·4H2O	PCy3	16	30
13	—	PCy3	16	0
14	Ni(OAc)2·4H2O	—	16	0
15^g	Ni(OAc)2·4H2O	PCy3	16	98
16^h	Ni(OAc)2·4H2O	PCy3	16	83

---

Encouraged by this result, we have tested other nickel(II) sources using the same ligand: with commercial Ni(OAc)₂·4H₂O and dried Ni(OAc)₂,¹⁶ the benzaldehyde was totally reduced, whereas with either NiCl₂ or NiBr₂, no benzylalcohol was detected (Table 1, entries 2–5). We have then screened classical phosphines: with monodentate PPh₃, P(o-tolyl)₃, or with the bidentate bis-diphenylphosphinoethane (dppe) no conversion was obtained, while the more basic PMe₂Ph leads to a full conversion as in the case of PCy₃ (Table 1, entries 7–10). Alternatively, N-heterocyclic carbene, such as 1,3-dimesitylimidazol-2-ylidene (Mes₂NHC), generated in situ by the addition of n-butyllithium¹⁷ was found to be a less active ligand than phosphine for this reaction (entry 11). Moreover, changing the solvent from THF to toluene has a deleterious effect on the conversion (entry 12). Blank experiments were also performed: Ni(OAc)₂·4H₂O or PCy₃ alone did not promote the hydrosilylation reaction (Table 1, entries 13 and 14). Finally, the catalyst loading could be decreased and the limits of the catalytic effectiveness of the system were reached for the reduction of benzaldehyde using 0.1 mol% as only 83% conversion was obtained (entries 15 and 16).

With these optimized conditions in hand, we then examined the scope of the hydrosilylation of aldehydes with the combination of Ni(OAc)₂·4H₂O (5 mol%) and PCy₃ (10 mol%) in refluxing THF for 16 h using 3 equiv. of PMHS.¹⁸ Benzaldehydes bearing electron donating substituents such as methoxy- and N,N-dimethylamino groups in the para-position, or a methyl group in the ortho position were fully reduced and the corresponding alcohols obtained in high yields (Table 2, entries 2, 3, and 9). The reduction of the 4-nitrobenzaldehyde was slightly more difficult, as only 83% of the corresponding alcohol was obtained. Interestingly, under such conditions, the reduction is quite selective as only traces of the over-reduced product, namely 4-aminobenzylalcohol, were detected (Table 2, entry 4). For halogenated benzaldehydes (Table 2, entries 5 and 6), under standard conditions, conversions were modest (26% and 43%, respectively, for the p-chloro and p-bromobenzaldehyde). For both the chloro- and bromo-derivatives, low but significant amounts of benzaldehyde and benzylalcohol (3–4%) were detected by GC-MS analysis in the crude mixture after reaction, which shows that reductive dehalogenation occurred during the reaction, probably leading to halogenated nickel species which are inactive for the hydrosilylation reaction. If the quantity of silane is increased to 10 equiv., the rate of the hydrosilylation is increased and the conversion rose, respectively, to 58% and 68%. It must be pointed out that a similar phenomenon was observed with a well-defined nickel-hydride catalyst.^14,19 Interestingly, this system is tolerant toward amide and ester functional groups, as shown by the sole reduction of the C=O bond of the aldehyde (entries 7 and 8). The hydrosilylation of 10-undecenaldehyde was completed, but a mixture of 1 : 1 undecan-1-ol and undecen-1-ols was obtained coming from either the reduction and the isomerisation of the terminal C=C double bond.²⁰ This result contrasts with the one obtained for the internal C=C double bond, which remained intact in the case of 2,6-dimethylhept-5-enal (entries 10 and 11).¹³ Heterocyclic aldehydes derived from furan and pyrrole were also nicely converted to the corresponding alcohols (entries 12 and 13). Finally, ferrocenylcarboxaldehyde was totally reduced under these conditions (entry 14).

Table 2 Scope of the nickel-catalysed hydrosilylation of aldehydes

Entry^a	Substrate		Conversion^b (%)	Yield (%)
a Typical procedure: Ni(OAc)2·4H2O (5 mol%), THF (4 mL), PCy3 (10 mol%), the aldehyde (2 mmol) and PMHS (3 equiv., 6 mmol) are added in this order and the reaction was stirred at 70 °C for 16 h.b Conversions determined by ^1H NMR after methanolysis.c PMHS 10 equiv., 0.5 mmol scale.d 1 mmol scale.e A mixture of 1 : 1 undecan-1-ol and undecen-1-ols was obtained.
1		R = H	>97	85
2		R = OMe	>97	95
3		R = NMe2	>97	90
4		R = NO2	83	70
5		R = Cl	26	—
			58^c	—
6		R = Br	43	—
			68^c	—
7^d		R = COOCH3	>97	83
8		R = NHCOCH3	>97	88
9			>97	87
10			>97	77^e
11			95	74
12			>97	70
13			89	49
14			>97	83

---

Encouraged by these satisfying results, we then explored the reduction of ketones with this nickel catalytic system. Using Ni(acac)₂ (5 mol%), PCy₃ (10 mol%) in THF at 70 °C, the conversion of acetophenone to 1-phenylethanol was only 10% after 24 h with 4 equiv. of PMHS. Nevertheless, with Ni(OAc)₂·4H₂O (5 mol%) and PCy₃ (10 mol%) in toluene at 100 °C for 24 h, the conversion was complete. We have examined the scope of the reaction using these conditions (Table 3). The reduction of acetophenone substituted at the para position with electron donating groups such as methyl and methoxy leads to the corresponding alcohols with high conversions and good isolated yields (Table 3, entries 2 and 3). As for aldehydes, bromo and chloro ketone derivatives were not suitable for this catalytic system, and no conversion was detected (Table 3, entries 4 and 5). Interestingly, electron-deficient acetophenones were nicely converted to the corresponding alcohols (entries 6–8). Moreover, encumbered ketones, such as 2,4,6-trimethylacetophenone, isobutyrophenone or pivalophenone, are fully reduced, which demonstrated that steric hindrance does not hamper the reaction (entries 9–11). With linear and cyclic aliphatic ketones, the reaction also proceeds in good yields (entries 12–14). It is noteworthy that tetralone and indanone were more difficult substrates to be reduced as the conversions were only of 45% and 79% respectively (entries 15 and 16). With heteroaromatic ketones, the reaction proceeds well with furan derivatives (90% conversion, entry 17) and modestly with pyridine derivatives (61% conversion, entry 18). Unfortunately, with sulfur containing heterocycles, the conversion was very low (11%, entry 19). Finally, 1-ferrocenylethanol can be obtained in moderate yield (55%, entry 20).

Table 3 Scope of the nickel-catalysed hydrosilylation of ketones

Entry^a	Substrate		Conversion^b (%)	Yield (%)
a Typical procedure: Ni(OAc)2·4H2O (5 mol%), toluene (4 mL), PCy3 (10 mol%), the ketone (2 mmol) and PMHS (4 equiv., 8 mmol) are added in this order and the reaction was stirred at 100 °C for 16 h.b Conversions determined by ^1H NMR after methanolysis.
1		R = H	>97	86
2		R = Me	>97	70
3		R = OMe	>97	68
4		R = Br	<5	—
5		R = Cl	<5	—
6		R = F	>97	65
7		R = CF3	75	—
8			>97	92
9			85	79
10		R = iPr	>97	90
11		R = tBu	>97	95
12			>97	79
13			>97	94
14			92	70
15			45	42
16			79	64
17			90	62
18			61	—
19			11	—
20			74	55

---

In conclusion, we have shown that the combination of air-stable Ni(OAc)₂·4H₂O and PCy₃ in THF can efficiently catalyse the reduction of aldehydes and ketones using cheap PMHS as the reducing reagent. The present methodology is an appealing inexpensive and convenient methodology for the hydrosilylation reaction. We believe that nickel has high potential in homogenous catalysed reduction, thus, further developments to enlarge the scope of this catalytic system, including asymmetric reductions, are under current investigation by our group.

Acknowledgements

We are grateful to the Université de Rennes 1, CNRS, Rennes Métropole and Ministère de l'Enseignement Supérieur et de la Recherche for support, and to Axa Research Fund for a grant to J.Z.

Notes and references

1. Catalysis without Precious Metals, ed. M. Bullock, Wiley-VCH, Weinheim, 2010.
2. For general reviews about hydrosilylation, see: (a) Comprehensive Handbook on Hydrosilylation, ed. B. Marciniec, Pergamon Press, Oxford, 1992; (b) Hydrosilylation: A Comprehensive Review on Recent Advances, ed. B. Marciniec, Springer, Heidelberg, 2009; (c) J.-F. Carpentier and V. Bette, Curr. Org. Chem., 2002, 6, 913–936; (d) O. Riant, N. Mostefaï and J. Courmarcel, Synthesis, 2004, 2943–2958; (e) H. Nishiyama and K. Itoh, in Transition Metals for Organic Synthesis, ed. M. Beller and C. Bolm, Wiley-VCH, Weinheim, 2nd edn, 2004, vol. 2, pp. 182–191.
3. (a) H. Mimoun, J. Org. Chem., 1999, 64, 2582; (b) L. S. Nitzsche and M. Wick, Angew. Chem., 1957, 69, 96; (c) N. J. Lawrence, M. D. Drew and S. M. Bushell, J. Chem. Soc., Perkin Trans. 1, 1999, 3381; (d) M. Suguro, Y. Yamamura, T. Koike and A. Mori, React. Funct. Polym., 2007, 67, 1264; (e) H. Mimoun and S. A. Firminich, WO pat., 00/37540 A1, 2000.
4. D. Addis, S. Das, K. Junge and M. Beller, Angew. Chem., Int. Ed., 2011, 50, 6004.
5. For representative reviews on Cu-catalysed hydrosilylation, see: (a) S. Rendler and M. Oestreich, Angew. Chem., Int. Ed., 2007, 46, 498; (b) C. Deutsch, N. Krause and B. H. Lipshutz, Chem. Rev., 2008, 108, 2916; (c) B. H. Lipshutz, Synlett, 2009, 509.
6. Selected examples of Cu-catalysed hydrosilylation: (a) H. Brunner and W. Mehling, J. Organomet. Chem., 1984, 275, C17; (b) B. H. Lipshutz, K. Noson and W. Chrisman, J. Am. Chem. Soc., 2001, 123, 12917; (c) B. H. Lipshutz, A. Lower and K. Noson, Org. Lett., 2002, 4, 4045; (d) J. T. Issenhuth, S. Dagorne and S. Bellemin-Laponnaz, Adv. Synth. Catal., 2006, 348, 1991.
7. Selected examples of Zn-catalysed hydrosilylation: (a) H. Mimoun, J. Y. Saint Laumer, L. Giannini, R. Scopelliti and C. Floriani, J. Am. Chem. Soc., 1999, 121, 6158; (b) V. Bette, A. Mortreux, C. W. Lehmann and J.-F. Carpentier, Chem. Commun., 2003, 332; (c) V. Bette, A. Mortreux, D. Savoia and J.-F. Carpentier, Adv. Synth. Catal., 2005, 347, 289; (d) S. Das, D. Addis, S. Zhou, K. Junge and M. Beller, J. Am. Chem. Soc., 2010, 132, 1770.
8. For representative reviews on Fe-catalysed hydrosilylation, see: (a) M. Zhang and A. Zhang, Appl. Organomet. Chem., 2010, 24, 751; (b) K. Junge, K. Schröder and M. Beller, Chem. Commun., 2011, 47, 4849.
9. Selected examples of iron-catalysed hydrosilylation: (a) H. Brunner and K. Fisch, Angew. Chem., Int. Ed. Engl., 1990, 29, 1131; (b) H. Nishiyama and A. Furuta, Chem. Commun., 2007, 760; (c) N. S. Shaikh, K. Junge and M. Beller, Org. Lett., 2007, 9, 5429; (d) A. M. Tondreau, E. Lobkovsky and P. J. Chirik, Org. Lett., 2008, 10, 2789; (e) D. V. Gutsulyak, L. G. Kuzmina, J. A. K. Howard, S. F. Vyboishichikov and G. I. Nikonov, J. Am. Chem. Soc., 2008, 130, 3732; (f) J. Yang and T. D. Tilley, Angew. Chem., Int. Ed., 2010, 49, 10186; (g) V. V. K. M. Kandepi, J. M. S. Cardoso, E. Peris and B. Royo, Organometallics, 2010, 29, 2777; (h) J. M. S. Cardoso and B. Royo, Chem. Commun., 2012, 48, 4944; (i) L. C. Misal Castro, D. Bézier, J.-B. Sortais and C. Darcel, Adv. Synth. Catal., 2011, 353, 1279; (j) J. Zheng, L. C. Misal Castro, T. Roisnel, C. Darcel and J.-B. Sortais, Inorg. Chim. Acta, 2012, 380, 301; (k) L. C. Misal Castro, J.-B. Sortais and C. Darcel, Chem. Commun., 2012, 48, 151; (l) D. Bézier, G. T. Venkanna, J.-B. Sortais and C. Darcel, ChemCatChem, 2011, 3, 1747; (m) F. Jiang, D. Bézier, J.-B. Sortais and C. Darcel, Adv. Synth. Catal., 2011, 353, 239–244; (n) S. Zhou, K. Junge, D. Addis, S. Das and M. Beller, Angew. Chem., Int. Ed., 2009, 48, 9507; (o) Y. Sunada, H. Kawakami, Y. Motoyama and H. Nagashima, Angew. Chem., Int. Ed., 2009, 48, 9511; (p) D. Bézier, G. T. Venkanna, L. C. Misal Castro, J. Zheng, T. Roisnel, J.-B. Sortais and C. Darcel, Adv. Synth. Catal., 2012, 354, 1879; (q) H. Jaafar, H. Li, L. C. Misal Castro, J. Zheng, J.-B. Sortais and C. Darcel, Eur. J. Inorg. Chem., 2012, 3546.
10. Examples of Ni-catalysed hydrosilylation of carbonyls derivatives: (a) F.-G. Fontaine, R.-V. Nguyen and D. Zargarian, Can. J. Chem., 2003, 81, 1299; (b) T. Irrgang, T. Schareina and R. Kempe, J. Mol. Catal. A: Chem., 2006, 257, 48; (c) Y. K. Kong, J. Kim, S. Choi and S.-B. Choi, Tetrahedron Lett., 2007, 48, 2033; (d) S. Chakraborty, J. A. Krause and H. Guan, Organometallics, 2009, 28, 582; (e) B. L. Tran, M. Pink and D. J. Mindiola, Organometallics, 2009, 28, 2234; (f) S. Kundu, W. W. Brennessel and W. D. Jones, Inorg. Chem., 2011, 50, 9443.
11. Example of Ni-catalysed hydrosilylation of imine derivatives: A. H. Vetter and A. Berkessel, Synthesis, 1995, 419.
12. Examples of Ni-catalysed hydrosilylation of alkenes and/or alkynes: (a) M. R. Chaulagain, G. M. Mahandru and J. Montgomery, Tetrahedron, 2006, 62, 7560; (b) J. Berding, J. A. van Paridon, V. H. S. van Rixel and E. Bouwman, Eur. J. Inorg. Chem., 2011, 2450; (c) M. I. Lipschutz and T. D. Tilley, Chem. Commun., 2012, 48, 7146.
13. For examples of selective Ni-catalysed hydrosilylation of alkenes and/or alkynes versus C–heteroatom multiple bonds, see: (a) P. Boudjouk, B.-H. Han, J. R. Jacobsen and B. J. Hauck, J. Chem. Soc., Chem. Commun., 1991, 1424; (b) P. Boudjouk, S.-B. Choi, B. J. Hauck and A. B. Rajkumar, Tetrahedron Lett., 1998, 39, 3951.
14. L. P. Bheeter, M. Henrion, L. Brelot, C. Darcel, M. J. Chetcuti, J.-B. Sortais and V. Ritleng, Adv. Synth. Catal., 2012 DOI:10.1002/adsc.201200460.
15. V. P. Ananikov, K. A. Gayduk, Z. A. Starikova and I. P. Beletskaya, Organometallics, 2010, 29, 5098.
16. Ni(OAc)₂·4H₂O “99.998% trace metals basis” purchased from Aldrich was used to performed this study, ICP analysis was also performed on this salt, see ESI.† For critical review about impurities in catalysis see: I. Thomé, A. Nijs and C. Bolm, Chem. Soc. Rev., 2012, 41, 979.
17. (a) E. Buitrago, L. Zani and H. Adolfsson, Appl. Organomet. Chem., 2011, 25, 748; (b) E. Buitrago, F. Tinnis and H. Adolfsson, Adv. Synth. Catal., 2012, 354, 217.
18. The use of 1 mol% of Ni(OAc)₂·4H₂O and 2 mol% of PCy₃ led to a full conversion for the reduction of p-methoxybenzaldehyde, but only to 57% conversion for p-nitrobenzaldehyde while when using 5 mol% of nickel salt and 10 mol% of phosphine, the conversion for the nitro derivative rose to 87% (Table 2, entry 4). Indeed, these latter conditions were used as standard conditions for the scope of the reaction.
19. J. Breitenfeld, R. Scopelliti and X. Hu, Organometallics, 2012, 31, 2128.
20. (a) L. W. Gosser and G. W. Parshall, Tetrahedron Lett., 1971, 12, 2555; (b) A. Wille, S. Tomm and H. Frauenrath, Synthesis, 1998, 305; (c) H. J. Lim, C. R. Smith and T. V. RajanBabu, J. Org. Chem., 2009, 74, 4565.

---

Footnote

† Electronic supplementary information (ESI) available: Full experimental details and NMR spectra. See DOI: 10.1039/c2cy20509b

---