DOI: 10.1002/chem.201403497
Communication
& Hydrosilylation
Cesium Carbonate Catalyzed Chemoselective Hydrosilylation of Aldehydes and Ketones under Solvent-Free Conditions Mengdi Zhao, Weilong Xie, and Chunming Cui*[a] Abstract: Cs2CO3 has been found to be an efficient and chemoselective catalyst for reduction of aldehydes and ketones to alcohols with one equivalent of Ph2SiH2 as the reductant under solvent-free conditions. Most of the aldehydes employed can be effectively hydrosilated quantitatively to give the corresponding silyl ethers in 2 h at room temperature, whereas the hydrosilylation of ketones proceeded smoothly at 80 8C. The catalyst system tolerates a number of functional groups including halogen, alkoxyl, olefin, ester, nitro, cyano, and heteroaromatic groups; the selective hydrosilylation of aldehydes in the presence of ketone can be effectively controlled by temperature; and hydrosilylation of a,b-unsaturated carbonyls resulted in the 1,2-addition products. The catalytic hydrosilylation of suitable dicarbonyls can be applied to the synthesis of poly(silyl ether)s with a high molecular weight and narrow molecular distribution.
The hydrosilylation of carbonyl compounds is a valuable method for the production of alcohols and silyl ether intermediates for organosilane materials, and thus has been widely employed in academia and industry.[1] Precious metal catalysts, particularly Rh-, Ru-, and Ir-based catalysts, have been developed as the most widely employed protocols.[2] However, the drawbacks of these catalysts are their high costs and toxicity, which have become the main concerns in modern synthetic chemistry. Recent studies have been focused on the exploration of environmental benign and inexpensive alternatives.[3] In this regard, abundant and inexpensive iron catalysts reported by Beller, Nagashima, Chirik, and Tilley have attracted a great deal of attention.[3f, 4–7] These iron catalysts exhibit a high chemoselectivity for hydrosilylation of aldehydes and ketones. On the other hand, Lewis acid and base catalysts are also nontoxic alternatives,[8, 9] particularly B(C6F5)3 and KOtBu have been successfully employed as catalysts for the hydrosilylation of carbonyl compounds. These relatively simple catalysts feature distinct mechanisms from transition-metal systems and some of them exhibit a unique selectivity. Very recently, it has been [a] M. Zhao, W. Xie, Prof. Dr. C. Cui State Key Laboratory of Elemento-Organic Chemistry Nankai University, Tianjin 300071 (P. R. China) Fax: (+ 86) 22-23503461 E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201403497. Chem. Eur. J. 2014, 20, 9259 – 9262
shown that KOH and KOtBu are active catalysts for hydrosilylation of ketones and esters, but the reaction with the more general catalyst KOtBu required an excess of hydrosilanes and long reaction times.[9c] Despite the progress in this area, there is still a great demand for the development of practical and chemoselective alternatives. We recently reported on the efficient reduction of carboamides with PhSiH3 catalyzed by cesium carbonate under solvent-free conditions.[10] We found that the catalyst is very sensitive to the hydrosilanes that are employed for the reduction reaction. To investigate further applications of this commercially available and cheap source and its activation mode for hydrosilanes, we have studied the hydrosilylation of aldehydes and ketones with this catalyst. We envisioned that it is quite possible to realize selective reduction of aldehydes and ketones by careful choices of hydrosilanes. Herein, we report the results on cesium carbonate-catalyzed chemoselective reduction of aldehydes and ketones by using Ph2SiH2 as the reductant under solvent-free and relatively mild conditions [Eq. (1)]. This catalytic system tolerates a large range of functional groups that are susceptible to reduction and the hydrosilylation of most of the aldehydes is complete in 2 h to give the corresponding silyl ethers in quantitative yield. The system represents one of the most chemoselective catalytic systems and practical protocols for the reduction of aldehydes and ketones.
The studies on the Cs2CO3-catalyzed reduction of aldehydes and ketones were initiated by using the commercially available Ph2SiH2 and (EtO)3SiH as the reductants. They are not reactive enough for the reduction of carboamides with Cs2CO3 as the catalyst. It was found that reduction of benzaldehyde and acetophenone with Ph2SiH2 catalyzed by 5.0 mol % Cs2CO3 at room temperature under solvent-free conditions led to a complete reduction in 2 and 24 h, respectively (Table 1 and Table 2). As shown in Table 1, Ph2SiH2 (entries 1–4) is much more reactive for the reduction of benzaldehyde than (EtO)3SiH (entries 5–7). The reduction of benzaldehyde under the optimized conditions (entry 2) yielded Ph2SiH(OCH2Ph) and Ph2Si(OCH2Ph)2 in quantitative yield. The results for the reduction of acetophenone are summarized in Table 2, which indicated that Ph2SiH2 is also effective for the reduction of ketones, albeit the relatively slow reduction reaction in comparison with
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Communication that of the aldehyde. Nevertheless, the reduction of the ketone can be significantly accelerated at 80 8C; a high conversion (94 %) was achieved in 8 h under the optimized conditions (Table 2, entry 4). These results demonstrated that hydrosilylation of aldehydes and ketones can be accomplished with Ph2SiH2 as the reductant. Furthermore, this reduction system may be employed for the selective reduction of aldehydes in the presence of ketone functionalities at ambient temperature. To investigate the scope of the Cs2CO3/Ph2SiH2 hydrosilylation system, various aldehydes and ketones were examined under optimized conditions. The crude hydrosilylated products were analyzed by 1H NMR spectroscopy for the determination of the conversions and the ratios of mono- and disilylated products. The results indicated that most of these substrates can be converted to the corresponding silyl ethers in almost quantitative yields. The alcohol products listed in Tables 3 and 4 were obtained by hydrolysis of the silylated products with 10 % NaOH aqueous solution in methanol followed by separation and purifications. The results are summarized in Tables 3 and 4 for aldehydes and ketones, respectively. The reduction of the most substituted aromatic aldehydes (Table 3) went to completion at room temperature within 2 h in the presence of 5 mol % Cs2CO3 under solvent-free conditions. However, the 4-NMe2-substituted benzaldehyde (entry 6) requires a much longer reaction time (24 h), whereas the substrate with the CN group at the para position of the phenyl ring (entry 8), which is insoluble in Ph2SiH2, required the addition of a small amount of THF as the solvent. It appeared that electron-donating and electron-withdrawing groups on the
Table 1. Cs2CO3-catalyzed hydrosilylation of benzaldehyde.[a] Entry
Silane ([equiv])
Catalyst loading [mol %]
t [h]
Yield[b] [%]
1 2[c] 3 4 5 6 7[d]
Ph2SiH2 (1.0) Ph2SiH2 (1.0) Ph2SiH2 (1.0) Ph2SiH2 (0.5) (EtO)3SiH (1.0) (EtO)3SiH (2.0) (EtO)3SiH (2.0)
5.0 5.0 2.0 5.0 5.0 5.0 5.0
1 2 2 4 48 18 18
77 100 (37:63) 1 8 12 22 47
[a] Reaction conditions: benzaldehyde (3.0 mmol), room temperature. [b] Yields were determined from the 1H NMR spectra of the crude products. [c] The value in parentheses refers to the molar ratio of Ph2SiH(OCH2Ph) and Ph2Si(OCH2Ph)2. [d] 80 8C.
Table 2. Cs2CO3-catalyzed Ph2SiH2.[a]
hydrosilylation
of
acetophenone
with
Entry
Silane [equiv]
Temp. [oC]
t [h]
Yield[b][%]
1 2 3 4 5
Ph2SiH2 Ph2SiH2 Ph2SiH2 Ph2SiH2 Ph2SiH2
r.t. 60 80 80 80
24 10 5 8 8
94 89 92 94 78
(1.0) (1.0) (1.0) (1.0) (0.5)
[a] Reaction conditions: acetophenone (3.0 mmol) with 5.0 mol % Cs2CO3 and Ph2SiH2. [b] Yields were determined from the 1H NMR spectra of the crude reaction mixture.
Table 3. Cs2CO3-catalyzed hydrosilylation of aldehydes by Ph2SiH2.[a]
Yield [%][b]
Entry
Substrate
t [h]
2
80
9
i
24
60
b
2
83
10
j
2
68
3
c
2
75
11[d]
k
2
100
4
d
2
74
12
l
2
84
5
e
2
73
13[e]
m
2
90
6
f
24
80
14
n
2
84
7
g
30
83
15
o
2
82
8[c]
h
5
81
16
p
2
86
Entry
Substrate
t [h]
1
a
2
Product
Product
Yield [%][b]
[a] Reaction conditions: carbonyl compounds (3 mmol) with 5.0 mol % Cs2CO3 in Ph2SiH2 (3 mmol) at room temperature under solvent-free conditions. [b] The values below the structures refer to the isolated yields (%). [c] 1.5 mL THF was added. [d] NMR yield. [e] 1.5 mmol of Ph2SiH2 was used. Chem. Eur. J. 2014, 20, 9259 – 9262
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Communication Table 4. Cs2CO3-catalyzed hydrosilylation of ketones by Ph2SiH2.[a]
Entry
Substrate
1
q
Product
Yield[b] [%]
77 Scheme 2. Hydrosilylation of 1,4-phthalaldehyde and p-acetylbenzaldehyde.
2
r
84
3
s
75
4[c]
t
74
5
u
83
[a] Reaction conditions: carbonyl compounds (3 mmol) with 5.0 mol % Cs2CO3 in Ph2SiH2 (3 mmol) at 80 8C in 5 h under solvent-free conditons. [b] Conversion of ketone, the values below the structures of products refer to the isolated yields. [c] 1.5 mL THF was added.
phenyl ring did not have noticeable effects on the performance of the catalyst except for the very strong electrondonating NMe2 group. The a,b-unsaturated aldehydes (Table 3, entries 7 and 10) can also be reduced under the mild conditions, which selectively yielded the 1,2-addition products (Scheme 1). This chemoselectivity for a,b-unsaturated alde-
Scheme 1. Hydrosilylation of a,b-unsaturated aldehydes and ketones.
hydes can also be achieved with a few other catalytic systems, whereas most transition metal catalysts resulted in 1,4-addition. Aliphatic aldehydes (entries 9 and 11) can also be completely hydrosilylated at ambient temperature as indicated by the NMR analysis of crude products. However, the isolation of the hydrolyzed products led to the modest yields due to the volatile nature of the resulting alcohols. Most importantly, the hydrosilylation of aldehydes with the present catalytic system features a wide substrate scope and the catalytic system tolerates a number of functional groups including olefin, NO2, CN, ester, and ketone functionalities that are susceptible to reduction and challenging ones for most of the existing catalytic systems (Table 3). Furthermore, the hydrosilylation of the heteroaromatic aldehydes (entries 15 and 16) is also viable, and pyridine and thiophene carbaldehydes can be converted to the corresponding alcohols in high yields (82 and 86 %). It is noted that hydrosilylation of 1,4-phthalaldehyde (entry 14) with one equivalent of Ph2SiH2 in THF yielded the Chem. Eur. J. 2014, 20, 9259 – 9262
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corresponding polymeric silyl ether A (Scheme 2) in an excellent yield. Silyl ether A has been characterized by GPC analysis (Mn = 6721) and could be converted to the corresponding alcohols in good yield (84 %) by the standard hydrolysis. The hydrosilylation of p-acetylbenzaldehyde at room temperature for 2 h led to the selective hydrosilylation of the aldehyde group with only 1/2 equivalent of the silane Ph2SiH2. The silylated product B can be isolated in an excellent yield (90 %, Scheme 2). The ketones listed in Table 4 were effectively reduced with Ph2SiH2 at 80 8C within 5 h at a catalyst loading of 5 mol %. Although the hydrosilylation of ketones requires the relatively harsh conditions, the C=C double bond, pyridine, and CF3 functionalities in the substrates (Table 4, entries 2, 4, and 5) remained intact under the reaction conditions. The reaction worked equally well for an aliphatic ketone (entry 3), and an a,b-unsaturated ketone (entry 2) yielded the corresponding secondary alcohols in good yields (75 and 84 %). Similar to the hydrosilylation of an a,b-unsaturated aldehyde with the Cs2CO3/Ph2SiH2 system, the latter reaction led to the selective 1,2-hydrosilylation of the unsaturated ketone (Scheme 1). In addition, it was found that the reaction of two equivalents of acetophenone with only one equivalent of Ph2SiH2 and PhMeSiH2 also led to the complete Si H bond addition at 80 8C in 12 h. Likewise, reaction of PhSiH3 with three equivalents of acetophenone under the same conditions resulted in the selective formation of PhSi(OCHPhMe)3 in good yield. These results indicated that the hydrosilyaltion is an atom-efficient protocol in terms of the utilization of Si H bonds. The initial mechanism for the Cs2CO3-catalyzed hydrosilylation of aldehydes and ketones might be very similar to that proposed for the reduction of amides.[10] It is quite possible that the interaction of Ph2SiH2 with the “naked” CO3 dianion yielded a hypervalent hydrosilicate intermediate, which may transfer the hydride donor to the carbonyl groups. The formation of hypervalent hydrosilicates by reactions of fluoride, alkoxide, and hydride ligands with hydrosilanes has been welldocumented in the literature.[9, 11] The present results further demonstrated that the Cs2CO3-catalyzed hydrosilane transformations are dependent on the hydrosilanes employed. We reasoned that Cs2CO3 combined with other hydrosilanes could be applied to the selective reduction of other unsaturated systems. In conclusion, we have developed a general and practical protocol for the hydrosilylation of aldehydes with the Cs2CO3/ Ph2SiH2 system. Both of the components are commercially available, cost-effective, and non-toxic. The catalytic system is
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Communication very efficient and chemoselective for aldehydes and ketones under solvent-free conditions in the presence of a variety of functional groups. The hydrosilylation of a,b-unsaturated carbonyls led to 1,2-addition, and hydrosilyaltion of 1,4-phthalaldehyde led to the formation of the corresponding poly(silyl ether). Further studies on the Cs2CO3-catalyzed hydrosilane transformations and the mechanism for the reduction process are currently in progress.
[2]
[3]
Experimental Section General procedure for the reduction of aldehydes: A 25 mL oven-dried Schlenk tube containing a stir bar was loaded with 5.0 mol % Cs2CO3 (49 mg, 0.15 mmol). Subsequently, substrate (3 mmol) and Ph2SiH2 (553 mg, 3 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. Longer reaction times were required for the aldehydes f and i (24 h), g (30 h), and h (5 h) (Table 3). For the substrate h, 1.5 mL THF was added. General procedure for the reduction of ketones: A 25 mL ovendried Schlenk tube containing a stir bar was loaded with 5.0 mol % Cs2CO3 (49 mg, 0.15 mmol). Subsequently, the substrate (3 mmol) and Ph2SiH2 (553 mg, 3 mmol) was added. The reaction mixture was stirred at 80 8C for 5 h.
[4] [5]
Acknowledgements This work was supported by the National Natural Science Foundation of China and the 973 Program (Grant No. 2012CB821600). Keywords: alcohols · aldehydes · hydrosilylation · ketones · silyl ethers
cesium
carbonate
www.chemeurj.org
[8] [9]
·
[1] a) B. Marciniec in Hydrosilylation: A Comprehensive Review on Recent Advances (Eds.: B. Marciniec), Springer, Netherlands, 2008; b) A. K. Roy, Adv. Organomet. Chem. 2007, 55, 1 – 59; c) I. Ojima; Z. Li, J. Zhu in The Chemistry of Organic Silicon Compounds, Vol. 2 (Eds.: Z. Rappoport, Y. Apeloig), Wiley, New York, 1998, 2, 1687; d) I. Ojima in The Chemistry of
Chem. Eur. J. 2014, 20, 9259 – 9262
[6] [7]
[10] [11]
Organic Silicon Compounds (Eds.: S. Patai, Z. Rappoport), Wiley, New York, 1989, 25, 1479; e) J. Magano, J. R. Dunetz, Org. Process Res. Dev. 2012, 16, 1156. a) B. Li, J. B. Sortais, C. Darcel, Chem. Commun. 2013, 49, 3691 – 3693; b) C. Cheng, M. Brookhart, Angew. Chem. 2012, 124, 9556; Angew. Chem. Int. Ed. 2012, 51, 9422; c) C. Cheng, M. Brookhart, J. Am. Chem. Soc. 2012, 134, 11304 – 11307; d) Y. Sunada, H. Kawakami, T. Imaoka, Y. Motoyama, H. Nagashima, Angew. Chem. 2009, 121, 9675 – 9678; Angew. Chem. Int. Ed. 2009, 48, 9511 – 9514; e) S. Hanada, T. Ishida, Y. Motoyama, H. Nagashima, J. Org. Chem. 2007, 72, 7551 – 7559; f) K. Matsubara, T. Iura, T. Maki, H. Nagashima, J. Org. Chem. 2002, 67, 4985 – 4988. a) S. Chakraborty, J. A. Krause, H. Guan, Organometallics 2009, 28, 582; b) B. L. Tran, M. Pink, D. J. Mindiola, Organometallics 2009, 28, 2234 – 2243; c) S. Enthaler, K. Junge, M. Beller, Angew. Chem. 2008, 120, 3363; Angew. Chem. Int. Ed. 2008, 47, 3317; d) D. J. C. Constable, P. J. Dunn, J. D. Hayler, G. R. Humphrey, J. L. Leazer, R. J. Linderman, K. Lorenz, J. Manley, B. A. Pearlman, A. Wells, A. Zaks, T. Y. Zhang, Green Chem. 2007, 9, 411 – 420; e) B. H. Lipshutz, B. A. Frieman, Angew. Chem. 2005, 117, 6503; Angew. Chem. Int. Ed. 2005, 44, 6345; f) C. Bolm, J. Legros, J. Le Paih, L. Zani, Chem. Rev. 2004, 104, 6217; g) B. H. Lipshutz, K. Noson, W. Chrisman, A. Lower, J. Am. Chem. Soc. 2003, 125, 8779; h) D. J. Parks, J. M. Blackwell, W. E. Piers, J. Org. Chem. 2000, 65, 3090; i) J. Yun, S. L. Buchwald, J. Am. Chem. Soc. 1999, 121, 5640 – 5644. D. Bzier, G. T. Venkanna, L. C. M. Castro, J. Zheng, T. Roisnel, J. B. Sortais, C. Darcel, Adv. Synth. Catal. 2012, 354, 1879 – 1884. a) T. Inagaki, L. T. Phong, A. Furuta, J. Ito, H. Nishiyama, Chem. Eur. J. 2010, 16, 3090; b) D. Addis, N. Shaikh, S. Zhou, S. Das, K. Junge, M. Beller, Chem. Asian J. 2010, 5, 1687 – 1691; c) A. Furuta, H. Nishiyama, Tetrahedron Lett. 2008, 49, 110; d) N. S. Shaikh, S. Enthaler, K. Junge, M. Beller, Angew. Chem. 2008, 120, 2531 – 2535; Angew. Chem. Int. Ed. 2008, 47, 2497 – 2501; e) H. Nishiyama, A. Furuta, Chem. Commun. 2007, 760 – 762; f) N. S. Shaikh, K. Junge, M. Beller, Org. Lett. 2007, 9, 5429 – 5432. A. M. Tondreau, E. Lobkovsky, P. J. Chirik, Org. Lett. 2008, 10, 2789. J. Yang, T. D. Tilley, Angew. Chem. 2010, 122, 10384; Angew. Chem. Int. Ed. 2010, 49, 10186. For selected references, see: S. Rendler, M. Oestreich, Angew. Chem. 2008, 120, 6086; Angew. Chem. Int. Ed. 2008, 47, 5997, and ref. [3h]. a) R. R. Holmes, Chem. Rev. 1996, 96, 927; b) S. V. Maifeld, D. Lee, Org. Lett. 2005, 7, 4995; c) K. Revunova, G. I. Nikonov, Chem. Eur. J. 2014, 20, 839; d) A. Volkov, F. Tinnis, H. Adolfsson, Org. Lett. 2014, 16, 680. W. Xie, M. Zhao, C. Cui, Organometallics 2013, 32, 7440. C. Chuit, R. J. P. Corriu, C. Reye, J. C. Young, Chem. Rev. 1993, 93, 1371.
Received: May 12, 2014 Published online on July 2, 2014
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Communication
& Hydrosilylation
Cesium Carbonate Catalyzed Chemoselective Hydrosilylation of Aldehydes and Ketones under Solvent-Free Conditions Mengdi Zhao, Weilong Xie, and Chunming Cui*[a] Abstract: Cs2CO3 has been found to be an efficient and chemoselective catalyst for reduction of aldehydes and ketones to alcohols with one equivalent of Ph2SiH2 as the reductant under solvent-free conditions. Most of the aldehydes employed can be effectively hydrosilated quantitatively to give the corresponding silyl ethers in 2 h at room temperature, whereas the hydrosilylation of ketones proceeded smoothly at 80 8C. The catalyst system tolerates a number of functional groups including halogen, alkoxyl, olefin, ester, nitro, cyano, and heteroaromatic groups; the selective hydrosilylation of aldehydes in the presence of ketone can be effectively controlled by temperature; and hydrosilylation of a,b-unsaturated carbonyls resulted in the 1,2-addition products. The catalytic hydrosilylation of suitable dicarbonyls can be applied to the synthesis of poly(silyl ether)s with a high molecular weight and narrow molecular distribution.
The hydrosilylation of carbonyl compounds is a valuable method for the production of alcohols and silyl ether intermediates for organosilane materials, and thus has been widely employed in academia and industry.[1] Precious metal catalysts, particularly Rh-, Ru-, and Ir-based catalysts, have been developed as the most widely employed protocols.[2] However, the drawbacks of these catalysts are their high costs and toxicity, which have become the main concerns in modern synthetic chemistry. Recent studies have been focused on the exploration of environmental benign and inexpensive alternatives.[3] In this regard, abundant and inexpensive iron catalysts reported by Beller, Nagashima, Chirik, and Tilley have attracted a great deal of attention.[3f, 4–7] These iron catalysts exhibit a high chemoselectivity for hydrosilylation of aldehydes and ketones. On the other hand, Lewis acid and base catalysts are also nontoxic alternatives,[8, 9] particularly B(C6F5)3 and KOtBu have been successfully employed as catalysts for the hydrosilylation of carbonyl compounds. These relatively simple catalysts feature distinct mechanisms from transition-metal systems and some of them exhibit a unique selectivity. Very recently, it has been [a] M. Zhao, W. Xie, Prof. Dr. C. Cui State Key Laboratory of Elemento-Organic Chemistry Nankai University, Tianjin 300071 (P. R. China) Fax: (+ 86) 22-23503461 E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201403497. Chem. Eur. J. 2014, 20, 9259 – 9262
shown that KOH and KOtBu are active catalysts for hydrosilylation of ketones and esters, but the reaction with the more general catalyst KOtBu required an excess of hydrosilanes and long reaction times.[9c] Despite the progress in this area, there is still a great demand for the development of practical and chemoselective alternatives. We recently reported on the efficient reduction of carboamides with PhSiH3 catalyzed by cesium carbonate under solvent-free conditions.[10] We found that the catalyst is very sensitive to the hydrosilanes that are employed for the reduction reaction. To investigate further applications of this commercially available and cheap source and its activation mode for hydrosilanes, we have studied the hydrosilylation of aldehydes and ketones with this catalyst. We envisioned that it is quite possible to realize selective reduction of aldehydes and ketones by careful choices of hydrosilanes. Herein, we report the results on cesium carbonate-catalyzed chemoselective reduction of aldehydes and ketones by using Ph2SiH2 as the reductant under solvent-free and relatively mild conditions [Eq. (1)]. This catalytic system tolerates a large range of functional groups that are susceptible to reduction and the hydrosilylation of most of the aldehydes is complete in 2 h to give the corresponding silyl ethers in quantitative yield. The system represents one of the most chemoselective catalytic systems and practical protocols for the reduction of aldehydes and ketones.
The studies on the Cs2CO3-catalyzed reduction of aldehydes and ketones were initiated by using the commercially available Ph2SiH2 and (EtO)3SiH as the reductants. They are not reactive enough for the reduction of carboamides with Cs2CO3 as the catalyst. It was found that reduction of benzaldehyde and acetophenone with Ph2SiH2 catalyzed by 5.0 mol % Cs2CO3 at room temperature under solvent-free conditions led to a complete reduction in 2 and 24 h, respectively (Table 1 and Table 2). As shown in Table 1, Ph2SiH2 (entries 1–4) is much more reactive for the reduction of benzaldehyde than (EtO)3SiH (entries 5–7). The reduction of benzaldehyde under the optimized conditions (entry 2) yielded Ph2SiH(OCH2Ph) and Ph2Si(OCH2Ph)2 in quantitative yield. The results for the reduction of acetophenone are summarized in Table 2, which indicated that Ph2SiH2 is also effective for the reduction of ketones, albeit the relatively slow reduction reaction in comparison with
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Communication that of the aldehyde. Nevertheless, the reduction of the ketone can be significantly accelerated at 80 8C; a high conversion (94 %) was achieved in 8 h under the optimized conditions (Table 2, entry 4). These results demonstrated that hydrosilylation of aldehydes and ketones can be accomplished with Ph2SiH2 as the reductant. Furthermore, this reduction system may be employed for the selective reduction of aldehydes in the presence of ketone functionalities at ambient temperature. To investigate the scope of the Cs2CO3/Ph2SiH2 hydrosilylation system, various aldehydes and ketones were examined under optimized conditions. The crude hydrosilylated products were analyzed by 1H NMR spectroscopy for the determination of the conversions and the ratios of mono- and disilylated products. The results indicated that most of these substrates can be converted to the corresponding silyl ethers in almost quantitative yields. The alcohol products listed in Tables 3 and 4 were obtained by hydrolysis of the silylated products with 10 % NaOH aqueous solution in methanol followed by separation and purifications. The results are summarized in Tables 3 and 4 for aldehydes and ketones, respectively. The reduction of the most substituted aromatic aldehydes (Table 3) went to completion at room temperature within 2 h in the presence of 5 mol % Cs2CO3 under solvent-free conditions. However, the 4-NMe2-substituted benzaldehyde (entry 6) requires a much longer reaction time (24 h), whereas the substrate with the CN group at the para position of the phenyl ring (entry 8), which is insoluble in Ph2SiH2, required the addition of a small amount of THF as the solvent. It appeared that electron-donating and electron-withdrawing groups on the
Table 1. Cs2CO3-catalyzed hydrosilylation of benzaldehyde.[a] Entry
Silane ([equiv])
Catalyst loading [mol %]
t [h]
Yield[b] [%]
1 2[c] 3 4 5 6 7[d]
Ph2SiH2 (1.0) Ph2SiH2 (1.0) Ph2SiH2 (1.0) Ph2SiH2 (0.5) (EtO)3SiH (1.0) (EtO)3SiH (2.0) (EtO)3SiH (2.0)
5.0 5.0 2.0 5.0 5.0 5.0 5.0
1 2 2 4 48 18 18
77 100 (37:63) 1 8 12 22 47
[a] Reaction conditions: benzaldehyde (3.0 mmol), room temperature. [b] Yields were determined from the 1H NMR spectra of the crude products. [c] The value in parentheses refers to the molar ratio of Ph2SiH(OCH2Ph) and Ph2Si(OCH2Ph)2. [d] 80 8C.
Table 2. Cs2CO3-catalyzed Ph2SiH2.[a]
hydrosilylation
of
acetophenone
with
Entry
Silane [equiv]
Temp. [oC]
t [h]
Yield[b][%]
1 2 3 4 5
Ph2SiH2 Ph2SiH2 Ph2SiH2 Ph2SiH2 Ph2SiH2
r.t. 60 80 80 80
24 10 5 8 8
94 89 92 94 78
(1.0) (1.0) (1.0) (1.0) (0.5)
[a] Reaction conditions: acetophenone (3.0 mmol) with 5.0 mol % Cs2CO3 and Ph2SiH2. [b] Yields were determined from the 1H NMR spectra of the crude reaction mixture.
Table 3. Cs2CO3-catalyzed hydrosilylation of aldehydes by Ph2SiH2.[a]
Yield [%][b]
Entry
Substrate
t [h]
2
80
9
i
24
60
b
2
83
10
j
2
68
3
c
2
75
11[d]
k
2
100
4
d
2
74
12
l
2
84
5
e
2
73
13[e]
m
2
90
6
f
24
80
14
n
2
84
7
g
30
83
15
o
2
82
8[c]
h
5
81
16
p
2
86
Entry
Substrate
t [h]
1
a
2
Product
Product
Yield [%][b]
[a] Reaction conditions: carbonyl compounds (3 mmol) with 5.0 mol % Cs2CO3 in Ph2SiH2 (3 mmol) at room temperature under solvent-free conditions. [b] The values below the structures refer to the isolated yields (%). [c] 1.5 mL THF was added. [d] NMR yield. [e] 1.5 mmol of Ph2SiH2 was used. Chem. Eur. J. 2014, 20, 9259 – 9262
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Communication Table 4. Cs2CO3-catalyzed hydrosilylation of ketones by Ph2SiH2.[a]
Entry
Substrate
1
q
Product
Yield[b] [%]
77 Scheme 2. Hydrosilylation of 1,4-phthalaldehyde and p-acetylbenzaldehyde.
2
r
84
3
s
75
4[c]
t
74
5
u
83
[a] Reaction conditions: carbonyl compounds (3 mmol) with 5.0 mol % Cs2CO3 in Ph2SiH2 (3 mmol) at 80 8C in 5 h under solvent-free conditons. [b] Conversion of ketone, the values below the structures of products refer to the isolated yields. [c] 1.5 mL THF was added.
phenyl ring did not have noticeable effects on the performance of the catalyst except for the very strong electrondonating NMe2 group. The a,b-unsaturated aldehydes (Table 3, entries 7 and 10) can also be reduced under the mild conditions, which selectively yielded the 1,2-addition products (Scheme 1). This chemoselectivity for a,b-unsaturated alde-
Scheme 1. Hydrosilylation of a,b-unsaturated aldehydes and ketones.
hydes can also be achieved with a few other catalytic systems, whereas most transition metal catalysts resulted in 1,4-addition. Aliphatic aldehydes (entries 9 and 11) can also be completely hydrosilylated at ambient temperature as indicated by the NMR analysis of crude products. However, the isolation of the hydrolyzed products led to the modest yields due to the volatile nature of the resulting alcohols. Most importantly, the hydrosilylation of aldehydes with the present catalytic system features a wide substrate scope and the catalytic system tolerates a number of functional groups including olefin, NO2, CN, ester, and ketone functionalities that are susceptible to reduction and challenging ones for most of the existing catalytic systems (Table 3). Furthermore, the hydrosilylation of the heteroaromatic aldehydes (entries 15 and 16) is also viable, and pyridine and thiophene carbaldehydes can be converted to the corresponding alcohols in high yields (82 and 86 %). It is noted that hydrosilylation of 1,4-phthalaldehyde (entry 14) with one equivalent of Ph2SiH2 in THF yielded the Chem. Eur. J. 2014, 20, 9259 – 9262
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corresponding polymeric silyl ether A (Scheme 2) in an excellent yield. Silyl ether A has been characterized by GPC analysis (Mn = 6721) and could be converted to the corresponding alcohols in good yield (84 %) by the standard hydrolysis. The hydrosilylation of p-acetylbenzaldehyde at room temperature for 2 h led to the selective hydrosilylation of the aldehyde group with only 1/2 equivalent of the silane Ph2SiH2. The silylated product B can be isolated in an excellent yield (90 %, Scheme 2). The ketones listed in Table 4 were effectively reduced with Ph2SiH2 at 80 8C within 5 h at a catalyst loading of 5 mol %. Although the hydrosilylation of ketones requires the relatively harsh conditions, the C=C double bond, pyridine, and CF3 functionalities in the substrates (Table 4, entries 2, 4, and 5) remained intact under the reaction conditions. The reaction worked equally well for an aliphatic ketone (entry 3), and an a,b-unsaturated ketone (entry 2) yielded the corresponding secondary alcohols in good yields (75 and 84 %). Similar to the hydrosilylation of an a,b-unsaturated aldehyde with the Cs2CO3/Ph2SiH2 system, the latter reaction led to the selective 1,2-hydrosilylation of the unsaturated ketone (Scheme 1). In addition, it was found that the reaction of two equivalents of acetophenone with only one equivalent of Ph2SiH2 and PhMeSiH2 also led to the complete Si H bond addition at 80 8C in 12 h. Likewise, reaction of PhSiH3 with three equivalents of acetophenone under the same conditions resulted in the selective formation of PhSi(OCHPhMe)3 in good yield. These results indicated that the hydrosilyaltion is an atom-efficient protocol in terms of the utilization of Si H bonds. The initial mechanism for the Cs2CO3-catalyzed hydrosilylation of aldehydes and ketones might be very similar to that proposed for the reduction of amides.[10] It is quite possible that the interaction of Ph2SiH2 with the “naked” CO3 dianion yielded a hypervalent hydrosilicate intermediate, which may transfer the hydride donor to the carbonyl groups. The formation of hypervalent hydrosilicates by reactions of fluoride, alkoxide, and hydride ligands with hydrosilanes has been welldocumented in the literature.[9, 11] The present results further demonstrated that the Cs2CO3-catalyzed hydrosilane transformations are dependent on the hydrosilanes employed. We reasoned that Cs2CO3 combined with other hydrosilanes could be applied to the selective reduction of other unsaturated systems. In conclusion, we have developed a general and practical protocol for the hydrosilylation of aldehydes with the Cs2CO3/ Ph2SiH2 system. Both of the components are commercially available, cost-effective, and non-toxic. The catalytic system is
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Communication very efficient and chemoselective for aldehydes and ketones under solvent-free conditions in the presence of a variety of functional groups. The hydrosilylation of a,b-unsaturated carbonyls led to 1,2-addition, and hydrosilyaltion of 1,4-phthalaldehyde led to the formation of the corresponding poly(silyl ether). Further studies on the Cs2CO3-catalyzed hydrosilane transformations and the mechanism for the reduction process are currently in progress.
[2]
[3]
Experimental Section General procedure for the reduction of aldehydes: A 25 mL oven-dried Schlenk tube containing a stir bar was loaded with 5.0 mol % Cs2CO3 (49 mg, 0.15 mmol). Subsequently, substrate (3 mmol) and Ph2SiH2 (553 mg, 3 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. Longer reaction times were required for the aldehydes f and i (24 h), g (30 h), and h (5 h) (Table 3). For the substrate h, 1.5 mL THF was added. General procedure for the reduction of ketones: A 25 mL ovendried Schlenk tube containing a stir bar was loaded with 5.0 mol % Cs2CO3 (49 mg, 0.15 mmol). Subsequently, the substrate (3 mmol) and Ph2SiH2 (553 mg, 3 mmol) was added. The reaction mixture was stirred at 80 8C for 5 h.
[4] [5]
Acknowledgements This work was supported by the National Natural Science Foundation of China and the 973 Program (Grant No. 2012CB821600). Keywords: alcohols · aldehydes · hydrosilylation · ketones · silyl ethers
cesium
carbonate
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[8] [9]
·
[1] a) B. Marciniec in Hydrosilylation: A Comprehensive Review on Recent Advances (Eds.: B. Marciniec), Springer, Netherlands, 2008; b) A. K. Roy, Adv. Organomet. Chem. 2007, 55, 1 – 59; c) I. Ojima; Z. Li, J. Zhu in The Chemistry of Organic Silicon Compounds, Vol. 2 (Eds.: Z. Rappoport, Y. Apeloig), Wiley, New York, 1998, 2, 1687; d) I. Ojima in The Chemistry of
Chem. Eur. J. 2014, 20, 9259 – 9262
[6] [7]
[10] [11]
Organic Silicon Compounds (Eds.: S. Patai, Z. Rappoport), Wiley, New York, 1989, 25, 1479; e) J. Magano, J. R. Dunetz, Org. Process Res. Dev. 2012, 16, 1156. a) B. Li, J. B. Sortais, C. Darcel, Chem. Commun. 2013, 49, 3691 – 3693; b) C. Cheng, M. Brookhart, Angew. Chem. 2012, 124, 9556; Angew. Chem. Int. Ed. 2012, 51, 9422; c) C. Cheng, M. Brookhart, J. Am. Chem. Soc. 2012, 134, 11304 – 11307; d) Y. Sunada, H. Kawakami, T. Imaoka, Y. Motoyama, H. Nagashima, Angew. Chem. 2009, 121, 9675 – 9678; Angew. Chem. Int. Ed. 2009, 48, 9511 – 9514; e) S. Hanada, T. Ishida, Y. Motoyama, H. Nagashima, J. Org. Chem. 2007, 72, 7551 – 7559; f) K. Matsubara, T. Iura, T. Maki, H. Nagashima, J. Org. Chem. 2002, 67, 4985 – 4988. a) S. Chakraborty, J. A. Krause, H. Guan, Organometallics 2009, 28, 582; b) B. L. Tran, M. Pink, D. J. Mindiola, Organometallics 2009, 28, 2234 – 2243; c) S. Enthaler, K. Junge, M. Beller, Angew. Chem. 2008, 120, 3363; Angew. Chem. Int. Ed. 2008, 47, 3317; d) D. J. C. Constable, P. J. Dunn, J. D. Hayler, G. R. Humphrey, J. L. Leazer, R. J. Linderman, K. Lorenz, J. Manley, B. A. Pearlman, A. Wells, A. Zaks, T. Y. Zhang, Green Chem. 2007, 9, 411 – 420; e) B. H. Lipshutz, B. A. Frieman, Angew. Chem. 2005, 117, 6503; Angew. Chem. Int. Ed. 2005, 44, 6345; f) C. Bolm, J. Legros, J. Le Paih, L. Zani, Chem. Rev. 2004, 104, 6217; g) B. H. Lipshutz, K. Noson, W. Chrisman, A. Lower, J. Am. Chem. Soc. 2003, 125, 8779; h) D. J. Parks, J. M. Blackwell, W. E. Piers, J. Org. Chem. 2000, 65, 3090; i) J. Yun, S. L. Buchwald, J. Am. Chem. Soc. 1999, 121, 5640 – 5644. D. Bzier, G. T. Venkanna, L. C. M. Castro, J. Zheng, T. Roisnel, J. B. Sortais, C. Darcel, Adv. Synth. Catal. 2012, 354, 1879 – 1884. a) T. Inagaki, L. T. Phong, A. Furuta, J. Ito, H. Nishiyama, Chem. Eur. J. 2010, 16, 3090; b) D. Addis, N. Shaikh, S. Zhou, S. Das, K. Junge, M. Beller, Chem. Asian J. 2010, 5, 1687 – 1691; c) A. Furuta, H. Nishiyama, Tetrahedron Lett. 2008, 49, 110; d) N. S. Shaikh, S. Enthaler, K. Junge, M. Beller, Angew. Chem. 2008, 120, 2531 – 2535; Angew. Chem. Int. Ed. 2008, 47, 2497 – 2501; e) H. Nishiyama, A. Furuta, Chem. Commun. 2007, 760 – 762; f) N. S. Shaikh, K. Junge, M. Beller, Org. Lett. 2007, 9, 5429 – 5432. A. M. Tondreau, E. Lobkovsky, P. J. Chirik, Org. Lett. 2008, 10, 2789. J. Yang, T. D. Tilley, Angew. Chem. 2010, 122, 10384; Angew. Chem. Int. Ed. 2010, 49, 10186. For selected references, see: S. Rendler, M. Oestreich, Angew. Chem. 2008, 120, 6086; Angew. Chem. Int. Ed. 2008, 47, 5997, and ref. [3h]. a) R. R. Holmes, Chem. Rev. 1996, 96, 927; b) S. V. Maifeld, D. Lee, Org. Lett. 2005, 7, 4995; c) K. Revunova, G. I. Nikonov, Chem. Eur. J. 2014, 20, 839; d) A. Volkov, F. Tinnis, H. Adolfsson, Org. Lett. 2014, 16, 680. W. Xie, M. Zhao, C. Cui, Organometallics 2013, 32, 7440. C. Chuit, R. J. P. Corriu, C. Reye, J. C. Young, Chem. Rev. 1993, 93, 1371.
Received: May 12, 2014 Published online on July 2, 2014
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