An iron-catalysed hydrosilylation of ketones

Article abstract of DOI:10.1039/b617388h

The combination of Fe(OAc)₂ and multi-nitrogen-based ligands such as N,N,N′,N′-tetramethyethylenediamine, bis-tert-butyl- bipyridine, or bis(oxazolinyl)pyridine can efficiently catalyse hydrosilylation of ketones to give the corresponding alcohols in high yields including asymmetric catalysis. The Royal Society of Chemistry.

Full text of DOI:10.1039/b617388h

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An iron-catalysed hydrosilylation of ketones
Hisao Nishiyama* and Akihiro Furuta
Received (in Cambridge, UK) 28th November 2006, Accepted 7th December 2006
First published as an Advance Article on the web 20th December 2006
DOI: 10.1039/b617388h
The combination of Fe(OAc)2 and multi-nitrogen-based
Table 1 Iron-catalysed hydrosilylation of methyl 4-phenylphenyl
ketone (1)a
ligands such as N,N,N9,N9-tetramethyethylenediamine, bis-
tert-butyl-bipyridine, or bis(oxazolinyl)pyridine can efficiently
catalyse hydrosilylation of ketones to give the corresponding
alcohols in high yields including asymmetric catalysis.
Temp/time
(uC/h)
Yield (%) 2
(recvd 1)
Run
Ligand
Hydrosilane
1
2
3
4
5
6
7
8
a
—
bipy
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
PMHS
(EtO)3SiH
(EtO)2MeSiH
(EtO)2MeSiH
65/24
65/24
65/24
65/20
65/5
65/24
65/34
65/24
6 (94)
90 (6)b
85 (6)b
94 (3)b
90 (2)b
65 (20)
95 (3)b
7 (93)
Use of iron as a catalyst core metal, being inexpensive and
environmentally sound, has long been required in organic
synthesis.1 Recently, some efficient reactions with iron salts or
complexes have been reported in terms of C–C bond formations
such as coupling, cycloaddition or polymerization reactions.
However, examples related to reduction are scarce and limited
for alkene- or nitro-reductions.2 As we have studied hydrosilyla-
tion of ketones with rhodium catalysts, we were greatly interested
in finding a new iron catalyst for that purpose.3,4 In this context, to
the best of our knowledge, Brunner et al. described only one
instance of hydrosilylation of acetophenone with Fe(Cp)(CO)
complex under photo-irradiation.5 Although much attention has
been focused in this decade on copper or titanium catalysts as well
as rhodium ones as the hydosilylation catalysts in both asymmetric
and non-asymmetric reduction of ketones,4,6–9 we have attempted
to find a new iron-catalysed system. Very recently, iron-catalysed
transfer hydrogenative reduction of ketones was reported by Beller
et al. as an environmentally benign process.10 Here, we disclose an
efficient iron-catalysed hydrosilylation of ketones with several
hydrosilanes as a versatile and valuable reduction method.
bipy-tb
tmeda
tmeda
tmeda
pybox-dm
bimpy
Ketone (1) (1.0 mmol), Fe(OAc)2 (5 mol%), ligand: bipy, bipy-tb,
and tmeda (10 mol%), pybox-dm and bimpy (7 mol%), hydrosilane:
(EtO)2MeSiH and (EtO)3SiH (2.0 mmol), PMHS (ca. 3.0 mmol),
b
THF (3.0 mL). Conversion of 1 was ca. 100%. Small amount of
the ketone 1 was recovered by hydrolysis of the corresponding silyl
ether derived from dehydrogenative silylation.
N,N,N9,N9-tetramethylethylenediamine (tmeda) (10 mol%) even-
tually attained 94% yield for 20 h reaction time (run 4).{{ The
addition of the nitrogen-based additives made ferrous acetate
readily soluble in THF by facile coordination to give a reddish
brown solution, and the generated lower-valent iron species might
efficiently act as catalysts. Polymethylhydrosilane (PMHS) also
worked well as a hydrogen donor in the combination of ferrous
acetate (run 5). Next, we adopted terdentate ligands such as
bis(oxazolinyl)pyridine (pybox-dm)11 and bisiminopyridine
(bimpy).12 The case of pybox-dm retarded the reduction somewhat
but gave high yield 94% (run 7), whereas the reaction with bimpy
was very slow (run 8). At room temperature, the catalysis was very
slow. In addition, the active iron catalysts were very sensitive
toward oxygen. The catalysis therefore should be used under an
inert atmosphere. As other iron salts, FeCl2?(H2O)4, Fe(acac)2, and
Fe(acac)3 (5 mol%) were examined with tmeda and (EtO)2MeSiH
at 65 uC but resulted in no reduction or formation of only trace
amounts of 2. Probably, the iron catalysts decomposed in the
failure cases, where by addition of (EtO)2MeSiH the color of the
reaction mixtures turned to pale yellow from dark orange.
We examined several commercially available iron salts such as
ferrous acetate, ferrous chloride, or ferrous and ferric acetylace-
tonato as candidate catalysts. First, we carried out the reduction of
methyl 4-phenylphenyl ketone (1) as a probe substrate using
ferrous acetate, Fe(OAc)2, (5 mol%) and (EtO)2MeSiH (2 equiv.)
in THF (3 mL) solution at 65 uC (Scheme 1). However, ferrous
acetate changed to black precipitates by reaction with the
hydrosilane to promote the reduction only in 6% yield (Table 1,
run 1). Addition of bipyridine (bipy) and bis-tert-butyl-bipyridine
(bipy-tb) (10 mol%) dramatically improved the yield to 90 and 85%
of the alcohol 2, respectively (run 2,3). Furthermore, an addition of
Under the optimized conditions, other aromatic ketones were
reduced to the corresponding secondary alcohols in high yields at
65 uC (Table 2). Ether, ester, and bromide groups can tolerate the
reduction conditions (run 2–5). In the cases of 1-acetonaphthone
(15), a-tetralone (19), tetralone derivative 21, and benzyl ketone 29,
the yields were decreased to 48–67% (run 7, 10–12, 13, 17) to form
the corresponding silyl enol ether, which were recovered as the
starting ketones. Use of pybox-dm slightly improved the yields for
16 and 20 up to 72% and 62%, respectively (run 8 and 11).
Although the benzyl ketone 29 resulted in a lower yield, an
aliphatic ketone 4-phenyl-2-butanone (31) was reduced in a good
Scheme 1
Department of Applied Chemistry, Graduate School of Engineering,
Nagoya University, Chikusa, Nagoya, 464-8603, Japan.
E-mail: hnishi@apchem.nagoya-u.ac.jp; Fax: 81 52 789 3209
760 | Chem. Commun., 2007, 760–762
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Table 2 Iron-catalysed hydrosilylation of other ketonesa
Yield (%)
Run
Ketone
Product
(recvd)
1
2
3
4
5
6
93 (2)
94 (4)b
90 (5)b
91 (5)
92 (3)
94 (2)b
Fig. 1 Multi-nitrogen-based ligands.
pybox-bn and bopa-ip and -tb in place of tmeda (Fig. 2).13 Use of
pybox-bn gave 37% ee of (R)-2 in 93% yield. Interestingly, bopa-ip
and tb increased the ee up to 57% and 79% for (R)-2 [yield: 82%
(65 uC, 24 h), 75% (65 uC, 48 h)], respectively.14 The other ketones
17 and 25 were reduced in 65% ee for (R)-18 (59% yield) and 59%
ee for (R)-26 (39% yield), respectively, at 65 uC for 48 h with
Fe(OAc)2 (5 mol%) and bopa-tb (7 mol%).§
7
8
67 (31)
72 (24)c
9
94 (3)
Other findings are as follows: p-anisaldehyde 35 was smoothly
reduced to the alcohol 36 in 97% yield. Benzalacetone (37) was
reduced to the alcohol 38 in 80% yield accompanied with a small
amount of conjugate reduction (1,4-reduction) product (4%). The
conjugate reduction of ethyl cinnamate (39) was not observed.15"
In conclusion, we have thus found a new catalytic system for
hydrosilylation of ketones with ferrous acetate and nitrogen-based
ligands as a convenient and environmentally benign method. We
now have under way further study on efficient asymmetric
reduction and reduction of other unsaturated substrates.
10
11
12
55 (42)
62 (32)c
50 (35)d
13
67 (28)b
14
91 (5)b
15
16
94 (2)
89 (10)
17
18
48 (51)
88 (5)
19
71 (23)
cis:trans =
73:27
Fig. 2 Chiral ligands and product alcohols.
a
Ketone (1.0 mmol), Fe(OAc)2 (5 mol%), tmeda (10 mol%),
(EtO)2MeSiH (2.0 mmol), THF (3.0 mL), 65 uC, 20y24 h, work up
with hydrochloric acid. Conversion was almost 100%. Some amount
of the starting ketone was recovered by hydrolysis of the
corresponding silyl ether derived from dehydrogenative silylation.
b
Work up with KF (2 mmol), TBAF (tetra-n-butylammonium
c
fluoride (1.0 mL, 1 M in THF), 0 uC, 2 h. In place of tmeda,
pybox-dm (7 mol%) was used. In place of tmeda, bipyridine
(10 mol%) was used.
d
yield of 88% (run 18). 4-tert-Butylcyclohexanone (33) was cis-
selectively reduced (run 19).
We in turn examined asymmetric hydrosilylation of the ketone 1
using chiral tridentate bisoxazoline ligands (7 mol%) such as
Fig. 3 Other substrates and products.
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Organometallics, 2005, 24, 5518; S. C. Bart, E. Lobkovsky, E. Bill and
This research was partially supported by a Grant-in-Aid for
Scientific Research from the Japan Society for the Promotion of
Science (183500049) and The Mitsubishi Foundation.
P. J. Chirik, J. Am. Chem. Soc., 2006, 128, 5302; E. J. Dalda and
J. C. Peteres, Inorg. Chem., 2004, 43, 7474 and references sited therein.
3 Y. Kanazawa, Y. Tsuchiya, K. Kobayashi, T. Shiomi, J. Itoh,
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12, 63; Y. Tsuchiya, Y. Kanazawa, T. Shiomi, K. Kobayashi and
H. Nishiyama, Synlett, 2004, 2493.
Notes and references
4 For review of hydrosilylation: H. Nishiyama, Transition Metals for
Organic Synthesis, ed. M. Beller and C. Bolm, Wiley-VCH, Weinheim,
2004, chapt. 1.4.2, 182; H. Nishiyama and K. Itoh, Catalytic
Asymmetric Synthesis, ed. I. Ojima, Wiley-VCH, Weinheim, 2000,
chapt. 2., 111; O. Riant, N. Mosterai and J. Courmarcel, Synthesis,
2004, 2943.
{ By addition of other bidentate or tridentate nitrogen ligands, 1,4-
dimethylpiperazine (dmp), proton sponge (bdmn), bisimine (bim-meo), and
terpyridine (terpy), the reduction did not proceed or was very slow under
the same condition. Use of Ph2SiH2 resulted in 76% yield of 2, whereas with
Et2MeSiH there was no reduction.
5 H. Brunner and K. Fisch, J. Organomet. Chem., 1991, 412, C11;
H. Brunner and M. Ro¨tzer, J. Organomet. Chem., 1992, 425, 119.
6 For copper catalysts: for examples, B. H. Lipshutz, K. Noson,
W. Chrisman and A. Lower, J. Am. Chem. Soc., 2003, 125, 8779;
B. H. Lipshutz, K. Noson and W. Chrisman, J. Am. Chem. Soc., 2001,
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4045; B. H. Lipshutz and B. A. Frieman, Angew. Chem., Int. Ed., 2005,
44, 6345; J. Yun, D. Kim and H. Yun, Chem. Commun., 2005, 5181;
D.-W. Lee and J. Yun, Tetrahedron Lett., 2004, 45, 5415. For reduction
of hindered ketones, S. D´ıez-Gonza´lez, H. Kauer, F. K. Zinn,
E. D. Stevens and S. P. Nolan, J. Org. Chem., 2005, 70, 4784.
7 For titanium catalysts: X. Verdaguer, U. E. W. Lange, M. T. Reding
and S. L. Buchwald, J. Am. Chem. Soc., 1996, 118, 6784; X. Verdaguer,
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1103 and references sited in ref. 4b.
8 For rhodium catalysts: for examples, B. Tao and G. C. Fu, Angew.
Chem., Int. Ed., 2002, 41, 3892; V. Ce´sar, S. Bellemin-Lapnnaz,
H. Wadepohl and L. H. Gade, Chem.–Eur. J., 2005, 11, 2862.
9 For other metal catalysts: rhenium catalyst, J. J. Kennedy, K. A. Nolin,
H. P. Gunterman and F. D. Toste, J. Am. Chem. Soc., 2003, 125, 4056;
K. A. Nolin, R. W. Ahn and F. D. Toste, J. Am. Chem. Soc., 2005, 127,
12462.Zinc catalyst, H. Mimoun, J. Y. S. Laumer, L. Giannini,
R. Scopelliti and C. Floriani, J. Am. Chem. Soc., 1999, 121, 6158;
V. Bette, A. Mortreux, C. W. Lehmann and J. F. Carpentier, Chem.
Commun., 2003, 332; V. Bette, A. Montreu, S. Savoia and J.-F.
Carpentier, Tetrahedron, 2004, 60, 2837; V. M. Mastranzo, L. Quintero,
C. A. de Parrodi, E. Juaristi and P. J. Walsh, Tetrahedron, 2004, 60,
1781; H. Ushio and K. Mikami, Tetrahedron Lett., 2005, 46, 2903.
10 S. Enthaler, B. Hagemann, G. Erre, K. Junge and M. Beller, Chem.–
Asian J., 2006, 1, 598.
11 H. Nishiyama, M. Kondo, T. Nakamura and K. Itoh, Organometallics,
1991, 10, 501. For a recent review, G. Desimoni, G. Faita and
P. Quadreil, Chem. Rev., 2003, 103, 3119.
12 G. J. P. Britovsek, M. Bruce, V. C. Gibson, B. S. Kimberley,
P. J. Maddox, S. Mastroianni, S. J. McTavish, C. Redshaw, G. A. Solan,
S. Stro¨mberg, A. J. P. White and D. J. Williams, J. Am. Chem. Soc.,
1999, 121, 8728 see also ref. 2.
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J. Org. Chem., 2002, 67, 8566; S.-F. Lu, D.-M. Du, S.-W. Zhang and
J. Xu, Tetrahedron: Asymmetry, 2004, 15, 3433; D.-M. Du, S.-F. Lu,
T. Fang and J. Xu, J. Org. Chem., 2005, 70, 3712.
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R. Kourist, J. Gonza´kez-Sab´ın, R. Liz and F. Rebolledo, Adv. Synth.
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{ Typical procedure: reduction of methyl 4-phenylphenyl ketone (1): ferrous
acetate (8.7 mg, 0.05 mmol) and the ketone (196 mg, 1.0 mmol) were placed
in a flask. Under an argon atmosphere, absolute THF (3.0 mL) and
TMEDA (N,N,N9,N9-tetramethylethylenediamine, 15 mL, 0.10 mmol) were
added at room temperature. The mixture was stirred for 10 min. at 65 uC to
give a reddish brown homogeneous solution. (EtO)2MeSiH (320 mL,
2.0 mmol) was then added by a syringe. The mixture was stirred for 20 h at
65 uC, and the reaction was monitored by TLC examination; hexane : ethyl
acetate = 5 : 1, Rf = 0.40 for the ketone, 0.66 for silyl ether, and 0.14 for
alcohol. At 0 uC, aq. HCl (2N, 2 mL) was added to quench the reaction.
After stirred for 1 h, the mixture was extracted with ethyl acetate (10 mL
x3), and the extract was washed with brine and aq. NaHCO3 and was dried
over Na2SO4. After concentration, the residue was purified by silica-gel
column chromatography to give the desired alcohol (187 mg, 0.94 mmol) in
94% and the ketone (5.9 mg, 0.03 mmol).
§ Several chiral ligands were examined. Spartein and other bidentate
bis(oxazoline) ligands gave low yields. BINAP (10 mol%) gave 54% yield of
racemic 2 under the same reaction condition above described.
For analysis of (R)-2: CHIRALCEL OD (hex/ipa = 95 : 5, 0.8 mL
min21), 17.8 min (S), 19.0 min (R), 79% ee; [a]D23 = +33.8 (c 0.75, CHCl3);
Lit,16 [a]D28 = 243.7 (c 0.75, CHCl3) for S. For (R)-18: CHIRALCEL OD
(hex/ipa = 95 : 5, 0.8 mL min21), 21.9 min (S), 23.7 min (R), 65% ee;
[a]D23 = +31.7 (c 1.0, CHCl3); Lit,17 [a]D28 = +46 (c 1.1, CHCl3) for R. For
(R)-26: CHIRALCEL OD-H (hex/ipa = 97 : 3, 0.8 mL min21), 14.0 min
23
24
(R), 15,4 min (S), 59% ee; [a]D = +20.8 (c 1.0, CHCl3); Lit,16 [a]D
=
235.0 (c 0.88, CHCl3) for S.
" Under the standard conditions of Table 2, PhCHLNPh could be reduced
at 65 uC in 75% yield with Fe(OAc)2 and tmeda. The details will be
reported in the near future. Several catalyst-combinations of Fe(OAc)2 and
nitrogen or oxygen ligands with PMHS have been reported not to give
sufficient yields (,10%) for reduction of imines.15
15 T. Ireland, F. Fontanet and G.-G. Tchao, Tetrahedron Lett., 2004, 45,
4383.
16 N. A. Salvi and S. Chattopadhyay, Tetrahedron, 2001, 57, 2833.
17 P. N. Liu, J. G. Deng, Y. Q. Tu and S. H. Wang, Chem. Commun.,
2004, 2070.
1 C. Bolm, J. Legros, J. L. Paih and L. Zani, Chem. Rev., 2004, 104, 6217.
For iron catalyzed cross coupling reactions, see: A. Fu¨rstner and
R. Martin, Chem. Lett., 2005, 624.
2 S. C. Bart, E. Lobkovsky and P. J. Chirik, J. Am. Chem. Soc., 2004, 126,
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762 | Chem. Commun., 2007, 760–762
This journal is ß The Royal Society of Chemistry 2007