FeCl3-catalyzed reduction of ketones and aldehydes to alkane compounds

Article abstract of DOI:10.1055/s-0028-1087664

Ketones can efficiently be reduced to the corresponding methylene compound using the convenient and inexpensive combination of PMHS and FeCl₃. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087664

2
76
LETTER
FeCl -Catalyzed Reduction of Ketones and Aldehydes to Alkane Compounds
3
R
C
eduction of
K
et
h
ones ristophe Dal Zotto, David Virieux, Jean-Marc Campagne*
Institut Charles Gerhardt Montpellier, ENSCM, 8 Rue de l’Ecole Normale, 34296 Montpellier, France
E-mail: jean-marc.campagne@enscm.fr
Received 18 September 2008
desirable. In this paper, we would like to describe the re-
duction of ketones (aromatic and aliphatic ones) and alde-
hydes under simple conditions in the presence of the
Abstract: Ketones can efficiently be reduced to the corresponding
methylene compound using the convenient and inexpensive combi-
nation of PMHS and FeCl3.
nonexpensive FeCl catalyst (10%) and PMHS reducing
3
Key words: iron, reduction, ketones
agent, both of them being simple, easy to handle, and in-
expensive reagents.
The use of iron-catalyzed reactions have recently emerged
as efficient alternatives to promote reactions, traditionally
Table 1 Reduction of Acetonaphthone (4) with PMHS
O
1
,2
carried out in the presence of noble metals. These devel-
opments have been driven up by the abundance, the low
toxicity, and the low price characteristics of the iron salts.
+
PMHS
3
The iron-catalyzed hydrosilylation of ketones (alde-
4
5
hydes) 1 for the synthesis of secondary (primary) alco-
Entry Conditions
GC yield (iso-
lated yield, %)
hols, have particularly been described, including
4
,5
asymmetric versions (Scheme 1).
1
NaAuCl ·2H O (5 mol%), DCE, MW, 1 h, 92
4 2
1
20 °C
[
Si]
O
O
H-[Si]
this paper
R1
R2
2
3
FeCl (10 mol%), DCE, MW, 1 h, 120 °C 91
3
R1
R2
R1
R2
Fe catalyst
1
2
3
FeCl
3
·6H
2
O (10 mol%), DCE, MW, 1 h,
100 (98)
1
20 °C
ref. 3,4 hydrolysis
4
5
6
FeCl ·6H O (10 mol%), toluene, MW, 1 h, 48
3
2
1
20 °C
OH
*
FeCl ·6H O (10 mol%), MeOH, MW, 1 h, NR
R1
R2
3
2
1
20 °C
Scheme 1 Iron-catalyzed ketone hydrosilylation and defunctionali-
FeCl ·6H O (10 mol%), DCE, reflux, 8 h, 34
zation
3
2
9
0 °C
In the context of the development of iron-catalyzed reac-
6
tions, we planned to use the Lewis acid character of the Thus, the reduction of the commercially available aceto-
iron salts to promote a further reduction of the O-silylated naphthone (4) with PMHS was first set up as a model
intermediate 2 in order to obtain the methylene derivative reaction (Table 1). Gratifyingly, under microwave irradi-
3
(Scheme 1). The defunctionalization of ketones to me- ation in DCE at 120 °C, very good conversions to the for-
thylenes is a key reaction in the organic chemist tool box mation of the reduced product 5 could be observed in the
and many methodologies have been described in the liter- presence of NaAuCl ·2H O and FeCl (Table 1, entries 1
and 2). Best conditions were, however, found to be in the
reactions are probably the most famous, but more recently presence of FeCl ·6H O (10% mol) where compound 5
4
2
3
7
8
ature. The textbook Clemensen and Wolff–Kischner
3
2
milder reactions have been developed. Among these is the was isolated in 98% yield (Table 1, entry 3). Testing
use of catalytic amounts, but expensive, B(C F ) Lewis methanol and toluene as alternative solvents led to more
6
5 3
acid in the presence of polymethylhydrosiloxane deceptive results (Table 1, entries 4 and 5). Finally, under
PMHS), a byproduct of the silicone industry which is in- traditional thermal conditions, in refluxing DCE at 90 °C,
expensive, easy to handle, and environmentally friendly a lower yield was observed (Table 1, entry 6).
(
9
reducing agent. The development of catalytic, simple,
and inexpensive reaction conditions is thus still highly
We then examined the PMHS reduction with a set of aro-
matic ketones in the presence of FeCl ·6H O (10% mol)
3
2
under microwave irradiation (Table 2). 1-Tetralone (6),
benzophenone (10), substituted acetophenone 8, and pro-
piophenone (12) have been reduced in good yields (81–
98%). Extension to nonaromatic ketones was next inves-
SYNLETT 2009, No. 2, pp 0276–0278
Advanced online publication: 15.01.2009
DOI: 10.1055/s-0028-1087664; Art ID: G28508ST
x
x.
x
x.
2
0
0
8
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Reduction of Ketones
277
Table 2 The PMHS Reduction of Aromatic Ketones in the Presence
Table 3 The PMHS Reduction of Nonaromatic Ketones in the Pres-
of FeCl ·6H O under Microwave Irradiation
ence of FeCl ·6H O under Microwave Irradiation
3
2
3
2
Entry
Ketone
Product
Yield (%)
98
Entry Ketone
Product
Yield
%)
(
O
O
1
1
83
1
1
4
5
7
4
6
5
7
O
2
3
51
2
3
4
91
81
94
O
16
O
O
64
MeO
MeO
9
8
17
16
O
O
4
5
63
61
O
O
1
1
8
9
13
20
1
1
3
1
0
2
5
82
1
1
O
O
O
O
O
O
O
O
2
8
29
30
tigated and results are summarized in Table 3. These sub-
strates are efficiently reduced in slightly lower yields.
Figure 1
Aromatic and aliphatic aldehydes are also suitable sub-
strates in these reactions as illustrated in Table 4. Limita-
tions of the methodology have been reached with esters,
anhydrides and b-keto esters 28–30 where no reaction or
extensive decomposition could be observed (Figure 1).
In conclusion, we have developed a simple and conve-
nient method for the reduction of ketones and aldehydes
(
aromatic and aliphatic ones) in the presence of PMHS
and FeCl (10 mol%) as catalyst.
3
Table 4 The PMHS Reduction of Aromatic and Aliphatic Aldehydes in the Presence of FeCl ·6H O under Microwave Irradiation
3
2
Entry
Aldehyde
Product
Yield (%)
O
H
1
73
2
2
21
CHO
2
3
74
78
2
3
4
13
25
CHO
2
CHO
4
62
Cl
Cl
26
27
Synlett 2009, No. 2, 276–278 © Thieme Stuttgart · New York

2
78
C. Dal Zotto et al.
LETTER
Experimental Procedure
(3) (a) Mimoun, H. J. Org. Chem. 1999, 64, 2582. (b) Riant,
O.; Mostefaï, N.; Courmacel, J. Synthesis 2004, 2943.
c) Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J.-X.;
To a solution of ketone or aldehyde (0.15 mmol) in DCE (4 mL) was
added FeCl ·6H O (0.015 mmol, 97% ACS reagent, finely ground)
(
3
2
Yamamoto, Y. J. Org. Chem. 2000, 65, 6179. (d) Mimoun,
H.; De Saint Laumer, J.-Y.; Giannini, L.; Scopelliti, R.;
Floriani, C. J. Am. Chem. Soc. 1999, 121, 6158.
and PMHS (0.4 mmol, Fluka, viscosity 15–40 mPa·s). The round-
bottom flask equipped with a magnetic stirring bar and sealed with
a septum. The flask was then placed in a microwave reactor [CEM
microwaves Discover (300W)] at 120 °C for 1 h. The gelatinous
mixture was next filtered under a plug of Celite and concentrated
under gentle vacuum. The crude material was then loaded on to a
(
4) (a) Brunner, H.; Fisch, K. J. Organomet. Chem. 1991, 412,
1
4
2
1. (b) Furuta, A.; Nishiyama, H. Tetrahedron Lett. 2008,
9, 110. (c) Furuta, A.; Nishiyama, H. Chem. Commun.
007, 760. (d) Bart, S. C.; Lobkovsky, E.; Chirik, P. J. Org.
SiO column and chromatographed with heptane to give the reduced
2
Lett. 2008, 10, 2789. (e) Tondreau, A. M.; Lobkovsky, E.;
product.
Chirik, P. J. J. Am. Chem. Soc. 2004, 126, 13794.
(
5
f) Shaikh, N. S.; Junge, K.; Beller, M. Org. Lett. 2007, 9,
429.
Acknowledgment
(
(
5) (a) Shaikh, N. S.; Enthaler, S.; Junge, K.; Beller, M. Angew.
Chem. Int. Ed. 2008, 47, 2497. (b) Langlotz, B. K.;
Wadepohl, H.; Gade, L. H. Angew. Chem. Int. Ed. 2008, 47,
4670.
We are grateful to the CNRS for financial support (ATIPE jeune
équipe) and the Institut de Chimie des Substances Naturelles for a
grant (CDZ).
6) (a) Michaux, J.; Terrasson, V.; Marque, S.; Wehbe, J.; Prim,
D.; Campagne, J. M. Eur. J. Org. Chem. 2007, 2601.
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