Development of the first iron chloride-catalyzed hydration of terminal alkynes

Article abstract of DOI:10.1002/adsc.200800666

The development of the first iron-catalyzed hydration of terminal alkynes is described using a catalytic amount of iron(III) chloride (10 mol%). The reaction leads selectively to the corresponding methyl ketone derivatives.

Full text of DOI:10.1002/adsc.200800666

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DOI: 10.1002/adsc.200800666
Development of the First Iron Chloride-Catalyzed Hydration of
Terminal Alkynes
Xiao-Feng Wu,a David Bezier,a and Christophe Darcela,*
a
Universitꢀ de Rennes I, UMR CNRS 6226, “Sciences Chimiques de Rennes”, team “Catalyse et Organomꢀtalliques”,
Campus de Beaulieu, 243 Av. du Gꢀnꢀral Leclerc, 35042 Rennes Cedex, France
Fax : (+33)-2-2323-6939; e-mail: christophe.darcel@univ-rennes1.fr
Received: October 29, 2008; Revised: December 30, 2008; Published online: January 27, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800666.
Abstract: The development of the first iron-cata-
lyzed hydration of terminal alkynes is described
using a catalytic amount of ironACTHNUTRGNEUNG(III) chloride (10
mol%). The reaction leads selectively to the corre-
sponding methyl ketone derivatives.
widely developed in the past decades, it is really sur-
prising that, until lately, iron was underrepresented in
the field of homogeneous catalysis compared to the
other transition metals. However, the last few years
have seen a rise of the use of iron as a catalyst and
very efficient processes that are now able to compete
with other metal-catalyzed ones have emerged in the
carbon-carbon bond formation, hydrosilylation, oxida-
tion, even hydrogenation areas.[10]
Keywords: alkynes; homogeneous catalysis; hydra-
tion; iron; methyl ketones
In the course of our investigations on the use of
iron compounds as environmentally friendly catalysts,
we found that alkynes in the presence of a catalytic
The use of water as an inexpensive and benign re- amount of an ironACTHNUTRGNEUG(N III) salt can be hydrated to yield
agent in organic synthesis is an important topic, and the corresponding methyl ketones in the presence of
the hydration of alkynes is a typical example of such water. To the best of our knowledge, only two exam-
use. It is one of the most useful methods for the func- ples of iron-mediated hydration have been reported
tionalization of unactivated alkynes, and has found in the literature and both involved stoichiometric
numerous synthetic uses.[1] The addition of water to amounts.[11] However, this reaction was selective only
alkynes with Hg(II) salts to form carbonyl compounds in the case of the hydration of phenylacetylene. With
was first reported by Berthelot in 1862, and since the other alkynes described, the authors observed be-
then, it is a classical textbook reaction.[2,3] However, tween 10 and 53% of a by-product, the 2-chloroalk-1-
the use of mercury salts is a dramatic barrier for ap- ene derivative, which was obtained via the formation
plications in both academic and industrial work. The of a 2-chlorovinyl-iron intermediate.[11b] Furthermore,
Markovnikov hydration of alkynes is also catalyzed one pioneering iron nucleophilic addition of methanol
by numerous complexes of transition metals such as to alkynes was reported by Bassetti, but proceeded
Au,[4] Ru,[5] Rh,[6] Pt,[7] and other metals.[8] The addi- only with poor yields.[12]
tion of water across terminal alkynes promoted by
Herein, we report a convenient FeCl3-catalyzed
these catalysts exclusively follows Markovnikovꢁs rule Markovnikov hydration of terminal alkynes to yield
to give methyl ketones. More recently, anti-Markovni- to ketones with good regioselectivities.
kov hydrations of terminal alkynes to lead selectively
to the corresponding aldehydes were also described hydration of alkynes, a 1,2-dichloroethane (DCE) so-
using ruthenium complexes.[9]
lution of phenylacetylene 1a (1 mmol) was allowed to
As an initial attempt to improve this iron-catalyzed
On the other hand, many catalysts are derived from react with water (3 equiv.) at 758C in the presence of
heavy or rare metals and their toxicity and prohibitive a catalytic amount of anhydrous FeCl3 (10 mol%)
prices can constitute severe drawbacks for large-scale under a small pressure of air (Scheme 1).
applications. In contrast, iron is one of the most abun-
After stirring for a period of 67 h, the reaction af-
dant metals on the earth, and consequently one of the forded the acetophenone 2 in a GC-yield of 96% with
most inexpensive and environmentally friendly ones. a small amount of a-chlorostyrene 3 as a by-product
Although the coordination chemistry of iron has been (4%). We carried out then extensive investigations to
Adv. Synth. Catal. 2009, 351, 367 – 370
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367

Xiao-Feng Wu et al.
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Table 2. Screening of solvents for the hydration of phenyl-
AHCTUNGTRENNUNG
acetylene.[a]
Entry Solvent
Time (h) Conv. [%][b] GC yield [%][b]
2
3
Scheme 1.
1
2
3
4
5
6
7
8
DCE
67
67
67
67
67
67
67
67
67
67
67
100
0
0
54
36
0
43
0
37
10
14
0
96
–
–
4
2
0
13
0
11
2
14
0
4
–
–
0
0
0
8
0
5
0
1
0
CHCl3
Cl3CCH3
CH3CN
THF
i-PrOH
Toluene
NMP
AcOEt
Dioxane
CH3NO2
Table 1. Screening of iron salts for the catalyzed hydration
of phenylacetylene.[a]
Entry Iron salt
Solvent Time [h] GC yield [%][b]
2
3
1
2
3
4
5
6
FeCl2
FeBr2
DCE
DCE
DCE
DCE
48
40
6
40
60
67
–
20
–
24
61
96
–
0
–
0
1
4
9
10
11
12
Fe
Fe
ACHTUNGTRENNUNG
A
AHCTUNGRTENN(GUN MeO)2CO 67
FeCl3·6 H2O DCE
FeCl3 DCE
[a]
Reaction conditions: phenylacetylene 1a (1 mmol), sol-
vent (2 mL), FeCl3 (10 mol%), water (3 equiv.) under air.
Calculated from GC response factors relative to tetrade-
cane internal standard.
[a]
Reaction conditions: phenylacetylene 1a (1 mmol), sol-
vent (2 mL), iron salt (10 mol%), water (3 equiv.) under
air.
Calculated from GC response factors relative to tetrade-
cane internal standard.
[b]
[b]
To get more information on the optimal catalyst
conditions, we carried out also intensive investigations
to define the best solvent for this transformation.
define the best reaction conditions, and Table 1 lists Twelve different solvents were tested at 758C for 67 h
representative data obtained for the hydration of phe- using 10 mol% of dry FeCl3 as catalyst in the presence
nylacetylene with various commercially available iron of 3 equivalents of water (Table 2).
salts. We studied the catalytic activity of various
iron(II) and iron(III) salts in the course of hydrating far better solvent than the other classic organic ones
phenylacetylene 1a with 3 equivalents of water in tested. Acetophenone 2 was obtained in 96% GC
DCE as solvent at 758C. yield and only 4% of a-chlorostyrene 3 as by-product
First of all, iron(II) species such as FeCl2 or was detected. In other classic solvents, the conver-
Fe(OAc)2 were not able to promote any hydration re- sions were moderate and, surprisingly, no reaction oc-
1,2-Dichloroethane (DCE) has been found to be a
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
action in our standard conditions and phenylacetylene curred in other chlorinated solvents (CHCl3,
1a remained unchanged after several days at 758C. CCl3CH3), isopropanyl alcohol, or N-methylpyrroli-
Conversely, on employing anhydrous FeCl3, a com- done (NMP). More remarkably, even if the conver-
mercially available precursor, as the catalyst, excellent sions were moderate in all the cases except for DCE,
conversion was obtained (96%) and the reaction oper- the GC yield of the desired acetophenone 2 was dra-
ated with perfect regioselectivity. Interestingly, the matically lowered (1–16%)! These results clearly indi-
conversion was moderate (61%) when FeCl3·6H2O cated that if the hydration reaction did not occur, a
was used, which shows the far better Lewis acid abili- degradation process could take place to convert phe-
ty of FeCl3. As no superior catalyst could be identi- nylacetylene 1a into a non-identified oligomer.
fied, we decided to focus on FeCl3. It must be pointed
out that FeCl3 must be perfectly dry and be kept chloroalk-1-ene are formed simultaneously in a 1/1
under argon atmosphere to avoid its moisturization. ratio at the beginning of the reaction and after a max-
From a kinetic point of view, methyl ketone and 2-
More interestingly, the presence of air is crucial for imum concentration of the 2-chloroalk-1-ene has
the progress of the reaction. If the reaction is con- been reached, the latter is then converted into aceto-
ducted under argon at 758C for 60 h, only 10% con- phenone. This observation was already made by
version was observed and a mixture 1/1 of acetophe- Postel in the stoichiometric version of this hydration
none 2 and a-chlorostyrene 3 was obtained. On the reaction.[11a] It must be pointed that this hydration of
contrary, when the reaction was performed under air, a-chlorostyrene 3 is also a catalytic reaction. Indeed,
the conversion was complete, and acetophenone 2 when the a-chlorostyrene 3 is treated using 10 mol%
was the major product. If the same reaction was per- of dry FeCl3 under the reaction conditions (3 equiv. of
formed under a small pressure of air, without water water in DCE at 758C for 4 days, under air) aceto-
as reagent, no ketone was detected and only non- phenone 2 was obtained quantitatively as single prod-
identified oligomers were observed.
uct of the reaction. Furthermore, without the iron cat-
368
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Adv. Synth. Catal. 2009, 351, 367 – 370

Development of the First Iron Chloride-Catalyzed Hydration of Terminal Alkynes
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than that with phenylacetylene itself (30 and 60 h, re-
spectively, compared to 67 h). These results seem to
indicate that the presence of an electron-donating
group in the para position of the aryl moiety acceler-
ates the reaction. In contrast, when an electron-draw-
ing substituent such as trifluoromethyl is placed in the
para position of the aryl moiety, the reaction rate de-
Scheme 2.
alyst under air, less than 5% of acetophenone 2 was creases (entry 4). This reaction tolerates the presence
detected, in the same reaction conditions. of an alkenyl moiety in the molecule which permits us
Using dry FeCl3 salt as catalyst, the scope of the to obtain the a,b-unsaturated methyl ketone in mod-
Markovnikov hydration of various 1-alkynes 1 was ex- erate yield (entry 8). It should be noted that, in this
amined in DCE at 758C. (Scheme 2 and Table 3).
example, the reaction was carried out at 408C to
Reactions using 10 mol% of FeCl3 gave the desired avoid degradation of the a,b-unsaturated ketone. In
ketones in excellent regioselectivities and good yields. contrast, the presence of a functional coordinating
Linear terminal alkynes furnished the corresponding group such as hydroxy seems to inhibit the activity,
methyl ketones with complete regioselectivity and because it may act as a competing ligand for the iron
good yields (entries 6 and 7).
centre (entries 9 and 10). This result is in agreement
Interestingly, the hydration reaction is faster with with the one obtained with alcohol as solvents.
alkyl-substituted alkynes than aryl-substituted ones (Table 2, entry 4) Furthermore, when the propargylic
(compare entries 6 and 7 vs. 1). On the other hand, in systems bear a carbonyl group such as an acetate, no
the aryl series, when the phenylacetylene is substitut- reaction occurs, even after one week at 758C. It
ed by a methyl (entry 2) or a tert-butyl (entry 3) seems to prove that the carbonyl moiety can also co-
group in the para-position, the reaction goes faster ordinate the iron centre and inhibit the hydration re-
action. Furthermore, when using internal alkynes
under these conditions, no reaction occurs.
Table 3. Regioselective hydration of alkynes with FeCl3 as
At this stage of the project, even if the origin of the
catalytic activity remains unknown and if any mecha-
nistic discussion is speculative, we might pointed out
crucial role of both 1,2-dichloroethane and air in the
iron catalyzed process as 1,2-dichloroethane was al-
ready known to be a mild oxidant where it plays the
role of a reoxidant of the metal.[13,14] Additionally, in
some palladium-catalyzed homo-coupling reactions,
air was also use as re-oxidizing agent.[15]
Furthermore, we believe that the catalyzed hydra-
tion proceeds via an iron-Lewis acid activation of the
triple bond as Miranda already demonstrated by ab
initio calculations.[11b] One experimental result sup-
ported this opinion: when the reaction of oct-1-yne
was performed in the presence of 3 equivalents of
concentrated hydrochloric acid, no reaction occurs in
the absence of the iron catalyst after 72 h at 758C
under air. In contrast, when the same reaction was
performed in the presence of 10 mol% of FeCl3, a hy-
drochloration reaction took place leading to a mixture
of 2-chlorooct-1-ene 5 (major product) and (E)- and
(Z)-1-chlorooct-1-ene 6 (GC yield: 72%, 5/6=78/22).
Octan-2-one was detected after a prolonged reaction
time. (Scheme 3).
catalyst.[a]
Entry Alkyne
Time Conv. Ratio Yield of
[h]
[%][b] 4/5[b]
4 [%][c]
À ꢀ
1
2
Ph C CH
67
30
100
100
96/4
80
100/0 99
100/0 77
100/0 57
3
4
5
60
88
65
100
100
100
100/0 94
100/0 70
98/2
À ꢀ
6
7
n-C4H9 C H
46
48
40[d]
100
100
À ꢀ
n-C6H13 C CH
87
8
100
95/5
56
ꢀ
9
10
HO
HO
G
0
0
–
–
–
–
[a]
Reaction conditions: alkyne (1 mmol), DCE (2 mL),
FeCl3 (10 mol%), water (3 equiv.) under air.
Calculated from GC response factors relative to tetrade-
cane internal standard.
[b]
[c]
[d]
Isolated yields.
The reaction was performed at 408C.
Scheme 3.
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369

Xiao-Feng Wu et al.
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In summary, the above results show that the FeCl3-
catalyzed hydration of terminal alkynes leads to the
formation of methyl ketone derivatives with good
yields and regioselectivities. This work represents the
first report of the catalytic hydration of alkynes using
iron salts as the catalyst. This addition of water to a
ꢀ
C C bond is a clean reaction: in general, the reaction
mixture simply consists of solvent, water, and the
product methyl ketone, regardless of the conversion,
with only trace, if any, of 2-chloroalkene by-products.
At this stage, even if the origin of the catalytic activity
remains unknown, the role of 1,2-dichloroethane and
air seems crucial. Further investigations into the
mechanism of this reaction are now in progress.
Experimental Section
Representative Procedure
To a solution of commercially available FeCl3 (16.2 mg,
10 mol%) in 1,2-dichloroethane (2 mL) were added succes-
sively 1-phenylacetylene (0.13 mL, 1.0 mmol) and water
(54 mg, 3 mmol). The mixture was heated under a small
pressure of air for 67 h at 758C and the reaction progress
was monitored by GC. After cooling to room temperature,
the solvent was removed under vacuum and the residue was
filtered through a plug of silica, and concentrated under re-
duced pressure to furnish acetophenone as a colorless oil;
yield: 96 mg (80%). The small pressure of air is maintained
inside the Schlenk tube using a connecting U-shaped tube
containing oil with two different levels, using the principle
of communicating vessels (see Supporting Information).
[11] a) J. P. Damiano, M. Postel, J. Organomet. Chem. 1996,
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Chaboche, F. Mahuteau-Betzer, M. Ahr, Org Lett.
2005, 7, 1943–1946.
Acknowledgements
We thank the French Research Ministry and the CNRS for
support of our research.
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Adv. Synth. Catal. 2009, 351, 367 – 370