Iron(III) chloride-promoted isomerization of propargyl alcohols to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1080/00397911003611810

Aryl propargyl alcohols bearing a terminal alkynyl moiety can undergo a facile iron(III) chloride-promoted transformation to the corresponding α,β-unsaturated aldehyde in good yield and excellent stereoselectivity.

Full text of DOI:10.1080/00397911003611810

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Iron(III) Chloride–Promoted Isomerization
of Propargyl Alcohols to α,β-Unsaturated
Carbonyl Compounds
Ahmad Samih El Douhaibi a , Zaher M. A. Judeh b , Hedaya Basri b ,
Ziad Moussa a , Mouslim Messali a & Gao Qi b
a Department of Chemistry , Taibah University , Madina, Saudi
Arabia
b School of Chemical and Biomedical Engineering, Nanyang
Technological University , Singapore
Published online: 02 Feb 2011.
To cite this article: Ahmad Samih El Douhaibi , Zaher M. A. Judeh , Hedaya Basri , Ziad Moussa ,
Mouslim Messali & Gao Qi (2011) Iron(III) Chloride–Promoted Isomerization of Propargyl Alcohols to
α,β-Unsaturated Carbonyl Compounds, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 41:4, 533-540, DOI: 10.1080/00397911003611810
To link to this article: http://dx.doi.org/10.1080/00397911003611810
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Synthetic Communications1, 41: 533–540, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003611810
IRON(III) CHLORIDE–PROMOTED ISOMERIZATION OF
PROPARGYL ALCOHOLS TO a,b-UNSATURATED
CARBONYL COMPOUNDS
Ahmad Samih El Douhaibi,1 Zaher M. A. Judeh,2
Hedaya Basri,2 Ziad Moussa,1 Mouslim Messali,1 and Gao Qi2
1Department of Chemistry, Taibah University, Madina, Saudi Arabia
2School of Chemical and Biomedical Engineering, Nanyang Technological
University, Singapore
Abstract Aryl propargyl alcohols bearing a terminal alkynyl moiety can undergo a facile
iron(III) chloride–promoted transformation to the corresponding a,b-unsaturated aldehyde
in good yield and excellent stereoselectivity.
Keywords Iron(III) chloride; isomerization; propargyl alcohols
a,b-Unsaturated carbonyl compounds are important building blocks for synthesis of
complex molecules.[1] Classical methods that are used for their synthesis include
aldol, Claisen–Schmidt,[2] and other condensation reactions. The Meyer–Schuster
reaction,[3] which involves isomerization of propargyl alcohols, is another less fre-
quently used method to prepare these compounds. Since its discovery in 1922, and
because of its atom economy, the Meyer–Schuster rearrangement has received con-
siderable interest among the chemical community. The acid-catalyzed classical form
of this rearrangement requires harsh conditions and suffers from poor selectivity,
although it may be efficient in terms of ease of preparation and access to the starting
materials.[3b] Numerous studies involving reactions catalyzed by transition-metal
complexes such as those of Ru,[4] Rh,[5] Mo,[6] V,[7] Pd,[8] Ir,[9] Ti,[10] and Ag[11] have
been reported. More recently, various gold complexes were used as catalysts in the
synthesis of a,b-unsaturated ketones and other carbonyl derivatives.[12] However,
Received October 18, 2009.
This article is dedicated to Professor John Montgomery.
Address correspondence to Ahmad Samih El Douhaibi, Department of Chemistry, Taibah
University, P.O. Box 30002, Madina, Saudi Arabia. E-mail: aldheiby@hotmail.com
533

534
A. S. EL DOUHAIBI ET AL.
Scheme 1. Iron chloride–promoted isomerization of propargyl alcohols.
most of these reactions require the use of expensive catalysts, some of which require
preparation and special handling. Sugawara et al. reported carbon dioxide–mediated
rearrangement of propargyl alcohols to the corresponding a,b-unsaturated
ketones,[11] and Meng et al. reported the gold-catalyzed synthesis of such compounds
starting from propargyl acetates.[13] Herein, we report on the iron(III) chloride-
promoted rearrangement of propargyl alcohols to the corresponding a,b-
unsaturated aldehydes.
Our preliminary experiments involved treating commercially available propar-
gyl alcohol 1a with a stoichiometric amount of anhydrous FeCl3 in tetrahydrofuran
(THF) at room temperature (Scheme 1). The reaction proceeded smoothly, produc-
ing the corresponding unsaturated aldehyde 2a in 56% yield. However, it took a rela-
tively long time to proceed to completion (Table 1, entry 1). Running the reaction
under reflux conditions slightly increased the yield to 64% while shortening the reac-
tion time to 10 h. Under reflux conditions, dichloromethane gave only 42%, whereas
toluene proved inefficient, producing only 15% yield of the desired product with 70%
recovery of the starting material. Both methanol and dimethylformamide (DMF)
gave similar results, producing 56% yield of compound 2a under reflux conditions.
A control experiment performed in refluxing THF without the use of FeCl3 resulted
in complete recovery of the starting material 1a. To compare the effectiveness of this
methodology to the classical Brønsted acid–catalyzed reaction, alcohol 1m was
treated with catalytic amounts of each of toluene sulfonic acid (TsOH) and triflic
acid (TfOH) in refluxing THF for 24 h to produce compound 2m in 47 and 51%
yields, respectively, with E as the major isomer and 30% recovery of the staring
material (E=Z ¼ 9:1, for both reactions). Using stoichiometric amounts of TsOH
and TfOH boosted the yields to 53 and 56%, respectively, keeping the stereochemical
outcome unchanged.
Our next goal was to investigate the scope of this reaction on different propar-
gyl alcohols prepared by simple Gringard addition of ethynyl magnesium bromide to
aldehyde 3 (Scheme 2, Table 2). p-Methylphenyl and p-ethylphenyl propargyl alco-
hols tolerated the reaction conditions, resulting in the corresponding p-methyl and
Table 1. Isomerization of 1a to 2a under different reaction conditions
Entrya
Solvent
Temp.
Time (h)
Yield (%) (isolated)
1
2
3
4
5
THF
rt=reflux
reflux
reflux
24=10
10
24
56=64
42
15
CH2Cl2
Toluene
Methanol
DMF
reflux
reflux
10
10
56
56

IRON(III) CHLORIDE–PROMOTED ISOMERIZATION
535
Scheme 2. Synthesis of various propargyl alcohols followed iron chloride–promoted isomerization.
p-ethylcinnamyl aldehydes in very good yield and complete stereoselectivity, produc-
ing exclusively the E isomer (Table 2, entries 1 and 3). Likewise, o-methyl phenyl
propargyl alcohol produced o-methyl cinnamyl aldehyde in moderate yield
(Table 2, entry 2). Electron-donating groups such as p-benzyloxy, o-methoxy, and
p-methoxy groups worked also well, producing the corresponding aldehyde in
81%, 72%, and 66% yield, respectively, with excellent stereoselectivity (Table 2,
entries 4–6). The best results were obtained when compound 1h bearing a p-chloro-
phenyl moiety was used, producing 2h in 85% yield and complete stereoselectivity
(Table 2, entry 7). Trisubstituted phenyl propargyl alcohols such as 1i resulted in
decomposition of the starting material, probably because of sterric factors, whereas
alcohols bearing highly electron-withdrawing groups on the phenyl ring resulted in
complete recovery of the starting material (Table 2, entries 8 and 9). It is possible
that the much stronger inductive effect of the CF3- group (compared to that of
1h) is behind the failure of the reaction of compound 1j. The a- and b-naphtyl pro-
pargyl alcohols were also good targets, producing aldehydes 2k and 2l in 67% and
68% yields, respectively, as the only isomers (Table 2, entries 10 and 11). Commer-
cially available compounds 1m gave aldehyde 2m in 82% yield as a single isomer,
whereas commercially available 1n gave aldehyde 2n in 80% yield, with E as the
major stereoisomer (Table 2, enteries 12 and 13), and no product that could result
from the Rupe rearrangement could be observed. While all our experiments focused
on the use of aryl aldehydes as starting materials, all experiments involving the use of
propargyl alcohols derived from simple aliphatic aldehydes or ketones failed, unfor-
tunately. Progress in making such starting materials good targets for this method-
ology is currently underway.
Because all reactions were performed under a dry nitrogen atmosphere (see the
Experimental section), the presence of HCl, which could be obtained by the hydroly-
sis of iron(III) chloride in an wet THF solution (undistilled), can be ruled out. In
other words, HCl could be produced when dissolving an anhydrous (highly hygro-
scopic) amount of iron(III) chloride in an undistilled solution of THF. This amount
of HCl would be enough to promote the classical acid-catalyzed Meyer–Schuster
reaction. Such a possibility could be ruled out in our case, because all reactions were
performed in a dry atmosphere using dry THF, and the iron complex was weighed
directly from a freshly opened bottle under a nitrogen atmosphere. Therefore, we can
confidently disclose that the reaction was driven solely by the presence of iron(III)
chloride as a promoter. All attempts to convert internal alcohols bearing internal
alkynyl moieties to the corresponding a,b-unsaturated ketones failed, and work on
driving such conversion to success is progressing in our laboratories.
Although the mechanism of the Meyer–Schuster rearrangement is well known,
a widely acceptable reaction pathway involves the loss of the hydroxyl group to form

536
Entry
1
A. S. EL DOUHAIBI ET AL.
Table 2. FeCl3-promoted isomerization of different propargyl alcohols
Unsaturated aldehyde
(% yield, E=Z ratio)
Aldehyde
Alcohol (% yield)
2
3
4
5
6
7
(Continued )

IRON(III) CHLORIDE–PROMOTED ISOMERIZATION
537
Table 2. Continued
Unsaturated aldehyde
(% yield, E=Z ratio)
Entry
Aldehyde
Alcohol (% yield)
8
Decomposition
9
0%
10
11
12a
—
—
13a
aAlcohols 1m and 1n are commercially available.
the corresponding carbocation, followed by p bond delocalization to form the allenyl
cation. Attack of the hydroxyl group or water forms the corresponding allenyl alco-
hol, which tautomerizes to form the unsaturated carbonyl product.[14] A plausible

538
A. S. EL DOUHAIBI ET AL.
Scheme 3. Pathway for iron(III)-promoted isomerization of propargyl alcohols.
reaction pathway for the reaction is summarized in Scheme 3. The hydroxyl group
may coordinate to the iron complex, producing another complex. Allenyl cation
may be formed afterward, together with a ferrate complex. Coordination of the
ferrate complex to the allenyl cation, followed by aqueous workup, may produce
the corresponding allenyl alcohol, which will tautomerize to the corresponding
aldehyde.[15]
Isomerization of propargyl alcohols is a powerful reaction for the synthesis of
a,b-unsaturated carbonyl compounds. Such reaction has received considerable
interest in recent years, and numerous organometallic complexes have been used
to catalyze or promote this reaction. We have shown that iron(III) chloride can
be a very effective complex to promote such a reaction, and various propargyl
alcohols have been proved to tolerate this reaction and produce the corresponding
unsaturated aldehyde. Studies to make this reaction applicable to internal alkynyl
alcohols and catalytic in terms of iron chloride are currently underway in our
laboratories.
EXPERIMENTAL
All reactions were run in a completely dry atmosphere under nitrogen.
Anhydrous iron(III) chloride was used, and the complex was weighed from a freshly
opened bottle under a nitrogen atmosphere to avoid contact with moisture.
General Procedure for the Transformation of Aryl Propargyl Alcohols
to the Corresponding Unsaturated Aldehydes
Aryl propargyl alcohol (1.0 mmol, 1.0 equiv) was added to a 10-mL dry THF
solution of iron(III) chloride (1.1 mmol, 1.1 equiv). The reaction was refluxed until
the starting material was consumed (typically 10 h). The reaction was cooled down,
washed with brine, and extracted three times with ethyl acetate, and the organic layer
was dried over MgSO4. The solvent was evaporated, and the crude mixture was pur-
ified via column chromatography on silica gel (hexane=ethyl acetate) to yield pure
aldehyde. All propargyl alcohols and a,b-unsaturated aldehydes reported in this arti-
cle are known compounds, and their full data can be obtained from the reported
literature.

IRON(III) CHLORIDE–PROMOTED ISOMERIZATION
539
ACKNOWLEDGMENTS
We thank Taibah University and Nanyang Technological University for
financial support.
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