Mo-Au combo catalysis for rapid 1,3-rearrangement of propargyl alcohols into α,ss-unsaturated carbonyl compounds

Article abstract of DOI:10.1021/ol800596c

The combination of Mo and cationic Au catalysts dramatically accelerated the rearrangement of diverse propargyl alcohols, which includes a short reaction time, mild conditions, and high product yields. A practical application to the highly challenging primary propargyl alcohols and the N-alkynyl amides is achieved.

Full text of DOI:10.1021/ol800596c

ORGANIC
LETTERS
2008
Vol. 10, No. 9
1867-1870
Mo-Au Combo Catalysis for Rapid
1,3-Rearrangement of Propargyl
Alcohols into r,ꢀ-Unsaturated Carbonyl
Compounds
Masahiro Egi, Yoshiko Yamaguchi, Noboru Fujiwara, and Shuji Akai*
School of Pharmaceutical Sciences, UniVersity of Shizuoka, 52-1, Yada, Suruga-ku,
Shizuoka, Shizuoka 422-8526, Japan
akai@u-shizuoka-ken.ac.jp
Received March 14, 2008
ABSTRACT
The combination of Mo and cationic Au catalysts dramatically accelerated the rearrangement of diverse propargyl alcohols, which includes a
short reaction time, mild conditions, and high product yields. A practical application to the highly challenging primary propargyl alcohols and
the N-alkynyl amides is achieved.
R,ꢀ-Unsaturated carbonyl compounds are versatile interme-
diates for the synthesis of biologically active natural products,
Scheme 1
.
The 1,3-Rearrangement of Propargyl Alcohols (the
pharmaceuticals, agrochemicals, and other useful materials.
One of the main methods to prepare such compounds is the
1,3-rearrangement of propargyl alcohols, which is known as
the Meyer-Schuster rearrangement (Scheme 1).1
Meyer-Schuster Rearrangement)
Especially, due to its high atom economy, extensive efforts
have been devoted to the development of efficient catalysts.
Protic and Lewis acids have been widely utilized; however,
they often showed low selectivities leading to poor yields.1a,c
Such rearrangements were better catalyzed by transition
metals, such as oxovanadium,2 oxomolybdenum,3 and Ti(O-
Bu)4/CuCl,4 which required elevated temperature (>100 °C).
Although nBu4NReO4 was employed to catalyze the reaction
under milder conditions, the relatively high loading of the
catalyst was used and dehydrated compounds were produced
as side products.5 The rearrangements were also mediated
by Ru complexes, which went through a mechanism different
than that of the above-mentioned acid- or transition-metal-
catalyzed reactions;6 however, the Ru-assisted rearrangement
required 50-100 °C and acidic conditions which often led
to poor yields of the products. Very recently, the transforma-
tions mediated by Au7 and Ag8 at room temperature have
been published. Nonetheless, there is yet no adequate or
(1) (a) Meyer, K. H.; Schuster, K. Chem. Ber. 1922, 55, 819. (b) The´ron,
F.; Verny, M.; Vessie`re, R. In The Chemistry of the Carbon-Carbon Triple
Bond; Patai, S., Ed.; John Wiley & Sons: Chichester, 1978; Part 1, Chapter
10. (c) Swaminathan, S.; Narayanan, K. V. Chem. ReV. 1971, 71, 429 and
references cited therein.
(2) (a) Pauling, H.; Andrews, D. A.; Hindley, N. C. HelV. Chim. Acta
1976, 59, 1233. (b) Chabardes, P.; Kuntz, E.; Varagnat, J. Tetrahedron
1977, 1775.
(4) Mercier, C.; Chabardes, P. Pure Appl. Chem. 1994, 66, 1509.
(5) Narasaka, K.; Kusama, H.; Hayashi, Y. Tetrahedron 1992, 48, 2059.
(3) Lorber, C. Y.; Osborn, J. A. Tetrahedron Lett. 1996, 37, 853.
10.1021/ol800596c CCC: $40.75
Published on Web 04/08/2008
2008 American Chemical Society

practical method used for the primary alcohols. On the other
hand, the rearrangement of the corresponding propargyl esters
has also been investigated.1b While Zhang’s group developed
Au-catalyzed reactions under mild conditions, which gave
good yields of the products,9 Nishizawa and co-workers
demonstrated an example of the efficient 1,3-rearrangement
of the primary propargyl esters using Hg(OTf)2.10 However,
the 1,3-rearrangement of the propagyl alcohols is still more
advantageous from the perspective of the atom economy and
synthetic aspects. Herein, we describe a novel and practical
method by the combined use of Mo, Au, and Ag compounds,
which dramatically accelerates the 1,3-rearrangement even
at room temperature and affords a diverse range of R,ꢀ-
unsaturated carbonyl compounds in good to excellent yields.
First, to develop a more effective catalytic system, a highly
challenging primary propargyl alcohol 1a was used as the
substrate. When the rearrangement of 1a was carried out in
CH2Cl2 at room temperature for 1 h, no observable reaction
occurred in the presence of only the Mo, Au, or Ag catalyst
(entries 2-4, Table 1). Moreover, all combinations of two
oxo-metal compounds and gold catalysts, MoO2(acac)2 and
AuCl(PPh3) were determined to be the most effective for
generating 2a. No significant difference in efficiency was
noted among the silver catalysts such as AgOTf, AgClO4,
AgBF4, and AgPF6, all of which produced 2a in NMR yields
between 84 and 92%. The screening of solvents also revealed
that toluene and CH2Cl2 showed comparable effects, although
toluene was somewhat superior (99% as measured by NMR).
Next, the reactivity of diverse propargyl alcohols was tested
using the combination of 1 mol % each of MoO2(acac)2,
AuCl(PPh3), and AgOTf in toluene at room temperature. The
results are depicted in Table 2. Our protocol showed an excellent
generality and provided good to excellent isolated yields of
unsaturated ketones 2a-n from primary, secondary, and tertiary
propargyl alcohols 1a-n. The time required to reach completion
was typically less than 1 h, while 3 h was sufficient for the less
reactive tertiary substrates 1i-m. Furthermore, the oxidation
of a hydroxyl group did not occur at all.3 Even in the case when
the catalyst loading was reduced to 0.5 mol %, excellent yields
were obtained, although a slightly longer reaction time was
needed (entries 2 and 4). Besides, the rearrangement of
secondary propargyl alcohols 1d-g produced ꢀ-monosubsti-
tuted compounds 2d-g with a high E-selectivity (entries 6-9).
Entries 1, 3, 5, 7, 11, and 14 show that the yields are higher
and the times are shorter than the reactions conducted with
Hg(OTf)2,10a AgOMs,8 NaAuCl4·2H2O,7a or Bu4NReO4.5 It is
notable that our method has an advantage over the previous
applications, especially for the primary propargyl alcohol.
The developed method was also useful for the rearrange-
ment of the propargyl alcohols bearing proton 1o-p, oxygen
1q-r, and nitrogen groups 1s at the end of the acetylene
functionality to give the R,ꢀ-unsaturated aldehydes 2o,p, the
phenyl esters 2q,r,11 and the amide 2s, respectively. In these
cases, the choice of a proper solvent brought about high
yields of the products. To the best of our knowledge, this is
the first example of the 1,3-rearrangement of the N-alkynyl
amide, and 2s was produced with complete E-selectivity. The
substrates (1o and 1p) were conveniently prepared by the
reaction of carbonyl compounds with ethynylmagnesium
bromide. Similarly, the preparation of 1q-s was also
effectively achieved by the reaction of the lithiated phe-
noxyacetylene 3a12 or the lithiated N-substituted ynamine
3b13 with aldehydes or ketones (Table 3).
Table 1. Preliminary Survey for the Rearrangement of 1aa
entry MoO2(acac)2 AuCl(PPh3) AgOTf NMR yield (%)b
1
2
3
4
5
6
7
+
+
-
-
+
-
+
+
-
+
-
+
+
-
+
-
-
+
-
+
+
92
0
0
0
4
25
0
a +: with, -: without. b NMR yield using 1,1,2,2-tetrachloroethane as
the internal standard.
catalysts among them afforded no or poor yields of the
desired compound 2a (entries 5-7). However, in stark
contrast, the use of all these catalysts showed a significant
improvement in the rate and the yield of 2a. That is, the
reaction was completed within 1 h to provide 2a in 92%
yield (entry 1). Subsequently, the effect of each metal catalyst
on this reaction was further surveyed. Among a variety of
R,ꢀ-Unsaturated aldehydes, esters, and amides have so
far been synthesized by the aldol condensation,14 Wittig
and Horner-Wadsworth-Emmons reactions,15 and Peter-
son reaction.16 For the aldol reactions, either an acidic or
a basic catalyst was required, and self-condensation often
(6) (a) Suzuki, T.; Tokunaga, M.; Wakatsuki, Y. Tetrahedron Lett. 2002,
43, 7531. (b) Cadierno, V.; Garc´ıa-Garrido, S. E.; Gimeno, J. AdV. Synth.
Catal. 2006, 348, 101.
(11) We found that the rearrangement of the corresponding ethoxyethy-
nyl derivative using AgOTf (1 mol %) alone was completed at room
temperature for 0.5 h; however, that of 1q with AgOTf (2 mol %) alone
gave 2q in less than 5% NMR yields. Thus, the trimetallic catalytic system
was revealed to be highly effective for less activated alkynes. For details,
see Supporting Information.
(7) (a) Georgy, M.; Boucard, V.; Campagne, J.-M. J. Am. Chem. Soc.
2005, 127, 14180. (b) Lopez, S. S.; Engel, D. A.; Dudley, G. B. Synlett
2007, 949. (c) Lee, S. I.; Baek, J. Y.; Sim, S. H.; Chung, Y. K. Synthesis
2007, 2107.
(8) Sugawara, Y.; Yamada, W.; Yoshida, S.; Ikeno, T.; Yamada, T.
J. Am. Chem. Soc. 2007, 129, 12902.
(12) Bru¨ckner, D. Synlett 2000, 1402.
(9) (a) Yu, M.; Zhang, G.; Zhang, L. Org. Lett. 2007, 9, 2147. (b) Yu,
M.; Li, G.; Wang, S.; Zhang, L. AdV. Synth. Catal. 2007, 349, 871. (c)
Wang, S.; Zhang, L. Org. Lett. 2006, 8, 4585.
(13) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera,
E. L. Org. Lett. 2004, 6, 1151.
(14) Heathcock, C. H. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon, Oxford, 1991; Vol. 2, p, 133.
(15) Maryanoff, B. E.; Reitz, A. B. Chem. ReV. 1989, 89, 863.
(16) Ager, D. J. Org. React. 1990, 38, 1.
(10) (a) Imagawa, H.; Asai, Y.; Takano, H.; Hamagaki, H.; Nishizawa,
M. Org. Lett. 2006, 8, 447. (b) Nishizawa, M.; Hirakawa, H.; Nakagawa,
Y.; Yamamoto, H.; Namba, K.; Imagawa, H. Org. Lett. 2007, 9, 5577.
1868
Org. Lett., Vol. 10, No. 9, 2008

Table 2. Mo-Au Combo Catalysis for Rearrangement of 1 into R,ꢀ-Unsaturated Ketones 2
substrate 1
R2
product 2
entry
R1
R3
time (h)
isolated yield (%)
1
1a
1a
1b
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
H
H
H
H
H
H
H
H
H
H
H
H
(CH2)2Ph
(CH2)2Ph
n-C7H15
n-C7H15
Ph
n-C6H13
n-C4H9
n-C6H13
Ph
n-C7H15
Ph
Me
n-C4H9
n-C4H9
n-C6H13
Me
0.5
2
0.5
1
2a
2a
2b
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
93
92
84
87
61
2a
3
4a
5
6
7
8
H
Me
Ph(CH2)2
Ph
Me
Me
Me
Bn
t-C4H9
Ph(CH2)2
1
0.25
0.25
0.5
1
0.5
2.5
1.5
3
97 (E/Z 93:7)
94 (E/Z 93:7)
86 (E/Z 97:3)
88 (E/Z 82:18)
92
90
91
88 (E/Z 75:25)
94 (E/Z 67:33)
88
94
9
H
10
11
12
13
14
15
16
Me
Me
Bn
Me
Me
-(CH2)5-
-(CH2)6-
2
1.5
0.5
1m
1n
2m
2n
a Using 0.5 mol % each of the Mo, Au, and Ag catalysts.
occurred, providing poor yields of the products, while all
the remaining above-mentioned olefination reactions are
accompanied with the discharge of an equimolar amount
of phosphorus or silicon compounds. In addition, few
direct approaches to prepare unsaturated aldehydes have
been reported.17 In contrast, Table 3 presents another
promising method that features the two-step synthesis of
the unsaturated carbonyl compounds (2o-s) from the
carbonyl compounds and the production of smaller
amounts of waste materials.
In conclusion, we have disclosed that the combination of
1 mol % each of MoO2(acac)2, AuCl(PPh3), and AgOTf
provides a highly powerful catalytic system for the rapid 1,3-
rearrangement of propargyl alcohols.18 The reactions proceed
at room temperature within 1 h in most cases to afford a
variety of R,ꢀ-unsaturated carbonyl compounds in excellent
yields. Especially, it is noteworthy that it is applicable to
primary propargyl alcohols and N-alkynyl amides as the
substrate. Although we have not yet conducted detailed
mechanistic studies, we consider a synergetic mechanism in
Table 3. Two-step Preparation of R,ꢀ-Unsaturated Aldehydes,
Esters, and Amide from Carbonyl Compounds
(17) In general, R,ꢀ-unsaturated aldehydes are synthesized by a few reaction
steps; viz., the reaction of carbonyl compounds with (EtO)2POCH2CO2Et or
(EtO)2POCH2CN, followed by reduction (and oxidation). For the recent use
of this approach, see: (a) Hong, B.-C.; Tseng, H.-C.; Chen, S.-H. Tetrahedron
2007, 63, 2840. (b) Maddess, M. L.; Tackett, M. N.; Watanabe, H.; Brennan,
P. E.; Spilling, C. D.; Scott, J. S.; Osborn, D. P.; Ley, S. Angew. Chem.,
Int. Ed. 2007, 46, 591. Alternative condensation reactions using acetaldehyde
equivalents have also been developed; however, they produce wastes and/
or byproducts. (c) Cabezas, J. A.; Oehlschlager, A. C. Tetrahedron Lett.
1995, 36, 5127. (d) Mahata, P. K.; Barun, O.; Ila, H.; Junjappa, H. Synlett
2000, 1345.
(18) Typical Experimental Procedure: MoO2(acac)2 (2.1 mg, 0.0063
mmol), AuCl(PPh3) (3.1 mg, 0.0063 mmol), and AgOTf (1.6 mg, 0.0063
mmol) were added in this order to a solution of 5-phenyl-2-pentyn-1-ol 1a
(0.10 g, 0.63 mmol) in toluene (1.6 mL) at room temperature. The reaction
mixture was stirred for 30 min and then quenched with saturated aqueous
NH4Cl. The organic materials were extracted with Et2O, and the combined
organic layer was washed with brine, dried over MgSO4, and evaporated
in vacuo. The residue was purified by column chromatography (silica gel,
hexanes/Et2O 10:1) to give 5-phenyl-1-penten-3-one 2a (93 mg, 93%) as a
colorless oil.
a Run in CH2Cl2. b Run at 35 °C using MoO2(acac)2 (5 mol %),
AuCl(PPh3) (1 mol %), and AgOTf (1 mol %). c Run in acetone. d Run in
toluene.
Org. Lett., Vol. 10, No. 9, 2008
1869

which a cationic Au catalyst, generated from AuCl(PPh3)
and AgOTf, activates the acetylene bond, while MoO2(acac)2
isomerizes the propargyl alcohol via the rearrangement of
an intermediate molybdate. Further developments of this
method and elucidation of the mechanism are now in
progress in our laboratory.
COE program from the Ministry of Education, Culture,
Sports, Science and Technology (Japan).
Supporting Information Available: Experimental details.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL800596C
Acknowledgment. This work was supported by the global
1870
Org. Lett., Vol. 10, No. 9, 2008