1,2,3-triazole bound Au(I) (TA-Au) as chemoselective catalysts in promoting asymmetric synthesis of substituted allenes

Article abstract of DOI:10.1021/ol200714h

The triazole-Au (TA-Au) complexes were identified as effective chemoselective catalysts in promoting propargyl ester/ether 3,3-rearrangements. The highly reactive allenes, which could not be isolated by simple cationic gold catalysts, were prepared in exc

Full text of DOI:10.1021/ol200714h

ORGANIC
LETTERS
2011
Vol. 13, No. 10
2618–2621
1,2,3-Triazole Bound Au(I) (TA-Au) as
Chemoselective Catalysts in Promoting
Asymmetric Synthesis of Substituted
Allenes
Dawei Wang,† Lekh Nath S. Gautam,† Cynthia Bollinger,† Aleksandra Harris,†
Minyong Li,‡ and Xiaodong Shi*,†
C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown,
West Virginia 26506, United States, and Department of Medicinal Chemistry, School of
Pharmacy, Shandong University, Ji’nan, Shandong, 250012, PR China
Xiaodong.Shi@mail.wvu.edu
Received March 18, 2011
ABSTRACT
The triazole-Au (TA-Au) complexes were identified as effective chemoselective catalysts in promoting propargyl ester/ether 3,3-rearrangements.
The highly reactive allenes, which could not be isolated by simple cationic gold catalysts, were prepared in excellent yields (1% catalyst loading,
>90% yields). Unlike other reported Au catalysts, the TA-Au provided effective chirality transfer without racemization over a long period of time,
giving enantioenriched allenes with excellent stereoselectivity (1% catalyst loading, up to 99% ee).
One aspiration for synthetic chemists is to develop new
methods that account for effective chemo-, regio-, and
stereoselective transformations.1 The Au catalyzed pro-
pargyl ester rearrangement was considered as one of the
most important reaction modes in the recent surge of
homogeneous gold catalysis.2,3 With support from recent
mechanistic studies, it became clear that this transforma-
tion occurred through a 3,3-rearrangement.4 Moreover,
† West Virginia University.
‡ Shandong University.
(1) For recent reviews, see: (a) Doyle, M. P.; Duffy, R.; Ratnikov, M.;
(3) For selected recent publications, see: (a) Boogaerts, I. I. F.;
Nolan, S. P. J. Am. Chem. Soc. 2010, 132, 8858–8859. (b) Boogaerts,
I. I. F.; Fortman, G. C.; Furst, M. R. L.; Cazin, C. S. J.; Nolan, S. P.
Angew. Chem., Int. Ed. 2010, 49, 8674–8679. (c) Zhang, Z.; Lee, S. D.;
Widenhoefer, R. A. J. Am. Chem. Soc. 2009, 131, 5372–5373. (d) Brown,
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2009, 109, 3227–3274. (d) Dıez-Gonzalez, S.; Nolan, S. P. Acc. Chem.
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Res. 2008, 41, 349–358. (e) Deutsch, C.; Krause, N.; Lipshutz, B. H.
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(2) For selected recent reviews on homogeneous Au catalysis, see: (a)
Hashmi, A. S. K.; Rudolph, M. Chem. Soc. Rev. 2008, 37, 1766–1775. (b)
Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351–
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Chem. Soc. 2005, 127, 16804–16805. (b) Zhang, L.; Wang, S. J. Am.
Chem. Soc. 2006, 128, 1442–1443. (c) Buzas, A.; Istrate, F.; Gagosz, F.
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r
10.1021/ol200714h
Published on Web 04/19/2011
2011 American Chemical Society

both experimental and theoretical investigations con-
firmed the reversibility between allene and propargyl ester
(Scheme 1), which led to a considerable challenge: how to
achieve chemoselective activation of alkyne over allene.
stereoselectivity due to the rapid racemization on the pro-
pargyl stereogenic center (Scheme 2B; complete racemization
at the propargyl position occurred in 2 min). Therefore,
effective new catalytic systems that can achieve selective
alkyne activation over allene are highly desirable. Herein,
we report the triazole coordinated PPh3Auþ complexes as
chemoselective catalysts to achieve good selectivity in activat-
ing alkyne over allene, which allowed the effective synthesis
of highly reactive allene esters in excellent yields (1% loading,
up to 95% yields). In addition, through chirality transfer,
asymmetric synthesis of substituted allenes was achieved
using these simply modified triazole Au(I) catalysts with
excellent stereoselectivity (up to 99% ee).
Scheme 1. A Challenge in Cationic Au Catalysis: How to
Achieve Chemoselective Activation of Alkyne over Allene?
Our interest in developing 1,2,3-triazoles8 as new ligands
to adjust transition metal reactivity9 has led to the recent
discovery of 1,2,3-triazole-Au (TA-Au) complexes 4.10
These complexes showed significantly improved thermal
and substrate stability in addition to good reactivity
toward alkyne.11 One particularly interesting result was
the TA-Au catalyzed synthesis of kinetically favored E-R-
haloenones, which suggested that the TA-Au catalysts did
not interrupt the allene reactivity.12 Encouraged by this
result, we decided to investigate whether the triazole-Au
complexes could be applied as effective chemoselective
catalysts for propargyl ester 3,3-rearrangement. The reac-
tions of 1a were set up with TA-Au as the catalysts. The
results are shown in Scheme 3.
According to the literature, the current strategy for
applications of gold catalyzed 3,3-rearrangement was the
introduction of proper reaction partners to trap the Au-
activated allene intermediates. The indene synthesis re-
ported by Nolan and co-workers5 along with the cyclo-
propanyl propargyl ester rearrangement6 reported by
Toste and co-workers7 are two examples that highlight
the power of this transformation in complex molecule
synthesis (Scheme 2).
Scheme 2. Trapping the Allene by Proper Synthetic Partners
Scheme 3. Proposed SN20 Addition Mechanism by Nolan
However, the lack of chemoselectivity by cationic Au
catalysts generated significant limitations for this transfor-
mation: (a) although functional allenes were important
building blocks in organic synthesis, the Au catalyzed 3,3-
rearrangement was not considered as a practical approach
for allene synthesis due to the good reactivity of the Au
activated allene toward many other groups (even a simple
benzene ring, Scheme 2A); (b) the rapid equilibrium between
alkyne and allene under the reaction conditions caused poor
As shown in Scheme 3, both 4a and 4b catalysts indi-
cated good reactivity toward alkyne activation, promoting
the 3,3-rearrangement with high efficiency (1% loading).
Impressively, excellent chemoselectivity was achieved, where
no further reactions proceeded, giving the desired allene
(8) (a) Sengupta, S.; Duan, H.; Lu, W.; Petersen, J. L.; Shi, X. Org.
Lett. 2008, 10, 1493–1496. (b) Chen, Y.; Liu, Y.; Petersen, J. L.; Shi, X.
Chem. Commun. 2008, 3254–3256. (c) Liu, Y.; Yan, W.; Chen, Y.;
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Yan, W.; Sengupta, S.; Shi, X. Bioorg. Med. Chem. Lett. 2009, 19, 3899–
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2010, 12, 3308–3311.
(9) (a) Duan, H.; Sengupta, S.; Petersen, J. L.; Shi, X. Organometal-
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Petersen, J. L.; Shi, X. Chem. Commun. 2009, 6436–6438. (c) Chen, Y.;
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(5) (a) Marion, N.; Dıez-Gonzalez, S.; Fremont, P.; Noble, A. R.;
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Chem.;Eur. J. 2007, 13, 6437–6451.
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Hiersemann, M.; Abraham., L. Eur. J. Org. Chem. 2002, 1461–1471.
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Toste, F. D. J. Am. Chem. Soc. 2009, 1131, 4513–4520.
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Org. Lett., Vol. 13, No. 10, 2011
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products in excellent yields. This simple modification of
catalysts provided one effective strategy in the preparation
of functional allenes.
Scheme 5
Encouraged by the good chemoselectivity, we then
wondered whether TA-Au could be used as an effective
catalyst for the stereospecific transformation by overcom-
ing the rapid racemization associated with other reported
cationic Au catalysts. In particular, could TA-Au catalysts
help to achieve the asymmetric synthesis of chiral allenes
by effective chirality transfer from enantiomeric enriched
propargyl alcohols (readily available). The example shown
in Scheme 2B highlighted the challenges for this proposed
chirality transfer: rapid epimerization on the propargyl
position (2 min) due to the Au activation of allene caused a
loss of stereochemistry at the propargyl position. To
investigate the chirality transfer, enantiomeric enriched
1a was first used to react with TA-Au 4a (Scheme 4).
in Scheme 5B, treating the allene 9a with the gold-oxo
catalyst over time resulted in significant racemization of
the allenes. As a result, the gold-oxo catalyst 4c suffered
from the limited substrate scope, where significantly dif-
ferent reaction rates between alkyne activation and allene
racemization were required to ensure the chirality transfer.
Overall, the gold-oxo complexes were the precatalysts, which
could slowly release the L-Auþ catalysts. Therefore, it adop-
ted the similar reactivity of the L-Auþ catalysts. This lack of
chemoselectivity with gold-oxo catalysts was further demon-
strated by the synthesis of dihydropyran 7 from intramole-
cular trapping of gold activated allenes (Scheme 5A).7b This
reaction, despite providing very attractive new synthetic
methods, highlighted the strong desire for a “true” chemose-
lective gold catalyst. The TA-Au catalyst not only could
effectively promote this transformation with excellent chir-
ality transfer but also successfully avoid the undesired race-
mization of allene 9a over a long period of time (12 h,
Scheme 5B). To the best of our knowledge, this result
revealed TA-Au as the first successful chemoselective
catalyst, selectively activating alkyne over allenes, which
would likely further extend the reaction scope for fast
growing homogeneous gold catalysis research.
Scheme 4
Unfortunately, allene 2a was obtained as racemic mix-
tures (0% ee) even with TA-Au as the catalyst at low
temperature (ꢀ40 °C). However, a closer look of this
reaction revealed a rather surprising observation: no epi-
merization of propargyl ester occurred during the reaction,
which strongly suggested the lack of equilibrium between
allene 2a and propargyl ester 1a while TA-Au catalysts
were used. The loss of allene 2a stereochemistry was likely
caused by the low energetic barrier for the allene racemiza-
tionprocess (no enantiomeric enrichedallene acetates have
ever been reported). This hypothesis was supported by the
DFT computational studies, where the relative low energy
barrier (5 kcal/mol) was revealed between the two reso-
nance structures of allene acetate.13
Considering the promising chemoselectivity from the
TA-Au catalyst, we postulated that asymmetric synthesis
of allenes could be achieved if the resulting allenes have a
high epimerization barrier. To verify this hypothesis,
propargyl-vinyl-ether 5a was prepared for the chirality
transfer investigation. As expected, excellent chirality
transfer was obtained with propargyl vinyl ether 5a while
TA-Au was used (1% catalyst, Scheme 5A).
To explore the reaction substrate scope, various chiral
propargyl vinyl ethers were prepared. The results are sum-
marized in Figure 1.
As shown in Figure 1, TA-Au was an effective catalyst
for a large scope of substrates. Both terminal and internal
alkynes were suitable for this transformation, giving the
It has been reported that gold-oxo complex [(Ph3PAu)3-
O]BF4 4c could also promote this reaction with good to
modest yields and good chirality transfer.7a However, this
complex was not a chemoselective catalyst. As demonstrated
(14) The substrates generally favoured 2,3-migration over 3,3-migra-
tion. Therefore, a stepwise 2,3-migration was one possible mechanism,
which accounts for the loss of stereochemistry information. Shi, X.;
Gorin, D. J.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 5802–5803.
(15) During the preparation of this manuscript, Nolan and cow-
orkers reported the application of amine and pyridine modified Au
catalysts for the allene synthesis. Nun, P.; Gaillard, S.; Slawin, A. M. Z.;
Nolan, S. P. Chem. Commun. 2010, 46, 9113–9115. This interesting work
provided another example of a neutral coordination ligand in tuning the
Au(I) catalyst reactivity. However, no chirality transfer was reported.
Our recent brief screening with that catalyst indicated quick racemiza-
tion at the propargyl position (similar to other cationic gold), which
further highlighted the unique reactivity of the TA-Au catalyst.
(13) The DFT computational studies were carried out by the Gaus-
sian 03 program to a B3LYP/6-311G level. See details from Supporting
Information.
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Org. Lett., Vol. 13, No. 10, 2011

allene products in good to excellent yields. Effective chir-
ality transfers were observed in terminal alkynes and alkyl
substituted internal alkynes. The excellent diastereoselec-
tivity obtained in 8f suggested a chairlike transition state in
the rearrangement.7a Racemic allenes were obtained with
phenyl substituted internal alkynes, which implied possible
higher reactivity or a different mechanism14 for these
substrates. Nevertheless, the high efficiency and good
stereoselectivity made the reported strategy one practical
approach for the asymmetric synthesis of chiral allenes. It
was worth noting that the true chemoselectivity reaction
nature of the TA-Au catalysts opened the possibility for
the development of new reactions that could take advan-
tage of the good reactivity of a gold cation toward alkyne
activationwithout sufferingtheundesiredsequentialallene
activation by the same catalyst.
In conclusion, we report herein the application of 1,2,3-
triazole Au (TA-Au) complexes as chemoselective cata-
lysts for propargyl ester/ether rearrangements. Excellent
yields of allenes were obtained.15 This method was applied
to the synthesis of chiral allenes, giving good yields and
excellent chirality transfer. The interesting new reactivity
by TA-Au not only provided an efficient strategy for the
synthesis of enantioenriched allenes, which were challen-
ging using other methods, but also, more importantly,
revealed TA-Au complexes as a new class of catalysts in
promoting alkyne activation with different reactivity than
the L-Auþ catalysts, which would likely benefit from the
discovery of new efficient organic transformations.
Acknowledgment. We thank the NSF (CHE-0844602),
WVU-PSCoR for financial support.
Figure 1. Reaction substrate scope for chiral allenes. General
reaction conditions: 5 (0.25 mmol), 4a (1.0%), DCM (2.5 mL),
The reactions were monitored by TLC (0.5ꢀ12 h), rt; ee was
determined by HPLC. For products 8iꢀj, 4a (3.0%) was used.
Supporting Information Available. Experimental de-
tails, spectrographic data. This material is available free
of charge via the Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 10, 2011
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