Highly efficient gold(I)-catalyzed Overman rearrangement in water

Article abstract of DOI:10.3762/bjoc.7.88

A highly efficient gold(I)-catalyzed Overman rearrangement of allylic trichloroacetimidates to allylic trichloroacetamides in water is reported. With this environmentally benign and scalable protocol, a series of C3-alkyl substituted allylic trichloroacet

Full text of DOI:10.3762/bjoc.7.88

Highly efficient gold(I)-catalyzed
Overman rearrangement in water
Dong Xing and Dan Yang*
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 781–785.
Department of Chemistry, The University of Hong Kong, Pokfulam
Road, Hong Kong, China
doi:10.3762/bjoc.7.88
Received: 09 April 2011
Accepted: 24 May 2011
Published: 08 June 2011
Email:
Dong Xing - xingdong@hku.hk; Dan Yang* - yangdan@hku.hk
* Corresponding author
This article is part of the Thematic Series "Gold catalysis for organic
synthesis".
Keywords:
allylic trichloroacetamides; allylic trichloroacetimidate; gold(I) chloride;
Overman rearrangement; water
Guest Editor: F. D. Toste
© 2011 Xing and Yang; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
A highly efficient gold(I)-catalyzed Overman rearrangement of allylic trichloroacetimidates to allylic trichloroacetamides in water
is reported. With this environmentally benign and scalable protocol, a series of C3-alkyl substituted allylic trichloroacetamides were
synthesized in good to high yields.
Introduction
The aza-Claisen rearrangement of allylic trichloroacetimidates Overman rearrangements. In recent years, gold catalysts have
to allylic trichloroacetamides (Overman rearrangement) is a been successfully applied to a series of [3,3]-sigmatropic
powerful and attractive strategy for the synthesis of allylic rearrangements, such as the rearrangement of propargylic esters
amines from readily available allylic alcohols [1,2]. This trans- to allenyl esters [16-21], allenyl carbinol esters to 1,3-butadien-
formation can be conducted thermally at high temperatures or 2-ol esters [22] and the isomerization of allylic acetates [23,24].
by transition metal catalysis under very mild conditions [3-7]. However, when they were used as catalysts for the Overman
Asymmetric induction has been achieved with certain types of rearrangement, the substrate scope was limited and only poor to
transition metal catalysts (e.g., palladium complexes) in combi- moderate yields were achieved [25-28]. Very recently, our
nation with chiral ancillary ligands [8-13]. However, although a group developed an efficient gold(I)-catalyzed decarboxylative
large number of late transition metal catalysts have been used aza-Claisen rearrangement of allylic N-tosylcarbamates for the
for different types of [3,3]-sigmatropic rearrangements [14,15], synthesis of N-tosyl allylic amines [29]. This reaction was
only Pd(II) and Hg(II) salts have found wide application in performed in water and therefore represented an environ-
781

Beilstein J. Org. Chem. 2011, 7, 781–785.
mentally benign protocol [30-34]. We decided to apply this
extremely mild catalytic system to the Overman rearrangement
of allylic trichloroacetimidates.
Table 1: Optimization of reaction conditions.a
Results and Discussion
Trichloroacetimidate 1a was prepared by the DBU-catalyzed
addition of trans-2-penten-1-ol to trichloroacetonitrile [10,35].
With this substrate, the catalytic activities of different gold(I)
complexes in H2O were examined. When 1a was subjected to
the optimal catalytic conditions previously reported by our
group (5 mol % AuCl/AgOTf at 75 °C) [29], the desired allylic
trichloroacetamide 2a was obtained in 91% yield in a reaction
time of 1 h (Table 1, entry 1). Gold(I) complexes with phos-
phine ligands, Au(PPh3)Cl or Au[P(t-Bu)2(o-Ph)Ph]Cl, in place
of AuCl gave none of the desired product (Table 1, entries 2
and 3). Further screening revealed that AuCl alone could
catalyze this reaction with high efficiency to give 2a in 92%
yield in 2 h (Table 1, entry 4). On the other hand, with only
AgOTf as the catalyst, the formation of 2a was not observed
and substrate 1a decomposed completely (Table 1, entry 5). In
the absence of AuCl, substrate 1a remained unreacted, even
when the temperature was increased to 100 °C for 3 h (Table 1,
entry 6), indicating that the gold(I) catalyst is indispensible for
this transformation. This gold(I)-catalyzed reaction could be
Temp
(°C)
Time
(h)
Yield
(%)b
Entry Catalyst (mol %)
1
2
AuCl/AgOTf
75
75
2
91
<5
AuPPh3Cl/AgOTf
12
Au[P(t-Bu)2(o-Ph)Ph]Cl
/AgOTf
3
75
12
<5
4
5
6
7
8
AuCl
AgOTf
–
75
75
100
rt
2
12
3
92
<5
<5
90
94
AuCl
AuCl
12
2
55
aReaction conditions: 0.3 mmol of substrate, 5 mol % of the catalyst,
3 mL H2O; byield determined by 1H NMR with nitrobenzene as internal
standard.
performed at room temperature, albeit with a prolonged reac- surveyed. Different alkyl substituents at the C1 position of
tion time (Table 1, entry 7). When the temperature was raised to allylic trichloroacetimidates, including methyl (1b), ethyl (1a),
55 °C the reaction was complete within 2 h and in excellent n-propyl (1c) and phenethyl (1d) groups, underwent the desired
yield (94%; Table 1, entry 8).
transformation smoothly to afford the corresponding C3-alkyl
substituted allylic trichloroacetamides in high yields (Table 2,
With the optimized reaction conditions in hand, the substrate entries 1–4). The C1-diethylmethyl substituted substrate (1e)
scope of this gold(I)-catalyzed Overman rearrangement was also underwent the desired rearrangement, affording the desired
Table 2: Gold(I)-catalyzed Overman rearrangement in H2O.a
Entry
1
Substrate
Product
Time (h)
Yield (%)b
92
2
1a
1b
2a
2b
2
2
96
782

Beilstein J. Org. Chem. 2011, 7, 781–785.
Table 2: Gold(I)-catalyzed Overman rearrangement in H2O.a (continued)
3
2
2
95
90
1c
2c
2d
4
1d
5
3
3
67c
1e
2e
6
n.d.d
1f
2f
2g
2h
2i
7
3
3
2
n.d.d
86
1g
8
1h
9
79
1i
10
6
71c
1j
2j
aUnless otherwise indicated, all reactions were carried out on a 0.5 mmol scale with 5 mol % of AuCl in 5 mL H2O at 55 °C for the indicated time;
bunless otherwise indicated, crude yields were reported with >95% purities as determined by 1H NMR; cisolated yield after flash chromatography;
dn.d. = not detected.
product (2e) in 67% isolated yield (Table 2, entry 5). However, allylic amines. For example, substrates containing either
neither the substrates with phenyl (1f) nor dimethyl (1g) TBDMS- or THP-protected hydroxy groups (1h and 1i) effi-
substituents at the C1 position gave the rearranged product ciently underwent the desired rearrangement to afford the
(Table 2, entries 6 and 7), indicating that both electronic and corresponding products, which are precursors for the synthesis
steric effects at the C1 position play roles in the rearrangement. of a variety of β-substituted β-amino alcohols (Table 2, entries 8
Although the substrate scope is currently limited to C1-alkyl and 9). Compound 2j was also obtained in 71% yield under the
substituted trichloroacetimidates, this method is still very con- reaction conditions from the corresponding trichloroacetimi-
venient and attractive for the preparation of synthetically useful date 1j (Table 2, entry 10). Trichloroacetamide 2j could be
783

Beilstein J. Org. Chem. 2011, 7, 781–785.
transformed to vigabatrin, a GABA aminotransaminase
inhibitor [36], in one single step [37].
Supporting Information
Supporting Information File 1
One of the most remarkable features of this gold(I)-catalyzed
Overman rearrangement is that it is performed in water under
very mild reaction conditions. Moreover, this method is
extremely clean. After completion of the reaction, simple
extraction gave the desired product in high purity, and no
further purification step was required. To illustrate the potential
utility of this method for industrial applications, a gram-scale
synthesis of 2a was performed with 2 mol % of AuCl in H2O
(Scheme 1). After reacting at 55 °C for 4 h, the desired product
was obtained in 92% yield.
1H NMR data and NMR spectra of products 2a–2d, 2g–2i.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-88-S1.pdf]
Acknowledgements
This work was supported by The University of Hong Kong and
Hong Kong Research Grants Council (HKU 706109P).
References
1. Overman, L. E. J. Am. Chem. Soc. 1974, 96, 597–599.
doi:10.1021/ja00809a054
2. Overman, L. E. J. Am. Chem. Soc. 1976, 98, 2901–2910.
doi:10.1021/ja00426a038
3. Overman, L. E. Acc. Chem. Res. 1980, 13, 218–224.
doi:10.1021/ar50151a005
4. Overman, L. E. Angew. Chem., Int. Ed. Engl. 1984, 23, 579–586.
doi:10.1002/anie.198405791
5. Metz, P.; Mues, C.; Schoop, A. Tetrahedron 1992, 48, 1071–1080.
doi:10.1016/S0040-4020(01)88203-X
6. Johannsen, M.; Jørgensen, K. A. Chem. Rev. 1998, 98, 1689–1708.
doi:10.1021/cr970343o
Scheme 1: Gram-scale synthesis of 2a.
7. Overman, L. E.; Carpenter, N. E. In Organic Reactions;
Overman, L. E., Ed.; Wiley: Hoboken, NJ, 2005; Vol. 66, pp 653–760.
8. Nomura, H.; Richards, C. J. Chem.–Asian J. 2010, 5, 1726–1740.
doi:10.1002/asia.201000131
Conclusion
In summary, we have developed an efficient gold(I)-catalyzed
Overman rearrangement for the synthesis of a series of C3-alkyl
substituted allylic trichloroacetamides. This transformation was
performed in water under very mild reaction conditions and
could be carried out on the gram-scale with low catalyst loading
and simple work-up procedure, making it potentially applicable
to the industrial community for large-scale synthesis. Further
exploration of the substrate scope and the development of an
asymmetric version of this transformation are currently
underway in our group.
9. Hollis, T. K.; Overman, L. E. J. Organomet. Chem. 1999, 576,
290–299. doi:10.1016/S0022-328X(98)01065-1
10.Anderson, C. E.; Overman, L. E. J. Am. Chem. Soc. 2003, 125,
12412–12413. doi:10.1021/ja037086r
11.Kirsch, S. F.; Overman, L. E.; Watson, M. P. J. Org. Chem. 2004, 69,
8101–8104. doi:10.1021/jo0487092
12.Watson, M. P.; Overman, L. E.; Bergman, R. G. J. Am. Chem. Soc.
2007, 129, 5031–5044. doi:10.1021/ja0676962
13.Peters, R.; Xin, Z.-q.; Maier, F. Chem.–Asian J. 2010, 5, 1770–1774.
doi:10.1002/asia.201000386
14.Lutz, R. P. Chem. Rev. 1984, 84, 205–247. doi:10.1021/cr00061a001
15.Majumdar, K. C.; Alam, S.; Chattopadhyay, B. Tetrahedron 2008, 64,
597–643. doi:10.1016/j.tet.2007.10.079
Experimental
Typical procedure: Synthesis of 2,2,2-trichloro-N-
(pent-1-en-3-yl)acetamide (2a)
16.Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750–2752.
doi:10.1002/anie.200604773
AuCl (5.8 mg, 0.025 mmol) was added to a solution of (E)-
pent-2-enyl 2,2,2-trichloroacetimidate (1a) (115 mg, 0.5 mmol)
in H2O (5 mL) with vigorously stirring in a 25 mL reaction
tube. The reaction mixture was heated at 55 °C for 2 h, then
cooled to room temperature, diluted with H2O and extracted
with CH2Cl2 three times. The combined organic layers were
dried over MgSO4, filtered through a short pad of celite and
concentrated in vacuo to provide 107 mg of 2,2,2-trichloro-N-
(pent-1-en-3-yl)acetamide (2a) (>95% purity as determined by
1H NMR). Products 2a–2d, 2h and 2j are known compounds
and their data were identical to those reported in the literature.
17.Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804–16805.
doi:10.1021/ja056419c
18.Marion, N.; Díez-González, S.; de Frémont, P.; Noble, A. R.;
Nolan, S. P. Angew. Chem., Int. Ed. 2006, 45, 3647–3650.
doi:10.1002/anie.200600571
19.Buzas, A.; Istrate, F.; Gagosz, F. Org. Lett. 2006, 8, 1957–1959.
doi:10.1021/ol0606839
20.Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006, 128, 1442–1443.
doi:10.1021/ja057327q
21.Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414–8415.
doi:10.1021/ja062777j
22.Buzas, A. K.; Istrate, F. M.; Gagosz, F. Org. Lett. 2007, 9, 985–988.
doi:10.1021/ol063031t
784

Beilstein J. Org. Chem. 2011, 7, 781–785.
23.Marion, N.; Gealageas, R.; Nolan, S. P. Org. Lett. 2007, 9, 2653–2656.
doi:10.1021/ol070843w
24.Gourlaouen, C.; Marion, N.; Nolan, S. P.; Maseras, F. Org. Lett. 2009,
11, 81–84. doi:10.1021/ol802430m
25.Jaunzeme, I.; Jirgensons, A. Synlett 2005, 2984–2986.
doi:10.1055/s-2005-918952
26.Jamieson, A. G.; Sutherland, A. Org. Biomol. Chem. 2006, 4,
2932–2937. doi:10.1039/b607014k
27.Swift, M. D.; Sutherland, A. Tetrahedron Lett. 2007, 48, 3771–3773.
doi:10.1016/j.tetlet.2007.03.161
28.Jaunzeme, I.; Jirgensons, A. Tetrahedron 2008, 64, 5794–5799.
doi:10.1016/j.tet.2008.03.099
29.Xing, D.; Yang, D. Org. Lett. 2010, 12, 1068–1071.
doi:10.1021/ol100056f
30.Hutchings, G. J. Catal. Today 2007, 122, 196–200.
doi:10.1016/j.cattod.2007.01.018
31.Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2003, 125, 9584–9585.
doi:10.1021/ja0359299
32.Huang, B.; Yao, X.; Li, C.-J. Adv. Synth. Catal. 2006, 348, 1528–1532.
doi:10.1002/adsc.200606118
33.Lo, V. K.-Y.; Liu, Y.; Wong, M.-K.; Che, C.-M. Org. Lett. 2006, 8,
1529–1532. doi:10.1021/ol0528641
34.Xing, D.; Guan, B.; Cai, G.; Fang, Z.; Yang, L.; Shi, Z. Org. Lett. 2006,
8, 693–696. doi:10.1021/ol052830t
35.Nishikawa, T.; Asai, M.; Ohyabu, N.; Isobe, M. J. Org. Chem. 1998, 63,
188–192. doi:10.1021/jo9713924
36.Rogawski, M. A.; Löscher, W. Nat. Rev. Neurosci. 2004, 5, 553–564.
doi:10.1038/nrn1430
37.Casara, P. Tetrahedron Lett. 1994, 35, 3049–3050.
doi:10.1016/S0040-4039(00)76824-9
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.7.88
785