Gold-catalyzed regioselective oxidation ofterminal allenes: Formation of α-methanesulfonyloxy methyl ketones

Article abstract of DOI:10.3762/bjoc.7.69

Synthetically useful α-methanesulfonyloxy methyl ketones are readily prepared in one-step from terminal allenes in fair to good yields. The chemistry relies on a gold-catalyzed intermolecular oxidation of the 1,2-diene unit using 3,5-dichloropyridine N-ox

Full text of DOI:10.3762/bjoc.7.69

Gold-catalyzed regioselective oxidation of
terminal allenes: formation of α-methane-
sulfonyloxy methyl ketones
Yingdong Luo, Guozhu Zhang, Erik S. Hwang, Thomas A. Wilcoxon
and Liming Zhang*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 596–600.
Department of Chemistry and Biochemistry, University of California,
Santa Barbara, California, 93106, USA
doi:10.3762/bjoc.7.69
Received: 16 March 2011
Accepted: 15 April 2011
Published: 11 May 2011
Email:
Liming Zhang* - zhang@chem.ucsb.edu
* Corresponding author
This article is part of the Thematic Series "Allene chemistry".
Guest Editor: K. M. Brummond
Keywords:
allene; catalysis; gold; oxidation; regioselectivity
© 2011 Luo et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Synthetically useful α-methanesulfonyloxy methyl ketones are readily prepared in one-step from terminal allenes in fair to good
yields. The chemistry relies on a gold-catalyzed intermolecular oxidation of the 1,2-diene unit using 3,5-dichloropyridine N-oxide
as the oxidant. The reaction tolerates a range of functional groups and shows excellent regioselectivity.
Introduction
While alkynes are the most studied substrates in homogeneous mediates. This led us to consider whether or not allenes could
gold catalysis [1-9], allenes [10] occupy a not-so-distant second also be oxidized by these N-oxides in the presence of gold cata-
place, and many versatile transformations have been developed lysts. As shown in Scheme 1B, intermediate C, likely formed
either using allenes as substrates [11-17] or via allenes gener- via an initial nucleophilic attack of a gold-activated allene,
ated in situ [18-21]. We have recently shown that highly reac- cannot undergo elimination in the same way as intermediate A,
tive gold carbenes can be generated from alkynes via gold- hence gold carbene intermediate B would not be formed. While
promoted intermolecular oxidation by pyridine/quinoline C may revert back to the allene substrate, we suspect that a
N-oxides [22-25], making benign alkynes effective surrogates SN2'-type reaction by an external nucleophile could facilitate
of toxic and potentially explosive α-diazo ketones (Scheme 1A). the fragmentation of the O–Y bond, ultimately leading to useful
Synthetically useful structures such as oxetan-3-ones [22], dihy- products via intermediate D. Herein we report our preliminary
drofuran-3-ones [23], azetidin-3-ones [24] and α,β-unsaturated studies, which led to a facile synthesis of α-methanesulfony-
ketones [25] are readily accessed via these gold carbene inter- loxy methyl ketones.
596

Beilstein J. Org. Chem. 2011, 7, 596–600.
Scheme 1: Gold-catalyzed intermolecular oxidation of alkynes and allenes.
Results and Discussion
catalysts, such as IPrAuNTf2 (entry 6) and Cy-John-
Initially, trideca-1,2-diene (1a) was treated with commercially PhosAuNTf2 (entry 7), did not fare as well as Ph3PAuNTf2, the
available pyridine N-oxide in the presence of MsOH (5 equiv) more Lewis acidic (4-CF3Ph)3PAuNTf2 was better, and 2a was
and Ph3PAuNTf2 (5 mol %) in DCE at room temperature. formed in 77% isolated yield (entry 8). A decrease in the
Consumption of 1a was initially observed and was complete in amount of MsOH was counterproductive (entry 9), whilst no
two days. A relatively polar compound was detected and subse- desired product was observed in the absence of a gold catalyst
quently isolated (Table 1, entry 1). NMR and MS analysis (entry 10).
showed it to be the α-methanesulfonyloxy ketone 2a. Interest-
ingly, its regioisomer (i.e., 3) was not observed, suggesting With the optimized reaction conditions established (Table 1,
excellent regioselectivity in terms of the MsO delivery. The entry 8), the scope of this chemistry was studied. As shown in
reaction time was shortened to 8 h by increasing the reaction Table 2, remote functional groups were readily tolerated. For
temperature (entry 2). Attempts to increase the reaction effi- example, good yields were obtained in the presence of a distal
ciency by varying the N-oxide (entries 3–5) revealed that 3,5- acetoxy (entry 1) or benzoyloxy (entry 2) group; moreover,
dichloropyridine N-oxide was a superior oxidant, and 2a was reactive tosyloxy and mesyloxy groups were also tolerated
formed in 75% NMR yield. While less reactive but bulky gold (entries 3 and 4). A chloro (entry 5), a benzyloxy (entry 6), a
Table 1: Initial studies and condition optimizationa.
Entry
Catalyst (5 mol %)
N-Oxide (2 equiv)
Reaction conditions
Yieldb (%)
1
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
IPrAuNTf2
pyridine N-oxide
rt, 2 d
46
2
pyridine N-oxide
40 °C, 8 h
40 °C, 8 h
40 °C, 8 h
40 °C, 8 h
40 °C, 8 h
40 °C, 8 h
40 °C, 8 h
40 °C, 8 h
40 °C, 8 h
52
3
quinoline N-oxide
51/6c
44/10c
75
4
2-bromopyridine N-oxide
3,5-dichloropyridine N-oxide
3,5-dichloropyridine N-oxide
3,5-dichloropyridine N-oxide
3,5-dichloropyridine N-oxide
3,5-dichloropyridine N-oxide
3,5-dichloropyridine N-oxide
5
6
10/53c
47/7c
80(77d)
55/13c
—
7
Cy-JohnPhosAuNTf2
(4-CF3Ph)3PAuNTf2
(4-CF3Ph)3PAuNTf2
—
8
9e
10
a[1a] = 0.05 M; bdetermined by 1H NMR using diethyl phthalate as the external standard; cunreacted starting material; disolated yield; e2.5 equiv of
MsOH.
597

Beilstein J. Org. Chem. 2011, 7, 596–600.
Table 2: Reaction scopea.
Entry
1
Allene
Products
Yieldb
79%
1b
1c
2b
2c
2
75%
3
4
5
6
1d
1e
1f
2d
2e
2f
80%
73%
63%
61%
1g
2g
7
1h
2h
76%
8
9
1i
1j
2i
2j
60%
72%
10
1k
2k
59%
a[1] = 0.05 M; bisolated yield.
598

Beilstein J. Org. Chem. 2011, 7, 596–600.
protected amino (entry 7) and a phenyl group (entry 8) were copper, whilst the latter suffers from low regioselectivities. This
also allowed, and the corresponding α-functionalized ketones gold-catalyzed approach offers an attractive alternative that is
were isolated in useful yields. Besides linear allenes, exocyclic highly regioselective, catalytic on gold and takes place under
allenes such as 1j and 1k were also suitable substrates and gave relatively mild reaction conditions.
mesylates 2j and 2k in 72% and 59% yield, respectively (entries
9 and 10).
The mechanism of this highly regioselective gold-catalyzed oxi-
dation of allenes is proposed in Scheme 3. The first step, as in
Some substrates, however, did not participate in this reaction the case of alkyne oxidation [22,23,25], is probably an attack by
effectively. For example, allenes derived by replacing the the pyridine N-oxide on the gold-activated allene. Selective
acetoxy group of 1b with a free OH or an OTBS group did not reaction at the terminal C–C double bond should occur due to
lead to the desired products. Presumably, the nucleophilic OH steric preference. The allyl gold intermediate E can then
group in the substrate, or one generated via acidic desilylation, undergo protonation to form intermediate F with MsO− as the
interfered with the reaction. This reasoning was supported by counter anion. An SN2'-type substitution by the anion would
the isolation of piperidine 4 upon subjecting 1l to the optimized afford the observed product. This substitution is facilitated by
reaction conditions (Scheme 2). In addition, allenylbenzene was the fragmentation of the weak N–O bond and the annihilation of
not a good substrate, and <10% of the desired ketone was the charges.
detected by NMR. Somewhat surprisingly, pentadeca-7,8-diene
[26], an internal allene, did not participate in the reaction.
Conclusion
We have successfully realized the first gold-catalyzed intermol-
ecular oxidation of allenes. With 3,5-dichloropyridine N-oxide
as the oxidant and in the presence of MsOH, α-methanesulfony-
loxy methyl ketones are formed in one step in fair to good yield
with excellent regioselectivities under relatively mild reaction
conditions. The reaction tolerates a wide range of functional
groups. Studies to explore the synthetic potential of this allene
oxidation strategy are currently underway.
Scheme 2: A side reaction from 1l.
Supporting Information
It is of note that α-methanesulfonyloxy ketones are versatile
synthetic intermediates that can undergo various reactions [27],
including substitution [28], elimination [29], the formation of
zinc homoenolates [30], the formation of cyclopropane rings
under photo-irradiation [31-33], the formation of aminoimida-
zoles [34], the generation of cyclopropanone–oxyallyl inter-
mediates [35], and ring contraction [36]. Their direct synthesis
from corresponding ketones can be realized via oxidation by
using either CuO/MsOH [37,38] or PhI(OH)OMs [39].
However, the former method uses stoichiometric amounts of
Supporting Information File 1
Experimental procedures and characterization data.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-69-S1.pdf]
Supporting Information File 2
NMR spectra of compounds.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-69-S2.pdf]
Scheme 3: A proposed reaction mechanism.
599

Beilstein J. Org. Chem. 2011, 7, 596–600.
28.Hisanaga, Y.; Asumi, Y.; Takahashi, M.; Shimizu, Y.; Mase, N.;
Yoda, H.; Takabe, K. Tetrahedron Lett. 2008, 49, 548–551.
doi:10.1016/j.tetlet.2007.11.065
Acknowledgements
The authors thank NSF (CAREER CHE-0969157) and UCSB
for general financial support. LZ is an Alfred P. Sloan fellow.
29.Hui, B. W.-Q.; Chiba, S. Org. Lett. 2009, 11, 729–732.
doi:10.1021/ol802816k
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