Dehydrogenative Meyer-Schuster-like rearrangement: A gold-catalyzed reaction generating an alkyne

Article abstract of DOI:10.1002/anie.201307647

Easily accessible propargylic esters are converted to the inverted alkynyl ketones in an oxidative gold-catalyzed reaction. Gagosz's catalyst in combination with PhI(OAc)₂ is the best system for this conversion and 18 examples with yields up to 80 % are reported. The results indicate that the triple bond in the product is formed by elimination from a vinylgold intermediate. In a formal sense the new conversion overall is a dehydrogenative Meyer-Schuster rearrangement. It takes alkynes: Propargyl esters can be converted into alkynyl ketones by a new oxidative gold-catalyzed reaction. The best catalyst system is Ph₃PAuCl/AgNTf₂ in combination with the oxidant PhI(OAc)₂. The yields are as high as 80 % and the reaction can be conducted in the presence of air. Copyright

Full text of DOI:10.1002/anie.201307647

.
Angewandte
Communications
DOI: 10.1002/anie.201307647
Homogeneous Gold Catalysis
Dehydrogenative Meyer–Schuster-Like Rearrangement: A Gold-
Catalyzed Reaction Generating an Alkyne**
Yang Yu, Weibo Yang, Daniel Pflꢀsterer, and A. Stephen K. Hashmi*
Abstract: Easily accessible propargylic esters are converted to
the inverted alkynyl ketones in an oxidative gold-catalyzed
reaction. Gagoszꢁs catalyst in combination with PhI(OAc)2 is
the best system for this conversion and 18 examples with yields
up to 80% are reported. The results indicate that the triple
bond in the product is formed by elimination from a vinylgold
intermediate. In a formal sense the new conversion overall is
a dehydrogenative Meyer–Schuster rearrangement.
H
omogeneous gold-catalyzed reactions involving an AuI/
AuIII catalytic cycle have attracted much attention owing to
the development of cross-coupling reactions that complement
the more traditional transition-metal-catalyzed methods.[1]
Recently, several groups have achieved the combination of
gold catalysis based on alkyne/allene activation and external-
oxidant-facilitated gold redox processes. For example, in 2009
Zhang and co-workers reported that the gold-catalyzed
conversion of propargyl esters in the presence of the oxidant
Selectfluor, which is also a source of electrophilic fluorine,
delivers enone dimers (Scheme 1a).[2] Furthermore, they
Scheme 1. Gold-catalyzed oxidation of propargyl esters.
À
developed a gold-catalyzed oxidative C O bond-forming
reaction for the preparation of a-benzoxyenones from
propargyl esters not substituted at the propargylic position
(Scheme 1b).[3] However, during this type of gold redox
process, protodeauration was a major side reaction reducing
the yields. PhI(OAc)2 has also been employed in AuI/AuIII
catalytic cycles. In this context, a gold-catalyzed oxidative
dimerization of nonactivated arenes in the presence of
PhI(OAc)2 was reported by Tse and co-workers;[4] related
results were obtained by Wegner et al.[5] Additionally, Nevado
and co-workers developed the gold-catalyzed ethynylation of
“deactivated” arenes with electron-deficient alkynes by using
PhI(OAc)2 as an oxidant.[6] To our surprise, there is no
example of a gold-catalyzed conversion of propargylic esters
Table 1: Optimization studies on the gold-catalyzed reaction of 1a.[a]
Entry Catalyst/oxidant
Solvent
t
Yield[b]
1
2
3
4
TA-Au[c]/AgNTf2/PhI(OAc)2
DCE
DCE
DCE
DCE
DCE
DCE
DCE
CH3CN 24 h
toluene 1.5 h
DCE
DCE
15 min 41%
15 min 56%
20 min 62%
15 min 39%
TA-Au/AgNTf2/PhI(OAc)2
Ph3PAuCl/AgNTf2/PhI(OAc)2
IPrAuCl/AgNTf2/PhI(OAc)2
[AuIII]/PhI(OAc)2
Ph3PAuCl/AgSbF6/PhI(OAc)2
AgNTf2/PhI(OAc)2
[*] M. Sc. Y. Yu, M. Sc. W. Yang, M. Sc. D. Pflꢀsterer,
Prof. Dr. A. S. K. Hashmi
5[d]
6
20 min
–
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢀt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
E-mail: hashmi@hashmi.de
10 min 32%
7
8
24 h
10%
30%
28%
31%
Ph3PAuCl/AgNTf2/PhI(OAc)2
Ph3PAuCl/AgNTf2/PhI(OAc)2
Homepage: http://www.hashmi.de
9
10[e] Ph3PAuCl/AgNTf2/PhI(OAc)2
5 h
Prof. Dr. A. S. K. Hashmi
Chemistry Department, Faculty of Science
King Abdulaziz University
11
12
13
Ph3PAuCl/AgNTf2/Selectfluor
Ph3PAuCl/AgNTf2/Cu(OAc)2·H2O DCE
Ph3PAuCl/AgNTf2/O2 DCE
50 min unselective
4 h unselective
20 min unselective
Jeddah 21589 (Saudi Arabia)
[**] Y. Yu and W. Yang are grateful to the CSC (Chinese Scholarship
Council) for fellowships and they contributed equally to this work.
Gold salts were generously provided by Umicore AG & Co. KG.
[a] Reaction conditions: Substrate (100 mmol), [Au] (2 mol%), [Ag]
(2 mol%), PhI(OAc)2 (100 mmol), solvent (1 mL), in air, 808C. The
reaction was monitored by TLC. [b] Yield of isolated product. [c] See
Scheme 3 for structure of TA-Au. [d] [AuIII]=Dichloro(2-picolinato)-
gold(III). [e] Reaction at 408C.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201307647.
1144
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1144 –1147

Angewandte
Chemie
Table 2: Scope and limitations of the AuI-catalyzed synthesis of 2.[a]
in combination of PhI(OAc)2 as an oxidant. Based
on the known successful studies, we want to explore
this novel redox chemistry involving propargylic
esters. Herein, we disclose the first example of a new
type of homogeneous gold-catalyzed oxidative rear-
rangement reaction which proceeds with the for-
ꢀ
mation of a new C C bond. This reaction is
important because of the formation of 1,3-ynone
moieties which are versatile substrates for the
synthesis of natural products.[7] More important,
the formation of triple bonds is very rare in
homogeneous gold catalysis;[8] so far the field has
been dominated by reactions which efficiently
transform triple bonds of the substrate.
Entry Substrate
1
Product
Yield[b]
62%
1a
2a
2b
2b
2b
2
3
4
5
1b
70%
67%
46%
65%
We chose 1-phenylhept-2-ynyl pivalate (1a),
readily available from 1-hexyne, benzaldehyde,
and pivaloyl chloride, as a model substrate. Differ-
ent reaction conditions were investigated and the
results are listed in Table 1. Among the catalysts
tested, Ph3PAuCl/AgNTf2 was found to be the most
effective for this transformation (Table 1, entries 1–
4). The desired product 2a was obtained in 62%
yield in the presence of 2 mol% of this catalyst at
808C for 20 min in air. With dichloro(2-
picolinato)gold(III)[9] no conversion was detected
(Table 1, entry 5). With regard to the counter ion,
AgSbF6 was less effective (only 32% yield; Table 1,
entry 6). Notably, AgNTf2 alone gave 2a in only
10% yield (Table 1, entry 7). Changing to CH3CN
or toluene as the solvent failed to improve the yield
(Table 1, entries 8 and 9). Decreasing the temper-
ature to 408C also decreased the yield to 31%
(Table 1, entry 10). Moreover, other oxidants such
1b’
1b’’
1c
1d
1e
1 f
2c
2d
2e
2 f
6
55%
51%
34%
7
.
[10]
as Selectfluor, Cu(OAc)2 H2O, and O2
were
unselective (Table 1, entries 11–13).
8[c]
The scope of this conversion of propargylic
pivalates derived from aldehydes and alkynes is
shown in Table 2. The transformations proceeded
smoothly with substrates having both an aromatic
group at the propargylic position and an aliphatic or
aromatic group on the alkyne (Table 2, entries 1–
15). The desired ynone products were formed in
moderate to good yields. In addition to 1a (Table 1,
entry 1), 1b bearing a tolyl substituent also reacted
smoothly. We compared the reaction of substrate 1b
(70%, entry 2) with that of the corresponding
acetate 1b’ (67% yield, entry 3) and benzoate 1b’’
(46% yield, entry 4) and thus used pivalates for the
subsequent optimization studies. Fluoro and chloro-
substituted aryl groups were tolerated (55–70%
yield; Table 2, entries 5–7). The strongly electron-
deficient nitro group proved to be less reactive and
the desired product could be obtained in only 34%
yield together with allene 2 f’ as the side product in
17% yield (Table 2, entry 8). As illustrated in these
examples, the electron density on the aromatic ring
had a strong influence on this transformation;
electron-donating groups were more favorable
than electron-withdrawing groups. Additional sub-
2 f’
17%
9
1g
1h
1i
2g
2h
2i
63%
66%
24%
67%
40%
10
11
12
13
1j
2j
1k
2k
Angew. Chem. Int. Ed. 2014, 53, 1144 –1147
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1145

.
Angewandte
Communications
Table 2: (Continued)
Entry Substrate
Product
Yield[b]
52%
14
15
16
1l
2l
1m
1n
2m 65%
2n
2o
65%
77%
17
1o
18
19
1p
1q
2p
2q
81%
80%
Scheme 3. Mechanistic experiments.
1 undergoes an AuI-catalyzed 1,3-acyloxy shift,[12] lead-
ing to the AuI-containing oxocarbenium intermediate
A.[13] After hydrolysis of the intermediate A, the AuI
complex B is formed. Intermediate B reacts with the
oxidant PhI(OAc)2 to form the active acetyl AuIII
intermediate C by releasing the acetate and PhI.[14]
Considering the cationic AuIII center in intermediate C,
it is easy to understand why electron-donating groups on
the aromatic ring led to better results. Since intermediate B is
more electron-rich than the preceding intermediates, we
assume that the oxidation of this intermediate is faster than
oxidation of other intermediates, but we cannot exclude that
other intermediates might be oxidized. With the assistance of
acetate, which is produced during the formation of inter-
mediate C, the b-H was eliminated, which led to the
formation of the final product 2. Furthermore, we attempted
to isolate the allene intermediate with the novel and efficient
catalyst Triazole-Au (TA-Au), which was developed by Shi
et al.[15] To our delight, the allene intermediate could be
isolated in 85% yield. With this allene species the trans-
formation proceeded smoothly and the
[a] Reaction conditions: substrate (200 mmol), [Au] (2 mol%), [Ag] (2 mol%),
PhI(OAc)2 (200 mmol), solvent (1 mL), in air, 808C. The reaction was monitored by
TLC. [b] Yield of isolated product. [c] Allene 2 f’ was also isolated in 17% yield.
strates with an aliphatic group on the alkyne, bearing either
a branched chain or a ring, led to the corresponding ynones in
good yields (Table 2, entries 9 and 10). However, an aromatic
group on the alkyne was problematic; 2i was isolated in only
24% yield (Table 2, entry 11). To explore the scope further,
a variety of additional substrates were investigated, and the
results were satisfactory (Table 2, entries 12–19). For exam-
ple, propargyl pivalates bearing a m-Br, a p-F, or a o-Me
substituent led to corresponding ynones in excellent yields of
77%, 81%, and 80% respectively (Table 2, entries 17–19).
For the mechanism[11] of this reaction, we propose the
sequence of steps shown in Scheme 2. Propargylic pivalate
desired product 2a was indeed formed in
45% yield (Scheme 3).
In summary, we have developed the
first example of a homogeneous gold-
catalyzed rearrangement of propargylic
pivalates followed by oxidation with PhI-
(OAc)2. This reaction provides a new
efficient approach to ynones under air;
usually these are synthetized under anhy-
drous, oxygen-free conditions. The mech-
anism of this reaction, a 1,3-oxygen trans-
position of a propargylic leaving group
which resembles a Meyer–Schuster rear-
rangement, is of high interest as until now
only few reports indicate that gold(III)
can acting as a leaving group.[16] In
Scheme 2. Proposed mechanism.
addition it is remarkable that a gold-
1146
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1144 –1147

Angewandte
Chemie
[8] There are only two examples in which a triple bond reappears at
catalyzed reaction generates an alkyne. Further studies to
expand the synthetic scope of this reaction and addressing
further mechanistic details will be reported in due course.
the same position in the product at the end of the reaction:
a) A. S. K. Hashmi, W. Yang, Y. Yu, M. M. Hansmann, M.
Rudolph, F. Rominger, Angew. Chem. 2013, 125, 1368 – 1371;
Angew. Chem. Int. Ed. 2013, 52, 1329 – 1332; b) W. Yang, Y. Yu,
T. Zhang, M. M. Hansmann, D. Pflästerer, A. S. K. Hashmi, Adv.
Synth. Catal. 2013, 355, 2037 – 2043; there is only one example in
which a triple bond reappears at a different position in the
product at the end of the reaction: S. López, E. Herrero-Gómez,
P. Pꢀrez-Galµn, C. Nieto-Oberhuber, A. M. Echavarren, Angew.
Chem. 2006, 118, 6175 – 6178; Angew. Chem. Int. Ed. 2006, 45,
6029 – 6032.
Received: August 30, 2013
Published online: December 11, 2013
Keywords: alkynes · allenes · esters · gold · hypervalent iodine
.
[1] For selected reviews on Au catalysis, see: a) M. Rudolph,
A. S. K. Hashmi, Chem. Soc. Rev. 2012, 41, 2448 – 2462;
b) A. S. K. Hashmi, M. Rudolph, Chem. Soc. Rev. 2008, 37,
1766 – 1775; c) A. Arcadi, Chem. Rev. 2008, 108, 3266 – 3325;
d) Z. Li, C. Brouwer, C. He, Chem. Rev. 2008, 108, 3239 – 3265;
e) D. J. Gorin, B. D. Sherry, F. D. Toste, Chem. Rev. 2008, 108,
3351 – 3378; f) R. Skouta, C. J. Li, Tetrahedron 2008, 64, 4917 –
4938; g) E. Jimꢀnez-NfflÇez, A. M. Echavarren, Chem. Rev. 2008,
108, 3326 – 3350; h) A. Fürstner, P. W. Davis, Angew. Chem.
2007, 119, 3478 – 3519; Angew. Chem. Int. Ed. 2007, 46, 3410 –
3449; i) A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180 – 3211; j) L.
Zhang, J. Sun, S. A. Kozmin, Adv. Synth. Catal. 2006, 348, 2271 –
2296.
[9] A. S. K. Hashmi, J. P. Weyrauch, M. Rudolph, E. Kurpejovic,
Angew. Chem. 2004, 116, 6707 – 6709; Angew. Chem. Int. Ed.
2004, 43, 6545 – 6547.
[10] A. S. K. Hashmi, M. C. B. Jaimes, A. M. Schuster, F. Rominger,
J. Org. Chem. 2012, 77, 6394 – 6408.
[11] A. S. K. Hashmi, Angew. Chem. 2010, 122, 5360 – 5369; Angew.
Chem. Int. Ed. 2010, 49, 5232 – 5241.
[12] a) L. Zhang, J. Am. Chem. Soc. 2005, 127, 16804 – 16805; b) L.
Zhang, S. Wang, J. Am. Chem. Soc. 2006, 128, 1442 – 1443; c) J.
Zhao, C. O. Hughes, F. D. Toste, J. Am. Chem. Soc. 2006, 128,
7436 – 7437; d) D. Garayalde, E. Gómez-Bengoa, X. Huang, A.
Gçeke, C. Nevado, J. Am. Chem. Soc. 2010, 132, 4720 – 4730;
e) A. S. K. Hashmi, W. Yang, Y. Yu, M. M. Hansmann, M.
Rudolph, F. Rominger, Angew. Chem. 2013, 125, 1408 – 1410;
Angew. Chem. Int. Ed. 2013, 52, 1368 – 1371; f) W. Yang, Y. Yu, T.
Zhang, M. M. Hansmann, D. Pflästerer, A. S. K. Hashmi, Adv.
Synth. Catal. 2013, 355, 2037—2043; g) Y. Yu, W. Yang, F.
Rominger, A. S. K. Hashmi, Angew. Chem. 2013, 125, 7735 –
7738; Angew. Chem. Int. Ed. 2013, 52, 7586—7689.
[13] a) G. Zhang, Y. Peng, L. Cui, L. Zhang, Angew. Chem. 2009, 121,
3158 – 3161; Angew. Chem. Int. Ed. 2009, 48, 3112 – 3115; b) T.
de Haro, C. Nevado, Chem. Commun. 2011, 47, 248 – 249.
[14] a) H. J. Kim, S. H. Cho, S. Chang, Org. Lett. 2012, 14, 1424 –
1427; b) T. B. Liam, C. L. Guy, A. R. Christopher, Science 2012,
337, 1644 – 1648.
[2] a) L. Cui, G. Zhang, L. Zhang, Bioorg. Med. Chem. Lett. 2009,
19, 3884 – 3887; for preceding work, see: A. S. K. Hashmi, T. D.
Ramamurthi, F. Rominger, J. Organomet. Chem. 2009, 694, 592 –
597.
[3] Y. Peng, L. Cui, G. Zhang, L. Zhang, J. Am. Chem. Soc. 2009,
131, 5062 – 5063.
[4] A. Kar, N. Mangu, H. M. Kaiser, M. Beller, M. K. Tse, Chem.
Commun. 2008, 386 – 388.
[5] H. A. Wegner, M. Auzias, Angew. Chem. 2011, 123, 8386 – 8397;
Angew. Chem. Int. Ed. 2011, 50, 8236 – 8247.
[6] T. Haro, C. Nevado, J. Am. Chem. Soc. 2010, 132, 1512 – 1513.
[7] a) C. J. Forsyth, J. Xu, S. T. Nguyen, I. A. Samdal, L. R. Briggs, T.
Rundberget, M. Sandvik, C. O. Miles, J. Am. Chem. Soc. 2006,
128, 15114 – 15116; b) K. C. Nicolaou, D. Sarlah, D. M. Shaw,
Angew. Chem. 2007, 119, 4792 – 4795; Angew. Chem. Int. Ed.
2007, 46, 4708 – 4711; c) B. H. Xu, G. Kehr, R. Frçhlich, B.
Wibbeling, B. Schirmer, S. Grimme, G. Erker, Angew. Chem.
2011, 123, 7321 – 7324; Angew. Chem. Int. Ed. 2011, 50, 7183 –
7186.
[15] a) D. Wang, Y. Zhang, R. Cai, X. Shi, Beilstein J. Org. Chem.
2011, 7, 1014 – 1020; A. S. K. Hashmi, C. Lothschütz, Chem-
CatChem 2010, 2, 133 – 134.
[16] T. de Haro, C. Nevado, Angew. Chem. 2011, 123, 936 – 940;
Angew. Chem. Int. Ed. 2011, 50, 906 – 910.
Angew. Chem. Int. Ed. 2014, 53, 1144 –1147
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1147