Gold-Catalyzed One-Pot Synthesis of 1,3-Disubstituted Allenes from Benzaldehydes and Terminal Alkynes

Article abstract of DOI:10.1002/adsc.201900824

A new and facile one-pot synthesis of 1,3-disubstituted allenes, using cheap and readily available terminal alkynes, benzaldehyde derivatives and morpholine, was developed. A small library of 20 allenes demonstrates a broad applicability, with yields up t

Full text of DOI:10.1002/adsc.201900824

Title: Gold-Catalyzed One-Pot Synthesis of 1,3-Disubstituted Allenes
from Benzaldehydes and Terminal Alkynes
Authors: Danilo Lustosa, Simon Clemens, Matthias Rudolph, and A.
Stephen K. Hashmi
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10.1002/adsc.201900824
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201900824
Gold-Catalyzed One-Pot Synthesis of 1,3-Disubstituted Allenes
from Benzaldehydes and Terminal Alkynes
Danilo M. Lustosa,a Simon Clemens,a Matthias Rudolph,a A. Stephen K. Hashmia*
a
Organisch-Chemisches Institut, Heidelberg University, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
E-mail: hashmi@hashmi.de
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A new and facile one-pot synthesis of 1,3-
disubstituted allenes, using cheap and readily available
terminal alkynes, benzaldehyde derivatives and morpholine,
was developed. A small library of 20 allenes demonstrates a
broad applicability, with yields up to 86%. Isotopic-labelling
and cross-over experiments strongly indicate that our reaction
proceeds via a two-step A3-coupling followed by a 1,5-
hydrogen shift process..
Keywords: Aldehydes; Alkynes; Gold; Deuterium;
Reaction mechanisms
alkynes to generate allenes.[6] While the original
Crabbé report was restricted to formaldehyde, some
efforts toward the development of a more general
synthesis of allenes were made (Scheme 1.b).[7] In
2010, Ma and coworkers used 0.7 equivalents of ZnI2
to access 1,3-disubstituted allenes, having the
formation of a propargylamine as intermediate
(Scheme 1.c).[7a] In 2011 Mukai reported a Cu(I)-
catalyzed method to achieve the same transformation
(Scheme 1.d),[7b] but still, the large amount of metal
salt or the need for high temperatures and high
catalytic loadings are not ideal. In addition, Mukai´s
method is not suitable for 1,3-diaryl-substituted
allenes - with yields of 30% for benzaldehyde and only
14% for phenylacetylene.
Introduction
During the past decade, the chemistry of allenes has
shifted from a chemical curiosity toward its use as a
common building block for the synthesis of complex
molecules. This can be underlined by 31 relevant
reviews highlighting their transformation from basic
organic chemistry to applied sciences (years of 2007-
2018).[1] In gold catalysis, allenes have early been
recognized
as
interesting
substrates[2]
for
cycloisomerizations,[3] as electrophiles, or as
intermediates for [3,3]-sigmatropic rearrangements of
propargylic esters.[1d] However, a limiting factor for
the application of allenes in organic synthesis is still
the synthesis of the allenes themselves.[1s,1u,1z,1aa]
Illustrated by one of the first popular methodologies
for the synthesis of allenes - the Doering-Moore-
Skattebol synthesis,[4] often highly reactive bases have
to be applied, accompanied by a low functional group
tolerance and a large generation of chemical waste
(Scheme 1.a). Other modern approaches, such as
sigmatropic
rearrangements
or
alkyne
isomerizations,[1z,5] can indeed furnish allenes by using
milder and more environmentally-friendly conditions,
but the need for spatially constrained arrangements
between functional groups in a given molecule in order
to allow the transformation is a drawback. No
activating groups, neither strict spatial arrangement of
functional groups are needed with the Crabbé
synthesis, an outstanding reaction between
formaldehyde, diisopropylamine and a terminal
1
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10.1002/adsc.201900824
Advanced Synthesis & Catalysis
Indeed, we herein report the first gold(I)-catalyzed
Crabbé-like reaction, applicable to the synthesis of a
wide range of 1,3-disubstituted allenes using as little
as 2.5 mol% of catalyst, mild conditions, open flask
techniques and commercially available starting
materials, such as morpholine, benzaldehyde
derivatives and terminal alkynes (Scheme 2c).
Scheme 1. Previous work.
A Crabbé-like process is not reported to be mediated
by gold catalyst. A closely related report is the
conversion of the propargylamines to allenes mediated
by gold(III)-catalyst reported by Che in 2008 (Scheme
2.b).[8] Che’s propargylamines were synthesized using
an Au(III)(Salen)Cl as a catalyst, following a method
reported previously by himself in 2006 (Scheme 2a).[9]
Although in a first sight the combination of the two
steps towards an Au-catalyzed Crabbé-like process
seems to be an obvious extension, a careful look into
the reported reaction conditions will unveil that this is
not the case: First, the propargylamines were
synthesized in water, a solvent which would most
probably lead to full hydrolysis of the allene in
presence of Au(III). Second, and most importantly, the
propargylamine synthesis was catalyzed by an Au(III)
species, whereas Che`s suggest that the synthesis of
allenes was achieved via Au(I) catalysis and that
KAu(III)Cl4 was solely used as a precursor for the real
catalytic species, meaning that catalysts with
completely different electronic characteristics are
required for each step.
Scheme 2. Planned gold-catalyzed Crabbé-like reaction for
the synthesis of 1,3-disubstituted allenes.
Results and Discussion
Table 1 summarizes the main steps of our
investigation, starting with the evaluation of different
gold catalysts (entries 1-6). Just as expected, similar
conditions to Che’s, using Au(III) species, such as
.
AuBr3 (entry 1) and KAuCl4 H2O (entry 2), promoted
the formation of the A3-coupling product 4a, but with
no formation of the desired allene 5a. After that, two
different counter ions[13] were tested in combination
with the common IPr gold(I) species: The nitrile-
stabilized preactivated [IPrAu(NCCH3)]SbF6 catalyst
(entry 4) only delivered a poor yield of propargylic
amine 4a, however, to our delight, the stronger
coordinating counter ion of IPrAuNTf2 (entry 6),
successfully yielded the allene 5a. As a next step,
different solvents were also tested (entries 7 – 12).
Both THF and toluene (entry 7 and 8) yielded the A3-
coupling product 4a in very good yield, but only 25%
Furthermore, as Au is already known to be a potent
mediator for A3-couplings (aldehyde-alkyne-amine
reactions)[10] and has also been reported to mediate
hydride shifts,[11] we envisioned that a combination of
these elementary steps under adjusted conditions
would open up a more efficient entry towards valuable
allenes. On the other hand, one has to keep in mind that
allenes are substrate in gold-catalyzed reactions.[12]
2
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10.1002/adsc.201900824
Advanced Synthesis & Catalysis
of the allene 5a. When DCE was applied, the allene 5a
was obtained in 31% yield, after 48 h (entry 9).
Shifting to common alcoholic solvents (entry 10 -11)
delivered the allene in moderate yield, while the use of
trifluoroethanol (TFE) - a solvent known for high
conversion rates in gold-catalyzed A3-coupling
reactions,[14] led to the final product in 65% yield
(entry 11). 70% of allene were obtained when
molecular sieves were added as an additive (entry 12).
Table 1. Catalyst screening for the gold-catalyzed Crabbé-
5a [%][b]
70
homologation.[a]
Entry
IPrAuNTf2 [mol %]
1
2
3
4
5
6
10
5
70
2.5
1
70
60
0.5
47
65[c]
2.5
a) Reaction conditions: 0.7 mL solvent (dried over molecular
sieve), 50 µmol of 1a, 60 µmol of 2, 75 µmol of 3a with ~25
b)
1
mg of molecular sieve. Yield determined by H NMR
Entry
Catalyst
Solvent
4
5a
c)
using 2-picoline as internal standard. isolated yield: 1.22
[%][b] [%][b]
g of the product was obtained.
1
AuBr3
KAuCl4 x H2O
HAuCl4 x H2O
[IPrAu(NCCH3)]SbF6
PPh3AuNTf2
IPrAuNTf2
D3COD
D3COD
D3COD
D3COD
D3COD
D3COD
d8-THF
Toluene
DCE
48
56
37
26
12
36
74
75
0
0
0
2
Under the optimal conditions we prepared several
~allenes bearing both, electron-donating and electron-
withdrawing groups (Table 3). When 4-
chlorobenzaldehyde was used, the corresponding
allene was obtained in 74%, whereas other acceptor-
substituted benzaldehyde derivatives furnished the
desired products in yields ranging from 39% of 5h to
58% of 5g. the substitution effect of donor-substituted
benzaldehydes was less pronounced and neither the
change from methyl to methoxyl (5l to 5i) nor a change
of the position of the methoxyl group (5i, 5j and 5k)
resulted in a substantial change of the observed yield.
Only in the case of a trifold donor substitution, a slight
drop in yield was observed (5m).
3
0
4
5
0
0
6
59
25
25
31
31
65
70
7
IPrAuNTf2
8
IPrAuNTf2
9
IPrAuNTf2
10
11[c]
12[c,d]
IPrAuNTf2
tBuOH
25
10
18
IPrAuNTf2
TFE
IPrAuNTf2
TFE
a)
Reaction conditions: 0.7 mL solvent, 50 µmol of 1a, 60
b)
µmol of 2 and 3a and 6.5 µmol of gold catalyst. Yield
determined by 1H NMR using 2-picoline as internal
standard. c) 10 mol% catalyst. d) 25 mg of molecular sieve (3
Ǟ).
Table 3. Scope with respect to the aldehyde.[a]
Next, the amount of catalyst was reduced stepwise,
from 10 to 0.5 mol% (Table 2). It was possible to
reduce the amount of catalyst to 2.5 mol% (entry 3)
without affecting the yield of 5a. If even lower
amounts were used the allene was also formed, but in
reduced yields (entries 4-5). With 2.5 mol% of catalyst,
the reaction was scaled-up to 8 mmol scale. After 48 h,
the reaction crude was purified to afford 5a in 65%
yield (1.22 g) (entry 6).
Table 2. Catalyst-loading screening for the gold-catalyzed
Crabbé homologation.[a]
3
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10.1002/adsc.201900824
Advanced Synthesis & Catalysis
a) Reaction conditions: 0.7 mL solvent (dried over molecular
sieve), 50 µmol of 1a, 60 µmol of 2, 75 µmol of 3 with ~25
mg of molecular sieve. b) yield determined by 1H NMR.
In analogy to the reported Crabbé-like process
promoted by zinc iodine[7a] and related processes,[15]
we suggest that the formation of the allenes 5 from
morpholine 2 and alkyne 3 happens in a multistep
process in which, at first, a A3 coupling reaction takes
place and, the formed propargylamine 4t then reacts
further to generate the allene 5a. It is necessary to
stress that the propargylamine has been isolated during
the optimization of the reaction conditions, but to
prove its participation as a reaction intermediate,
propargylamine 4a was synthesized and, after
isolation, submitted to our standard reaction
conditions. As expected, allene 5a was formed in 78%
yield (Scheme 3). Additionally, a blank test was
performed, but no conversion of 4 was observed if
gold is not added to the reaction.
a) Reaction conditions: 0.7 mL solvent (dried over molecular
sieve), 50 µmol of 1a, 60 µmol of 2, 75 µmol of 3a with
~25 mg of molecular sieve.
A variety of different alkyl-substituted alkynes were
also evaluated. Generally, the desired allenes were
furnished in good yields (5n-5p and 5r) (Table 4).
Exceptions can be made to entries 5q and 5s, where
the low boiling points of the products led to losses
during the work-up. It is worth mentioning that a 1,3-
diaryl-substituted allene 5t was only obtained in
moderate yield. Three of the products were very
sensitive towards polymerization, 5d, 5m, and 5p even
directly after the purification already show a baseline
spot in TLC and polymer signals in the NMR samples.
We repeated these experiments a number of times,
after several days, even in the freezer, these products
show complete polymerization.
For 5f and 5h no full conversion was observed, the
aldehyde was still present, but the propargyl amine
was consumed (probably polymerized), thus the
relative rate of allene formation versus decomposition
of the propargyl amine in these cases is responsible for
the low yield.
Scheme 3. Stepwise process.
Table 4. Scope with respect to the alkyne.[a]
To proof a potential 1,5-hydrogen shift as key step
for the transformation of the A3-Coupling product
(propargylamine 4) to the final allene, deuterated
propargylamine 4u was synthesized and submitted to
the reaction condition after its isolation. Once the
reaction was complete (after 24 h), complete
4
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10.1002/adsc.201900824
Advanced Synthesis & Catalysis
deuterium incorporation was found at the expected
1
position of 5u (analyzed by H NMR and mass
spectrometry) which strongly supports that a 1,5-
hydrogen shift indeed takes place (Scheme 4).
Scheme 4. Isotopic labelling experiment: Synthesis of 4u
from 5u.
Scheme 6. Mechanistic proposal.
Conclusion
Finally, a cross-over reaction using equal amounts
of 4u and 4v as starting material was performed
(Scheme 5). After complete conversion of the starting
materials, mass analysis showed that only about 3% of
deuterium/hydrogen scrambling in the products 5u and
5v, reinforcing the suggesting that an intramolecular
1,5-hydrogen shift dominates.
To sum up, the limitations of the Crabbé allene
synthesis have been overcome, 1,3-disubstituted
allenes are now accessible from cheap commercial
starting materials. A small library of 20 allenes
demonstrates a broad applicability, with yields up to
86%. Isotopic-labelling and cross-over experiments
provide new mechanistic insights. This method
perfectly complements the toolbox of allene syntheses,
offering a simple approach that can be upscaled.
The increase of yield when using molecular sieves,
supports the idea of formation of the iminium species
being reversible in the presence of the by-product
water. A recent study by Lopez et al.[15d] discussed that
even future enantioselective variations can be
envisioned.
Experimental Section
Au-catalzyed one-pot synthesis of 1,3-dissubstituted
allenes
The benzaldehyde derivative (1.0 eq.), morpholine (1.2 eq.)
and the alkyne (1.5 eq.) were dissolved in TFE (0.1 M),
followed by addition of 2.5 mol% of catalyst and molecular
sieves (3A, ~25 mg). The reaction mixture was let to stir in
a glass vial, for 48 h at 70 °C. Lastly, solvent was removed
under reduced pressure and the reaction crude was purified
via chromatographical methods with no prior work-up.
Scheme 5. Cross-over experiment between 4u and 4v.
5a was synthesized according to that procedure, using 21.2
mg benzaldehyde (200 µmol, 1.0 eq.), 30.0 mg morpholine
(241 µmol, 1.2 eq.) and 33.0 mg 1-octyne (300 µmol, 1.5
eq.). Purification was accomplished by flash column
chromatography (silica gel, PE). Appearance: colorless oil;
Yield: 65% (26 mg,130 µmol); 1H NMR (500 MHz, CDCl3)
 7.31 (d, J = 4.3 Hz, 3H), 7.20 (dq, J = 8.7, 4.2 Hz, 1H),
6.14 (dt, J = 6.1, 2.9 Hz, 1H), 5.58 (q, J = 6.7 Hz, 1H), 2.15
(qd, J = 7.2, 2.9 Hz, 2H), 1.54 – 1.47 (m, 2H), 1.42 – 1.27
(m, 6H), 0.90 (t, J = 6.8 Hz, 3H); 13C NMR (126 MHz,
CDCl3) δ 205.30 (s), 135.32 (s), 128.67 (2C; d), 126.73 (d),
126.71 (d), 95.25 (d), 94.67 (d), 31.80 (t), 29.29 (t), 29.02
(t), 28.91 (t), 5.79 (t), 14.21 (q).
Based on the present data we propose a sequential
process with two different catalytic cycles that are
mediated by the same catalyst. While a common A3-
coupling delivers propargylamine
4
via the
intermediates A, B and C, an activation of this
intermediate and I via the -complex II, induces a 1,5-
hydrogen shift under formation of vinyl gold species
III. Allene 5 is then formed via -elimination of the
imine moiety 6 under release of the active catalyst
(Scheme 6).
5b was synthesized according to that procedure using 28.3
mg 4-chlorobenzaldehyde (200 µmol, 1.0 eq.), 20.5 mg
morpholine (235 µmol, 1.2 eq.) and 33.0 mg 1-octyne (299
µmol, 1.5 eq.). Purification was accomplished by flash
column chromatography (silica gel, PE)
5
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10.1002/adsc.201900824
Advanced Synthesis & Catalysis
Appearance: colorless oil; Yield: 74% (34.7 mg ,147 µmol);
1H NMR (301 MHz, CDCl3)  7.28 – 7.17 (m, 4H), 6.07 (dt,
J = 6.2, 3.0 Hz, 1H), 5.57 (q, J = 6.7 Hz, 1H), 2.12 (ddd, J =
14.4, 7.0, 3.0 Hz, 2H), 1.46 (dd, J = 14.7, 7.7 Hz, 2H), 1.41
– 1.24 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz,
CDCl3)  205.40 (s), 133.91 (s), 132.25 (s), 128.79 (2C; d),
127.86 (2C; d), 95.65 (d), 93.83 (d), 31.76 (t), 29.20 (t),
28.97 (t), 28.79 (t), 5.76 (t), 14.17 (q). IR (reflection, cm-1):
ν = 2956, 2928, 2857, 1708, 1593, 1491, 1466, 1092, 1014,
834; HR-MS (EI) m/z calcd for C15H19Cl: 234.1175; found:
234.1175.
130, 6940-6941; c) C. Winter, N. Krause, Angew. Chem.
Int. Ed. 2009, 48, 6339-6342; d) N. Morita, N. Krause,
Angew. Chem. Int. Ed. 2006, 45, 1897-1899; e) N.
Morita, N. Krause, Org. Lett. 2004, 6, 4121-4123; f) B.
Gockel, N. Krause, Org. Lett. 2006, 8, 4485-4488.
[3] X. Jiang, X. Ma, Z. Zheng, S. Ma, Chem. Eur. J. 2008,
14, 8572-8578.
[4] a) L. Skattebøl, S. Solomon, Org. Synth. 2003; b) J. A.
Marshall, E. D. Robinson, A. Zapata, J. Org. Chem.
1989, 54, 5854-5855.
Acknowledgements
[5] a) Y. Matsumoto, M. Naito, Y. Uozumi, T. Hayashi, J.
Chem. Soc., Chem. Commun. 1993, 1468-1469; b) L.
Zhang, J. Am. Chem. Soc. 2005, 127, 16804-16805; c) E.
González-Cantalapiedra, Ó. de Frutos, C. Atienza, C.
Mateo, M. Echavarren Antonio, Eur. J. Org. Chem.
2006, 2006, 1430-1443; d) D. Wang, L. N. S. Gautam,
C. Bollinger, A. Harris, M. Li, X. Shi, Org. Lett. 2011,
13, 2618-2621.
D. M. Lustosa is grateful for a Science without Borders fellowship
of the Brazilian Council for Scientific and Technological
Development (CNPQ).
References
[1] a) S. Ma, Chem. Rev. 2005, 105, 2829-2872; b) S. Yu, S.
Ma, Angew. Chem. Int. Ed. Engl. 2012, 51, 3074-3112;
c) J. Ye, S. Ma, Acc. Chem. Res. 2014, 47, 989-1000; d)
W. Yang, A. S. K. Hashmi, Chem. Soc. Rev. 2014, 43,
2941-2955; e) M. A. Tius, Chem. Soc. Rev. 2014, 43,
2979-3002; f) D. Tejedor, G. Mendez-Abt, L. Cotos, F.
Garcia-Tellado, Chem. Soc. Rev. 2013, 42, 458-471; g)
P. Rivera-Fuentes, F. Diederich, Angew. Chem. Int. Ed.
Engl. 2012, 51, 2818-2828; h) T. M. V. D. Pinho e Melo,
Monatsh. Chem. 2011, 142, 681-697; i) M. North,
Angew. Chem. Int. Ed. Engl. 2009, 48, 4104-4105; j) C.
Mukai, F. Inagaki, S. Kitagaki, Synlett 2011, 2011, 594-
614; k) S. Montserrat, G. Ujaque, F. Lopez, J. L.
Mascarenas, A. Lledos, Top. Curr. Chem. 2011, 302,
225-248; l) S. Ma, Pure Appl. Chem. 2006, 78, 197-208;
m) F. Lopez, J. L. Mascarenas, Chem. Eur. J. 2011, 17,
418-428; n) A. Lledo, A. Pla-Quintana, A. Roglans,
Chem. Soc. Rev. 2016, 45, 2010-2023; o) N. Krause, C.
Winter, Chem. Rev. 2011, 111, 1994-2009; p) M.
Jeganmohan, C. H. Cheng, Chem Commun. 2008, 3101-
3117; q) A. Hoffmann-Röder, N. Krause, Angew. Chem.
Int. Ed. Engl. 2004, 43, 1196-1216; r) I. Dion, A. M.
Beauchemin, Angew. Chem. Int. Ed. Engl. 2011, 50,
8233-8235; s) W.-D. Chu, Y. Zhang, J. Wang, Catal. Sci.
Technol. 2017, 7, 4570-4579; t) S. R. Chemler, Org
Biomol Chem 2009, 7, 3009-3019; u) K. Brummond, J.
DeForrest, Synthesis 2007, 2007, 795-818; v) R. W.
Bates, V. Satcharoen, Chem. Soc. Rev. 2002, 31, 12-21;
w) E. V. Banide, P. Oulié, M. J. McGlinchey, Pure Appl.
Chem. 2009, 81, 1-17; x) C. Aubert, L. Fensterbank, P.
Garcia, M. Malacria, A. Simonneau, Chem. Rev. 2011,
111, 1954-1993; y) B. Alcaide, P. Almendros, C.
Aragoncillo, Chem. Soc. Rev. 2010, 39, 783-816; z) S.
Yu, S. Ma, Chem Commun (Camb) 2011, 47, 5384-
5418; aa) M. Ogasawara, Tetrahedron: Asymmetry 2009,
20, 259-271; ab) T. Bai, S. Ma, G. Jia, Coord. Chem.
Rev. 2009, 253, 423-448; ac) A. S. K. Hashmi, Angew.
Chem. Int. Ed. 2000, 39, 3590-3593; ad) S. Ma, Acc.
Chem. Res. 2009, 42, 1679-1688; ae) M. Brasholz, H.-
U. Reissig, R. Zimmer, Acc. Chem. Res. 2009, 42, 45-56.
[6] P. Crabbé, H. Fillion, D. André, J.-L. Luche, J. Chem.
Soc., Chem. Commun. 1979, 859-860.
[7] a) J. Kuang, S. Ma, J. Am. Chem. Soc. 2010, 132, 1786-
1787; b) S. Kitagaki, M. Komizu, C. Mukai, Synlett
2011, 2011, 1129-1132; c) J. Kuang, S. Ma, J. Org.
Chem. 2009, 74, 1763-1765.
[8] V. K.-Y. Lo, M.-K. Wong, C.-M. Che, Org. Lett. 2008,
10, 517-519.
[9] V. K.-Y. Lo, Y. Liu, M.-K. Wong, C.-M. Che, Org. Lett.
2006, 8, 1529-1532.
[10] a) F. Xiao, Y. Chen, Y. Liu, J. Wang, Tetrahedron
2008, 64, 2755-2761; b) J. Li, M. Rudolph, F. Rominger,
J. Xie, Adv. Synth. Catal. 2016, 358, 207-211; c) B. Yan,
Y. Liu, Org. Lett. 2007, 9, 4323-4326; d) Q. Zhang, M.
Cheng, X. Hu, B.-G. Li, J.-X. Ji, J. Am. Chem. Soc. 2010,
132, 7256-7257.
[11] T. Wirtanen, M. Muuronen, M. Melchionna, M.
Patzschke, J. Helaja, J. Org. Chem. 2014, 79, 10269-
10283
[12] a) A. S. K. Hashmi, T. M. Frost, J. W. Bats, J. Am.
Chem. Soc. 2000, 122, 11553-11554; b) A. S. K. Hashmi,
L. Schwarz, J.-H. Choi, T. M. Frost, Angew. Chem. Int.
Ed. 2000, 39, 2285-2288.
[13] J. Schießl, J. Schulmeister, A. Doppiu, E. Wörner, M.
Rudolph, R. Karch, A. S. K. Hashmi, Adv. Synth. Catal.
2018, 360, 3949-3959.
[14] a) C. Cativiela, J. I. García, J. Gil, R. M. Martínez, J.
A. Mayoral, L. Salvatella, J. S. Urieta, A. M. Mainar, M.
H. Abraham, J. Chem. Soc., Perk. Trans. 2 1997, 653-
660; b) G. A. Price, A. K. Brisdon, K. R. Flower, R. G.
Pritchard, P. Quayle, Tetrahedron Lett. 2014, 55, 151-
154.
[15] For a related copper-catalyzed process, see: a) H.
Fillion, U. Andrd, J.-L. Luche, Tetrahedron Lett. 1980,
21, 929-930; for gold-catalyzed reactions of propargylic
ethers, see: b) B. Bolte, Y. Odabachian, F. Gagosz, J. Am.
Chem. Soc. 2010, 132, 7294-7296; For a computational
study on the copper catalysis, see: c) M. Gonzalez, R.
[2] a) A. W. Sromek, M. Rubina, V. Gevorgyan, J. Am.
Chem. Soc. 2005, 127, 10500-10501; b) Y. Xia, A. S.
Dudnik, V. Gevorgyan, Y. Li, J. Am. Chem. Soc. 2008,
6
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10.1002/adsc.201900824
Advanced Synthesis & Catalysis
Alvarez Rodrıguez, M. M. Cid, C. Silva Lopez, J.
Computational Chem. 2012, 33, 1236-1239; for
computations on copper, silver and gold catalysis, see:
d) M. M. Cid, M. Lago-Silva, M. G. Comesaña, O. N.
Faza, C. S. López, Org. Chem. Front. 2019, 6, 1780-
1786.
7
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10.1002/adsc.201900824
Advanced Synthesis & Catalysis
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Gold-Catalyzed One-Pot Synthesis of 1,3-
Disubstituted Allenes from Benzaldehydes and
Terminal Alkynes
Adv. Synth. Catal. Year, Volume, Page – Page
Danilo M. Lustosa, Simon Clemens, Matthias
Rudolph, A. Stephen K. Hashmi*
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