Propargylsilanes as Reagents for Synergistic Gold(I)-Catalyzed Propargylation of Carbonyl Compounds: Isolation and Characterization of σ-Gold(I) Allenyl Intermediates

Article abstract of DOI:10.1002/anie.201905159

Reported herein is the isolation and characterization, for the first time, of a σ-gold allenyl complex as an intermediate in gold catalysis. This intermediate was captured during the study of a novel gold(I)-catalyzed propargylation of carbonyl compounds with propargylsilanes. Notably, the gold-catalyzed propargylation reaction, which proceeds with aldehydes and ketones, can be driven to the formation of either homopropargyl silyl ethers or the in situ synthesis of corresponding 2-silyl-4,5-dihydrofurans.

Full text of DOI:10.1002/anie.201905159

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Accepted Article
Title: Propargylsilanes as Reagents for Synergistic Gold(I) Catalyzed
Propargylation of Carbonyl Compounds. Isolation and
Characterization of σ-Gold(I) Allenyl Intermediates
Authors: Sergio Fernández, Jairo González, Javier Santamaría, and
Alfredo Ballesteros
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201905159
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10.1002/anie.201905159
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Propargylsilanes as Reagents for Synergistic Gold(I) Catalyzed
Propargylation of Carbonyl Compounds. Isolation and
Characterization of -Gold(I) Allenyl Intermediates
Sergio Fernández,[a] Jairo González, [a] Javier Santamaría[a],* and Alfredo Ballesteros[a],*
Abstract: Herein we report the isolation and characterization, for the
first time, of a -gold allenyl complex as intermediate in gold
catalysis. This intermediate was captured in the course of the study
of a novel gold(I) catalyzed propargylation of carbonyl compounds
with propargylsilanes. On the other hand, gold catalyzed
Here we present an efficient and synergistic gold catalyzed
carbonyl propargylation reaction, to form homopropargyl silyl
ethers, starting from propargylsilanes. This transformation
seems to involve a -gold allenyl complex intermediate that
could be isolated and characterized. In addition, homopropargyl
propargylation reaction, which proceeds with aldehydes and ketones, silyl ethers can undergo a gold catalyzed cycloisomerization
can be driven to the formation of homopropargyl silyl ethers or the in
situ synthesis of the corresponding 2-silyl-4,5-dihydrofurans.
yielding the corresponding 4,5-dihydrofurans (Figure 1; bottom).
Homogeneous gold catalysis has emerged as a powerful tool
promoting a large number of processes in modern organic
synthesis.[1] However, propargylation reactions, which have
been reported with several metalates,[2] remains as an elusive
field in gold catalysis, further than the recent work by Zhang and
co-workers.[3] In this sense, Zhang et al., published very
recently[3b] an excellent and very carefully designed gold(I)
catalyzed propargylation reaction of aldehydes (Figure 1; top).
On the other hand, the quest for the isolation and
characterization of gold intermediates has been a target largely
pursued.[4] In this field, our group was able to characterize a -
gold allylic cation, closely related to allenyl gold complexes,[5] as
intermediate in gold catalyzed enyne cycloisomerizations.[6]
However, although several -gold allenyl[7] and gold
allenylidene[8] complexes have been isolated and characterized,
-gold
allenyl
complexes
remained
unknown
until
characterization by Gimeno and co-workers,[9] and very recently
by Hashmi et al.,[10] although in both cases, without catalytical
relevance. These species have also received low attention as
intermediates in gold catalytic reactions, with the exception of
the very recent works by Zhang and co-workers[3b] and Pyne,
Hyland and co-workers.[11]
In the course of our investigations related to the use of
alkynylsilanes in gold catalyzed transformations,[12] we decided
to investigate the behavior of these compounds wearing two
potentially reactive silylated positions in their structure. With this
target in mind, we focused our work in 1,3-disilylpropyne
derivatives, which include an additional silyl group placed at the
propargylic position. Propargylsilanes usually react, catalytically
or not, with carbonyls in the presence of a Lewis acid, to form
allenyl alcohols,[13] although silyl migrations have also been
described.[14]
Figure 1. Gold catalyzed propargylations. TMS = Trimethylsilyl; TBS = Tert-
butyldimethylsilyl.
Following our investigations with gold catalyzed reactions using
trimethylsilylalkynes and carbonyl compounds,[12a-b] we initially
reacted 3-phenyl-1,3-bis(trimethylsilyl)-1-propyne 1, as the
model compound, with p-tolualdehyde 2a or benzophenone 2b,
in dichloromethane at room temperature, using a gold catalyst
with
a
tris(2,4-di-tert-butylphenyl)phosphite
ligand.
Bis(trifluoromethanesulfonyl)imidate was used as counteranion
to avoid the use of silver salts for the generation of the
corresponding catalyst. To our surprise, we did not observed the
formation of any product related to an initial gold acetylide
addition to the aldehyde, but compounds 3a and 3b were formed
in moderate yields and as an almost equimolecular mixture of
diastereoisomers for 3a (Scheme 1). The structure of the
[a]
S. Fernández, Dr. J. González, Dr. J. Santamaría, Prof. Dr. A.
Ballesteros
trimethylsilyloxyhomopropargyl
compounds
3a,b
was
unambiguously determined by NMR and by an X-Ray analysis
performed on a monocrystal of compound 3b.[15]
Instituto Universitario de Química Organometálica “Enrique Moles”
and Departamento de Química Orgánica e Inorgánica
Universidad de Oviedo
c/ Julián Clavería 8, 33007, Oviedo (Spain)
E-mail: abg@uniovi.es, jsv@uniovi.es.
Supporting information for this article is given via a link at the end of
the document-
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10.1002/anie.201905159
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Table 1. Scope of the reaction
Scheme 1. Preliminary results and X-ray structure of 3b.
Due to partial decomposition of alkyne 1 through the formation
of an allene derivative, the use of 3 equivalents of 1 dramatically
increased the yield of compound 3a to a ca. 80%, after
chromatographic
trimethylsilyl group of the alkynyl position by
purification.
Alternatively,
replacing
tert-
a
butyldimethylsilyl allowed an almost equimolecular employ of
both reagents presumably due to their higher stability. In this
sense, the reaction of 1.2 equivalents of 3-phenyl-1-tert-
butyldimethylsilyl-3-trimethylsilyl-1-propyne
4a
with
p-
tolualdehyde 2a, under the selected reaction conditions, arises
in the formation of silyloxy compound 5a in quantitative yield
(Table 1; 5a). Finally, from a ligand screening,[16] phosphite
ligand emerged as the best choice.
We next analyzed the scope of the reaction in terms of the
nature of the carbonyl compound 2. Additionally, as a proof of
the goodness of the reaction, the catalyst load was reduced to
2.5 mol%. Finally, a ca. 5 mol% of a phosphine ((p-MeO-
C6H4)3P) was added at the end of the reaction to inactivate the
gold catalyst and avoid potential decomposition. Although
almost negligible diastereoselectivity was observed,[16] the
reaction occurs in very high yields and the propargylation can be
performed with aldehydes (5a-o,5s-u) and also aliphatic or
aromatic ketones (5p-r) (Table 1). In terms of the substitution
pattern in the aromatic ring of carbonyl compounds 2, it tolerates
the presence of donor (5a,5c,d,5g-i) and acceptor groups (5e,f)
and it could also be accomplished with heterocyclic aldehydes
(5j,k). Finally, the reaction works also satisfactorily for aliphatic
propargylic silanes (5l,m). Moreover, in addition to tert-
butyldimethylsilylalkynes, to our surprise, high sterically
demanding systems, such as alkynyl substituted triisopropylsilyl
and triphenylsilyl compounds, were also able to perform the
reaction quantitatively, to form the corresponding silyl ethers 5s,t.
Finally, in order to establish, whether or not, the presence of an
alkynyl silyl moiety is a requirement for the reaction, we
observed that propargylation could also be achieved, in 84%
yield (5u), using a tert-butylacetylene derivative.
[a]Performed at -20 ºC. [b]3h of reaction. [c]5 mol% of catalyst. [d]3 Equivalents of
4. [e]16h of reaction. TIPS = Triisopropylsilyl
Next, a mechanistic proposal for the catalytic formation of
compounds 5 could be formulated and it is outlined in Scheme 2.
Initially, a -coordination of gold catalyst to the alkyne could
occur, to form intermediate I. This intermediate
I could
subsequently evolve towards the formation of -gold(I) allenyl
intermediate II. This evolution might be facilitated by the
participation of the triflimidate anion and also by the carbonyl
compound that, in term, could be synergistically activated.[12a-
b],[17] Next, a nucleophilic attack from the gold allenyl derivative II
to the activated carbonyl compound III, would drive the reaction
to the formation of intermediate IV. Finally, intermediate IV
would evolve giving rise to the formation of homopropargyl silyl
ethers 5 and the recovering of the gold catalyst.
We have also explored, as a control experiment, the use of
trimethylsilyl triflimidate as a catalyst in the absence of gold(I)
complex. Under the same reaction conditions, compound 5a
was obtained in a ca. 20% yield (99% yield under gold catalysis)
indicating a prominent participation of the gold catalyst in the
silicon release.
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10.1002/anie.201905159
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Next, in an attempt to evaluate the participation of the -gold
allenyl complex in the catalytic process, a stoichiometric reaction
was performed (Scheme 4). Thus, addition of complex 6a to a
solution of TMS-activated p-tolualdehyde resulted in the
formation of the expected compound 5a, in moderate yield. No
product was observed in absence of TMSNTf2; even at high
temperature (Toluene-d8; reflux). Similarly, in the presence of
CD3OD instead of aldehyde, corresponding deuterated
propargylic compound 7a was obtained. Moreover, a successful
experiment could also be achieved using catalytic amounts of
complex 6a and TMSNTf2 (2.5 mol%).
Scheme 2. Mechanistic proposal. [Au] = AuP(OAr)3
In order to give light to the reaction mechanism we focused our
efforts in the isolation of elusive -allenyl gold intermediate II.
Thus, stoichiometric gold treatment of propargylsilanes 4a,s, in
toluene-d8 at low temperature, and in presence of dry cesium
carbonate, yields the formation of corresponding -gold allenyl
complexes 6a(IIa) and 6s(IIs) (Scheme 3). Both compounds
could be partially purified after filtration of cesium carbonate,
removal of the solvent, and the residue been dissolved in
pentane and filtrated twice through a celite pad. Compound 6a
could be isolated as a white solid by precipitation from dry
methanol. Both compounds 6a,s were characterized by mono-
and bidimensional 1H, 13C and 31P-NMR experiments. As
representative signals for 6a it is worth to mention the
phosphorus coupled allene carbon (Cb), the gold bounded
carbon (Ca) and Cc-H (Scheme 3; bottom). On the other hand,
Scheme 4. Stoichiometric and catalytic experiments with of -gold(I) allenyl
complex 6a.
long distance couplings J3(C,H) are observed, in
a
These results represent the first -gold allenyl complex,
participating in a gold(I) catalyzed transformation, that could be
isolated and characterized, as the only other two examples of
characterization of this type of gold complexes did not involve
catalytically competent species.[9],[10]
bidimiensional HMBC (1H-13C), between Ca and the hydrogen
atom at Cc; and also between Ca and TBS-methyl hydrogens.[16]
Finally, trimethylsilyl propargyl compounds 4 could also be, in
situ, transformed into 4,5-dihydrofurans 8. Thus, after 25 min of
gold catalyzed reaction of compounds 4 with corresponding
carbonyls 2, 20 equivalents of methanol were added (for
deprotection of the silyl ether) and the reaction heated at 60 °C
for 6 hours. Following this procedure, 2-tert-butyldimethylsilyl-
4,5-dihydrofurans 8 were obtained in almost quantitative overall
yields from propargylsilanes 4 and isolated as an almost
equimolecular mixture of diastereoisomers (Scheme 5; top).
Scheme 3. Synthesis of -gold allenyl complexes 6a and 6s.
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characterized from a catalytic process and its reactivity proved.
Finally, as an interesting complement for the reaction, a one-pot
transformation, from propargylsilanes to corresponding 4,5-
dihydrofurans, could be efficiently achieved. Reported gold
catalyzed carbonyl propargylation and unprecedented isolation
of a -gold allenyl intermediate, contribute to fill two important
gaps in the field of homogeneous gold catalysis.
Acknowledgements
Authors gratefully acknowledge support by Spanish Government
MINECO/FEDER (CTQ-2016-76840-R (AEI/FEDER, UE)). S.F.
thanks MINECO for a predoctoral fellowship. Authors also thank
D. Allegue and A.L. Suárez-Sobrino for their assistance with X-
Ray analysis and J.M González for helpful discussions.
Keywords: Catalysis • Gold • Intermediates • Propargylation •
Furans
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and ketones and the isolation of a -gold allenyl intermediate.
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COMMUNICATION
Sergio Fernández, Jairo González,
Javier Santamaría* and Alfredo
Ballesteros*
Page No. – Page No.
Propargylsilanes as Reagents for
Synergistic Gold(I) Catalyzed
Propargylation of Carbonyl
Compounds. Isolation and
Characterization of -Gold Allenyl
Intermediates
Text for Table of Contents
Golden capture: A -gold allenyl intermediate was isolated and characterized in
the course of the study of a novel gold catalyzed propargylation reaction.
Propargylsilanes emerged as very effective reagents for a propargylation reaction of
carbonyl compounds, reaction with just a single precedent in gold catalysis.
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