Synthesis and Isolation of Organogold Complexes through a Controlled 1,2-Silyl Migration

Article abstract of DOI:10.1002/chem.201501648

During our efforts toward the synthesis of naturally occurring polyprenylated polycyclic acylphloroglucinol using a Au^I-catalyzed 6-endo dig carbocyclization, we isolated stable vinyllic gold intermediates. Optimization lead to isolated yields of up to 98 %, using 2-(di-tert-butylphosphino)biphenyl as the ligand. This transformation is derived from a silyl rearrangement that can be fully controlled according to the nature of the substituent on the ynone. This selective transformation does not require basic conditions to prevent protodeauration. These vinylgold complexes are the first isolated intermediates during a silyl migration with gold(I). More than 16 new organogold complexes were synthesized and characterized by single-crystal X-ray diffraction. Reactivity of these complexes is also presented.

Full text of DOI:10.1002/chem.201501648

DOI: 10.1002/chem.201501648
Communication
&
Cyclization
Synthesis and Isolation of Organogold Complexes through
a Controlled 1,2-Silyl Migration
[
a]
Philippe McGee, Gabriel Bellavance, Ilia Korobkov, Anika Tarasewicz, and Louis Barriault*
rial (>90%), we were able to isolate a very small quantity of
Abstract: During our efforts toward the synthesis of natu-
1
an unexpectedly stable vinyllic gold intermediate 8L , resulting
rally occurring polyprenylated polycyclic acylphlorogluci-
from a 1,2-silyl migration.
I
nol using a Au -catalyzed 6-endo dig carbocyclization, we
[6]
[7]
Independent research from Fürstner and Gervorgvan re-
ported gold(I/III)-catalyzed cascade cycloisomerizations involv-
ing 1,2-migration of halides and silicon groups. It was pro-
posed that the migration proceeds through the formation of
gold vinylidene intermediates. Although the alkyne-vinylidene
reaction is a common process for W, Ru, Rh, Mo, Ir, Co, Re, and
isolated stable vinyllic gold intermediates. Optimization
lead to isolated yields of up to 98%, using 2-(di-tert-butyl-
phosphino)biphenyl as the ligand. This transformation is
derived from a silyl rearrangement that can be fully con-
trolled according to the nature of the substituent on the
ynone. This selective transformation does not require
basic conditions to prevent protodeauration. These vinyl-
gold complexes are the first isolated intermediates during
a silyl migration with gold(I). More than 16 new organo-
gold complexes were synthesized and characterized by
single-crystal X-ray diffraction. Reactivity of these com-
plexes is also presented.
[8]
Mn complexes, there are few examples with gold com-
[9]
plexes. However, in some specific cases, the migration can
[10]
proceed via the generation of gold carbenoid species. To the
best of our knowledge, the isolation of intermediates during
processes involving a silyl rearrangement has yet to be report-
ed.
Intrigued by this result, we further investigated this transfor-
mation. As a first step, we performed the reaction using a stoi-
1
chiometric amount of gold complex [L AuNCMe][SbF ] in di-
6
The distinctive reactivity and chemoselectivity of gold com-
plexes have provided a fertile playground for the discovery of
chloromethane (Scheme 2). After 30 min, enol ether 9 was con-
verted to afford the vinyl gold intermediate 10L in 32% yield
1
[1]
unique and innovative transformations in organic chemistry.
along with a significant amount of hydrolyzed enol ether prod-
uct 11 (> 50%). To prevent the hydrolysis of 9, the reaction
was carried out in the presence of various bases such as K CO ,
Notably, phosphinogold(I) complexes have been widely used
as catalysts in the formation of complex carbocyclic frame-
2
3
[
2]
works. These complexes are soft Lewis acids that selectively
coordinate to alkynes, alkenes, and allenes, thus favoring the
Et N, or proton sponge. In all of the cases, only starting materi-
3
al was recovered. An increase of the loading of 9 from 1 equiv
[
3]
1
[11]
addition of various nucleophiles. In 2009, our group devel-
oped a mild and efficient method using cationic phosphino-
gold(I) species to generate bicyclo[m.n.1]alkenones 2 from
to 3.3 equiv gave 10L in 84% yield. Interestingly, this trans-
formation does not require basic conditions to prevent proto-
[12]
deauration.
[
4]
enol ethers 1 (Scheme 1). This method was successfully ap-
plied in the concise total syntheses of biologically active poly-
prenylated polycyclic acylphloroglucinols (PPAPs) such as hy-
The vinyl gold stability could be attributed to the electron-
deficient moiety of the complex, which has also been pro-
[13]
posed by Hammond et al. To further understand and opti-
mize the formation of the vinyllic gold species, other ligands
[
5]
perforin (3), nemorosone (4), and papuaforins A (5). During
these syntheses, we investigated the gold(I)-catalyzed 6-endo
dig carbocyclization of 6 containing a substituted TBS-alkyne
to produce the bridgehead ketone 7. Based on previous re-
sults, we anticipated that alkyne substitution would not affect
the cyclization process. However, along with the starting mate-
2
3
were examined. Organogold compounds 10L and 10L were
isolated in 63% and 70% yields respectively. Migration of the
tert-butyldimethylsilyl group was observed in each case, unaf-
fected by the type of ligands. The structure was confirmed by
single-crystal X-ray diffraction.
The optimized conditions were then applied to a wider vari-
ety of R Si-alkynes (Scheme 3). At first glance, we found that
+
3
[
a] P. McGee, G. Bellavance, Dr. I. Korobkov, A. Tarasewicz, Prof. L. Barriault
Department of Chemistry
the nature of the silyl group controlled the selectivity of the
1,2-shift (Table 1, sections A and B). Noteworthy, a selective
Centre for Catalysis, Research and Innovation
University of Ottawa
0 Marie Curie, Ottawa, ON, K1N 6N5 (Canada)
1,2-migration/cyclization proceeded in good yields in a sterical-
1
ly demanding environment. For example, chromatographically
stable vinylgold complexes 13a, 13b, 13d, and 13e were iso-
lated as the exclusive regioisomers. The replacement of the
TBS by a TMS or a TES group on the alkyne had no incidence
on the reaction yield; organogold complexes 13c and 13 f
E-mail: lbarriau@uottawa.ca
+
[
] Inquiries regarding X-ray diffraction methods should be addressed to this
author (korobkov_ilia@yahoo.com).
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201501648.
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Communication
that both compounds were gen-
erated through two specific
pathways (path A and path B). In
light of these results, one can
conclude that the 1,2-silyl migra-
tion: 1) occurs mainly with ali-
phatic silyl groups at the termi-
nal position, 2) proceeds by an
intramolecular
process,
and
3) the cyclization proceeds most
likely through the formation of
a gold(I) vinylidene intermediate
16, as depicted in Scheme 4.
We took advantage of the
synthesis of these vinyl gold
complexes to further explore
their
chemical
reactivity
(
Table 1). Recently, it was shown
that new CÀC bonds can be
generated through Pd-catalyzed
cross-coupling of vinylgold spe-
cies with aryl and alkyl hal-
[14,15]
ides.
We identified Pd(OAc)2
Scheme 1. The first organogold complexes isolated during the synthesis of PPAPs natural products.
(5 mol%) and tricyclohexylphos-
Scheme 2. Ligand optimization in the isolation of vinyl gold species.
a] 1 equiv of 9. [b] 3.3 equiv of 9.
[
were obtained in 77 and 83% yields, respectively. However, an
increase of the R Si bulkiness led to a significant decrease in
3
yield, because 13g was isolated in 30% yield. Surprisingly, the
treatment of 12h afforded a separable mixture of 13h (27%)
and 14h (20%). When the silicon group was adorned with two
phenyls (DPS), only the non-migrated product 14i was isolated
in 25% yield. Moving from DPS to TPS, only the retention
products 14j and 14k were produced, in 98 and 40% yields,
respectively. These results clearly demonstrated that the nature
of the silicon group on the alkyne dictates the 1,2-silyl migra-
tion. All the structural features of the organogold complexes
mentioned above were confirmed by single-crystal X-ray dif-
fraction and NMR analysis.
Scheme 3. Scope of the cyclization. TBS=tert-butyldimethylsilane, TMS=tri-
methylsilane, TES=triethylsilane, TIPS=triisopropylsilane, DPS=tert-butyldi-
phenylsilane, DMPS=dimethylphenylsilane, TPS=triphenylsilane.
phine (15 mol%) in PhCF at 1008C to be the optimal condi-
3
To gain more insight on the cascade 1,2-migration/cycliza-
tion, we performed crossover experiments using 9 and 12d.
Only cyclized products 10L and 13d were observed in crude
tions for cross-coupling reactions. Under these conditions, the
1
vinylgold 10L was converted to 17a in 83% yield (entry 1). To
1
our surprise, 14j proved to be inert under these conditions,
and only starting material was recovered. One might suggest
that the transmetalation process is thwarted by steric conges-
reaction mixture (Scheme 4). In addition, the resubmission of
13h did not lead to a mixture of 13h/14h, which confirms
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Communication
1
8b in 75% and 65% yields respectively (entry 2). These re-
[
a]
Table 1. Vinylgold complexes cross-coupling reactions.
[14a–c]
sults are in contrast with previous findings.
Other electro-
philes such as propargyl bromide, methyl iodide, and ethyl
iodide provided the corresponding ketones 17c–e and 18c–
1
e in 32–98% yields (entries 3–5). Treatment of 10L and 14j
with electrophilic fluorinating agents proved to be more chal-
lenging. Vinylfluoro 17 f was obtained in 33% yield, whereas
[15]
[
a]
[a]
Entry
1
RX
Product
17 ([%])
18 ([%])
the conversion of 14j gave a complex mixture (entry 6). As
expected, halogenation using NBS and NIS provided the de-
sired halogenated bridgehead ketones 17g, 17h, 18g, and
[
b]
[b]
17a (83)
18a (–)
1
8h in quantitative yields (entries 7 and 8).
In summary, we reported the isolation of 16 new bicy-
[
c]
[c]
2
3
17b (75)
17b (65)
clo[3.3.1]nonane organogold complexes characterized by X-ray
crystallography. Access to these air and chromatographically
stable vinylgold complexes was possible through a silyl rear-
rangement, which was regioselective according to the sub-
stituent on the silyl group. Alkyl TBS and TPS groups offer the
best yields for the rearranged and not-rearranged products, re-
spectively. Assessment of the chemical properties of these or-
ganogold complexes showed that they participated in Pd-cata-
lyzed aryl cross-coupling reactions. It also led to the formation
[
c]
[c]
[c]
17c (63)
18c (32)
[
c]
4
5
6
MeI
EtI
17d (98)
18d (98)
[
c]
[c]
17e (92)
18e (92)
[
d]
[d]
NFSI
17 f (33)
17g (98)
17h (98)
18 f (–)
[
d]
d]
[d]
[d]
7
8
NBS
NIS
18g (98)
18h (98)
[
[a] Isolated yield. [b] Pd(OAc)
2
3 3
(5 mol%), PCy (15 mol%). [c] RX, PhCF ,
3
2
of a C(sp )ÀC(sp ) bond using electrophilic reagents without
the use of Pd catalysts. Adaptation of this transformation into
a synergistic dual-catalysis is underway, as is a more detailed
mechanistic evaluation and a greater evaluation of the
1
008C, 24 h. [d] Acetone, 358C. NIS=N-iodosuccinimide, NBS=N-bromo-
succinimide, NFSI=N-fluorodibenzenesulfonimide.
[16]
scope.
Acknowledgements
We thank the Natural Sciences and Engineering Research
Council (for Accelerator and Discovery grants to L.B.), Fonds de
Recherche du QuØbec - Natures et Technologies (for post-grad-
uate scholarship to P.M.) and the University of Ottawa (for
a University Research Chair to L.B.) for support of this research.
Keywords: 1,2-shift · catalysis · cross-coupling · cyclization ·
gold
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Published online on June 3, 2015
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