Gold-catalyzed intramolecular redox reaction of sulfinyl alkynes: Efficient generation of α-oxo gold carbenoids and application in insertion into R-CO bonds

Article abstract of DOI:10.1002/anie.200701449

(Chemical Equation Presented) Golden touch: α-Oxo Au carbenoids are efficiently generated by Au-catalyzed intramolecular redox reactions of sulfinyl alkynes. Besides cyclization to form benzo-fused sulfur-containing rings, these intermediates can particip

Full text of DOI:10.1002/anie.200701449

Communications
DOI: 10.1002/anie.200701449
Gold Carbenoids
Gold-Catalyzed Intramolecular Redox Reaction of Sulfinyl Alkynes:
Efficient Generation of a-Oxo Gold Carbenoids and Application in
À
Insertion into R CO Bonds**
Guotao Li and Liming Zhang*
Gold catalysts are powerful soft Lewis acids for activating
alkynes toward nucleophilic attack.[1] A remarkable feature of
such systems is that the alkenylgold intermediate can react as
an a-deprotonated gold carbenoid, reminiscent of an enolate,
and be nucleophilic. Consequently, the Au alkyne complex
can be considered equivalent to an a-carbene gold carbenoid
(A in Scheme 1a). This rather unique reactivity has been
addition–elimination process, donating an oxygen atom and
leading to oxidative formation of a synthetically versatile a-
oxo gold carbenoid B (Scheme 1b).[7] Herein, we report this
Au-catalyzed redox process using a tethered sulfoxide as the
oxidant.
We chose sulfoxide as the oxidant because of its ease of
À
synthesis and handling; it was tethered to the C Ctriple bond
in order to facilitate the initial nucleophilic attack. Hence,
sulfinyl alkyne 1, readily prepared in two steps from
thiophenol, was treated with various gold catalysts. While
attempts to trap the expected a-oxo gold carbenoid inter-
mediate using various substrates including styrene, benzyl
alcohol, and ethyl vinyl ether failed, much to our surprise,
tetrahydrobenzothiepinone 2 was formed in excellent yield
when 5 mol% of dichloro(pyridine-2-carboxylato)gold(III)
(3)[8] was used as catalyst in the absence of any additional
substrate (Scheme 2).[9] The formation of 2 can be readily
explained following the hypothesis outlined in Scheme 1b:
À
Au activation of the C Ctriple bond promotes a facile 5- exo-
dig cyclization by the sulfoxide moiety; the resulting alkenyl-
gold species is then capable of pushing out the sulfide moiety,
forming Au carbenoid C; finally, cyclization by intramolecu-
lar reaction of the Au carbenoid moiety in C with the benzene
ring leads to product 2, presumably via electrophilic aromatic
substitution. It is conceivable that a Au-containing cyclic
sulfur ylide D may be formed reversibly upon sulfur attack of
the carbenoid carbon atom. This ylide may not only provide
temporary stabilization for the Au carbenoid but also serve to
bring the phenyl group into close proximity to overcome
unfavorable entropy for seven-membered ring formation.
This novel reactivity of the sulfinyl alkyne was also
observed when a methoxycarbonyl group was attached to the
Scheme 1. a) Nucleophilic/electrophilic reactivity of a Au alkyne com-
plex. b) Generation of an a-oxo gold carbenoid by the reaction of a
Au alkyne complex with an oxygen-delivering oxidant.
elegantly demonstrated in a range of reactions, including
cyclopropanation of internal C Cdouble bonds, [2] 1,2-acyloxy
À
migration of terminal propargyl esters,[3] the intramolecular
acetylenic Schmidt reaction,[4] formation of Au-bounded 1,3-
dipolar species,[5] and alkylthio migration.[6]
À
C Ctriple bond, and b-ketoester 4 was isolated in 93% yield
To further explore this chemistry, we envisioned that an
oxygen-delivering oxidant could react with the Au alkyne
complex or its equivalent a-carbene gold carbenoid via an
[Eq. (1)]. Interestingly, dihydrobenzothiocinones 5 can also
be formed from sulfoxides containing either a terminal alkyne
or an alkynoate, albeit in lower yields [Eq. (2)].
With the hypothesis in Scheme 1b verified, we explored
the synthetic potential of this chemistry. We envisioned that a
pinacol-type rearrangement[10] can be coupled with the
formation of a-oxo gold carbenoids. As shown in Scheme 3,
migration of R1 to the Au carbenoid in E would lead to the
formation of b-hydroxyenone 7 or its b-dicarbonyl tautomer
[*] Dr. G. Li, Prof. Dr. L. Zhang
Department of Chemistry
University of Nevada, Reno
1664 North Virginia Street, Reno, NV 89557 (USA)
Fax: (+1)775-784-6804
E-mail: lzhang@chem.unr.edu
Homepage: http://wolfweb.unr.edu/homepage/lzhang/
[**] The authors thank the University of Nevada, Reno, and ACS PRF
(#43905-G1) for support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or fromthe author.
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Scheme 2. Proposed mechanism for the formation of tetrahydrobenzothiepinone 2.
We began with phenyl sulfoxide 8a, which was obtained in
one step from cyclopentanone (Table 1). To our delight, the
expected insertion product, b-hydroxyenone 9a, was formed
in 36% yield using the reaction conditions in Scheme 2 (i.e.
complex 3 as catalyst; Table 1, entry 1). While side products
1
were difficult to purify and characterize, H NMR spectra of
partially purified fractions indicated that the 6-endo-dig
cyclization and the cyclization to form a fused system were
indeed the main causes for the low efficiency. Attempts to
improve this reaction by screening other Au catalysts
revealed that IPrAuNTf2 (Tf = CF3SO2) was
a much better catalyst (Table 1, entry 4). To
prevent the undesired Au carbenoid cycliza-
tion, the phenyl group was modified, and
both its 2- and 6-positions were blocked
(Table 1, entries 5 and 6). Surprisingly, the
reactions did not improve using those sub-
strates. Fortuitously, we found that 2-chlor-
ophenyl worked well, and the desired inser-
tion product 9d was formed in 63% yield (as
determined by NMR spectroscopy) using
IPrAuNTf2 as catalyst (Table 1, entry 7).
The yield was further improved when the
upon deauration. It is noteworthy that the benzenethio group
in 7 can be readily eliminated upon oxidation,[11] yielding a
versatile vinylcarbonyl moiety. While intermediate E might
Scheme 3. Design of a two-step sequence for carbonyl insertion via Au-catalyzed reactions
of sulfinyl propargylic alcohols.
substrate concentration was lowered to
0.005m (Table 1, entry 8). Among other
groups tested for R, a tert-butyl group led to
be accessible from propargylic
Table 1: Optimization for gold-catalyzed tandem reactions of sulfinyl propargylic alcohol 8.[a]
alcohol
6 by the Au-catalyzed
intramolecular redox reaction of
sulfinyl alkynes discussed above,
there are potential problems: one
is whether the 5-exo-dig cyclization
by the sulfoxide moiety remains
predominant over the alternative
6-endo-dig cyclization, especially
when neither R1 nor R2 is H; and
another, probably even more sig-
nificant, problem is how to avoid
the cyclization of the Au carbenoid
to the benzene ring. Nevertheless,
this sequence would constitute an
effective and novel two-step inser-
Entry[a]
R
Reaction conditions
Yield of 9 [%][b]
1
2
3
4
5
6
7
8
5 mol% 3, (ClCH2)2, RT, 3 h
36
11
22
53
37
44
63
77[d]
5 mol% Ph3PAuNTf2, (ClCH2)2, RT, 5 h
5 mol% IMesAuNTf2, (ClCH2)2, RT, 3 h
5 mol% IPrAuNTf2, (ClCH2)2, RT, 3 h
5 mol% IPrAuNTf2, (ClCH2)2, RT, 12 h
5 mol% IPrAuNTf2, (ClCH2)2, RT, 24 h
5 mol% IPrAuNTf2, (ClCH2)2, RT, 3 h
5 mol% IPrAuNTf2, (ClCH2)2, RT, 3h
5 mol% IPrAuNTf2, (ClCH2)2, RT, 3 h
5 mol% IPrAuNTf2, (ClCH2)2, RT, 2 h
Ph
8a
2,6-Me2C6H3
2,6-Cl2C6H3
2-ClC6H4
2-ClC6H4
tBu
8b
8c
8d
8d
8e
8 f
[c]
[e]
9
10
–
nBu
15[f]
tion of
a
latent vinylcarbonyl-
1
À
[a] The substrate concentration was 0.02m. [b] Estimated by 1H NMR spectroscopy using diethyl
phthalate as an internal standard. [c] The substrate concentration was 0.005m. [d] Yield of isolated
product. [e] 53% of 10 was isolated. [f] 18% of 11 was isolated.
methylene group into the R CO
bond and avoid using hazardous
diazo compounds.[12]
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Table 2: Scope of the IPrAuNTf2-catalyzed intramolecular redox reaction of sulfinyl propargylic alcohols:
À
a two-step insertion into R CO bonds.
Entry[a] Carbonyl com- Yield of
Dicarbonyl product[b]
Reaction Yield of
pound
12 [%]
time [h]
13 [%]
1
2
60
13a
13b
2
58[c,d]
60
2
87[d]
dihydrothiophenone 10 in 53%
3
4
5
59
89
88
13c 3.5
53[d,e]
yield (Table 1, entry 9), which
must be formed via a sulfur ylide
of type D;[13] moreover, an n-butyl
group led to the isolation of 6-
endo-dig cyclization product 11[14]
in 18% yield besides the insertion
product (Table 1, entry 10).
13d
13e
6
8
69[f]
Using the best protocol
70[f]
(Table 1, entry 8), we studied the
scope of this two-step insertion
reaction. As shown in Table 2,
acetophenone was a fairly good
substrate, and b-hydroxyenone 13a
was formed with selective phenyl
migration (Table 2, entry 1). Inter-
estingly, aryl migration was only
slightly favored in benzo-fused
cyclic ketones such as 1-indanone
(Table 2, entry 2) and a-tetralone
(Table 2, entry 3), which led to
mixtures with fairly good to excel-
lent combined yields. This two-step
sequence also worked well with
aromatic aldehydes. For example,
benzaldehyde was transformed
6
7
84
85
13 f
13g
6
3
75[f]
78[d]
8
9
85
76
13h 2.5
63[d,g]
into
b-hydroxy-a-phenylenone
13d in good yield (Table 2,
entry 4). Noteworthy is the highly
selective migration of the phenyl
group, as no H-migration product
was detected. Substituted benzal-
dehydes were good substrates as
well, and b-hydroxyenones 13e
13i 11
68[f]
[a] The substrate concentration was 0.005m. [b] R=2-ClC6H4. [c] Less than 2% methyl migration.
[d] ClCH2CH2Cl as solvent. [e] 37% of enyne product due to dehydration was isolated. [f] MeNO2 as
solvent. [g] The 1H NMR spectrumof the crude residue indicated there is 7% of H-migration product.
(Table 2,
entry 5)
and
13 f
(Table 2, entry 6) were isolated in good yields. Again, only
aryl migration was detected in both cases. This reaction
sequence was successfully extended to enals, and cyclic enals
(Table 2, entries 7 and 8) as well as 4-methoxycinnamalde-
hyde (Table 2, entry 9) all led to good yields of insertion
products. Noteworthy are the cases of aliphatic enals, where
the enal tautomers of the products were also observed.
Similar to the cases of aromatic aldehydes, the alkenyl group
migrated with high selectivity.
The highly selective migration of aryl or alkenyl groups
over H atoms to the Au carbenoid is rather unique and
mechanistically intriguing. Previous studies with transition-
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Chemie
[7] Au carbenoids a to ethyl carboxylates are likely the intermedi-
metal-catalyzed rearrangement of a-diazo-b-hydroxyester
revealed that migration of an H atom is preferred over that
of a phenyl or alkenyl group,[15] although the migratory
aptitudes were shown to be subject to electronic and steric
effects in rhodium(II)-catalyzed reactions when the b-hy-
droxy group was modified.[16,17] It is unlikely that the observed
selectivity is simply due to Au itself, as Liao and Wang
observed very little phenyl migration when ethyl-2-diazo-3-
hydroxy-3-phenylpropionate was treated with either AuCl or
AuCl3.[12d] Detailed mechanistic study to understand the
origin of this selectivity is underway and will be reported in
due course.
ates in the reaction of Au complexes with ethyl diazoacetate. For
references, see: a) Z. G. Li, X. Y. Ding, C. He, J. Org. Chem.
2006, 71, 5876; b) M. R. Fructos, T. R. Belderrain, P. de Fremont,
N. M. Scott, S. P. Nolan, M. M. Diaz-Requejo, P. J. Perez, Angew.
Chem. 2005, 117, 5418; Angew. Chem. Int. Ed. 2005, 44, 5284.
[8] The AuIII complex was first used as a precatalyst by Hashmi
et al., see: A. S. K. Hashmi, J. P. Weyrauch, M. Rudolph, E.
Kurpejovic, Angew. Chem. 2004, 116, 6707; Angew. Chem. Int.
Ed. 2004, 43, 6545. For other reactions catalyzed by this complex,
see: a) S. Wang, L. Zhang, J. Am. Chem. Soc. 2006, 128, 8414;
b) S. Wang, L. Zhang, J. Am. Chem. Soc. 2006, 128, 14274.
[9] During the preparation of this manuscript, a study reporting the
same result as well as the scope of this cyclization appeared:
N. D. Shapiro, F. D. Toste, J. Am. Chem. Soc. 2007, 129, 4160.
[10] For pinacol rearrangements involving Au catalysis, see: a) J. P.
Markham, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127,
9708; b) S. F. Kirsch, J. T. Binder, C. Liebert, H. Menz, Angew.
Chem. 2006, 118, 6010; Angew. Chem. Int. Ed. 2006, 45, 5878;
c) S. F. Kirsch, J. T. Binder, B. Crone, A. Duschek, T. T. Haug, C.
LiØbert, H. Menz, Angew. Chem. 2007, 119, 2360; Angew. Chem.
Int. Ed. 2007, 46, 2310.
[11] Y. Nakashita, M. Hesse, Helv. Chim. Acta 1983, 66, 845.
[12] Ethyl diazoacetate has been used to insert into carbonyl
compounds in the presence of acids or transition metal catalysts.
For selected examples, see: a) R. Pellicciari, R. Fringuelli, P.
Ceccherelli, E. Sisani, J. Chem. Soc. Chem. Commun. 1979, 959;
b) C. R. Holmquist, E. J. Roskamp, J. Org. Chem. 1989, 54, 3258;
c) S. Kanemasa, T. Kanai, T. Araki, E. Wada, Tetrahedron Lett.
1999, 40, 5055; d) M. Y. Liao, J. B. Wang, Tetrahedron Lett. 2006,
47, 8859; e) F. P. Xiao, J. Wang, J. Org. Chem. 2006, 71, 5789;
f) D. Benito-Garagorri, J. Wiedermann, M. Pollak, K. Mereiter,
K. Kirchner, Organometallics 2007, 26, 217.
In conclusion, we have discovered a novel Au-catalyzed
intramolecular redox reaction of sulfinyl alkynes, where the
À
sulfoxide moiety is reduced and the C Ctriple bond is
oxidized. The a-oxo Au carbenoid generated in this reaction
can efficiently cyclize the benzene ring, yielding tetrahydro-
benzothiepinones or dihydrobenzothiocinones. A two-step
insertion of a latent vinylcarbonylmethylene group into
ketones and aldehydes is developed. Noteworthy is the
highly selective migration of aryl or alkenyl groups in the
cases of aldehydes.
Experimental Section
Typical procedure for the Au-catalyzed reaction of sulfinyl prop-
argylic alcohol 12: IPrAuNTf2 (5 mol%, 0.05m in 1,2-dichloroethane)
was added to a solution of the alcohol (0.005m) in 1,2-dichloroethane
at room temperature under N2. The progress of the reaction was
monitored by TLC. When the reaction was judged to be complete, the
reaction mixture was concentrated under vacuum. The residue was
purified by flash silica gel chromatography (hexanes/ethyl acetate =
20:1).
[13] The mechanism for the formation of 10 is likely as shown below:
Received: April 3, 2007
Published online: June 1, 2007
Keywords: carbenes · gold · homogeneous catalysis · insertion ·
.
redox chemistry
[14] Here is the proposed mechanism for the formation of 11:
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[15] For selected examples, see: a) ref. [12a]; b) A. Padwa, S. Y.
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