Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition toward Vinyl-Gold Intermediate over Alkene

Article abstract of DOI:10.1021/jacs.5b05415

A dual catalytic approach enlisting gold and iron synergy is described. This method offers readily access to substituted heterocycle aldehydes via oxygen radical addition to vinyl-gold intermediates under Fe catalyst assistance. This system shows good fun

Full text of DOI:10.1021/jacs.5b05415

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Communication
Synergistic Gold and Iron Dual Catalysis: Preferred Radical
Addition toward Vinyl-Gold Intermediate over Alkene
Haihui Peng, Novruz G Akhmedov, Yu-Feng Liang, Ning Jiao, and Xiaodong Shi
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b05415 • Publication Date (Web): 02 Jul 2015
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Journal of the American Chemical Society
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Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition
toward Vinyl-Gold Intermediate over Alkene
Haihui Peng,a Novruz G. Akhmedov,a Yu-Feng Liang,b Ning Jiao,b,* and Xiaodong Shia,*
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a C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA
b State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road
38, Beijing 100191, China
Supporting Information Placeholder
Regarding the combination of gold catalysis and radical
chemistry, there are two typical reaction scenarios: A) reaction
relay (sequential alkyne activation and radical addition to alkene)
and B) synergistic catalysis (selective radical addition to vinyl
ABSTRACT: A dual catalytic approach enlisting gold and iron
synergy is described. This method offers a readily access to sub-
stituted heterocycle aldehydes via oxygen radical addition to vi-
nyl-gold intermediates under Fe catalyst assistance. This system
gold over alkene). In theory, synergistic catalysis would facilitate
shows good functional group compatibility for the generation of
new transformations that could not be achieved through simple
substituted oxazole, indole and benzofuran aldehydes. Mechanis-
stepwise reaction relay. This is particularly important for reac-
tic evidence greatly supports selective radical addition to an acti-
tions involving slow protodeauration step. The key concerns were
vated vinyl-Au double bond over alkene. This unique discovery
compatibility and orthogonal reactivity of the two catalytic sys-
offers a new avenue with great potential to further extend the
tems. To explore the possibility of this new gold/radical synergis-
synthetic power and versatility of gold catalysis.
tic catalysis, we selected the gold catalyzed propargyl amide cy-
clization as the model reaction.6
As shown in Figure 1, gold catalyst promotes the 5-exo-dig
cyclization of alkyne amide 1a under mild conditions. The alkene
product 2a can be isolated. Hashmi and coworkers reported the
During the last decade, gold complexes have been proven to
be one of the most effective catalysts for alkyne activation. In
many cases, vinyl-gold complexes are recognized as key interme-
diates through inter- or intra-molecular nucleophilic addition to-
oxidation of 2a by molecular oxygen over time to give oxazole
peroxide 3a.7
N3
ward alkyne-gold π-complexes.1 Thus, understanding vinyl-gold
complex reactivity is crucial for new reaction discovery.2 One of
the general reaction pathways of vinyl-gold intermediates is the
protodeauration, converting a C-Au bond into C-H bond.3 To
further expand the scope, efforts have been made by various re-
search groups in searching for new reactivity of vinyl-Au com-
plexes. One exciting recent breakthrough was the discovery of
Au(I)/Au(III) redox cycle originated from vinyl gold intermedi-
ates. Based on this new reaction mode, several new transfor-
mations have been achieved through gold catalyzed alkyne activa-
tion followed by vinyl-gold oxidative coupling (under either ex-
ternal oxidants or photocatalytic conditions, Scheme 1).4 It is
clear that uncovering new reactivity of vinyl-gold complexes will
benefit new transformation discovery. Herein, we report the syn-
ergistic Au/Fe catalysis as a new strategy to transform vinyl-gold
intermediates by iron-oxygen radical addition.5
10% AgNO3
TMSN3, 71%
new
[Au] cat.
no desired
products
X
O
Radical
conditions
not compatible
N
3b
Ph
Ph
CF3
O
10% FeCl2
5% PPh3AuNTf2
r.t., CH3CN
O
Ph
O
Togni reagent
55%
new
HN
N
3c
N
Ph
1a
2a
OOH
SO2Ph
known
THF, O2, 50 o
10% CuI
O
O
C
PhSO2H, 83%
new
48 h, 82%
Hashmi et al, ref 7
N
3a
N
3d
Ph
Ph
Figure 1. Gold catalysis and radical reaction-relay
To test the reaction compatibility with gold catalyst, we ex-
plored reactions of alkene 2a with various radical species. As
shown in Figure 1, new and mild radical conditions were devel-
oped for access to synthetically attractive oxazole derivatives,
including azide (3b), CF3 (3c) and sulfone (3d).8 Notably, oxa-
zole derivatives are very important building blocks in medicinal
and biological research and these new strategies offered practical
and efficient ways to synthesize this class of compounds.9 How-
ever, direct treatment of 1a with the combination of gold catalyst
and these newly developed radical conditions gave complex reac-
tion mixtures with no desired product observed. Clearly, the
compatibility between gold catalyst and radical conditions is one
crucial challenge for the development of the proposed synergistic
catalysis.
L
III
L Au R
R
Strong oxidant
R. E.
ref 4
or Photocatalyst
[Au]
Oxidation
Nu
Nu
H
-H+
Protodeauration
Nu
NuH
Nu
vinyl-gold
could not be achieved
through reaction relay
[Fe]/O
X
2
[Au]
This work: Au-radical
synergistic catalysis
-H2O
O
[Fe] cat.
O
O
[Fe]
The recent successes in photocatalyst promoted gold redox
chemistry suggested good compatibility between gold complexes
and photocatalysts.10 Inspired by those results, we tested the reac-
Nu
O2
Nu
Scheme 1. Vinyl-gold as crucial intermediates in gold catalysis
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Page 2 of 6
tivity of 1a with the combination of gold and photo catalysts un-
Good substrate compatibility was observed with this new du-
1
2
3
4
5
6
7
8
der 1 atm O2. Interestingly, as shown in Figure 2A, besides the
ring opening product 4a and aromatization product 4b, the oxa-
zole-aldehyde 5a was obtained, albeit in low yield. These results
suggested good compatibility of oxygen radical with gold catalyst.
To improve the reaction performance, we directed our attention
towards searching for other oxygen radical initiation conditions.11
As shown in Figure 2B, Fe(acac)3 was identified as the optimal
catalyst (see detailed screening conditions in SI), which promoted
the oxidation of 1a to oxazole-aldehyde 5a (80% conversion and
61% yield) simply with 1 atm molecular oxygen at room tempera-
ture. In addition, 18O labeled experiment confirmed that the alde-
hyde oxygen was originated from O2. Finally, addition of 50%
tBuOOH helped the reaction to reach completion, giving 5a in
83% isolated yield, which highlighted the great compatibility of
the Fe/O2 radical conditions with gold catalysis (Figure 2C).
al-catalytic system. First, substrates with EWGs and EDGs in the
benzene ring on compound 1 all furnished the oxazole aldehyde in
good yields (5a-5f). Heteroaromatic substrates (5g, 5h) and ali-
phatic substituted propargyl amides (5i, 5j) also worked well.
Notably, this reaction proceeded well with high efficiency and
selectivity even with α,β-unsaturated amide (5i). Moreover, to
further evaluate the synthetic utility and generality of this system,
we subjected natural amino acid derivatives (5l, 5m, 5o) and bio-
active molecule (5n) to this system. The desired oxazoles were
obtained with good to excellent yields, further highlighting the
generality and great potential of this new caalytic system.
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To explore whether this transformation went through syner-
gistic catalysis or stepwise reaction relay, we monitored the reac-
tion kinetics under various conditions using NMR (1H and 19F).
O
O
O
O
O
(A)
Ar
O
O
O
PPh3AuNTf2 (5 mol%)
O
HN
O
N
Ar
N
5e
Ar=p-C6H4-CF3
Ar
Ph
Ph
N
H
1e
2e
[Ir] or [Ru] (2.5 mol%)
N
Ph
HN
1a
N
Ph
hv, r.t.
5a
4b
4a
4a
4b
5a
conversion
photocat.
Ir(ppy)3
100%
0%
20%
35%
0%
[Ir(ppy)2(bpy)]+PF6
[Ru(bpy)3]2+
100%
100%
75%
33%
trace
15%
-
<5%
18O
PPh3AuNTf2 (5 mol%)
Fe(acac)3 (10 mol%)
(B)
O
O
Ph
HN
1a
conv 80%
yield 61%
Acetone, r.t., 18O2, 8 h
N
5a
Ph
(C)
PPh3AuNTf2 (5 mol%)
Fe(acac)3 (10 mol%)
O
O
Ph
HN
O
conv 100%
83% yield
tBuOOH (50 mol%)
Acetone, r.t., O2, 5h
N
5a
Ph
1a
Compatible Fe/O2 radical chemistry with gold catalysis
Figure 2. Fe/O2 as compatible conditions with gold catalysis
Figure 3. Reaction kinetic profiles under various conditions (see
detailed reaction conditions in SI)
Various alkyne-amides 1 were prepared to evaluate the reac-
tion scope. The results are summarized in Table 1.
As shown in Figure 3, interesting reaction kinetics was ob-
served. In the reaction of 1e to 5e with the combination of gold
and iron catalysts (reaction 3), a faster rate was seen than either
the Fe/O2 promoted oxidation of 2e to 5e (reaction 2) or the gold
catalyzed cyclization of 1e to 2e (reaction 1). The oxidation of 2e
to aldehyde 5e showed a more dramatic decrease in reaction rate
(more than 48 h) compared to the combined catalysis (see full
reaction kinetic in SI). This insight strongly ruled out the possi-
bility of a stepwise catalytic relay under the reaction conditions.
To explore the identity of reaction intermediates, we attempted to
isolate L-Au-vinyl intermediates. Notably, it has been reported in
literature that PPh3Au-vinyl complex was unstable at room tem-
perature and could not be isolated. Thus, more stable IPrAu-vinyl
complex was prepared and subjected to Fe/O2 catalytic system.12
Table 1. Reaction scope for synthesis of oxazole aldehydesa
O
O
O
O
O
O
O
O
N
N
N
N
p-Me-Ph
p-F-Ph
Ph
5a, 85%
5b, 81%
5c, 83%
5d, 77%
O
O
O
O
O
O
O
N
O
Br
N
N
N
p-CF3-Ph
O
S
Br
5h, 61%
5e, 71%
5g, 69%
5f, 75%
O
O
O
O
N
O
O
MeO
N
N
Alk
Alk=tBu, 5j, 46%
=p-CH2Tol,5k, 59%
O
IPrAuNTf2 (5 mol%)
Fe(acac)3 (20 mol%)
OMe
5i, 75% c
O
O
O
+
Ar
O
t-BuOOH (50 mol%)
Acetone, O2, r.t., 12h
HN
N
O
Ar
O
N
Ar
H
O
1e
O
O
2e
77%
5e
<10%
Ar= p-C6H4-CF3
H
Ph
H
N
IPrAuCl,
AgOTs
N
N
ref 11
NH
Boc
AcO
5m, 61% c
NH
H
NH
5l, 73% c
Boc
Boc
5n, 61% c
5o, 39% c
Reaction Conditions
+
2e
5e
AuIPr
Fe(acac)3 (20 mol%),
t-BuOOH (50 mol%), O2, 50 o
a General reaction conditions: 1 (0.2 mmol), PPh3AuNTf2 (5 mol%), Fe(acac)3
(10 mol%), tBuOOH (50 mol%) in Acetone (0.4 M) with O2 balloon, r.t.;
trace
30%
O
C
b
N
Ar
Isolated yield; c with ditBuXphosAuNTf2 (5 mol%), EtOAc (0.4 M), 50 oC, 5 h.
No [Fe]
t-BuOOH (50 mol%), O2, 50 o
trace
0%
6b
C
Figure 4. Mechanistic investigation
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As shown in Figure 4, reaction of 1e with [IPr-Au]+ and
Again, this dual catalytic system indicated good substrate
compatibility. Various indole and benzolfuran aldehydes were
prepared in good yields directly from alkyne 8. Both electron rich
(9d, 9l) and electron deficient (9e, 9f, 9g, 9k, 9m, 9n, 9p) substit-
uents were suitable for this transformation. Halogen functional
groups (9f, 9n) were also tolerated, which may offer a potential
synthetic handle for further functionalization. The aliphatic sub-
stituents (9h, 9i, 9j) were also compatible in this reaction, giving
the desired products. Substrates with internal alkyne did not work
under the standard conditions with starting material recovered.
1
2
3
4
5
6
7
8
[Fe]/O2 in catalytic fashion gave desired aldehyde in poor yield
(<10%). In contrast, reaction of vinyl-gold 6b with Fe/O2 under
the standard condition gave the desired aldehyde 5e in a better
yield. This result strongly suggested that the vinyl-gold was the
active reaction intermediate and a synergistic dual catalysis was
occurring. Treating 6b with tBuOOH alone (without iron cata-
lyst) gave no aldehyde 5e, which confirmed the importance of
iron catalyst in promoting the oxygen radical reaction toward
vinyl-gold. Moreover, addition of 1 equiv. TEMPO in the reac-
tion mixture quenched the reaction completely, which was con-
sistent with the proposed radical mechanism. All evidence
strongly suggested the iron activated oxygen radical addition to
vinyl gold as the key step in this dual catalytic transformation.
With this synergistic catalysis mechanism revealed, we put
our attention into the evaluation of more challenging cyclization.
As shown in Figure 5, gold catalyzed 5-exo-dig cyclization
should be a good strategy for the preparation of substituted indole
and benzofuran.13 However, these transformations generally pro-
ceeded poorly, making the overall strategy impractical.14
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Table 2. Reaction scope for synergistic catalysisa, b
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Ph
Tol
Ph-p-F
Ph-p-Br
O
O
O
O
NTs
NTs
NTs
NTs
9b, 78%
9d, 83%
9e, 71%
9f, 66%
nPent
Ph
O
O
O
O
Cl
O
NTs
NTs
9j, 58%
NTs
9g, 72%
Ph-o-F
NTs
9i, 83%
9h, 45%
Ph
Ph
Ph
Challenge 1: slow protodeauruation or alkene rearrangement
O
O
O
O
Cl
Br
Cl
[Au] (5 mol%)
NTs
9k, 53%
O
O
O
N
N
8 h, r.t.
70% conversion
NHTs
8a
9c, 70%
9l, 57%
9m, 75%
Ts
9a': not observed
Ts
9a'', 53%
Ph
Ph
Ph-o-Cl
Ph
O
O
O
O
Cl
Ph
OH
Ph
OH
[Au] (5 mol%)
Ph
O
O
O
NTs
complex reaction
mixtures
8 h, 50 o
100% conversion
C
9n, 71%
9o, 77%
9p, 78%
<5%
N
NHTs
OH
a General conditions for indole aldehyde synthesis: 8 (0.2 mmol), ditBuXpho-
Ts
8b
9b': 13%
sAu(CH3CN)SbF6 (5 mol%), FeCl2 (10 mol%) in EtOAc (0.4 M) with O2 bal-
loon, 50 C, 5h; General conditions for benzofuran aldehyde synthesis: 8 (0.2
o
Ph
[Au] (5 mol%)
very messy reaction,
no clear product identified
mmol), JackiephosAuNTf2 (3 mol%), FeCl2 (10 mol%) in 1,4-Dioxane (0.4 M)
with O2 balloon, 50 oC, 5h; b Isolated yield.
8 h, 50 o
100% conversion
C
OH
8c
Challenge 2: less reactive alkene
[Au] (5 mol%)
[Fe] (10 mol%)
Although the exact mechanism of the Fe/O2 radical addition
step is uncertain at this moment (detailed investigation is current
undergoing), the observed results are consistent with the proposed
oxygen radical addition toward vinyl-gold. Firstly, addition of
oxygen radical to vinyl-gold will form a new reactive species that
may help gold catalyst turnover (overcome slow protodeauration).
Secondly, with 10 d-electrons, Au(I) cation can donate electron
toward C=C double bond. Thus, the π bond in vinyl-gold com-
plex has higher electron density than the π bond in alkene. As a
result, vinyl-gold will be more reactive toward electron deficient
oxygen radical.15 Overall, the success of achieving these chal-
lenging transformations not only provided a highly efficient and
economical approach (the only waste is water) to prepare substi-
tuted indole and benzofuran, but also demonstrated the synergistic
catalysis of gold and radical chemistry, which would enhance the
versatility of gold catalysis.
Ph
OH
No aldehyde product
O2, 50 oC, 8 h
N
Ts
9b'
Figure 5. Challenges in gold catalyzed cyclization
The major challenge for this synthetic route was the slow
protodeauration, which led to the poor yields of the cyclization
products. In addition, some alkene products were not reactive
enough to be oxidized by the Fe/O2 condition. For example,
charging 9bʹ with Fe/O2 gave no desired product even with ex-
tended reaction time or at elevated temperature. To our great
satisfaction, these challenges were simply overcome by this new
synergistic catalytic system. As shown in Figure 6, charging 8b
and 8c with the combined gold and iron catalyst gave the desired
aldehydes in good yields under mild conditions with only 1 atm
O2. Reaction of 8a under the dual catalytic conditions gave alde-
hyde 9a in 46% yield along with indole 9aʺ (32%), suggesting the
fast double rearrangement. Various propargyl alcohols were then
prepared to verify the reaction scope. The results are summarized
in Table 2.
In summary, we report herein the successful example of se-
lective radical addition to vinyl-gold as a new general strategy for
synergistic gold-radical catalysis. This chemistry allows vinyl-
gold as the reactive intermediate to successfully bypass proto-
deauration. As a result, new transformations, which previously
could not be achieved through stepwise reaction relay, were suc-
cessfully achieved. Applications of this new reaction concept for
other challenging transformations are currently undergoing.
[Au] (5 mol%)
[Fe] (20 mol%)
Ph
Ph
OH
9b: X = NTs, 78%;
9c: X = O, 70%
O2, 50 oC, 5h
CHO
CHO
XH
X
[Au] (5 mol%)
[Fe] (20 mol%)
ASSOCIATED CONTENT
N
N
Ts
tBuOOH (50 mol%),
O2, 50 oC, 5h
Supporting Information. Experimental procedures, characteriza-
tion data, and NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
NHTs
Ts
9a: 46%
9a'', 32%
Figure 6. Achieving cyclization via synergistic catalysis
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AUTHOR INFORMATION
1
2
Corresponding Authors
8885; (f) Mankad, N.; Toste, F. D. J. Am. Chem. Soc. 2010, 132,
*Email: Xiaodong.Shi@mail.wvu.edu; Jiaoning@bjmu.edu.cn
3
4
5
6
7
8
9
12959; (g) Wegner, H. A.; Auzias, M. Angew. Chem., Int. Ed.
2011, 50, 8236; (h) Hopkinson, M. N.; Gee, A. D.; Gouverneur,
V. Chem.− Eur. J. 2011, 17, 8248; (i) Wolf, W. J.; Winston, M.
S.; Toste, F. D. Nature Chem. 2013, 6, 159; (j) Hopkinson, M. N.;
Sahoo, B.; Li, J.; Glorius, F. Chem. Eur. J. 2014, 20, 3874.
(5) (a) Radicals in Organic Synthesis; Sibi, M., Renaud, P., Eds.;
Wiley: Weinheim, Germany, 2001; Vols. 1 and 2. (b) Baralle, A.;
Baroudi, A.; Daniel, M.; Fensterbank, L.; Goddard, J.-P.; Lacôte,
E.; Larraufie, M.-H.; Maestri, G.; Malacria, M.; Ollivier, C. Radi-
cal Cascade Reactions. In Encyclopedia of Radicals in Chemistry,
Biology and Materials; Chatgilialoglu, C., Studer, A., Eds.; John
Wiley and Sons: Chichester, U.K., 2012; (c) F. Minisci, Acc.
Chem. Res. 1975, 8, 165; (d) C.-J. Wallentin, J. D. Nguyen, P.
Finkbeiner, C. R. J. Stephenson, J. Am. Chem. Soc. 2012, 134,
8875.
(6) (a) Nilsson, B. M.; Hacksell, U. J. Heterocycl. Chem. 1989,
26, 269; (b) Nilsson, B. M.; Vargas, H. M.; Ringdahl, B.;
Hacksell, U. J. Med. Chem. 1992, 35, 285; (c) Wipf, P.; Rahman,
L. T.; Rector, S. R. J. Org. Chem. 1998, 63, 7132; (d) Arcadi, A.;
Cacchi, S.; Cascia, L.; Fabrizi, G.; Marinelli, F. Org. Lett. 2001,
3, 2501; (e) Bacchi, A.; Costa, M.; Gabriele, B.; Pelizzi, G.; Sa-
lerno, G. J. Org. Chem. 2002, 67, 4450.; (f) Beccalli, E. M.; Bor-
sini, E.; Broggini, G.; Palmisano, G.; Sottocornola, S. J. Org.
Chem. 2008, 73, 4746.
ACKNOWLEDGMENT
We thank the NSF (CHE-1362057 and CHE-1228336) and NSFC
(21228204) for financial support.
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REFERENCES
(1) For selected recent reviews of homogeneous Au catalysis, see:
(a) Fürstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46,
3410; (b) Gorin, D.; Toste, F. D. Nature, 2007, 446, 395; (c)
Shapiro, N. D.; Toste, F. D. Synlett 2010, 675; (d) Corma, A.;
Pérez-Leyva, A.; Sabater, M. Chem. Rev. 2011, 111, 1657; (e)
Rudolph, M.; Hashmi, A. S. K. Chem. Soc. Rev. 2012, 41, 2448;
(f) Liu, L.-P.; Hammond, G. B. Chem. Soc. Rev. 2012, 41, 3129;
(g) Garayalde, D.; Nevado, C. ACS Catal. 2012, 2, 1462; (h) Ob-
radors, C.; Echavarren, A. M. Chem. Commun. 2014, 50, 16.
(2) For selected vinyl-Au complexes, see: (a) Yang, W.; Hashmi,
A. K. Chem. Soc. Rev., 2014, 43, 2941; (b) Hammond, G. B.; Liu,
L.-P. Chem. Soc, Rev., 2014, 41, 3129; (c) Akana, J. A.;
Bhattacharyya, K. X.; Muller, P.; Sadighi, J. P. J. Am. Chem. Soc.
2007, 129, 7736; (d) Liu, L-P.; Xu, B.; Mashuta, M. S.; Ham-
mond, G. B. J. Am. Chem. Soc. 2008, 130, 17642; (e) Seidel, I.
G.; Lehmann, C. W.; Fürstner, A. Angew. Chem., Int. Ed. 2010,
49, 8466; (f) Hashimi, A. S. K.; Schuster, A. M.; Gaillard, S.;
Cavallo, L.; Poater, A.; Nolan, S. P. Organometallics, 2011, 30,
6328; (g) Brown, T. J.; Weber, D.; Gagné, M. R.; Widenhoefer, R.
A. J. Am. Chem. Soc. 2012, 134, 9134; (h) Wand, W.; Hammond,
G. B.; Xu, B. J. Am. Chem. Soc. 2012, 134, 5697.
(3) For selected intra/inter molecular cycloisomerizations as trap-
ping of gold, see: (a) Nieto-Oberhuber, C.; Muñoz, M. P.; Neva-
do, C.; Cárdenas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed.
2004, 43, 2402; (b) Mamane, V.; Gress, T.; Krause, H.; Fürstner,
A. J. Am. Chem. Soc. 2004, 126, 8654; (c) Luzung, M. R.; Mark-
ham, J. P.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 10858; (d)
Kenedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc.
2004, 126, 4526; (e) Fürstner, A.; Morency, L. Angew. Chem., Int.
Ed. 2008, 47, 5030; (f) Hashmi, A. S. K. Angew. Chem., Int. Ed.
2008, 47, 6754; (g) Benitez, D.; Shapiro, N. D.; Tkatchouk, E.;
Wang, Y.; Goddard, W. A., III; Toste, F. D. Nat. Chem. 2009, 1,
482; (h) Obradors, C.; Echavarren, A. M. Acc. Chem. Res., 2014,
47, 902; (i) Ji, K.; Zheng, Z.; Wang, Z.; Zhang, L. Angew. Chem.,
Int. Ed. 2015, 54, 1245; For selected examples of electrophiles as
trapping of gold, see: (j) Yu, M.; Zhang, G.; Zhang, L.; Tetrahe-
dron 2009, 65, 1846; (k) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am.
Chem. Soc. 2005, 17, 5802; (l) Karmakar, S.; Kim, A.; Oh, C. H.
Synthesis 2009, 2, 194; (m) Zou, Y.; Garayalde, D.; Wang, Q.;
Nevado. C.; Goeke, A. Angew. Chem., Int. Ed. 2008, 47, 10110;
(n) Oh, C. H.; Kim, A. Synlett 2008, 5, 777; (o) Ye, L.; Zhang, L.
Org. Lett. 2009, 11, 3646; (p) Leyva-Pérez, A.; Rubio-Marqués,
P.; Al-Deyab, S. S.; Al-Resayes, S.; Corma, A. ACS Catal., 2011,
1, 601.
(7) Hashmi, A. S. K.; Jaimes, M. C. B.; Schuster, A. M.;
Rominger, F. J. Org. Chem. 2012, 77, 6394.
(8) See selected example for azide radical addition: (a) Yuan, Y.;
Shen, T.; Wang, K.; Jiao, N. Chem.-Asia. J. 2013, 8, 2932; (b)
Matcha, K.; Narayan, R.; Antonchick, A. P. Angew. Chem., Int.
Ed. 2013, 52, 7985. For selected examples for sulfinyl radical
addition to a carbon− carbon double bond, see: (c) Gancarz, R. A.;
Kice, J. L. J. Org. Chem. 1981, 46, 4899; (d) Fang, J.- M.; Chen,
M.-Y. Tetrahedron Lett. 1987, 28, 2853; (e) De Riggi, I.; Surzur,
J. M.; Bertrand, M. P. Tetrahedron 1988, 44, 7119; (f) Lu, Q. Q.;
Zhang, J.; Wei, F. L.; Qi, Y.; Wang, H. M.; Liu, Z. L.; Lei, A. W.
Angew. Chem., Int. Ed. 2013, 52, 7156; (g) Lu, Q. Q.; Zhang, J.;
Zhao, G.; Qi, Y.; Wang, H.; Lei, A. W. J. Am. Chem. Soc. 2013,
135, 11481; See selected example for Togni reagent in chemistry:
(h) Kieltsch, I.; Eisenberger, P.; Togni, A. Angew. Chem., Int. Ed.
2007, 46, 754; (i) Parsons, A. T.; Senecal, T. D.; Buckwald, S. L.
Angew. Chem., Int. Ed. 2012, 51, 2947; (j) Charpentier, J.; Früh,
N.; Togni, A. Chem. Rev., 2015, 115, 650.
(9) See, for example: (a) Kato, Y.; Fusetani, N.; Matsunaga, S.;
Hashimoto, K.; Fujita, S.; Furuya, T. J. Am. Chem. Soc. 1986,
108, 2780; (b) Carmeli, S.; Moore, R. E.; Patterson, G. M.;
Cortbett, T. H.; Valeriote, F. A. J. Am. Chem. Soc. 1990, 112,
8195; (c) Pattenden, G. J. J. Heterocycl. Chem. 1992, 29, 607. (d)
Brown, P.; Best, D. J.; Broom, N. J. P.; Cassels, R.; O’Hanlon, P.
J.; Mitchell, T. J.; Osborne, N. F.; Wilson, J. M. J. Med. Chem.
1997, 40, 2563; (e) Dalvie, D. K.; Kalgutkar, A. S.; Khojasteh-
Bakht, S. C.; Obach, R. S.; O’Donnell, J. P. Chem. Res. Toxicol.
2002, 15, 269.
(10) (a) Sahoo, B.; Hopkinson, M. N.; Glorius, F. J. Am. Chem.
Soc. 2013, 135, 5505; (b) Shu, X.; Zhang, M.; He, Y.; Frei, H. ;
Toste, F. D. J. Am. Chem. Soc. 2014, 136, 5844; (c) Hopkinson,
M. N.; Sahoo, B.; Glorius, F. Adv. Synth. Catal. 2014, 356, 2794;
(d) He, Y.; Wu, H.; Toste, F. D. Chem. Sci 2015, 6, 1194.
(11) For selected examples for oxygen radical addition: (a) Stark,
S. M. J. Am. Chem. Soc. 2000, 122, 4162; (b) Wong, M. W.;
Pross, A.; Radom, L. J. Am. Chem. Soc. 1994, 116, 11938.
(12) Hashmi, A. S. K.; Schuster, A. M.; Rominger, F. Angew.
Chem., Int. Ed. 2009, 48, 8247.
(4) (a) Zhang, G.; Peng, Y.; Cui, L.; Zhang, L. Angew. Chem., Int.
Ed. 2009, 48, 3112; (b) Peng, Y.; Cui, L.; Zhang, G.; Zhang, L. J.
Am. Chem. Soc. 2009, 131, 5062; (c) Hopkinson, M. N.; Ross, J.
E.; Giuffredi, G. T.; Gee, A. D.; Gouverneur, V. Org. Lett. 2010,
12, 4904; (d) Zhang, G.; Cui, L.; Wang, Y.; Zhang, L. J. Am.
Chem. Soc. 2010, 132, 1474; (e) Melhado, A. D.; Brenzovitch, W.
E.; Lackner, A. D.; Toste, F. D. J. Am. Chem. Soc. 2010, 132,
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(13) (a) Kothandaraman, P.; Rao, W.; Foo, S. J.; Chan, P. W. H.
(15)Based on the experimental results, a proposed reaction mech-
anism is shown below. The more detailed mechanism with com-
plete catalytic cycle is provided in SI.
Angew. Chem., Int. Ed. 2010, 49, 4619; (b) Kothandaraman, P.;
Mothe, S. R.; Toh, S. S. M.; Chan, P. W. H. J. Org. Chem. 2011,
76, 7633.
(14) With ditBuXphosAu(CH3CN)SbF6 (5 mol%) in CH3CN, the
yield of cyclized alkene 9bʹ is only 14%. However, with ditBu-
XphosAu(CH3CN)SbF6 (5 mol%) and FeCl2 (10 mol%) in
DMSO, the reaction got 90% yield of alkene 9bʹ. See detailed
information in SI.
O
FeIII
O
LAu
LAu
[LAu]+
FeII
AuL
O
O
O
FeIII
O
O
O
O
O
N
O
N
H
H
R
N
N
R
R
R
H2O
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Insert Table of Contents artwork here
[Au]
Nu
O
NuH
Nu
Synergistic catalysis
H2O
O2
[Fe],O2
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