Palladium enolate umpolung: Cyclative diacetoxylation of alkynyl cyclohexadienones promoted by a Pd/SPRIX catalyst

Article abstract of DOI:10.1002/anie.201311172

A novel palladium-catalyzed reaction involving an unusual nucleophilic attack on a palladium enolate was developed using a spiro-bis(isoxazoline) (SPRIX) ligand. Treatment of alkynyl cyclohexadienone substrates with a Pd/SPRIX catalyst in acetic acid under an oxygen atmosphere furnished diacetoxylated benzofuranone derivatives in good yields. This cyclative diacetoxylation proceeded enantioselectively in the presence of an optically pure SPRIX ligand. In a SPRIX: A new palladium-catalyzed reaction involving an unusual nucleophilic attack on a palladium enolate was developed using the SPRIX ligand. Treatment of alkynyl cyclohexadienone substrates with Pd/SPRIX in acetic acid under an oxygen atmosphere furnished diacetoxylated benzofuranone derivatives in good yields and with high enantioselectivity.

Full text of DOI:10.1002/anie.201311172

Angewandte
Chemie
DOI: 10.1002/anie.201311172
Synthetic Methods
Palladium Enolate Umpolung: Cyclative Diacetoxylation of Alkynyl
Cyclohexadienones Promoted by Pd/SPRIX Catalyst**
Kazuhiro Takenaka, Suman C. Mohanta, and Hiroaki Sasai*
Abstract: A novel palladium-catalyzed reaction involving an
unusual nucleophilic attack on a palladium enolate was
developed using a spiro-bis(isoxazoline) (SPRIX) ligand.
Treatment of alkynyl cyclohexadienone substrates with a Pd/
SPRIX catalyst in acetic acid under an oxygen atmosphere
furnished diacetoxylated benzofuranone derivatives in good
yields. This cyclative diacetoxylation proceeded enantioselec-
tively in the presence of an optically pure SPRIX ligand.
palladium enolate is however promising as a powerful
synthetic method of functionalized carbonyl compounds.
So far, we have succeeded in the development of a unique
ligand, spiro-bis(isoxazoline), abbreviated as SPRIX, which
possesses isoxazoline coordination sites on a rigid spiroback-
bone.[7] SPRIX has proven to be highly effective in various
palladium-catalyzed asymmetric cyclizations, wherein the low
s-donor ability of SPRIX contributes to their promotion.[8] To
explore a new enantioselective reaction catalyzed by Pd/
SPRIX, we focused on cyclization of the alkynyl cyclohexa-
dienones 1 reported by Harned and co-workers (Sche-
me 2).[9a,b] This reaction produces benzofuranone derivatives
T
he p-allyl palladium complex is known to react with a wide
range of nucleophiles, which is a key step in the palladium-
catalyzed allylic substitution referred to as the Tsuji–Trost
reaction (Scheme 1).[1] A great number of successful examples
Scheme 1. General reactivity of p-allyl palladium complexes and oxa-p-
allyl palladium complexes (palladium enolates).
of the asymmetric Tsuji–Trost reaction have been reported
and are extensively applied in organic synthesis.[2] In contrast,
palladium enolates, an analogue of p-allyl palladium com-
plexes wherein one carbon atom of the p-allyl ligand is
replaced by an oxygen atom, do not exhibit any reactivity
toward a nucleophile. Such oxa-p-allyl palladium species
commonly react with electrophiles, for example, aldehydes,
imines, and enones.[3–6] Nucleophilic interception of the
Scheme 2. Cyclative diacetoxylation of the alkynyl cyclohexadienones 1.
(2) through an initial acetoxypalladation of the alkyne
component, a subsequent migratory insertion, and a final
protonolysis of the resultant palladium enolate (Scheme 2,
path a).[10,11] During the course of the development of its
asymmetric version,[9c] we found a substantial amount of the
a-acetoxy ketone products 3. The formation of 3 implied that
nucleophilic acetoxylation of the palladium enolate inter-
mediate proceeded instead of the protonolysis (Scheme 2,
path b). This sequential reaction would potentially become
a useful transformation because the a-oxy benzofuranone
core is a ubiquitous structural motif in natural products,[12] for
example, (+)-dictyosphaeric acid A.[12a] Herein we disclose
cyclative diacetoxylation of 1 by utilizing a Pd/SPRIX
catalyst, and the reaciton involves, to our knowledge, the
first example of an umpolung nucleophilic attack on a palla-
dium enolate.[13,14]
[*] Dr. K. Takenaka, Dr. S. C. Mohanta, Prof. Dr. H. Sasai
The Institute of Scientific and Industrial Research (ISIR)
Osaka University
Mihogaoka, Ibaraki-shi, Osaka 567-0047 (Japan)
E-mail: sasai@sanken.osaka-u.ac.jp
[**] This work was supported by the Advanced Catalytic Transformation
program for Carbon utilization (ACT-C), Core Research for Evolu-
tionary Science and Technology (CREST), a Grant-in-Aid for
Scientific Research from MEXT, and the JSPS Japanese-German
Graduate Externship. We would like to thank the technical staff of
the ISIR Comprehensive Analysis Centre at Osaka University for
their assistance. SPRIX=spiro-bis(isoxazoline).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201311172.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
solvent (entry 2). The ratio of AcOH had an impact on the
reaction efficiency. Thus, 3a was obtained in a somewhat
lower 62% yield using a 1:1 mixed solvent, whereas the
reaction in a solvent mixture in which toluene was the major
component, hardly proceeded (entries 3 and 4). Other
oxidants such as Cu(OAc)2, PhI(OAc)2, and K2S2O8 were
applicable to this cyclative diacetoxylation (entries 5–7).
Molecular oxygen and air were also found to serve as the
oxidant, albeit sluggishly, to furnish 3a in 81 and 56% yields,
respectively (entries 8 and 9). The reaction under non-
oxidative conditions, that is, under an inert atmosphere,
produced only 8% of 3a, and was consistent with a single
turnover of the catalyst (entry 10). Based on this result, a PdII
species is believed to be an active catalyst in the present
reaction.[16] From an environmental viewpoint, we decided to
employ the conditions in entry 8 for further investigation.
Next, the substrate scope of this cyclative diacetoxylation
was examined with a variety of alkynyl cyclohexadienones (1;
Table 2). The substrate 1b, having a hexynyl chain, showed
a high reactivity, similar to that of 1a, to give 3b in 74% yield
(entry 2). Although a slight deleterious effect was detected
for a bulky substituent at the alkyne, 3c with an iPr group and
3d with a tBu group were isolated in 68 and 64% yields,
respectively (entries 3 and 4). Aryl acetylene was also tolerant
to this reaction, thus leading to 72% of 3e (entry 5). The
substrate 1 f, bearing a benzyl-protected hydroxymethyl
group at the alkyne terminus, was converted into the
Scheme 3. Initial attempt.
The result of an initial attempt using 4-(but-2-ynyloxy)-4-
methylcyclohexa-2,5-dienone (1a) in the presence of an
oxidant is depicted in Scheme 3. When 1a was treated with
5 mol% of Pd(OAc)2, 10 mol% of rac-iPr-SPRIX, and
4 equivalents of p-benzoquinone in AcOH at 808C for 10 h,
3a was obtained in 60% yield from the cyclative diacetox-
ylation. The structure of 3a was fully characterized by NMR
spectroscopy, IR, and HRMS. Upon addition of the 2,2’-
bipyridine ligand, employed under Harnedꢀs conditions, in
place of SPRIX, no umpolung reaction proceeded at all, thus
resulting in 68% of protonated product 2a. SPRIX was found
to be essential for this process because no other ligands
promoted this unusual nucleophilic acetoxylation of the
palladium enolate.[15]
Table 2: Cyclative diacetoxylation of 1.[a]
Table 1 shows selected optimization results for the
improvement of the chemical yield.[15] Complete consumption
of 1a was observed, even at lower temperature (608C), to give
3a in 60% yield (entry 1). The chemical yield was increased
to 82% by using a 9:1 mixture of AcOH and toluene as the
Entry Substrate R1
R2
X
Product Yield [%][b]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1 f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
Me
Pr
iPr
tBu
Ph
Me
Me
Me
Me
Me
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
3a
3b
3c
3d
3e
3 f
3g
3h
3i
81
74
68
64
72
71
–
75
76
Table 1: Optimization of reaction conditions.[a]
BnOCH2 Me
H
[c]
Me
Et
iPr
Ph
Me
Me
Me
Me
Me
Me
Me
Ph
9
Entry
Solvent
Oxidant
Yield [%][b]
10
11
12
13
14
15
16
17
3j
84
1
2
3
4
5
6
7
8
9
10
AcOH
p-benzoquinone
p-benzoquinone
p-benzoquinone
p-benzoquinone
Cu(OAc)2
60
82
62
trace
35
4-BrC6H4
MeO(CH2)2
Br(CH2)2
Nphth(CH2)2
Ph
Me
Me
Me
3k
3l
69
73
AcOH+toluene (9:1)
AcOH+toluene (1:1)
AcOH+toluene (1:9)
AcOH+toluene (9:1)
AcOH+toluene (9:1)
AcOH+toluene (9:1)
AcOH+toluene (9:1)
AcOH+toluene (9:1)
AcOH+toluene (9:1)
3m
3n
3o
67
70
71
[d]
PhI(OAc)2
40
80
Me
Me
Me
NTs 3p
CH2 3q
O
64
K2S2O8
79[e]
52[h]
O2
81[d]
56[d]
8[d]
18[f] 1a
3a’[g]
[c]
air[e]
[a] All reactions were carried out in the presence of 10 mol% of Pd(OAc)2
and 15 mol% of iPr-SPRIX in AcOH+toluene (9:1, 0.1m) for 40 h under
an O2 atmosphere. [b] Yield of isolated product. [c] Complex mixture.
[d] Nphth is phthalimidyl. [e] Isolated as a 3:1 mixture. See the
Supporting Information. [f] EtCO2H+toluene (9:1) was used. [g] EtCO2
groups were introduced into the product instead of the AcO group.
[h] Isolated as a 5:1 mixture. See the Supporting Information.
none[f]
[a] All reactions were carried out in the presence of 10 mol% of
Pd(OAc)2, 15 mol% of rac-iPr-SPRIX, and 4 equiv of oxidant in solvent
(0.1m) for 14 h under an O2 atmosphere. [b] Yield of isolated product.
[c] Under an O2 atmosphere. [d] 40 h. [e] In air. [f] Under an N2
atmosphere.
2
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
benzofuranone 3 f in 71% yield and no regioisomeric
products were observed (entry 6).[9c,11c] However, the terminal
alkyne substrate 1g was presumably too reactive to allow the
formation of the desired product (entry 7). When R2 at the
tetrasubstituted carbon atom was changed from Me to Et
(1h), iPr (1i), or Ph (1j), the reactions proceeded smoothly to
afford the corresponding a-acetoxy ketones in good yields
(entries 8–10). The aryl bromide moiety, known to be reactive
in palladium-catalyzed cross-couplings, remained intact
throughout this catalysis (entry 11). Other functional groups
such as methyl ether (1l), bromoalkyl (1m), and phthalimide
(1n) did not interfere with the umpolung acetoxylation of the
palladium enolate (entries 12–14). The product 3o, in which
a Ph group was introduced at both the alkyne tether and the
cyclohexadienone skeleton, was also obtained in 71% yield
(entry 15). Single-crystal X-ray analysis of 3o unambiguously
established its structure which consists of a 3-methylene-5-
oxo-hexahydrobenzofuran and two AcO groups.[15] The
relative configuration and the geometry at the olefinic
moiety were in good agreement with those determined
spectroscopically. No detrimental effects were observed
even upon alteration of the oxygen linker. The products 3p
with a sulfonamide linker and 3q with a methylene linker
were obtained in reasonable yields (entries 16 and 17). When
propanoic acid was used in place of AcOH, the propanoate
group was incorporated at the a-position of the carbonyl as
well as on the exocyclic double bond (entry 18).
Scheme 5. Control experiments.
palladium-catalyzed Rubottom oxidation,[17] we evaluated
the effect of a radical scavenger on our system. The reaction
of 1a in the presence of 1 equivalent of 2,2,6,6-tetramethyl-
piperidine 1-oxyl (TEMPO) or 2,6-di-tert-butyl-p-cresol
(BHT) provided 3a without significant loss of efficiency
(Scheme 5b). Furthermore, the groups of El-Qisairi and
Ritter independently demonstrated that a bimetallic palla-
dium complex worked as the catalytically active species in the
palladium-catalyzed Rubottom oxidation.[18] To gain insight
into the active catalyst, we performed kinetic studies on the
concentration of the catalyst. The initial reaction rate
displayed a linear correlation with the catalyst loading.[15]
These results clearly indicate little possibility of the direct
oxidation pathway by way of radical intermediates or
promotion by a bimetallic palladium complex.
A plausible catalytic cycle is illustrated in Scheme 6.
Initially, the coordination of 1 to the Pd/SPRIX catalyst A
gives the intermediate B. The following anti acetoxypallada-
tion of the activated carbon–carbon triple bond leads to the
vinyl palladium species C, which converts into the palladium
enolate D by migratory insertion of the intramolecular olefin.
In the presence of the SPRIX ligand, the nucleophilic
acetoxylation of D occurs over the protonolysis to afford
product 3 and Pd0, the latter of which is oxidized by the action
of O2 to regenerate A. The AcO group at the a-position to the
carbonyl is located trans to the fused furan ring. We therefore
In contrast, substituents on the cyclohexadienone core
exerted a considerable influence on the process. A complex
mixture was generated in the reaction of 1r, bearing Me
groups adjacent to the carbonyl, thus implying instability of
the resulting palladium enolate intermediate (Scheme 4a).
No reaction took place for the b-methylated 1s, thus
suggesting that the initial chelation step and/or the migratory
insertion step were susceptible to steric hindrance (Sche-
me 4b).
Scheme 4. Effect of substituents on the cyclohexadienone core on the
cyclative diacetoxylation.
Preliminary mechanistic investigations were then carried
out because oxidation of the carbonyl a-carbon atom
(Rubottom oxidation) might be regarded as an alternative
pathway for the formation of 3. When 2a was subjected to the
optimum reaction conditions, no conversion was observed
and resulted in the full recovery of the substrate (Scheme 5a).
Since a radical mechanism was also proposed for the
Scheme 6. Plausible catalytic cycle.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
[7] For a review, see: G. B. Bajracharya, M. A. Arai, P. S. Koranne,
T. Suzuki, S. Takizawa, H. Sasai, Bull. Chem. Soc. Jpn. 2009, 82,
285 – 302.
suppose that the acetate anion attacks the enolate from the
backside of the palladium in a similar manner to the
traditional Tsuji–Trost reaction.
[8] For recent applications, see: a) T. Tsujihara, K. Takenaka, K.
Onitsuka, M. Hatanaka, H. Sasai, J. Am. Chem. Soc. 2009, 131,
3452 – 3453; b) T. Tsujihara, T. Shinohara, K. Takenaka, S.
Takizawa, K. Onitsuka, M. Hatanaka, H. Sasai, J. Org. Chem.
2009, 74, 9274 – 9279; c) K. Takenaka, Y. Tanigaki, M. L. Patil,
C. V. L. Rao, S. Takizawa, T. Suzuki, H. Sasai, Tetrahedron:
Asymmetry 2010, 21, 767 – 770; d) K. Takenaka, S. C. Mohanta,
M. L. Patil, C. V. L. Rao, S. Takizawa, T. Suzuki, H. Sasai, Org.
Lett. 2010, 12, 3480 – 3483; e) G. B. Bajracharya, P. S. Koranne,
R. N. Nadaf, R. K. M. Gabr, K. Takenaka, S. Takizawa, H. Sasai,
Chem. Commun. 2010, 46, 9064 – 9066; f) C. Ramalingan, K.
Takenaka, H. Sasai, Tetrahedron 2011, 67, 2889 – 2894; g) K.
Takenaka, S. Hashimoto, S. Takizawa, H. Sasai, Adv. Synth.
Catal. 2011, 353, 1067 – 1070; h) K. Takenaka, M. Akita, Y.
Tanigaki, S. Takizawa, H. Sasai, Org. Lett. 2011, 13, 3506 – 3509;
i) R. K. Gabr, T. Hatakeyama, K. Takenaka, S. Takizawa, Y.
Okada, M. Nakamura, H. Sasai, Chem. Eur. J. 2013, 19, 9518 –
9525; j) K. Takenaka, Y. D. Dhage, H. Sasai, Chem. Commun.
2013, 49, 11224 – 11226.
Noteworthy is that this cyclative diacetoxylation turned
out to proceed enantioselectively by using optically pure
SPRIX. Thus, when reactions of 1a, 1i, and 1j were
conducted with (M,S,S)-iPr-SPRIX under otherwise identical
reaction conditions, the desired products 3a, 3i, and 3j were
obtained with 58, 71, and 82% ee, respectively.[19]
In summary, we have developed a palladium-catalyzed
cyclative diacetoxylation of alkynyl cyclohexadienones (1),
which proceeds using O2 gas as a green oxidant. A sequence of
alkyne acetoxylation, intramolecular cyclization, and the
umpolung acetoxylation produces the densely functionalized
benzofuranone derivatives 3. The use of a low s-donor SPRIX
ligand is indispensable for the unusual nucleophilic attack on
the palladium enolate. Additional investigations into the
reaction mechanism and the tolerance of other nucleophiles
are now in progress.
[9] a) R. Tello-Aburto, A. M. Harned, Org. Lett. 2009, 11, 3998 –
4000; b) J. K. Hexum, R. Tello-Aburto, N. B. Struntz, A. M.
Harned, D. A. Harki, ACS Med. Chem. Lett. 2012, 3, 459 – 464;
c) Enantioselective synthesis of 2 has recently been achieved by
using a chiral pyridine ligand. See: R. Tello-Aburto, K. A.
Kalstabakken, A. M. Harned, Org. Biomol. Chem. 2013, 11,
5596 – 5604.
[10] Similar palladium-catalyzed cyclizations triggered by acetoxya-
tion of an alkyne component have been developed by the group
of Lu. For representative examples, see: a) Q. Zhang, X. Lu, J.
Am. Chem. Soc. 2000, 122, 7604 – 7605; b) Q. Zhang, X. Lu, X.
Han, J. Org. Chem. 2001, 66, 7676 – 7684; c) L. Zhao, X. Lu,
Angew. Chem. 2002, 114, 4519 – 4521; Angew. Chem. Int. Ed.
2002, 41, 4343 – 4345; d) L. Zhao, X. Lu, W. Xu, J. Org. Chem.
2005, 70, 4059 – 4063; e) F. Zhou, X. Han, X. Lu, J. Org. Chem.
2011, 76, 1491 – 1494.
[11] A metal-catalyzed cyclization of alkynyl cyclohexadienone
substrates has recently attracted growing attention as a method
for the construction of a benzofuranone skeleton. See: a) Z.-T.
He, B. Tian, Y. Fukui, X. Tong, P. Tian, G.-Q. Lin, Angew. Chem.
2013, 125, 5422 – 5426; Angew. Chem. Int. Ed. 2013, 52, 5314 –
5318; b) J. Keilitz, S. G. Newman, M. Lautens, Org. Lett. 2013,
15, 1148 – 1151; c) P. Liu, Y. Fukui, P. Tian, Z.-T. He, C.-Y. Sun,
N.-Y. Wu, G.-Q. Lin, J. Am. Chem. Soc. 2013, 135, 11700 – 11703.
[12] a) A. R. Burns, G. D. McAllister, S. E. Shanahan, R. J. K. Taylor,
Angew. Chem. 2010, 122, 5706 – 5709; Angew. Chem. Int. Ed.
2010, 49, 5574 – 5577; b) S.-C. Lee, G. D. Brown, J. Nat. Prod.
1998, 61, 29 – 33; c) A. Loukaci, O. Kayser, K.-U. Bindseil, K.
Siems, J. Frevert, P. M. Abreu, J. Nat. Prod. 2000, 63, 52 – 56;
d) M. A. Al-Yahya, F. S. El-Feraly, D. C. Dunbar, I. Muhammad,
Phytochemistry 2002, 59, 409 – 414; e) S. Mꢄller, R. Murillo, V.
Castro, V. Brecht, I. Merfort, J. Nat. Prod. 2004, 67, 622 – 630.
[13] Cyclative difunctionalization of dienynes via a p-allyl palladium
intermediate was reported. See: a) J.-E. Bꢅckvall, Y. I. M.
Nilsson, P. G. Andersson, R. G. P. Gatti, J. Wu, Tetrahedron
Lett. 1994, 35, 5713 – 5716; b) Y. I. M. Nilsson, R. G. P. Gatti,
P. G. Andersson, J.-E. Bꢅckvall, Tetrahedron 1996, 52, 7511 –
7523.
Received: December 24, 2013
Revised: February 21, 2014
Published online: && &&, &&&&
Keywords: cyclization · enyne · palladium · spiro compounds ·
.
umpolung
[1] Handbook of Organopalladium Chemistry for Organic Synthesis,
Vol. 2 (Ed.: E. Negishi), Wiley, New York, 2002, chap. 5.2,
pp. 1669 – 2117.
[2] B. M. Trost, M. L. Crawley, Chem. Rev. 2003, 103, 2921 – 2943.
[3] For reviews, see: a) Y. Hamashima, M. Sodeoka, Chem. Rec.
2004, 4, 231 – 242; b) M. Sodeoka, Y. Hamashima, Bull. Chem.
Soc. Jpn. 2005, 78, 941 – 956; c) M. Sodeoka, Y. Hamashima,
Pure Appl. Chem. 2008, 80, 763 – 776.
[4] For recent examples, see: a) S.-i. Kiyooka, S. Hosokawa, S.
Tsukasa, Tetrahedron Lett. 2006, 47, 3959 – 3962; b) S.-i.
Kiyooka, Y. Takeshita, Y. Tanaka, T. Higaki, Y. Wada, Tetrahe-
dron Lett. 2006, 47, 4453 – 4456; c) N. Umebayashi, Y. Hama-
shima, D. Hashizume, M. Sodeoka, Angew. Chem. 2008, 120,
4264 – 4267; Angew. Chem. Int. Ed. 2008, 47, 4196 – 4199;
d) A. M. R. Smith, D. Billen, K. K. Hii, Chem. Commun. 2009,
3925 – 3927; e) J. Streuff, D. E. White, S. C. Virgil, B. M. Stoltz,
Nat. Chem. 2010, 2, 192 – 196; f) A. M. R. Smith, H. S. Rzepa,
A. J. P. White, D. Billen, K. K. Hii, J. Org. Chem. 2010, 75, 3085 –
3096.
[5] For studies on the reactivity of palladium enolates, see: a) A. C.
Albꢁniz, N. M. Catalina, P. Espinet, R. Redꢂn, Organometallics
1999, 18, 5571 – 5576; b) D. A. Culkin, J. F. Hartwig, J. Am.
Chem. Soc. 2001, 123, 5816 – 5817; c) A. Lei, M. Srivastava, X.
Zhang, J. Org. Chem. 2002, 67, 1969 – 1971; d) A. Lei, X. Zhang,
Tetrahedron Lett. 2002, 43, 2525 – 2528; e) T. Nishikata, Y.
Yamamoto, N. Miyaura, Organometallics 2004, 23, 4317 – 4324;
f) J. Cꢃmpora, C. M. Maya, P. Palma, E. Carmona, E. Gutiꢁrrez,
C. Ruiz, C. Graiff, A. Tiripicchio, Chem. Eur. J. 2005, 11, 6889 –
6904; g) I. Meana, A. C. Albꢁniz, P. Espinet, Organometallics
2012, 31, 5494 – 5499.
[14] For umpolung reactions at the a-position of carbonyl groups,
see: T. Miyoshi, T. Miyakawa, M. Ueda, O. Miyata, Angew.
Chem. 2011, 123, 958 – 961; Angew. Chem. Int. Ed. 2011, 50, 928 –
931, and references therein.
[15] For details, see the Supporting Information.
[16] When 1a was treated with a stoichiometric amount of a Pd-
(OAc)2(iPr-SPRIX) complex in the absence of any oxidants, 3a
[6] For reviews of other catalytic reactions engaging palladium
enolate intermediates, see: a) F. Bellina, R. Rossi, Chem. Rev.
2010, 110, 1082 – 1146; b) J. D. Weaver, A. Recio III, A. J.
Grenning, J. A. Tunge, Chem. Rev. 2011, 111, 1846 – 1913.
4
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
was obtained in 72% yield. This result evidently rules out the
possibility of the generation of a PdIV species in the catalytic
reaction. Hence, the present cyclative diacetoxylation involves
the Pd0/PdII redox couple.
[18] a) A. K. El-Qisairi, H. A. Qaseer, J. Organomet. Chem. 2002,
659, 50 – 55; b) G. J. Chuang, W. Wang, E. Lee, T. Ritter, J. Am.
Chem. Soc. 2011, 133, 1760 – 1762.
[19] A bulky substituent at the alkyne terminal provided a negative
effect on the enantioselectivity: Under identical reaction
conditions, 13 and 10% ee were observed for 3c and 3d,
respectively.
[17] Y. Monguchi, T. Takahashi, Y. Iida, Y. Fujiwara, Y. Inagaki, T.
Maegawa, H. Sajiki, Synlett 2008, 2291 – 2294.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Synthetic Methods
K. Takenaka, S. C. Mohanta,
H. Sasai*
&&&& — &&&&
Palladium Enolate Umpolung: Cyclative
Diacetoxylation of Alkynyl
Cyclohexadienones Promoted by Pd/
SPRIX Catalyst
In a SPRIX: A new palladium-catalyzed
reaction involving an unusual nucleo-
philic attack on a palladium enolate was
developed using the SPRIX ligand. Treat-
ment of alkynyl cyclohexadienone sub-
strates with Pd/SPRIX in acetic acid
under an oxygen atmosphere furnished
diacetoxylated benzofuranone derivatives
in good yields and with high enantio-
selectivity.
6
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!