Stereoselective β-C-glycosylation by a palladium-catalyzed decarboxylative allylation: Formal synthesis of aspergillide A

Article abstract of DOI:10.1002/anie.201210266

Mild and sweet: The title reaction proceeds under mild conditions with high regio- and diastereoselectivity (see scheme, PG=protecting group, DiPPF=1,1′-bis(diisopropylphosphino)ferrocene). This reaction is suitable for a wide range of glycal-derived γ-ketone esters and affords C-glycosides with exclusive β-selectivity. The method was further applied to a concise formal synthesis of aspergillideA. Copyright

Full text of DOI:10.1002/anie.201210266

Angewandte
Chemie
DOI: 10.1002/anie.201210266
C-Glycosylation
Stereoselective b-C-Glycosylation by a Palladium-Catalyzed
Decarboxylative Allylation: Formal Synthesis of Aspergillide A**
Jing Zeng, Jimei Ma, Shaohua Xiang, Shuting Cai, and Xue-Wei Liu*
The efficient stereoselective construction of glycosidic link-
ages is indubitably a principal focus in carbohydrate chemis-
try because it is necessary for the construction of natural
glycoconjugates.[1] Among the wide variety of glycosylation
methods, the Ferrier reaction has received considerable
attention as it provides convenient and direct access to 2,3-
unsaturated glycosides from glycals.[2] However, the stringent
requirement of glycosyl acceptors generally confines the
reaction to specific nucleophiles with strong reactivity and the
utilization of stoichiometric amounts of a Lewis acid is
inevitable in some cases. In addition, the dominant anomeric
effect leads to the stereoselective generation of a-glycosides
for Ferrier-type O-glycosylation and therefore accents the
rigidity of the reaction.[3] On the other hand, most results from
Ferrier C-glycosylation reactions remain mediocre as only
moderate a-selectivity has been achieved. The pursuit of high
b-selectivity is also extremely challenging and judging from
the lack of substantial reports, the barriers surrounding this
problem has not been solved. [Scheme 1, Eq. (1)].[4] Conse-
quently, the combination of limitations surrounding the
Ferrier reaction prompted researchers to develop other
Scheme 1. Various types of glycosylation.
methods to synthesize 2,3-unsaturated glycosides in exclusive
selectivity, especially b-selectivity.
and difficult.[7] To overcome this challenge, the more activated
pyranone system was generated and additional activators
were employed.[8] Following the removal of this hurdle, great
strides were made in decarboxylative allylation (DcA).[9,10] In
particular, intramolecular decarboxylative allylation has
developed into an area of great potential among the
transition-metal-catalyzed decarboxylative coupling reactions
Recent demonstrations on the efficiency of palladium-
catalyzed coupling reactions have stimulated considerable
interest in applying this strategy to carbohydrates, particularly
for the synthesis of 2,3-unsaturated glycosides. One of the
successful and prominent examples is the Heck-type glyco-
sylation of glycals with arylboronic acids or aryl halides by
transition-metal insertion and reductive elimination
[Scheme 1, Eq. (2)].[5] The allylic feature of glycals also
encouraged chemists to pursue the applicability of palla-
dium-catalyzed allylic alkylation[6] in glycosylation reactions
[Scheme 1, Eq. (3)]. However, the formation of Pd p-allyl
species in glycal systems has long been recognized as tedious
À
which have drawn considerable attention in the area of C C
bond formation.[11] The Tunge,[12] Trost,[13] and Stoltz
groups,[14] for instance, have reported a series of catalytic
decarboxylative allylation and benzylation reactions.[15]
Inspired by these reports, we envisioned that the palladium-
catalyzed decarboxylation of the C-3 ester of glycal would be
helpful in the formation of a Pd p-allyl intermediate which
might accomplish the desired C-glycosylation with high
stereoselectivity [Scheme 1, Eq. (4)]. In a continuation of
our work on developing efficient glycosylation methods,[5e,f,16]
we report herein on a palladium-catalyzed stereo- and
regioselective C-glycosylation by means of intramolecular
decarboxylative coupling.
[*] J. Zeng,[+] Dr. J. Ma,[+] S. Xiang, S. Cai, Prof. Dr. X.-W. Liu
Division of Chemistry and Biological Chemistry
School of Physical and Mathematical Sciences
Nanyang Technological University
Singapore 637371 (Singapore)
E-mail: xuewei@ntu.edu.sg
In initial studies, the decarboxylative coupling reaction of
compound 1a was carried out in the presence of a catalytic
amount of [Pd(PPh3)4] in DMF at 808C for 12 h. To our
delight, the regiospecific coupling product 2a was obtained in
50% yield with a b/a ratio of 6:1 (Table 1, entry 1). To
improve the yield and selectivity, various Pd catalysts were
screened with the 1,2-bis(diphenylphosphino)ethane (DPPE)
ligand in DMF (Table 1, entries 2–4). We found that the
reaction catalyzed by Pd(OAc)2 gave better yield and
[+] These authors contributed equally to this work.
[**] This work was supported by Nanyang Technological University
(RG50/08) and by the Ministry of Health, Singapore (NMRC grant
H1N1 R/001/2009). We thank the High Performance Computer
Center, NTU for providing the computational resources, Dr.
Yunpeng Lu for helpful discussions, and Yong-Xin Li and Dr.
Ganguly Rakesh for X-ray analysis.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201210266.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 1: Optimization of the decarboxylative glycosylation.
Entry
Cat./ligand
Solv.
T
Yield [%][a]
b/a
[8C]
1
[Pd(PPh3)4]
DMF
DMF
DMF
DMF
80
80
80
80
80
80
40
80
80
60
40
60
60
60
60
60
50
38
50
–
51
58
–
55
68
80
trace
70
71
–
6:1
2[b]
[Pd2(dba)3]/DPPE
Pd(OAc)2/DPPE
PdCl2/DPPE
20:1
20:1
–
>20:1
>20:1
–
>20:1
>20:1
>20:1
n.d.
5:1
10:1
–
b only
b only
3[b]
4[b]
5[b]
Pd(OAc)2/DPPE
Pd(OAc)2/DPPE
Pd(OAc)2/DPPE
Pd(OAc)2/DPPE
Pd(OAc)2/DPPE
Pd(OAc)2/DPPE
Pd(OAc)2/DPPE
Pd(OAc)2/PPh3
Pd(OAc)2/DPPP
Pd(OAc)2/PCy3
Pd(OAc)2/BINAP
Pd(OAc)2/DiPPF
THF
6[b]
toluene
CH2Cl2
MeCN
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
7[b]
8[b]
9[c]
10[c]
11[c]
12[c]
13[c]
14[c]
15[c]
16[c]
15
90
[a] Yield of isolated product.[b] The reaction was conducted for 12 h.
[c] The reaction was conducted for 2 h. BINAP=2,2’-bis(diphenylpho-
spino)-1-1’-binaphthyl, n.d.=not determined, PMP=4-methoxyphenyl.
Scheme 2. Decarboxylative glycosylation of glycal-derived b-keto-
esters.[a–c] [a] Reactions were carried out on a 0.2 mmol scale in the
presence of 0.01 mmol Pd(OAc)2 and 0.02 mmol DiPPF in 2 mL
toluene at 608C for 2 h. [b] Yield of isolated product. [c] PMP=
4-methoxyphenyl. [d] d.r. was determined by H NMR analysis. [e] Yield
for a gram-scale reaction.
diastereoselectivity (Table 1, entry 3) than those catalyzed by
[Pd2(dba)3] and PdCl2 (Table 1, entries 2 and 4). The diaste-
reoselectivity of the reaction catalyzed by Pd(OAc)2 and
DPPE in toluene is superior to that in DMF, THF, CH2Cl2,and
MeCN (Table 1, entries 5–9). Decreasing the reaction tem-
perature to 608C improved the yield to 80% (Table 1,
entry 10). This is because the sugar scaffold is prone to
decompose at high temperatures. However, when the temper-
ature was further decreased, the reaction was sluggish and
only a trace amount of the product was obtained (Table 1,
entry 11). In further ligand screening (Table 1, entries 12–16)
excellent yield (90%) and exclusive diastereoselectivity were
obtained when the model reaction was carried out under the
optimal conditions, which consists of Pd(OAc)2 and 1,1’-
bis(diisopropylphosphino)ferrocene (DiPPF) in toluene at
608C for 2 h. The stereoselective formation of compound 2a
was further confirmed by X-ray structure analysis (see the
Supporting Information).
This result motivated us to continue our study of this
decarboxylative glycosylation. Gratifyingly, similar results
were obtained for substrates with other protecting groups and
the results are summarized in Scheme 2. The protecting
groups on glucal, such as benzyl, TBS, and PMB groups, did
not have any undesirable effect on the reaction and similar
yields and b-anomers were afforded exclusively (Scheme 2,
2b–2d). Moreover, the decarboxylative glycosylation of the
4,6-benzyl galactal derivative gave pure b-anomer as well
(Scheme 2, 2e).
1
that sterically hindered substrates even with cyclic substitu-
ents were converted into the desired coupling products with
exclusive b-selectivity (Scheme 2, 2h–2j). However, the
secondary substituted b-ketone substrates provided a mixture
due to the prochirality of the a-carbon (Scheme 2, 2i and 2j).
In view of these promising results, we directed our attention
to ketones with aromatic substituents. An array of g-aryl-
substituted b-ketones were examined under the optimized
conditions (Scheme 2, 2k–2o). The coupling reactions pro-
ceeded well with aromatic ketones bearing electron-with-
drawing groups, which had only a minor influence on the
glycosylation. In contrast, the reactions of aromatic ketones
possessing electron-donating groups required longer reaction
times and gave lower yields. Because of the success of the
b-ketone substrates, the reaction was scaled up to examine the
possibility of commercial applications. Notably, the reaction
could be conducted on a gram scale without a reduction of
yield (2k, 86%).
Although a palladium-catalyzed DcA mechanism is most
feasible, an intramolecular rearrangement route (namely
Carroll rearrangement) was also taken into account.[17] To
identify this possibility, we carried out a crossover decarbox-
ylative coupling reaction (Scheme 3). A 1:1 mixture of 1a and
1q was subjected to the optimized reaction conditions.
Interestingly, we found that complete scrambling occurred,
the products were formed in a ratio of 1.7:1.2:1.6:1 (2a/2 f/2q/
2b), and only b-products were observed. This result clearly
Subsequently, the various substituted ketones were used
to investigate the scope of the decarboxylative glycosylation.
g-Aliphatic-substituted b-ketones were found to undergo the
decarboxylative coupling under the optimized conditions in
good to excellent yields (Scheme 2, 2 f–2j). It should be noted
2
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Scheme 3. Crossover decarboxylative coupling of 1a and 1q.
Scheme 5. Formal total synthesis of aspergillide A. Reagents and con-
ditions: a) Raney Ni, H2, EtOH/EtOAc 2:1, RT, 95%; b) DTBMP, Tf2O,
CH2Cl2, RT, 83%; c) DIBAL-H, CH2Cl2, À158C, 82%; d) TsCl, Et3N,
DMAP, RT, 91%; e) KCN, DMSO, 508C, 79%; f) KOH, EtOH/H2O 1:1,
808C, 87%; g) (S)-hept-6-en-2-ol, Yamaguchi esterification, 94%;
h) Ru-II, BQ, toluene, 1008C, 71%; i) DDQ, aq CH2Cl2, 90%.
DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone, DMAP=4-dimeth-
ylaminopyridine, DTBMP=2,6-Di-tert-butyl-4-methylpyridine,
Ru-II=2nd generation Grubbs catalyst, Tf=trifluorosulfonyl,
Ts =p-toluenesulfonyl.
indicates that the palladium-promoted ionization occurs at
the beginning of the reaction and an intramolecular rear-
rangement pathway is not involved.
Interestingly, unlike the 3,6-cis substrates, the 3,6-trans
substrate 1p gave a/b mixtures with 1.2:1 and 1.1:1 ratios
when DiPPFF and DPPE were used as the respective ligands
(Scheme 4). This can be explained by the fact that formation
In conclusion, we have developed a mild Pd-catalyzed
decarboxylative C-glycosylation of readily available glycal
derivatives. Essentially, this transformation is a tandem
sequence of rearrangement and decarboxylation on the
sugar scaffold. The versatility and flexibility of this method
is evident from its extensive substrate scope. Remarkably,
high yields and exclusive regioselectivity and diasteroselec-
tivity were obtained, demonstrating that the reaction toler-
ates a wide range of substituents. In addition, the reaction
could be conducted on a gram scale, highlighting its possible
industrial application. The potential of employing this method
to access natural products is intriguing, as C-glycosides
constitute a major component of many natural glycoconju-
gates. We aslo applied this strategy to achieve the concise
formal synthesis of aspergillide A.
Scheme 4. Decarboxylative coupling of compound 1p.
of p-allyl Pd complexes from both a and b faces of 1p by
ionization are close in energy. Given the experimental result
of selectivity differentials, we hypothesized that the ketone
enolate anion resulting from ionization may attack the allyl
group from the face opposite to the Pd complex; thus, the
reaction might proceed through an outer-sphere mecha-
nism.[18,19]
Received: December 24, 2012
Published online: && &&, &&&&
The synthetic utility of this transformation was further
demonstrated by the formal total synthesis of aspergillide A
(Scheme 5).[20] The synthesis started from the decarboxylative
coupling product 2k. Treament of 2k with Raney Ni and H2
reduced the alkene and carbonyl group. Elimination of the
newly formed hydroxy group of 3 generated the disubstituted
alkene 4 in 83% yield. Reduction of acetal group with
DIBAL-H freed the primary alcohol, which was further
transformed to a nitrile group in good yield. Further
hydrolysis of the nitrile group of 5 under basic conditions
produced carboxylic acid 6 in 87% yield. Coupling of acid 6
with (S)-hept-6-en-2-ol under Yamaguchi esterification con-
ditions[21] gave diene 7 in excellent yield. Treatment of diene 7
with the 2nd generation Grubbs catalyst (Ru-II) and 1,4-
benzoquinone (BQ)[22]furnished the Z alkene which was
further deprotected by DDQ to produce the known com-
pound 8.[23] Thus, starting from commercial available glucal,
we accomplished the formal synthesis of aspergillide A in
11 steps and 16% overall yield. Following the literature
procedures,[24] Z alkene 8 could be isomerized to give the E
alkene aspergillide A in one step.
Keywords: aspergillide A · C-glycosylation ·
.
decarboxylative allylation · glycals · palladium
[1] For reviews, see: a) M. H. D. Postema, Tetrahedron 1992, 48,
8545; b) Y. Du, R. J. Linhardt, I. R. Vlahov, Tetrahedron 1998,
54, 9913; c) K. C. Nicolaou, H. J. Mitchell, Angew. Chem. 2001,
113, 1624; Angew. Chem. Int. Ed. 2001, 40, 1576; d) L. Somsꢀk,
Chem. Rev. 2001, 101, 81.
[2] a) R. J. Ferrier, J. Chem. Soc. C 1964, 5443; b) R. J. Ferrier, D. M.
Ciment, J. Chem. Soc. C 1966, 441; c) R. J. Ferrier, N. Prasad, J.
Chem. Soc. Chem. Commun. 1968, 476; d) R. J. Ferrier, Adv.
Carbohydr. Chem. Biochem. 1969, 24, 199; e) R. J. Ferrier, N.
Prasad, J. Chem. Soc. C 1969, 570.
[3] For selected examples, see: a) A. Agarwal, S. Rani, Y. D. Vankar,
J. Org. Chem. 2004, 69, 6137; b) J. L. Badu, A. Khare, Y. D.
Vankar, Molecules 2005, 10, 884; c) D. D. David, O. M. Pedro,
I. P. Juan, S. M. Victor, Curr. Org. Chem. 2006, 10, 457; d) P.
Nagaraj, N. G. Ramesh, Tetrahedron Lett. 2009, 50, 3970.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
[4] For selected examples, see: a) R. D. Dawe, B. Fraser-Reid, J.
Chem. Soc. Chem. Commun. 1981, 1180; b) S. Danishefsky, J. F.
Kerwin, J. Org. Chem. 1982, 47, 3803; c) D. P. Steinhuebel, J. J.
Fleming, J. Du Bois, Org. Lett. 2002, 4, 293; d) A. S. Vieira, P. F.
Fiorante, T. L. S. Hough, F. P. Ferreira, Lꢁdtke, H. L. A. Stefani,
Org. Lett. 2008, 10, 5215; e) R. D. S. Balamurugan, S. R.
Koppolu, Tetrahedron 2009, 65, 8139.
[13] For selected examples, see: a) B. M. Trost, J. Xu, J. Am. Chem.
Soc. 2005, 127, 17180; b) B. M. Trost, R. N. Bream, J. Xu, Angew.
Chem. 2006, 118, 3181; Angew. Chem. Int. Ed. 2006, 45, 3109;
c) B. M. Trost, J. Xu, T. Schmidt, J. Am. Chem. Soc. 2009, 131,
18343; d) B. M. Trost, B. Schaffner, M. Osipov, D. A. A. Wilton,
Angew. Chem. 2011, 123, 3610; Angew. Chem. Int. Ed. 2011, 50,
3548.
[5] a) J. Ramnauth, O. Poulin, S. Rakhit, S. P. Maddaford, Org. Lett.
2001, 3, 2013; b) D.-C. Xiong, L.-H. Zhang, X.-S. Ye, Org. Lett.
2009, 11, 1709; c) H.-H. Li, X.-S. Ye, Org. Biomol. Chem. 2009, 7,
3855; d) M. Lei, L. Gao, J.-S. Yang, Tetrahedron Lett. 2009, 50,
5135; e) S. Xiang, S. Cai, J. Zeng„ X.-W. Liu, Org. Lett. 2011, 13,
4608; f) Y. Bai, M. Leow, J. Zeng, X.-W. Liu, Org. Lett. 2011, 13,
5648.
[6] For reviews, see: a) A. Pfaltz, M. Lautens, in Comprehensive
Asymmetric Catalysis, Vol. 2 (Eds.: E. N. Jacobsen, A. Pfaltz, H.
Yamamoto), Springer, New York, 1999, p. 833; b) B. M. Trost,
Chem. Pharm. Bull. 2002, 50, 1; c) B. M. Trost, M. L. Crawley,
Chem. Rev. 2003, 103, 2921; d) O. Belda, C. Moberg, Acc. Chem.
Res. 2004, 37, 159; e) B. M. Trost, J. Org. Chem. 2004, 69, 5813;
f) H. Miyabe, Y. Takemoto, Synlett 2005, 1641; g) B. M. Trost,
D. R. Fandrick, Aldrichimica Acta 2007, 40, 59; h) Z. Lu, S. Ma,
Angew. Chem. 2008, 120, 264; Angew. Chem. Int. Ed. 2008, 47,
258; i) J. F. Hartwig, L. M. Stanley, Acc. Chem. Res. 2010, 43,
1461.
[7] a) B. M. Trost, F. W. Gowland, J. Org. Chem. 1979, 44, 3448;
b) L. V. Dunkerton, A. J. Serino, J. Org. Chem. 1982, 47, 2812;
c) T. V. RajanBabu, J. Org. Chem. 1985, 50, 3642.
[8] a) R. S. Babu, G. A. OꢂDoherty, J. Am. Chem. Soc. 2003, 125,
12406; b) A. C. Comely, R. Eelkema, A. J. Minnaard, B. L.
Feringa, J. Am. Chem. Soc. 2003, 125, 8714; c) H. Kim, H. Men,
C. Lee, J. Am. Chem. Soc. 2004, 126, 1336; d) B. P. Schuff, G. J.
Mercer, H. M. Nguyen, Org. Lett. 2007, 9, 3173.
[9] For reviews, see: a) B. A. Arndtsen, R. G. Bergman, T. A.
Mobley, T. H. Peterson, Acc. Chem. Res. 1995, 28, 154; b) X.
Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu, Angew. Chem. 2009,
121, 5196; Angew. Chem. Int. Ed. 2009, 48, 5094; c) D. A. Colby,
R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624;
d) I. A. I. Mkhalid, J. H. Barnard, T. B. Marder, J. M. Murphy,
J. F. Hartwig, Chem. Rev. 2010, 110, 890; e) T. W. Lyons, M. S.
Sanford, Chem. Rev. 2010, 110, 1147.
[10] For selected early examples, see: a) T. Tsuda, Y. Chujo, S. Nishi,
K. Tawara, T. Saegusa, J. Am. Chem. Soc. 1980, 102, 6381; b) I.
Shimizu, T. Yamada, J. Tsuji, Tetrahedron Lett. 1980, 21, 3199;
c) J. Tsuji, I. Minami, Acc. Chem. Res. 1987, 20, 140; d) J. Tsuji, T.
Yamada, I. Minami, M. Yuhara, M. Nisar, I. Shimizu, J. Org.
Chem. 1987, 52, 2988.
[14] For selected examples, see: a) D. C. Behenna, B. M. Stoltz, J.
Am. Chem. Soc. 2004, 126, 15044; b) N. H. Sherden, D. C.
Behenna, S. C. Virgil, B. M. Stoltz, Angew. Chem. 2009, 121,
6972; Angew. Chem. Int. Ed. 2009, 48, 6840; c) D. C. Behenna, Y.
Liu, T. Yurino, J. Kim, D. E. White, S. C. Virgil, B. M. Stoltz, Nat.
Chem. 2012, 4, 130.
[15] Selected examples from other groups: a) M. Nakamura, A.
Hajra, K. Endo, E. Nakamura, Angew. Chem. 2005, 117, 7414;
Angew. Chem. Int. Ed. 2005, 44, 7248; b) N. T. Patil, Z. B. Huo,
Y. Yamamoto, J. Org. Chem. 2006, 71, 6991; c) D. Imao, A. Itoi,
A. Yamazaki, M. Shirakura, R. Ohtoshi, K. Ogata, Y. Ohmori, T.
Ohta, Y. Ito, J. Org. Chem. 2007, 72, 1652; d) S. B. J. Kan, R.
Matsubara, F. Berthiol, S. Kobayashi, Chem. Commun. 2008,
6354; e) W. H. Fields, A. K. Khan, M. Sabat, J. J. Chruma, Org.
Lett. 2008, 10, 5131; f) A. A. Yeagley, M. A. Lowder, J. J.
Chruma, Org. Lett. 2009, 11, 4022; g) D. Linder, M. Austeri, J.
Lacour, Org. Biomol. Chem. 2009, 7, 4057; h) J. Wang, Z. Cui, Y.
Zhang, H. Li, L. Wu, Z. Liu, Org. Biomol. Chem. 2011, 9, 663.
[16] a) J. Zeng, S. Vedachalam, S. Xiang, X.-W. Liu, Org. Lett. 2011,
13, 42; b) B. K. Gorityala, J. Ma, K. K. Pasunooti, S. Cai, X.-W.
Liu, Green Chem. 2011, 13, 573; c) S. Cai, S. Xiang, J. Zeng, B. K.
Gorityala, X.-W. Liu, Chem. Commun. 2011, 47, 8676.
[17] a) M. F. Carroll, J. Chem. Soc. 1940, 704; b) M. F. Carroll, J.
Chem. Soc. 1940, 1266; c) M. F. Carroll, J. Chem. Soc. 1941, 507;
d) W. Kimel, A. C. Cope, J. Am. Chem. Soc. 1943, 65, 1992.
[18] E. Keinan, Z. Roth, J. Org. Chem. 1983, 48, 1769, and Ref. [11e].
[19] For a detailed DFT study of mechanism, see the Supporting
Information. For mechanistic studies of decarboxyaltive allyla-
tion, see Ref. [11e]. For calculational studies of the decarbox-
ylative coupling reaction, see: a) J. A. Keith, D. C. Behenna, J. T.
Mohr, S. Ma, S. C. Marinescu, J. Oxgaard, B. M. Stoltz, W. A.
Goddard, J. Am. Chem. Soc. 2007, 129, 11876; b) S.-L. Zhang, Y
Fu, R. Guo, Q.-X. Shang, L. Liu, J. Am. Chem. Soc. 2010, 132,
638; for calculational studies of the Claisen rearrangement on
a sugar scaffold, see: c) S. Gꢁl, F. Schoenebeck, V. Aviyente,
K. N. Houk, J. Org. Chem. 2010, 75, 2115.
[20] For the isolation and structure revision of aspergillide A,
see:a) K. Kito, R. Ookura, S. Yoshida, M. Namikoshi, T. Ooi,
T. Kusumi, Org. Lett. 2008, 10, 225; b) R. Ookura, K. Kito, Y.
Saito, T. Kusumi, T. Ooi, Chem. Lett. 2009, 38, 384.
[11] For recent reviews, see: a) S.-L. You, L.-X. Dai, Angew. Chem.
2006, 118, 5372; Angew. Chem. Int. Ed. 2006, 45, 5246; b) J. T.
Mohr, B. M. Stoltz, Chem. Asian J. 2007, 2, 1476; c) J. T. Mohr,
D. C. Ebner, B. M. Stoltz, Org. Biomol. Chem. 2007, 5, 3571;
d) M. Austeri, F. Buron, S. Constant, J. Lacour, D. Linder, J.
Muller, S. Tortoioli, Pure Appl. Chem. 2008, 80, 967; e) J. D.
Weaver, A. Recio, A. J. Grenning, J. A. Tunge, Chem. Rev. 2011,
111, 1846.
[12] For selected examples, see: a) E. C. Burger, J. A. Tunge, Org.
Lett. 2004, 6, 2603; b) R. R. P. Torregrosa, Y. Ariyarathna, K.
Chattopadhyay, J. A. Tunge, J. Am. Chem. Soc. 2010, 132, 9280;
c) J. D. Weaver, B. J. Ka, D. K. Morris, W. Thompson, J. A.
Tunge, J. Am. Chem. Soc. 2010, 132, 12179; d) R. Jana, J. J.
Partridge, J. A. Tunge, Angew. Chem. 2011, 123, 5263; Angew.
Chem. Int. Ed. 2011, 50, 5157.
[21] a) J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi,
Bull. Chem. Soc. Jpn. 1979, 52, 1989; b) Y. Kawanami, Y.
Dainobu, J. Inanaga, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc.
Jpn. 1981, 54, 943.
[22] a) H. Fuwa, A. Saito, M. Sasaki, Angew. Chem. 2010, 122, 3105;
Angew. chem. Int. Ed. 2010, 49, 3041; b) D. Webb, A. van den
Heuvel, M. Kçgl, S. V. Ley, Synlett 2009, 2320; c) S. H. Hong,
D. P. Sanders, C. W. Lee, R. H. Grubbs, J. Am. Chem. Soc. 2005,
127, 17160.
[23] Compound 8 has been reported to have the best cytotoxic
activity among the naturally occurring aspergillides and their
analogues: S. Dꢃaz-Oltra, C. A. Angulo-Pachꢄn, J. Murga, E.
Falomir, M. Carda, J. A. Marco, Chem. Eur. J. 2011, 17, 675.
[24] S. Dꢃaz-Oltra, C. A. Angulo-Pachꢄn, J. Murga, M. Carda, J. A.
Marco, J. Org. Chem. 2010, 75, 1775.
4
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
C-Glycosylation
J. Zeng, J. Ma, S. Xiang, S. Cai,
X.-W. Liu*
&&&& — &&&&
Stereoselective b-C-Glycosylation by
a Palladium-Catalyzed Decarboxylative
Allylation: Formal Synthesis of
Aspergillide A
Mild and sweet: The title reaction pro-
ceeds under mild conditions with high
regio- and diastereoselectivity (see
scheme, PG=protecting group, DiPPF=
1,1’-bis(diisopropylphosphino)ferro-
cene). This reaction is suitable for a wide
range of glycal-derived g-ketone esters
and affords C-glycosides with exclusive b-
selectivity. The method was further
applied to a concise formal synthesis of
aspergillide A.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!