Enantiospecific synthesis and cytotoxicity evaluation of ligudentatol: A programmed aromatization approach to the 2,3,4-trisubstituted phenolic motif via visible-light-mediated group transfer radical cyclization

Article abstract of DOI:10.1002/asia.201400110

A facile enantiospecific approach to (+)-ligudentatol (1) and (-)-ligudentatol (ent-1) is reported. The approach features the construction of a trisubstituted phenolic motif fused to a chiral aliphatic ring by a sequence of visible-light-mediated radical seleno transfer cyclization, bromination, concomitant selenoxide elimination-dehydrobromination, and demethoxycarbonylation, namely, a programmed aromatization. Biological evaluation of the enantiomers of ligudentatol obtained by the present route revealed for the first time their cytotoxicity towards various cancer cell lines. Light gifts: A facile enantiospecific approach to (+)-ligudentatol (1) and (-)-ligudentatol (ent-1) is reported. The approach features the construction of a trisubstituted phenolic motif fused to a chiral aliphatic ring by a sequence of visible-light-mediated seleno transfer radical cyclization, bromination, concomitant selenoxide elimination-dehydrobromination, and demethoxycarbonylation, that is, a programmed aromatization.

Full text of DOI:10.1002/asia.201400110

COMMUNICATION
DOI: 10.1002/asia.201400110
Enantiospecific Synthesis and Cytotoxicity Evaluation of Ligudentatol: A
Programmed Aromatization Approach to the 2,3,4-Trisubstituted Phenolic
Motif via Visible-Light-Mediated Group Transfer Radical Cyclization
Gamal A. I. Moustafa, Hiroshi Suizu, Hiroshi Aoyama, Masayoshi Arai, Shuji Akai, and
Takehiko Yoshimitsu*[a]
Abstract: A facile enantiospecific approach to (+)-liguden-
tatol (1) and (ꢀ)-ligudentatol (ent-1) is reported. The ap-
proach features the construction of a trisubstituted phenolic
motif fused to a chiral aliphatic ring by a sequence of visi-
ble-light-mediated radical seleno transfer cyclization, bromi-
nation, concomitant selenoxide elimination–dehydrobromi-
nation, and demethoxycarbonylation, namely, a programmed
aromatization. Biological evaluation of the enantiomers of
ligudentatol obtained by the present route revealed for the
first time their cytotoxicity towards various cancer cell lines.
lines.[2] In our unrelenting effort to develop natural prod-
ucts-based medicinal resources,[3,4] ligudentatol (1) caught
our attention and prompted us to assess its potential biologi-
cal activity. Herein, we report a facile approach to the enan-
tiomers of ligudentatol, which features visible-light-mediat-
ed seleno transfer radical cyclization, followed by aromatiza-
tion. Furthermore, the cytotoxicity of synthetic (+)-liguden-
tatol (1) and (ꢀ)-ligudentatol (ent-1) toward various cancer
cell lines is demonstrated for the first time, paving the way
for the development of new antiproliferative agents of natu-
ral origin.
An enantioselective synthesis of natural (+)-ligudentatol
(1) was previously reported by Haddad and Salman, who
devised a [2+2] photochemical access to the phenolic
motif.[5] Our synthetic route to ligudentatol features the con-
struction of a phenolic core by facile aromatization of highly
functionalized decalin system iii that is accessible by seleno
transfer radical cyclization of iv (Scheme 1).[6,7] Intermediate
Natural phenols are a rich source of bioactive materials
that exhibit antioxidant, cytotoxic, and antibacterial activi-
ties. (+)-Ligudentatol (1), a unique trisubstituted phenolic
norsesquiterpene isolated from the rhizomes of the perenni-
al herb Ligularia dentata Hara in 1990 by Naya and co-
workers, is a member of 14-noreudesmanes (Figure 1).[1] In
1998, Jia and Gao reported that (+)-liguhodgsonal (2),
a closely related phenol isolated from the roots of Ligularia
dentata Cass., exhibited strong antiproliferative activities
against human hepatoma (H-7402), human myelogenous
leukemia (K562), and mouse melanin carcinoma (B16) cell
Figure 1. Ligudentatol (1) and liguhodgsonal (2).
Scheme 1. Retrosynthesis of (ꢀ)-ligudentatol (ent-1).
[a] G. A. I. Moustafa, H. Suizu, Prof. Dr. H. Aoyama, Prof. Dr. M. Arai,
Prof. Dr. S. Akai, Prof. Dr. T. Yoshimitsu
iv, the precursor of decalin scaffold iii, is readily obtainable
from perillyl bromide (3) in an optically pure form. It has
been well documented in the literature that, unlike reduc-
tive radical cyclizations that are commonly terminated by
hydrogen abstractions, atom or group transfer approaches
allow the cyclized material to bear functionalities suitable
Graduate School of Pharmaceutical Sciences, Osaka University
1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)
Fax : (+81)6-6879-8214
E-mail: yoshimit@phs.osaka-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201400110.
Chem. Asian J. 2014, 9, 1506 – 1510
1506
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Takehiko Yoshimitsu et al.
Table 1. Visible-light-mediated seleno transfer radical cyclization of 7.
for further chemical transformations. This is the case for our
approach to ligudentatol in which a phenylseleno functional-
ity is transferred to the ring system and a bromide is instal-
led thereafter to set the stage for dienone formation. Dien-
one i, obtainable by simple elimination reactions of the
functionalities is converted into phenol 1 by thermodynami-
cally favorable aromatization.
Entry
Additive
T [8C]
t
Yield [%]
8a:8b
1
2
3
no
0–5
0–5
reflux
3 h
3 h
70 min
30
88
90
3:1
3:1
2:1
0.2 equiv (PhSe)2
0.2 equiv (PhSe)2
(ꢀ)-Perillyl bromide (3),[8] which was obtained from (S)-
perillaldehyde in two steps, was reacted with a dienolate
generated from methyl acetoacetate (4) using two equiva-
lents of LDA at ꢀ788C to furnish ester 5 in 78% yield
(Scheme 2). Ester 5 was then treated with methyl iodide in
diphenyldiselenide in CH2Cl2 at 0 to 58C to produce cy-
clized products 8a and 8b in a diastereomeric ratio of 3:1
(the reaction time necessary for the consumption of 7 was
3 h; Table 1, entry 2). Diphenyldiselenide was essential for
efficient transformation: its omission led to poor conversion
(~30% yield after 3 h; Table 1, entry 1). It should be noted
that at higher temperature (i.e., in refluxing CH2Cl2), the re-
action was accelerated to provide the cyclized compounds in
90% yield, albeit with lower diastereoselectivity (8a:8b=
2:1; Table 1, entry 3). Although the stereochemistry of
major product 8a could not be elucidated at this stage,
minor cyclized material 8b fortunately gave a crystalline
material suitable for X-ray analysis. The analysis showed
that compound 8b has a trans-decalin architecture with a b-
configurational methyl substituent (Figure 2).[15] On the
Scheme 2. Total synthesis of (ꢀ)-ligudentatol (ent-1). Reagents and con-
ditions: a) LDA (2 equiv), THF, ꢀ788C; b) K2CO3, MeI, acetone, 608C;
c) PhSeCl, NaH, THF, ꢀ408C; d) cat. (PhSe)2, hn (visible light), CH2Cl2,
0 to 58C; e) LDA, NBS, THF, ꢀ788C; f) H2O2, THF, pyridine, rt, then
Me2S, DBU, rt, 50% over 2 steps; g) mW, NaCl, aq. DMSO, 2008C
Figure 2. X-ray crystallographic structure of minor isomer 8b with ther-
mal ellipsoids at 50% probability levels.
the presence of K2CO3 in acetone at 608C to afford com-
pound 6 in 87% yield. Selenylated compound 7 (d.r.=1:1)
was prepared by installing a phenylseleno functionality into
the a-position of b-keto ester 6 by treatment with NaH fol-
lowed by phenylselenyl chloride at ꢀ408C in THF.
other hand, after several trials to determine the stereochem-
istry of major product 8a, we were delighted to find that, by
visible-light irradiation in the presence of diphenyldiselenide
in refluxing dichloroethane, compound 8a (a diastereomeri-
cally enriched material with a ratio 8a:8b=7.5:1) under-
went epimerization at the selenylated carbon to afford com-
pound 10 (Figure 3). The stereochemistry of the ring junc-
ture of compound 10 was unambiguously confirmed again
by X-ray crystallography and to our surprise, it was trans.[16]
The epimerization likely took place via radical scission of
With this selenide 7, the key group transfer radical cycli-
zation was examined. Pioneering studies on the addition of
ꢀ
ꢀ
ꢀ
carbon selenium (C SePh) bonds to carbon carbon multi-
ple bonds were recorded by Byers,[9] Curran,[10] Back,[11] and
Renaud,[12] who disclosed the utility of the seleno transfer
processes under radical conditions.[13] Yang and co-workers
also reported highly stereoselective seleno transfer cycliza-
tions of alkenylated a-phenylseleno-b-keto and a-phenylse-
leno-b-hydroxyesters.[14]
ꢀ
ꢀ
the carbon selenium (C SePh) bond by SH2 reaction with
a phenylselenyl radical generated by photolysis of diphenyl-
diselenide, followed by capture of the resultant carbon radi-
cal with diphenyldiselenide to give the thermodynamically
ꢀ
We opted to adopt visible-light irradiation to promote the
seleno transfer processes. Substrate 7 was irradiated by
a tungsten lamp (150 W) in the presence of 0.2 equivalent of
more stable trans-decalin 10. As only the carbon selenium
bond is cleavable under the irradiation conditions, the trans
configuration of compound 10 suggested that major isomer
Chem. Asian J. 2014, 9, 1506 – 1510
1507
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Takehiko Yoshimitsu et al.
accelerated by facilitating the radical chain propagation
through efficient capture of the tertiary radical intermedi-
ates (vi/viii) with diphenyldiselenide.[17] It is also likely that
the visible-light irradiation of diphenyldiselenide generated
phenylselenyl radical[18] that efficiently produces radical in-
termediates (v/vii) via SH2 reaction with 7 to promote the
cyclization. Although seemingly the less stable cis-isomer 8a
was predominantly produced, this could be rationalized by
considering the steric interaction between the methoxycar-
bonyl substituent and the allylic hydrogen atom as exempli-
fied in vii, which underwent flipping to v that eventually
produced cis-selenide 8a rather than trans-isomer 8b. Fur-
thermore, the 1,3-diaxial interaction between the methoxy-
carbonyl group and the phenylselenyl donors (7 or diphenyl-
diselenide) in transient intermediate viii could retard radical
trapping and facilitate ring opening to give v via vii, thus
leading to the preferential production of 8a.
The next task was to aromatize cyclized products 8a and
8b to furnish the phenol motif by oxidative functionalization
of the B ring of the decalins. Firstly, a mixture of the two
decalins 8a/8b (d.r.=3:1) was subjected to bromination
with LDA/NBS in THF at ꢀ788C to furnish a-brominated
compounds as a diastereomeric mixture. Then, hydrogen
peroxide (H2O2)/pyridine were added to the crude mixture
Figure 3. Production of trans-decalin 10 from 8a via epimerization of the
selenylated carbon and its X-ray structure with thermal ellipsoids at 50%
probability levels.
followed by DBU (DBU=1,8-diazabicycloACHTNUTRGNEUNG[5.4.0]undec-7-
ene) to produce desired dienone 9 (d.r.ꢁ3.6:1) in 50%
yield over two steps via concomitant selenoxide–hydrogen
bromide eliminations. To ensure the complete conversion of
all the diastereomeric bromides, DBU was employed to en-
hance the dehydrobromination. As expected, the cis-config-
uration of the decalin architecture of major isomer 8a al-
lowed the preferential formation of internal tetrasubstituted
olefin ix over other regioisomeric olefins via syn-elimination
mechanisms (Scheme 4): bromination of diastereomerically
enriched selenide 8a (8a:8b=7.5:1) with NBS followed by
oxidation with H2O2/pyridine/DBU afforded exclusively di-
enone 9a (56%), whereas minor isomer 8b under the same
conditions gave dienone 9b (36%) along with regioisomeric
olefin 12 (22%). Careful examination of dienone formation
from 8b revealed that 9b was formed via x, which under-
went dehydrobromination via deprotonation at the d-posi-
tion. Nevertheless, it is worthy to note that both 8a and 8b
in those transformations could be converted into dienones
9a and 9b, respectively.
The end game in the total synthesis of (ꢀ)-ligudentatol
(ent-1) involved a facile aromatization-driven demethoxycar-
bonylation of dienone 9. Dienone 9 (d.r.=3.6:1) was heated
in wet DMSO in the presence of NaCl under microwave ir-
radiation (2008C) to efficiently furnish (ꢀ)-ligudentatol
(ent-1) in 82% yield (½aꢂ2D5 =ꢀ80.8 (c=0.325, CHCl3); the
reported value for (+)-1 is ½aꢂ2D2 =+82.4 (c=0.80, CHCl3)).[1]
The same synthetic protocol using an enantiomer of ketoest-
er 7 available from (R)-perillyl bromide (ent-3) provided
access to natural (+)-ligudentatol (1) (½aꢂ2D4 = +83.0 (c=
0.125, CHCl3); Scheme 5).
Scheme 3. Plausible mechanism for the production of selenides 8a and
8b.
8a originally produced by the radical cyclization possessed
the cis-decalin structure.
The preferential formation of cis-configurational decalin
8a over trans-congener 8b suggested that the visible-light-
mediated reaction favored kinetic control (Scheme 3). As
evidenced by the fact that the seleno transfer cyclization
took place in the absence of diphenyldiselenide, albeit in
ꢀ
poor yield (see above), the carbon selenium bond of sub-
strate 7 was indeed cleavable by photolysis, generating
carbon radicals (v/vii) stabilized by the two carbonyls. The
orientation of the two carbonyl groups of resultant radical
(v/vii) was likely due to the alleviation of their dipolar inter-
action. The carbon radical further underwent 6-endo mode
cyclization on the double bond to provide a tertiary radical
that captured a phenylselenyl group from another substrate
7, thereby creating a radical chain pathway. In the presence
of catalytic diphenyldiselenide, however, the cyclization was
With these enantiomerically pure (+)- and (ꢀ)-ligudenta-
tol (1) in hand, their antiproliferative activities were evaluat-
Chem. Asian J. 2014, 9, 1506 – 1510
1508
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Takehiko Yoshimitsu et al.
also allowed us to uncover the antiproliferative activities of
both natural and unnatural ligudentatol, adding a new di-
mension to the development of phenolic medicinal resour-
ces.
Experimental Section
The synthetic procedures and the characterization of the compounds
studied herein can be found in the Supporting Information.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology of
Japan (MEXT). G.A.I.M. acknowledges a scholarship awarded by the
Egyptian Ministry of Higher Education for his graduate study.
Keywords: cytotoxicity
·
natural products
·
radical
reactions · seleno transfer · total synthesis
Scheme 4. Sequential dienone formation from diastereomeric selenides
8a and 8b. Reagents and conditions: a) LDA, NBS, THF, ꢀ788C;
b) H2O2, pyridine, THF, rt; c) DBU, rt.
[1] K. Naya, T. Okayama, M. Fujiwara, M. Nakata, T. Ohtsuka, S.
Kurio, Bull. Chem. Soc. Jpn. 1990, 63, 2239.
[2] K. Gao, Z.-J. Jia, Phytochemistry 1998, 49, 167.
[3] Z. Li, D. Shigeoka, T. R. Caulfield, T. Kawachi, Y. Qiu, T. Kamon,
M. Arai, H. W. Tun, T. Yoshimitsu, Med. Chem. Commun. 2013, 4,
1093.
[4] G. A. I. Moustafa, S. Nojima, Y. Yamano, A. Aono, M. Arai, S. Mi-
tarai, T. Tanaka, T. Yoshimitsu, Med. Chem. Commun. 2013, 4, 720.
[5] N. Haddad, H. Salman, Tetrahedron Lett. 1997, 38, 6087.
[6] For selected reviews on atom/group transfer radical chemistry, see:
a) D. P. Curran, Synthesis 1988, 489; b) D. P. Curran in Comprehen-
sive Organic Synthesis, Vol. 4 (Eds.: B. M. Trost, I. Flemming), Per-
gamon, Oxford, 1991, Chap. 4.2; c) C. P. Jasperse, D. P. Curran, T. L.
Fevig, Chem. Rev. 1991, 91, 1237; d) S. Z. Zard, Angew. Chem. Int.
Ed. Engl. 1997, 36, 672; Angew. Chem. 1997, 109, 724; e) J. Byers in
Radicals in Organic Synthesis, Vol. 1 (Eds.: P. Renaud, M. P. Sibi),
Wiley-VCH, Weinheim, 2001, Chap. 1.5; f) S. Z. Zard in Radicals in
Organic Synthesis, Vol. 1 (Eds.: P. Renaud, M. P. Sibi), Wiley-VCH,
Weinheim, 2001, Chap. 1.6; g) S. Z. Zard, Radical Reactions in Or-
ganic Synthesis, Oxford University Press, New York, 2003, Chap. 6;
h) A. J. Clark, Chem. Soc. Rev. 2002, 31, 1–11; i) B. Quiclet-Sire,
S. Z. Zard, Top. Curr. Chem. 2006, 264, 201; j) G. J. Rowlands, Tetra-
hedron 2010, 66, 1593; k) B. Quiclet-Sire, S. Z. Zard, Chem. Eur. J.
2006, 12, 6002; l) C. Li in Encyclopedia of Radicals in Chemistry,
Biology and Materials, Vol. 2 (Eds.: C. Chatgilialoglu, A. Studer),
Wiley, Chichester, 2012, Chap. 32; m) T. Pintauer, K. Matyjaszewiski
in Encyclopedia of Radicals in Chemistry, Biology and Materials,
Vol. 4 (Eds.: C. Chatgilialoglu, A. Studer), Wiley-VCH, Weinheim,
2012, Chap. 62; n) B. Quiclet-Sire, S. Z. Zard, Beilstein J. Org.
Chem. 2013, 9, 557; o) R. A. Gossage, L. A. van de Kuil, G. van Ko-
ten, Acc. Chem. Res. 1998, 31, 423; p) J. Iqbal, B. Bhatia, N. K.
Nayyar, Chem. Rev. 1994, 94, 519; q) D. Bellus, Pure Appl. Chem.
1985, 57, 1827; r) F. Minisci, Acc. Chem. Res. 1975, 8, 165; s) S. Fran-
cois, A. Demonceau, A. F. Noels in Recent Research Developments
in Organic Chemistry, Vol. 3 (Pt. 2), Transworld Research Network,
1999, p. 455; t) K. Severin, Chimia 2012, 66, 386.
Scheme 5. Total synthesis of (+)-ligudentatol (1).
Table 2. IC50 values (mm) of (+)-ligudentatol (1) and (ꢀ)-ligudentatol
(ent-1) against cancer cell lines.
Compound
Cytotoxicity (IC50, mm)
S180
PANC-1
HeLa
DU145
(+)-ligudentatol (1)
(ꢀ)-ligudentatol (ent-1)
27.5
26.6
34.7
32.7
42.5
27.9
40.3
36.0
ed against several cancer cell lines, including mouse sarcoma
(S180), human pancreatic carcinoma (PANC-1), human cer-
vical cancer (HeLa), and human prostate cancer (DU145)
(Table 2). The evaluation revealed that both compounds ex-
erted similar, moderate antiproliferative activities against all
the tested cancer cells, with IC50 values ranging from 26.6 to
42.5 mm, suggesting their potential application in medicinal
research.
[7] For selected papers on atom/group transfer reactions in organic syn-
thesis, see: a) R. S. Grainger, P. Innocenti, Angew. Chem. Int. Ed.
2004, 43, 3445; Angew. Chem. 2004, 116, 3527; b) C.-J. Wallentin,
J. D. Nguyen, P. Finkbeiner, C. R. J. Stephenson, J. Am. Chem. Soc.
2012, 134, 8875; c) H. Yorimitsu, T. Nakamura, H. Shinokubo, K.
In conclusion, we have established a new expeditious
access to the enantiomers of the norsesquiterpene ligudenta-
tol, which involved a sequential seleno transfer reaction and
aromatization protocol. The present chemical synthesis has
Chem. Asian J. 2014, 9, 1506 – 1510
1509
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Takehiko Yoshimitsu et al.
Oshima, K. Omoto, H. Fujimoto, J. Am. Chem. Soc. 2000, 122,
11041; d) L. Chabaud, Y. Landais, P. Renaud, Org. Lett. 2005, 7,
2587; e) P. Renaud, C. Ollivier, P. Panchaud, Angew. Chem. Int. Ed.
2002, 41, 3460; Angew. Chem. 2002, 114, 3610; f) C. D. Edlin, J.
Faulkner, M. Helliwell, C. K. Knight, J. Parker, P. Quayle, J. Raftery,
Tetrahedron 2006, 62, 3004; g) S. Sumino, A. Fusano, I. Ryu, Org.
Lett. 2013, 15, 2826.
poport), 2012, p. 357; h) A. Nomoto, A. Ogawa in Chemistry of Or-
ganic Selenium and Tellurium Compounds, 3 (Pt. 1) (Eds.: S. Patai,
Z. Rappoport), 2012, p. 623.
[14] a) D. Yang, Q. Gao, O.-Y. Lee, Org. Lett. 2002, 4, 1239; b) D. Yang,
Q. Gao, B.-F. Zheng, N.-Y. Zhu, J. Org. Chem. 2004, 69, 8821; c) D.
Yang, B.-F. Zheng, Q. Gao, S. Gu, N.-Y. Zhu, Angew. Chem. Int. Ed.
2006, 45, 255; Angew. Chem. 2006, 118, 261; d) D. Yang, G.-Y. Lian,
H.-F. Yang, J.-D. Yu, D.-W. Zhang, X. Gao, J. Org. Chem. 2009, 74,
8610; e) J.-D. Yu, W. Ding, G.-Y. Lian, K.-S. Song, D.-W. Zhang, X.
Gao, D. Yang, J. Org. Chem. 2010, 75, 3232.
[8] a) R. Buchecker, U. Marti, C. H. Eugster, Helv. Chim. Acta 1982, 65,
896; b) G. Pelletier, S. Lie, J. J. Mousseau, A. B. Charette, Org. Lett.
2012, 14, 5464.
[9] a) J. H. Byers, G. C. Lane, Tetrahedron Lett. 1990, 31, 5697; b) J. H.
Byers, T. G. Gleason, K. S. Knight, J. Chem. Soc. Chem. Commun.
1991, 354.
[10] a) D. P. Curran, M. H. Chen, E. Spletzer, C. M. Seong, C. T. Chang,
J. Am. Chem. Soc. 1989, 111, 8872; b) D. P. Curran, C. M. Seong, J.
Am. Chem. Soc. 1990, 112, 9401; c) D. P. Curran, J. Tamine, J. Org.
Chem. 1991, 56, 2746; d) D. P. Curran, E. Eichenberger, M. Collis,
M. G. Roepel, G. Thoma, J. Am. Chem. Soc. 1994, 116, 4279.
[11] T. G. Back, P. L. Gladstone, Synlett 1993, 699.
[15] CCDC 981449 (8b) contains the supplementary X-ray crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[16] CCDC 980715 (10) contains the supplementary X-ray crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. The poor chemical yield of
isomerized material 10 from compound 8a (a diastereomerically en-
riched material with 8a:8b ratio=7.5:1) is attributed to the concom-
itant formation of a tetra-substituted alkene (24%), which was
likely produced by elimination of the phenylseleno group during the
isomerization process. The unreacted 8b was also recovered.
[17] A. Ogawa, H. Yokayama, K. Yokayama, T. Masawaki, N. Kambe, N.
Sonoda, J. Org. Chem. 1991, 56, 5721.
[18] a) U. Schmidt, A. Mꢁller, K. Markau, Chem. Ber. 1964, 97, 405;
b) R. Franzi, M. Geoffroy, J. Organomet. Chem. 1981, 218, 321.
Also, see: c) A. Ogawa, M. Doi, I. Ogawa, T. Hirao, Angew. Chem.
Int. Ed. 1999, 38, 2027; Angew. Chem. 1999, 111, 2066; d) A. Ogawa,
I. Ogawa, R. Obayashi, K. Umezu, M. Doi, T. Hirao, J. Org. Chem.
1999, 64, 86; e) T. G. Back, M. V. Krishna, J. Org. Chem. 1988, 53,
2533.
[12] a) S. Abazi, L. P. Rapado, K. Schenk, P. Renaud, Eur. J. Org. Chem.
1999, 477; b) P. Renaud, S. Abazi, Synthesis 1996, 253.
[13] For pertinent reviews on synthetic radical chemistry using organose-
leniums, see: a) T. G. Back, Organoselenium Chemistry, (Ed.: T. G.
Back), 1999, p. 173; b) P. Renaud in Topics in Current Chemistry:
Organoselenium Chemistry, Vol. 208 (Ed.: T. Wirth), Springer,
Berlin, 2000, p. 81; c) A. Ogawa in Main Group Metals in Organic
Synthesis, Vol. 2 (Eds.: H. Yamamoto, K. Oshima), Wiley-VCH,
Weinheim, 2004, Chap. 15.4; d) B. Cardinal-David, J.-F. Brazeau,
I. A. Katsoulis, Y. Guindon, Curr. Org. Chem. 2006, 10, 1939;
e) D. M. Freudendahl, S. A. Shahzad, T. Wirth, Eur. J. Org. Chem.
2009, 1649; f) W. R. Bowman in Organoselenium Chemistry: Synthe-
sis and Reactions (Ed.: T. Wirth), Wiley-VCH, Weinheim, 2011,
Chap. 3, p. 111; g) T. G. Back, D. J. Press in Chemistry of Organic Se-
lenium and Tellurium Compounds, 3 (Pt. 1) (Eds.: S. Patai, Z. Rap-
Received: January 23, 2014
Published online: April 2, 2014
Chem. Asian J. 2014, 9, 1506 – 1510
1510
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim