Magnesium salt promoted tandem nucleophilic addition-Oppenauer oxidation of aldehydes with organozinc reagents

Article abstract of DOI:10.1039/c6ob01668e

A magnesium salt promoted synthesis of ketones via tandem nucleophilic addition-Oppenauer oxidation of aldehydes using organozinc chemistry was demonstrated. Magnesium salts concomitantly generated via magnesium metal mediated organohalide zincation exhibit high efficacy for nucleophilic addition of organozinc reagents to aromatic aldehydes and thereafter Oppenauer oxidation whereby ketones are formed in high to excellent yields.

Full text of DOI:10.1039/c6ob01668e

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Magnesium Salt Promoted Tandem Nucleophilic Addition-
Oppenauer Oxidation of Aldehydes with Organozinc Reagents
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
b
a
a
a
Ying Fu, Xing Ling Zhao, Hulmet Hügel, Danfeng Huang, Zhengyin Du, Kehu Wang, and Yulai
a
Hu
DOI: 10.1039/x0xx00000x
www.rsc.org/
A magnesium salt promoted synthesis of ketones via tandem circumvent these problems, we believe that reactive Grignards
nucleophilic addition-Oppenauer oxidation of aldehydes using should be transmetalated to a weaker organometallic reagent
organozinc chemistry was demonstrated. Magnesium salts or, more directly, use a milder organometallic reagent. In this
concomitantly generated via magnesium metal mediated respect, organozinc reagents arise as an ideal candidate owing
organohalides zincation exhibit high efficacy for nucleophilic to their mild reactivity and wide range of functional groups
7
8
addition of organozinc reagents to aromatic aldehydes and tolerance. Based on our interests on organozinc reagents, we
thereafter Oppenauer oxidation whereby ketones were formed in are interested to employ organozinc reagents as nucleophiles
high to excellent yields.
in the nucleophilic addition/Oppenauer oxidation of aldehydes
whereby highly functionalized ketones could be expediently
produced.
Tandem reaction is widely recognized as a promising protocol
9
for C-C bond formation, functional group implantation and
1
one-pot operation. In this respect,
At the beginning, pivaldehyde was selected as the hydride
transformation in
a
acceptor owing to its low dielectric constant and high
0
2
strategies involving reactive organometallics are still rare. The
1
0 2
oxidation potential (E = 211 mV). Thus, reaction of Et Zn 1a
3
nucleophilic addition/Oppenauer oxidation of aldehydes has
and 4-methoxybenzaldehyde 2a was first examined to
evaluate the efficiency of organozinc reagents (Table 1).
Undoubtedly, this reaction did not occur without any
proven to be a practical and straightforward protocol for
3
ketone synthesis. Among them, the Mg-Oppenauer protocol
g
1
1
12
13
provided by Knochel et al. was considered to be the most
advantageous as the in situ formed magnesium alkoxides are
intrinsically powerful promoters for the forthcoming hydride
transference, thus allowing THF, the most commonly used
solvent for Grignards albeit a poor solvent for Oppenauer
additive (entry 1). Metallic salts such as LiX, MgCl2
,
1
4
15
CoBr2, NiCl2 etc. have significant positive effect on both
organometallics formation and their reactivity. LiCl, for
example, have been extensively explored by Knochel et al. as a
key additive for organometallic reagents, such as Grignard
3
b-3d
6
16
17
oxidation,
can be directly used without apparent inhibition
reagents,
organozinc,
organoindium
and
1
8
to hydride transference. Besides, the environmental friendly
benzaldehyde instead of carcinogenic chromium salts,
organoaluminum reagents formation. In our reaction system,
however, LiCl alone was tested as an inert additive and no
reaction were detected at all (entry 2). MgCl2 has been
frequently used as a key promoter in a plethora organozinc
enormous reagent excess (MnO ) or explosively exothemic
2
reagents (oxalyl chlorides/DMSO) was employed as oxidant.
4
However, as we previously mentioned, Grignard reagents
1
9
reagents involving reactions. Unfortunately, it is still an
invalid additive here, probably because of its bad solubility in
should be accurately titrated beforehand and transferred
carefully in case over- or less-loading will lead significant side
reactions such as Aldol condensation and Tishchenko
2
THF. Gratifyingly, one equivalent addition of MgBr promptly
0
2
initiated and completed this transformation within 2 hours,
giving ketone 3a in nearly quantitative yield and excellent
chemoselectivity (3a:4a = 20:1) (entry 4). MgI2 too, is a
powerful additive, delivering 3a in 90% yield (82% isolated
yield, entry 5). Combination an equal amount of LiCl and MgCl2
made a clear solution in THF, allowing addition reaction
completed in 6 h, albeit the desired ketone 3a was obtained in
only 57% isolated yield together with a significant amount of
secondary alcohol 4a remained (entry 6). An equal molar
5
esterifications. Additionally, routes starting from Grignard
reagents demand low reaction temperatures, and sensitive
6
functional groups are still found difficult to be tolerated. To
mixture of LiCl and MgBr also cleanly converted aldehyde 2a
2
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into ketone 3a in a similar yield as with MgBr
Journal Name
2
2
2
alone (ertry 7). mediated magnesium insertion.
Most interestingly,
These experimental facts implied that LiCl did not perform any magnesium salts concomitantly generated during organozinc
a
halides formation offer an immediate promoter for this type
a
Table 2. Reaction of aldehydes with organozinc reagents
Table 1 Optimization of reaction conditions
b
c
c
Entry Additive
3a (%)
3a/4a
e
n. r.
/
1
LiCl
2
n. r.
n. r.
/
MgCl
2
/
3
4
5
6
7
d
d
MgBr
MgI2
2
92(84)
90(82)
57
20:1
15:1
2:1
18:1
MgCl
2
·
LiCl
d
MgBr
2
·LiCl
90(82)
a
The reaction was performed with 1a (4.0 mmol), 2a (2.0
o
mmol), pivaldehyde (4.0 mmol) in THF (10 mL) under 0 C and
b
then stirred at room temperature. Additive (4.0 mmol).
c
a
The reaction was performed with R’
2
Zn
1
(4.0 mmol),
(4.0
1
Yields and the products ratios were determined by crude
d
NMR. isolated yield of 3a
H
aldehyde
2
(2.0 mmol), pivaldehyde (4.0 mmol), MgBr
2
e
. n. r. = no reaction.
mmol) and LiCl (4.0 mmol) in THF (10 mL) under ice-water bath
b
and then stirred at room temperature. Zn (4.0 mmol) and
pivotal role besides increase the solubility of magnesium salts
in THF (entries 2-7). Other metallic salts screened such as CsF,
CoCl , NiCl2 and CH OLi, Al(OiPr)3 are all failed in promoting
BrCH
2
CO
2
Et (4.0 mmol) was used instead of BrZnCH
2
2
CO Et.
2
3
transformation. Thus, treatment of PhZnBr·MgCl
prepared by in situ magnesiation of phenyl bromide in the
presence of ZnCl and LiCl, with a mixture of piperonyl
2
·LiCl 5a,
this type of transformation.
With this optimized condition in hand, we first examined
the applicability of organozinc reagents. As summarized in
Table 2, a wide range of aromatic or heteroaromatic aldehydes
could be successfully converted into corresponding ketones
2
aldehyde and two equivalents of pivaldehyde at room
temperature yielded ketone 6a in 79% isolated yield (Table 3).
Notably, only less than 7% byproducts, mainly derived from
nucleophilic addition-Oppenauer oxidation of organozinc
reagent 5a to pivaldehyde were detected according to GC-MS
analysis. This promising result encouraged us to further
examine the efficacy of other aromatic aldehydes. Gratifyingly,
aromatic aldehydes bearing both electro-donating groups such
as methyl(6b), methoxyl (6c) and electro-withdrawing groups,
using diorganozinc reagents such as Me Zn (3b-3d, 3p), Et Zn
2
2
(
3e-3g) and Ph Zn (3h-3n). Neither electron donating nor
2
electron accepting substituents appear to influence the
reaction course. Various heteroaromatic ketones, such as
thiophenyl (3g, 3m), furyl (3l) and pyridyl (3n) ketones are
easily prepared in good yields from corresponding aldehydes.
Notably, in the presence of 2 equiv of pivaldehydes, zinc, LiCl
such as fluoro (6d), chloro (6e, 6f), nitro (6g), nitrile (6h) and
and
MgBr2,
Reformatsky
type
reaction
of
4-
ester (6i) produced the desired ketones in good to excellent
methoxybenzaldehyde with ethyl 2-bromopropionate give the
desired ketone 3o in good yield. Importantly, ferrocenyl
ketone 3p was obtained from ferrocenecarbaldehyde in 72%
yield.
results. Steric hindered aromatic aldehyde, such as 2-methyl,
2
-methoxyl and 2-chlorobenzaldehydes are applicable with
corresponding ketones (6b, 6c, 6f) obtained in satisfactory
yields. Heteroaromatic organozincs as represented by 2-
furanyl, 2- and 3-thiophenylzinc halides were well applied,
Although
diorganozinc
species
reagents
here, highly
are
effective
organometallic
functionalized
2
giving corresponding heteroaomatic ketones
(6k-6m) in
1
diorganozinc reagents are not easily available.
It is
acceptable yields. Sensitive functional groups such as nitro (6g),
nitril (6h) and ester (6i) are well tolerated with corresponding
functionalized ketones obtained in good yields. Again,
advantageous to employ functionalized organozinc halides as
which can be easily prepared from cheap bromides by ZnCl2
2
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ferrocenyl ketone 6n and 6o were efficiently prepared from mmol) via LiCl promoted zincation, underwent complete
ferrocenecarbaldehyde in high yields.
conversion of 4-fluorobenzaldehyde (20 mmol) within 2h to
afford the 2-(4-fluorobenzoyl)thiophene in 78% isolated yield.
Table 4 Reaction of organozinc reagents prepared by ZnCl
LiCl mediated magnesium-halogen exchange reactions is
a
Table 3 Reaction of aldehydes with organozinc halides
2
a
mediated I/Mg exchange reaction.
a
a
Organozinc reagents were added to a mixture of aldehyde
Organozinc reagents generated from I/Mg exchange (about
mmol) were added to a mixture of aldehyde (2.0 mmol) and
(2.0 mmol) and pivaldehyde (4.0 mmol) under icer-water bath
4
and were then stirred at room temperature for 2h.
pivaldehyde (4.0 mmol) under icer-water bath and were then
stirred at room temperature for 2h.
now widely accepted as
functionalized Grignards reagents preparation, which, in the
presence of ZnCl , converted into corresponding organozinc
a common method for highly
2
3
2
2
1
reagents. In order to examine the efficiency of highly
functionalized organozinc reagents thus prepared, ethyl 4-
idobenzoate 7a was first magnesiated via I/Mg exchange with
2
4
2
i-PrMgCl·LiCl and was then treated with ZnCl to give the
desired organozinc reagents which, exhibited excellent
reactivity that the highly functionalized diaryl ketones 9a-9c
were obtained in high yields (Table 4). Iodobenzene bearing an
electron-withdrawing CF
3
substituent found difficulty in direct
Nevertheless, treatment of 3-
2
5
Scheme
fluorobenzoyl)thiophene
1
Gram
scale
synthesis
of
2-(4-
magnesium insertion.
iodotrifluorobenzene by Turbo Grignards (i-PrMgCl·LiCl) and
then transmetalated with ZnCl afforded the corresponding
2
organozinc reagents, which reacted with methyl 4-
formylbenzoate and 3,4,5-trimethoxybenzaldehyde in the
presence of 2 equivlents of pivaldehyde, giving functionalized
diaryl ketone 9d and 9e in 80% and 84% yields respectively
(
Table 4). Similarly, organozinc reagents derivated from 4-
fluoroiodobenzene 7c and 4-iodobenzonitrile 7d reacted with
-fluorobenzaldehyde and 3,4,5-trimethoxybenzaldehyde
4
respectively to give functionalized benzophenones 9f and 9g in
good yields.
The excellent efficiency of the present reaction system was
further highlighted by a 20 mmol scale synthesis of 2-(4-
fluorobenzoyl)thiophene 10, a key intermediate of a well-
[25]
known medicine Suprofen
(Scheme 1). Thus 2-thienylzinc
Scheme 2 Proposed reaction mechanism
bromide 5d, readily prepared from 2-bromothiophene (30
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Mechanistically, magnesium salt plays a pivotal role both in
addition reaction of organozinc reagents towards aromatic
aldehydes and Oppenauer oxidation. So we proposed that the
reaction proceeds as shown in Scheme 2. Initially, magnesium
salts act as Lewis acid to complex and activate aldehyde
Technol., 2015,
5
, 4341-4345; (k) C. Zhao, J. Yan, Z. Xi, J. Org.
Chem., 2003, 68, 4355–4360; (l) F. S. Melkonyan, D. E.
Kuznetsov, M. A. Yurovskaya, A. V. Karchava, RSC Adv. 2013,
3
, 8388-8397.
carbonyl (I) which further react with organozinc reagent to
4
5
Y. Fu, Y. Yang, H. M. Hügel, Z. Du, K. Wang, D. Huang, Y. Hu,
Org. Biomol. Chem., 2013, 11, 4429-4432.
(a) B. M. Day, W. Knowelden, M. P. Coles, Dalton Trans.,
give a magnesium alkoxide (II). Pivaldehyde then coordinates
to the magnesium complex (III) and a hydride transfer
2
012, 41, 10930-10933; (b) A. H. Essa, R. I. Lerrick, E. Çiftçi, R.
W. Harrington, P. G. Waddell, W. Clegg, M. J. Hall, Org.
Biomol. Chem., 2015, 13 5793-5803; (d) L. Cronin, F.
Manoni, C. J. O. Connor, S. J. Connon, Angew. Chem. Int. Ed.,
010, 49, 3045-3048.
(a) J. F. Garst, M. P. Soriaga, Coord. Chem. Rev., 2004, 248
23-652; b) Y. Fu, X.-L. Zhao, H. Hügel, B. Hou, D. Huang, Z.
occurred through complex (IV) to generate ketone (
In conclusion, a magnesium salt promoted synthesis of
aromatic ketones via tandem nucleophilic addition-
V).
,
a
Oppenauer oxidation of aldehydes using organozinc chemistry
was demonstrated. Magnesium salts concomitantly generated
via magnesium mediated organohalides zincation exhibit high
efficacy for nucleophilic addition of organozinc reagents to
aldehydes and thereafter Oppenauer oxidation whereby
ketones were formed in high to excellent yields. This
transformation offers an green and facile procedure for highly
functionalized aryl and alkyl ketones preparation. The
usefulness of this practical and efficient method was
2
6
,
6
Du, Curr. Org. Chem., 2015, 19, 2324-2343; (c) P. Knochel, W.
Dohle, N. Gommermann, F. F. Kneisel, F. Kopp, T. Korn, I.
Sapountzis, V. A. Vu, Angew. Chem. Int. Ed., 2003, 42, 4302-
4
320; (d) B. Haag, M. Mosrin, H. Ila, V. Malakhov, P. Knochel,
Angew. Chem. Int. Ed., 2011, 50, 9794-9824; (e) T. latt, J. T.
Markiewicz, C. Sämann, P. Knochel, J. Org. Chem., 2014, 79
253-4269.
,
4
7
8
(a) Z. Rappoport and I. Marek, The Chemistry of Organozinc
Compounds: R-Zn, Wiley, Chichester, UK, 2006; (b) P. Knochel
and P. Jones, Organozinc Reagents: A Practical Approach,
demonstrated
in
gram-scale
synthesis
of
2-(4-
fluorobenzoyl)thiophene, a key intermediate to non-steroidal
anti-inflammatory drug Suprofen.
Oxford University Press, Oxford, 1999
.
(a) Y. Fu, Y. Liu, Y. Chen, H. M. Hügel, M. Wang, D. Huang, Y.
Hu, Org. Biomol. Chem. 2012, 10, 7669-7672; (b) Y. Fu, X. Hu,
Y. Chen, Y. Yang, H. Hou, Y. Hu, Synthesis, 2012, 44, 1030-
Acknowledgements
1
036; (c) Y. Fu, W. Zhu, X. Zhao, H. Hügel, Z. Wu, Y. Su, Z. Du,
The authors are grateful for financial support from the
National Natural Science Foundation of China (No. 21262030).
D. Huang, Y. Hu, Org. Biomol. Chem., 2014, 12, 4295-4299.
T. Ooi, H. Otshuka, T. Miura, H. Ichikawa, K. Maruoka, Org.
Lett., 2002, 4, 2669-2672.
0 (a) R. Chorghade, C. Battilocchio, J. M. Hawkins, S. V. Ley,
Org. Lett., 2013, 15, 5698-5701; (b) H. Adkins, R. M. Elofson,
9
1
Notes and references
A. G. Rossow, C. C. Robinson, J. Am. Chem. Soc., 1949, 71
3622-3629.
,
a
College of Chemistry and Chemical Engineering, Northwest
1
1
1 (a) L. Pu, H.-B. Yu, Chem. Rev., 2001, 101, 757-824; (b) K.
Soai, S. Niwa, Chem. Rev., 1992, 92, 833-856.
2 K. Kobayashi, Y. Kondo, Org. Lett., 2009, 11, 2035-2037.
Normal UniVersity, Lanzhou, Gansu 730070, P. R. China. E-mail:
fuying@iccas.ac.cn.
b
Health Innovations Research Institute & School of Applied 13 F. Wu, W. Lu, Q. Qian, Q. Ren, H. Gong, Org. Lett., 2012, 14
3044-3047.
4 (a) M.-Y. Jin, N. Yoshikai, J. Org. Chem., 2011, 76, 1972-1978;
b) C. Gosmini, Y. Rollin, J.-Y. Nedelec, J. Perichon, J. Org.
,
Sciences, RMIT University, Melbourne, 3001 Australia.
1
(
Chem., 2000, 65, 6024-6026; (c) H. Fillon, C. Gosmini, J.
Perichon, J. Am. Chem. Soc., 2003, 125, 3867-3870; (d) I.
Kazmierski, C. Gosmini, J.-M. Paris, J. Perichon, Tetrahedron
Lett., 2003, 44, 6417-6420.
5 (a) A. H. Cherney, N. T. Kadunce, S. E. Reisman, Chem.
Rev. 2015, 115, 9587-9652; (b) V. P. Ananikov, ACS Catal.,
1
2
(a) H. Pellissier, Chem. Rev., 2013, 113, 442-524; (b) M. Ruiz,
P. López-Alvarado, G. Giorgi, J. C. Menéndez, Chem. Soc. Rev.,
2
011, 40, 3445-3454.
(a) F. Xue, J. Zhao, T. S. Andy Hor, T. Hayashi, J. Am. Chem.
Soc., 2015, 137, 3189-3192; (b) D.-C. Wang, H.-Y. Niu, M.-
1
1
S. Xie, G.-R. Qu, H.-X. Wang, H.-M. Guo, Org. Lett., 2014, 16
,
2
015, 5, 1964-1971; (c) X. Wang, S. Wang, W. Xue, H. Gong, J.
2
2
62-265; (c) C.-G. Dong, Q.-S. Hu, Tetrahedron, 2008, 64,
537-2552; (d) Z. Soradova, J. Mazikova, M. Mečiarova, R.
Am. Chem. Soc., 2015, 137, 11562-11565; (d) F. Zhu, Z.-X.
Wang, J. Org. Chem., 2014, 79, 4285-4292.
6 (a) K. Kobayashi, Y. Kondo, Org. Lett., 2009, 11, 2035-2037;
Šebesta, Tetrahedron: Asymmetry, 2015, 26, 271-275.
(a) B.Byrne, M. Karras, Tetrahedron Lett., 1987, 28, 769-772;
3
(
b) S. M. Manolikakes, M. Ellwart, C. I. Stathakis, P. Knochel,
(
b) B. K. Wilk, J. L. Helom, C. W. Coughlin, Org. Process Res.
Dev., 1998, , 407-411; (c) M. Schroeter, Synth. Commun.,
005, 35, 2203-2212; (d) J. L. Namy, J. Souppe, J. Collin, H. B.
Kagan, J. Org. Chem., 1984, 49, 2045-2049; (e) P. S. Sagara, R.
Chebolu, A. Bahuguna, P. C. Ravikumar, RSC Adv., 2014,
5011-15013; (f) V. Schulze, P. G. Nell, A. Burton, R. W.
Hoffmann, J. Org. Chem., 2003, 68, 4546-4548; (g) R. J.
Kloetzing, A. Krasovskiy, P. Knochel, Chem.–Eur. J., 2007, 13
15-227; (h) J. Yuan, J. Wang, G. Zhang, C. Liu, X. Qi, Y. Lan, J.
T. Miller, A. J. Kropf, E. E. Bunel, A. Lei, Chem. Commun.,
015, 51, 576-579; (i) L.-J. Gu, C. Jin, H.-T. Zhang, Chem. Eur.
J., 2015, 21, 8741-8744; (j) C. Jin, L. Gu, M. Yuan, Catal. Sci.
Chem. Eur. J., 2014, 20, 12289-12297; (c) D. R. Armstrong, W.
Clegg, P. Garca-lvarez, A. R. Kennedy, M. D. McCall, L. Russo,
E. Hevia, Chem. Eur. J., 2011, 17, 8333-8341; (d) S. Thapa, A.
Kafle, S. K. Gurung, A. Montoya, P. Riedel, R. Giri, Angew.
Chem. Int. Ed., 2015, 54, 8236-8240; (e) C. Smann, M. A.
Schade, S. Yamada, P. Knochel, Angew. Chem. Int. Ed., 2015,
54, 8236-8240; (f) M. Ellwart, P. Knochel, Angew. Chem. Int.
Ed., 2015, 54, 10662-10665.
7 (a) V. Papoian, T. Minehan, J. Org Chem., 2008, 73, 7376–
2
2
4,
1
,
2
1
7
2
379; (b) S.Bernhardt, Z.-L. Shen, Paul Knochel. Chem. Eur. J.,
013, 19, 828-833.
2
4
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1
1
8 (a) H. Minami, T. Saito, C. Wang, M. Uchiyama. Angew. Chem.
Int. Ed., 2015, 54, 4665-4668. (b) K. Groll, T. D. Blümke, A.
Unsinn, D. Haas, P. Knochel, Angew. Chem. Int. Ed., 2012, 51
1157–11161.
9 (a) L. Klier, T. Bresser, T. A. Nigst, K. Karaghiosoff, P. Knochel,
J. Am. Chem. Soc., 2012, 134, 13584-13587; (b) J. Yang, Q.-Q.
Min, Y. He, X. Zhang, Tetrahedron Lett., 2011, 52, 4675-4677;
,
1
(c) S. Ito, Y. Fujiwara, E. Nakamura, M. Nakamura, Org.
Lett., 2009, 11 4306-4309; (d) A. W. Buesking, T. D.
,
Baguley, J. A. Ellman, Org. Lett., 2011, 13, 964-967.
2
2
2
0 C. Liao, N. Sa, B. Key, A. K. Burrell, L. Cheng, L. A. Curtiss, J. T.
Vaughey, J.-J. Woo, L. Hu, B. Pan, Z. Zhang, J. Mater. Chem. A,
2
1 (a) A. Côté, A. B. Charette, J. Am. Chem. Soc., 2008, 130
015, 3, 6082-6087.
,
771-2773; (b) V. Tarwade, R. Selvaraj, J. M. Fox, J. Org.
2
Chem., 2012, 77, 9900-9904.
2 (a) Z. L. Shen, P. Knochel, ACS Catal., 2015,
5, 2324-2328; (b)
M. A. Schade, G. Manolikakes, P. Knochel, Org. Lett., 2010,
, 3648-3650; (c) F. M. Piller, A. Metzger, M. A. Schade, B. A.
Haag, A. Gavryushin, P. Knochel, Chem. Eur. J., 2009, 15
192-7202.
12
,
7
2
3 (a) D. Tilly, F. Chevallier, F. Mongin, P. C. Gros, Chem.
Rev., 2014, 114, 1207-1257; (b) R. L. Y. Bao, R. Zhao, L. Shi,
Chem. Commun., 2015, 51, 6884-6900; (c) N. M. Barl, V.
Werner, C. Sämann, P. Knochel, Heterocycles, 2014, 88, 827-
8
44.
2
2
4
D. Hauk, S. Lang, A. Murso, Org. Process Res.
Dev., 2006, 10, 733-738.
5 J. L. Leazer, Jr. R. Cvetovich, F.-R. Tsay, U. Dolling, T.Vickery,
D. Bachert, J. Org. Chem., 2003, 68, 3695-3698.
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