Efficient and chemoselective reduction of pyridines to tetrahydropyridines and piperidines via rhodium-catalyzed transfer hydrogenation

Article abstract of DOI:10.1002/adsc.201201034

Promoted by iodide anion the rhodium complex dimer, [Cp RhCl ₂]₂, catalyzes efficiently the transfer hydrogenation of various quaternary pyridinium salts under mild conditions, affording not only piperidines but also 1,2,3,6-tetrahydropyridines in a highly chemoselective fashion, depending on the substitution pattern at the pyridinium ring. The reduction is conducted in azeotropic formic acid/triethylamine (HCOOH-Et ₃N) mixture at 40 °C, with catalyst loadings as low as 0.005mol% being feasible. Copyright

Full text of DOI:10.1002/adsc.201201034

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DOI: 10.1002/adsc.201201034
Efficient and Chemoselective Reduction of Pyridines to
Tetrahydropyridines and Piperidines via Rhodium-Catalyzed
Transfer Hydrogenation
Jianjun Wu,a Weijun Tang,a Alan Pettman,b and Jianliang Xiaoa,*
a
Liverpool Centre for Materials & Catalysis, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K.
Fax : (+44)-151-794-3588; e-mail: j.xiao@liv.ac.uk (http://pcwww.liv.ac.uk/~jxiao)
Chemical R & D, Global Research & Development, Pfizer, Sandwich, Kent CT13 9NJ, U.K.
b
Received: November 21, 2012; Published online: December 23, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201201034.
Abstract: Promoted by iodide anion the rhodium
complex dimer, [Cp*RhCl2]2, catalyzes efficiently
the transfer hydrogenation of various quaternary
pyridinium salts under mild conditions, affording
not only piperidines but also 1,2,3,6-tetrahydropyri-
dines in a highly chemoselective fashion, depending
on the substitution pattern at the pyridinium ring.
The reduction is conducted in azeotropic formic
stance, among well-known prescription drugs are the
piperidine derivatives Risperdal used for treatment of
schizophrenia,[2] Concerta for ADHD,[3] Aricept for
Alzheimerꢀs disease,[4] Paroxetine as an antidepres-
sant[5] and Fentanyl as a pain reliever[6] (Figure 1).
Given their immense pharmaceutical utilities, the
synthesis of piperidines has been extensively stud-
ied.[1c,e–i] Hydrogenation of easily accessible pyridines
provides probably the most economic and efficient
route for accessing piperidines.[7] Over the past eighty
years, a variety of heterogeneous catalysts, such as
PtO2, Raney Ni, RuO2, Rh/C and Pd/C, have been
used to fully reduce pyridines with H2;[7–9] but most of
these catalysts are of low activity and selectivity and
require harsh reaction conditions. Recently, several
homogeneous Rh, Ir and Ru complexes[10] and an or-
ganocatalyst[11] have been reported to catalyze the hy-
drogenation.[12] However, special activating groups
acid/triACHTUNGTRENNUNGethylamine (HCOOH-Et3N) mixture at
408C, with catalyst loadings as low as 0.005 mol%
being feasible.
Keywords: piperidines; pyridines; rhodium cata-
lysts; tetrahydropyridines; transfer hydrogenation
Piperidines, which structurally exist in numerous natu- generally need to be installed on the pyridines and
ral products and synthetic bioactive compounds, have a relatively high catalyst loading is necessary.
attracted a tremendous amount of attention in the
Partial hydrogenation of pyridines to give tetrahy-
chemical and pharmaceutical industries.[1] For in- dropyridines is even more interesting, since the result-
Figure 1. Piperidine derivatives as prescription drugs.
Adv. Synth. Catal. 2013, 355, 35 – 40
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
35

Jianjun Wu et al.
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Table 1. Effect of metal compounds and iodide on the trans-
fer hydrogenation of 1a.[a]
ing unsaturated piperidines can be further trans-
formed into other value-added products via many
well-established reactions, such as asymmetric hydro-
genation, epoxidation, dihydroxylation, and allylic
substitution and isomerization.[13] Consequently,
a huge number of reactions have been carried out for
the partial reduction of pyridines.[8,14] In almost all of
the cases, however, stoichiometric reducing reagents,
such as NaBH4, LiAlH4 and metal Na, are employed.
Apart from being hazardous and generating copious
amounts of toxic waste, these reagents are character-
ized with poor selectivity, which limits their applica-
tion in modern synthesis. A few examples of the par-
tial hydrogenation of pyridines with heterogeneous
catalysts are also known, most of which afford 2,3-un-
saturated piperidines bearing electron-withdrawing
groups.[15] Therefore, it remains a great challenge to
reduce pyridines in a general, efficient, selective and
operationally benign manner. Herein, we disclose
a simple, effective catalytic system for the transfer hy-
drogenation of pyridines. Notably, this protocol af-
fords not only piperidines, but also the 3,4-unsaturated
variants highly chemoselectively.
Entry
X
Metal, mol%[b] Additive, equiv. Yield[c]
1
2
3
4
5
6
7
8
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
[Rh], 0.005
[Rh], 0.005
[Rh], 0.5
[Rh], 0.005
[Rh], 0.005
[Rh], 0.05
none
KI, 0.1
none
none
KI, 1.0
KI, 3.0
KI, 1.0
KI, 1.0
none
none
none
none
none
85
9
84
90
10
94
NR[d]
4
[Ir], 0.5
9
[Ru], 0.5
RhCl3, 1.0
[Rh], 0.005
NR[d]
NR[d]
92
10
11
12
SbF6 [Rh], 0.5
NR[d]
[a]
Reaction conditions: pyridinium salt 1a (0.5 mmol),
HCO2H-NEt3 azeotrope solution (5 mL), 408C, 24 h
under N2, Bn=benzyl.
[b]
[Rh]=[Cp*RhCl2]2, [Ir]=[Cp*IrCl2]2 and [Ru]=[RuCl2
We recently reported that, promoted by iodide, the
simple dimeric complex [Cp*RhCl2]2 allows for the
highly efficient transfer hydrogenation of quinolines,
isoquinolines and quinoxalines using the azeotropic
mixture HCOOH-Et3N as reductant.[16] Following this
AHCTUNGTRENN(GUN p-cymene)]2.
Isolated yields.
No reaction or no desired product observed.
[c]
[d]
success, we attempted to apply the [Cp*RhCl2]2-IÀ before.[16] The yield was slightly improved when in-
catalyst to the reduction of pyridines. No reaction was creasing the catalyst loading to 0.05 mol% (Table 1,
observed with the model substrate 2-methylpyridine entry 6). Control experiments show that no reduction
(pKa 6.0), which is expected to be protonated by occurs without the rhodium, and other metal com-
formic acid (pKa 3.6). Delightfully, we found that qua- pounds are ineffective (Table 1, entries 7–10). As ex-
ternized pyridines underwent the reduction readily. pected, when picolinium iodide was used, 2a was ob-
Given the simplicity of quaternization with benzyl tained in excellent yield without adding any KI
halides and the importance of benzyl-protected piper- (Table 1, entry 11). We note, however, that pyridinium
idines, we set out to examine the catalysis with N- iodide salts are generally much more difficult to
benzyl-2-picoline bromide, which can be conveniently access than the bromides. In contrast, no reaction was
prepared by alkylation of 2-picoline with benzyl bro- observed when the anion of the picolinium salt waÀs
mide. As can be seen from Table 1, catalyzed by only replaced with
a
non-coordinating anion, SbF6
0.005 mol% [Cp*RhCl2]2, the picoline bromide was (Table 1, entry 12), showing again the importance of
reduced in HCOOH-Et3N at 408C, affording N-ben- the coordinating anion to the catalytic activity.[16]
zylpiperidine in 85% isolated yield (Table 1, entry 1).
Having the optimized reaction conditions in hand,
As with the reduction of other N-heterocycles,[16] the a variety of pyridinium salts were subjected to trans-
iodide salt KI again shows a remarkable accelerating fer hydrogenation with 0.05 mol% [Cp*RhCl2]2. As
effect on the reduction (Table 1, entries 1 vs. 2). Al- shown in Scheme 1, a range of mono- or disubstituted
though the reaction proceeds without the iodide, the pyridiniums were reduced, affording the correspond-
same result can only be obtained by using a much ing N-benzylpiperidines in good to excellent yields.
higher catalyst loading (Table 1, entry 3). The concen- Thus, 2-alkyl-substituted pyridiniums underwent
tration of the iodide salt affects the reduction rates, smooth hydrogenation to give 2-alkylpiperidines in
with higher product yields obtained using one equiva- high yields (Scheme 1, 2a–2c). A lower yield was ob-
lent of KI (Table 1, entry 4), under which a turnover tained with the 2-phenylpiperidine (2d), probably due
number (TON) of 9000 is generated. To the best of to steric demand of the phenyl ring and/or its stabili-
our knowledge, this is the highest TON value ever re- zation of the intermediate iminium C=N bond (vide
ported in the catalytic reduction of pyridines. How- infra). Surprisingly somehow, the unsubstituted pyridi-
ACHTUNGTRENNUNG
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Adv. Synth. Catal. 2013, 355, 35 – 40

Efficient and Chemoselective Reduction of Pyridines to Tetrahydropyridines and Piperidines
Scheme 1. Transfer hydrogenation of pyridinium salts to pi-
peridines.[a]
Scheme 2. Partial transfer hydrogenation of 4-substituted
pyridinium salts.[a]
60% of the mixture. The formation of the unsaturated
piperidine is likely a result of competing 1,2-hydride
addition (vide infra). Most interestingly, substrates
bearing hydroxy and protected amino groups at either dine 4a (Scheme 2). Prompted by this finding while
2 or 3 positions were tolerated, generating synthetical- bearing in mind the importance of such products, we
ly valuable amino alcohols and diamines (2f–h, j, k). subsequently examined the hydrogenation of a series
For instance, 2j and 2k have found applications in the of 4-substituted pyridiniums. The results are found in
pharmaceutical industry as cyclic b-amino alcohols Scheme 2. To our delight, most of 4-substituted pyridi-
and diamines.[17] However, a conjugated C=C double niums were reduced with high or exclusive selectivi-
bond at the 2-postion was fully reduced, leading to 2i ties toward the 3,4-unsaturated piperidine products.
probably via 1,4-hydride addition beginning at the Thus, pyridiniums bearing different 4-alkyl substitu-
carbon a to the Ph group. Notably, 2,3-disubstituted ents were hydrogenated with excellent yields (4a–d),
pyridinium can be hydrogenated to piperidine exclu- with a bulkier substituent affording a higher chemose-
sively as the trans isomer (2m), whilst the 2,6-disubsti- lectivity favouring 4. For instance, in the case of 4c,
tuted pyridinium affords cis piperidine as the major no fully reduced product was observed. The same is
product (2l). Non-benzyl quaternized pyridine is also also true with 4-phenyl-substituted pyridinium 3e,
viable. Thus, the N-phenylethylpiperidine 2n, an ana- which led to 4e in excellent yield. Of particular note
logue of a well-known s receptor antagonist for treat- is that pyridiniums bearing electron-withdrawing and
ing methamphetamine abuse,[18] is generated from the electron-donating groups (3f, g) and other functionali-
corresponding pyridinium salt in excellent yield.
ties, such as hydroxy (3h), ester (3j, k) and protected
On applying the catalysis to 4-substituted pyridini- amine (3i), were viable as well, being reduced with ex-
ums we met with a surprise. Thus, under the same cellent chemoselectivities and high yields. In contrast
conditions as above, the reduction of 4-methylpyridi- to the reduction of 1i, the conjugated C=C double
nium 3a afforded primarily the 3,4-unsaturated piperi- bond in 3l was retained. The 4-styryl-substituted 4l
Adv. Synth. Catal. 2013, 355, 35 – 40
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37

Jianjun Wu et al.
COMMUNICATIONS
was isolated in 66% yield, exclusively in the s-cis con-
formation. Furthermore, 3,4-disubstituted pyridinium
(3m) was also reduced, although a higher catalyst
loading (0.25 mol%) was required. Finally, replacing
the benzyl group with phenylethyl did not affect
much the yield (4n), and more interestingly, the
benzyl could also be replaced with an allyl group
(4o), which would be problematic in heterogeneous
hydrogenation. The presence of alkene, diene, hy-
droxy, amino, ester and allyl units in these piperidines
opens a vast potential for further reactions, as indicat-
ed before. We note that 3,4-unsaturated piperidines
can be accessed generally only through reduction with
boron hydrides.[8]
To further showcase the utility of this new protocol,
we carried out the synthesis of compound 4e on
a gram scale. 4-Arylpiperidines are a valuable struc-
tural unit found in a number of drug discovery pro-
grams for potential treatment of symptoms such as
asthma, hypertension, depression, cocaine abuse,
benign prostatic hyperplasia, estrogen-related disor-
ders, and Alzheimerꢀs and Parkinsonꢀs diseases.[19]
Scheme 3. Plausible mechanism for the chemoselective
transfer hydrogenation.
Commercial 4-phenylpyridine was quaternized easily DCOOH-NEt3 was used to reduce 1a and 3c, respec-
with benzyl bromide affording 3e in quantitative tively (see the Supporting Information for details).
yield. Transfer hydrogenation of 3e (1.0 g) in the
In conclusion, we have developed a simple, efficient
HCO2H-NEt3 azeotrope with an even lower catalyst protocol for the chemoselective reduction of pyridini-
loading of 0.0125 mol% (0.25 mg) in air provided the um salts. A variety of piperidines and, more interest-
3,4-unsaturated piperidine product 4e in 97% isolated ingly, 1,2,3,6-tetrahydropyridines were obtained with
yield. This appears to us to be the most efficient way good to excellent yields, providing valuable inter-
for accessing this type of compound, regarding cost, mediates and feedstocks for chemical, pharmaceutical
effectiveness, practicability and scalability.[19,20] It is and agrochemical synthesis.
also worth noting that for most reactions in Scheme 1
and Scheme 2, the work-up simply involves direct ex-
traction after basifying the reaction mixture without Experimental Section
further purification, due to the high solubility of pyri-
dinium and other salts in aqueous solution.
Typical Procedure
A plausible mechanism explaining the role of
iodide and the observed chemoselectivity is shown in
Scheme 3. As suggested before,[16,21] the substrate is
A carousel reaction tube containing a magnetic stirring bar,
[Cp*RhCl2]2 (0.16 mg, 0.25 mmol, measured using a DCM
stock solution), N-benyl-2-methylpyridinium bromide (1a,
132 mg, 0.5 mmol) and potassium iodide (83 mg, 0.5 mmol)
in 5 mL HCOOH-Et3N azeotrope was sealed after degassing
and placed in the carousel reactor. The reaction mixture was
stirred at 408C for 24 h, cooled to room temperature and
then basified with an aqueous solution of KOH. The result-
ing mixture was extracted with ethyl acetate (3ꢂ20 mL) and
dried over Na2SO4. The solvent was removed under reduced
pressure. Analytically pure 2a was obtained after further
drying under vacuum; yield: 94%.
À
likely to be reduced with an anionic diiodo Rh H hy-
dride species. Both the iodide and anionic charge
would render the hydride more hydridic, facilitating
its transfer to the pyridinium. However, excess iodide
salt is needed in order to suppress the dissociation of
iodide anion from the active hydride species.[16,22] In
the absence of a 4-substituent, the hydride adds pref-
erentially at the 4 position initially (i.e., 1,4-addition);
the resulting enamine isomerizes to an iminium spe-
cies and is then reduced via a 1,2-hydride addition.
When the 4 position is substituted, 1,4-addition be-
comes impossible. Instead, 1,2-addtion takes place to
give 1,2-dihydropyridine; isomerization of the result-
ing enamine followed by another 1,2-adddition af-
fords the N-substituted 1,2,3,6-tetrahydropyridines 4.
Consistent with this picture, the 2,4,6-positions of 2a
and the 2,6-positions of 4c were deuterated when
Acknowledgements
We are grateful to Pfizer for funding (J. Wu), AstraZeneca
for support, S. Johnston for assistance in NMR and the
EPSRC NMSSC for mass spectral analysis.
38
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Efficient and Chemoselective Reduction of Pyridines to Tetrahydropyridines and Piperidines
References
Shi, Y. Duan, Y. G. Zhou, Angew. Chem. 2012, 124,
10328; Angew. Chem. Int. Ed. 2012, 51, 10181.
[11] M. Rueping, A. P. Antonchick, Angew. Chem. 2007,
119, 4646; Angew. Chem. Int. Ed. 2007, 46, 4562.
[12] Reviews on asymmetric hydrogenation of heteroaro-
matics: a) F. Glorius, Org. Biomol. Chem. 2005, 3, 4171;
b) D. S. Wang, Q. A. Chen, S. M. Lu, Y. G. Zhou,
Chem. Rev. 2012, 112, 2557; c) Z. Yu, W. Jin, Q. Jiang,
Angew. Chem. 2012, 124, 6164; Angew. Chem. Int. Ed.
2012, 51, 6060.
[13] Reviews on asymmetric functionalization of olefins: hy-
drogenation, a) H. U. Blaser, C. Malan, B. Pugin, F.
Spindler, H. Steiner, M. Studer, Adv. Synth. Catal.
2003, 345, 103; epoxidation, b) Q. H. Xia, H. Q. Ge,
C. P. Ye, Z. M. Liu, K. X. Su, Chem. Rev. 2005, 105,
1603; dihydroxylation, c) H. C. Kolb, M. S. VanNieu-
wenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483; al-
lylic substitution, d) C. G. Frost, J. Howarth, J. M. J.
Williams, Tetrahedron: Asymmetry 1992, 3, 1089; allylic
isomerization, e) S. Otsuka, K. Tani, Synthesis 1991,
665.
[14] For examples of hydrosilylation, hydroboration and si-
laboration of pyridines to form dihydro- or tetrahydro-
pyridines, see: a) N. C. Cook, J. E. Lyons, J. Am. Chem.
Soc. 1966, 88, 3396; b) L. Hao, J. F. Harrod, A. M.
Lebuis, Y. Mu, R. Shu, E. Samuel, H. G. Woo, Angew.
Chem. 1998, 110, 3314; Angew. Chem. Int. Ed. 1998, 37,
3126; c) D. V. Gutsulyak, A. van der Est, G. I. Nikonov,
Angew. Chem. 2011, 123, 1420; Angew. Chem. Int. Ed.
2011, 50, 1384; d) K. Osakada, Angew. Chem. 2011,
123, 3929; Angew. Chem. Int. Ed. 2011, 50, 3845; e) K.
Oshima, T. Ohmura, M. Suginome, J. Am. Chem. Soc.
2011, 133, 7324; f) K. Oshima, T. Ohmura, M. Sugi-
nome, J. Am. Chem. Soc. 2012, 134, 3699.
[1] a) U. Eisner, J. Kuthan, Chem. Rev. 1972, 72, 1; b) Y.
Kasꢃ, T. Miyata, Adv. Biochem. Psychopharmacol.
1976, 15, 5; c) V. Baliah, R. Jeyaraman, L. Chandrase-
karan, Chem. Rev. 1983, 83, 379; d) D. OꢀHagan, Nat.
Prod. Rep. 2000, 17, 435; e) S. Laschat, T. Dickner, Syn-
thesis 2000, 1781; f) P. M. Weintraub, J. S. Sabol, J. M.
Kane, D. R. Borcherding, Tetrahedron 2003, 59, 2953;
g) M. G. P. Buffat, Tetrahedron 2004, 60, 1701; h) S.
Kꢄllstrçm, R. Leino, Bioorg. Med. Chem. 2008, 16, 601;
i) P. Merino, T. Tejero, G. Greco, E. Marca, I. Delso, A.
Gomez-SanJuan, R. Matute, Heterocycles 2012, 84, 75;
j) B. T. Green, S. T. Lee, K. E. Panter, D. R. Brown,
Food Chem. Toxicol. 2012, 50, 2049.
[2] a) A. A. H. P. Megens, F. H. L. Awouters, A. Schotte,
T. F. Meert, C. Dugovic, C. J. E. Niemegeers, J. E.
Leysen, Psychopharmacology 1994, 114, 9; b) P. Tyrer,
P. C. Oliver-Africano, Z. Ahmed, N. Bouras, S. Cooray,
S. Deb, D. Murphy, M. Hare, M. Meade, B. Reece, K.
Kramo, S. Bhaumik, D. Harley, A. Regan, D. Thomas,
B. Rao, B. North, J. Eliahoo, S. Karatela, A. Soni, M.
Crawford, Lancet 2008, 371, 57.
[3] W. E. Pelham, E. M. Gnagy, L. Burrows-Maclean, A.
Williams, G. A. Fabiano, S. M. Morrisey, A. M. Chronis,
G. L. Forehand, C. A. Nguyen, M. T. Hoffman, T. M.
Lock, K. Fielbelkorn, E. K. Coles, C. J. Panahon, R. L.
Steiner, D. L. Meichenbaum, A. N. Onyango, G. D.
Morse, Pediatrics 2001, 107, 105.
[4] A. Burns, M. Rossor, J. Hecker, S. Gauthier, H. Petit,
H. J. Mçller, S. L. Rogers, L. T. Friedhoff, Dementia
Geriatr. Cognit. Disord. 1999, 10, 237.
[5] a) K. L. Dechant, S. P. Clissold, Drugs 1991, 41, 225;
b) M. Bourin, P. Chue, Y. Guillon, CNS Drug Rev.
2001, 7, 25.
[15] a) E. Wenkert, K. G. Dave, F. Haglid, J. Am. Chem.
Soc. 1965, 87, 5461; b) P. M. Quan, L. D. Quin, J. Org.
Chem. 1966, 31, 2487; c) E. Wenkert, K. G. Dave, F.
Haglid, R. G. Lewis, T. Oishi, R. V. Stevens, M. Terashi-
ma, J. Org. Chem. 1968, 33, 747.
[6] W. Jeal, P. Benfield, Drugs 1997, 53, 109.
[7] a) P. N. Rylander, Catalytic Hydrogenation in Organic
Synthesis, Academic Press, New York, 1979; b) R. L.
Augustine, Heterogeneous Catalysis for the Synthetic
Chemist, Marcel Dekker, New York, 1995; c) M. Frei-
felder, Adv. Catal. 1963, 14, 203.
[8] A search with SciFinder on hydrogenation of pyridines
to piperidines hit >270,000 reactions. A similar search
on partial reduction of pyridines to tetrahydropyridines
hit >45,000 reactions.
[9] For early studies, see: a) T. S. Hamilton, R. Adams, J.
Am. Chem. Soc. 1928, 50, 2260; b) H. Adkins, L. F.
Kuick, M. Farlow, B. Wojcik, J. Am. Chem. Soc. 1934,
56, 2425; c) M. Freifelder, G. R. Stone, J. Org. Chem.
1961, 26, 3805; d) M. Freifelder, R. M. Robinson, G. R.
Stone, J. Org. Chem. 1962, 27, 284.
[10] a) E. Baralt, S. J. Smith, J. Hurwitz, I. T. Horvꢅth, R. H.
Fish, J. Am. Chem. Soc. 1992, 114, 5187; b) M. Studer,
C. Wedemeyer-Exl, F. Spindler, H. U. Blaser, Monatsh.
Chem. 2000, 131, 1335; c) C. Y. Legault, A. B. Charette,
J. Am. Chem. Soc. 2005, 127, 8966; d) X. B. Wang, W.
Zeng, Y. G. Zhou, Tetrahedron Lett. 2008, 49, 4922;
e) W. J. Tang, J. Tan, L. J. Xu, K. H. Lam, Q. H. Fan,
A. S. C. Chan, Adv. Synth. Catal. 2010, 352, 1055;
f) W. J. Tang, Y. W. Sun, L. J. Xu, T. L. Wang, Q. H.
Fan, K. H. Lam, A. S. C. Chan, Org. Biomol. Chem.
2010, 8, 3464; g) Z. S. Ye, M. W. Chen, Q. A. Chen, L.
[16] J. Wu, C. Wang, W. Tang, A. Pettman, J. Xiao, Chem.
Eur. J. 2012, 18, 9525.
[17] a) M. B. Skaddan, M. R. Kilbourn, S. E. Snyder, P. S.
Sherman, T. J. Desmond, K. A. Frey, J. Med. Chem.
2000, 43, 4552; b) R. G. Wei, M. Adler, D. Davey, E.
Ho, R. Mohan, M. Polokoff, J. L. Tseng, M. Whitlow,
W. Xu, S. Yuan, G. Phillips, Bioorg. Med. Chem. Lett.
ˇ
ˇ
´
2007, 17, 2499; c) S. Kovackovꢅ, M. Dracꢆnsky, D.
Rejman, Tetrahedron 2011, 67, 1485; d) E. J. Hennessy,
J. C. Saeh, L. Sha, T. MacIntyre, H. Wang, N. A.
Larsen, B. M. Aquila, A. D. Ferguson, N. M. Laing,
C. A. Omer, Bioorg. Med. Chem. Lett. 2012, 22, 1690.
[18] R. R. Matsumoto, J. Shaikh, L. L. Wilson, S. Vedam, A.
Coop, Eur. Neuropsychopharmacol. 2008, 18, 871.
[19] C. Morrill, N. S. Mani, Org. Lett. 2007, 9, 1505, and ref-
erences cited therein.
[20] a) H. G. Chen, O. P. Goel, S. Kesten, J. Knobelsdorf,
Tetrahedron Lett. 1996, 37, 8129; b) H. Tsukamoto, Y.
Kondo, Angew. Chem. 2008, 120, 4929; Angew. Chem.
Int. Ed. 2008, 47, 4851; c) A. C. Spivey, L. J. Martin,
C. C. Tseng, G. J. Ellames, A. D. Kohler, Org. Biomol.
Chem. 2008, 6, 4093; d) R. J. Conway, C. Valant, A.
Adv. Synth. Catal. 2013, 355, 35 – 40
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
39

Jianjun Wu et al.
COMMUNICATIONS
Christopoulos, A. D. Robertson, B. Capuano, I. T.
Crosby, Bioorg. Med. Chem. Lett. 2012, 22, 2560.
[21] a) K. Fagnou, M. Lautens, Angew. Chem. 2002, 114, 26;
Angew. Chem. Int. Ed. 2002, 41, 26; b) P. M. Maitlis, A.
Haynes, B. R. James, M. Catellani, G. P. Chiusoli,
Dalton Trans. 2004, 3409.
[22] Too much iodide salt is not good either, as it would fa-
cilitate the displacement of the coordinated formate by
iodide, leading to catalytically inactive species. Also see
ref.[16]
40
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Adv. Synth. Catal. 2013, 355, 35 – 40