Synthesis of diverse di- to penta-substituted 1,2-dihydropyridine derivatives from gold(I)-catalyzed intramolecular addition of tertiary enamides to alkynes

Article abstract of DOI:10.1016/j.tetlet.2015.04.105

As 3-aza-1,5-enynes, internal and terminal alkyne-bearing tertiary enamides underwent an efficient Au(I)-catalyzed 6-endo-dig cyclization reaction to afford a variety of di- to penta-substituted 1,2-dihydropyridine derivatives in high yields. The cyclizat

Full text of DOI:10.1016/j.tetlet.2015.04.105

Accepted Manuscript
Synthesis of diverse di- to penta-substituted 1,2-dihydropyridine derivatives
from gold(I)-catalyzed intramolecular addition of tertiary enamides to alkynes
Xingyi Zhang, Xin-Ming Xu, Liang Zhao, Jingsong You, Jieping Zhu, Mei-
Xiang Wang
PII:
S0040-4039(15)00762-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.04.105
TETL 46245
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
7 April 2015
23 April 2015
27 April 2015
Please cite this article as: Zhang, X., Xu, X-M., Zhao, L., You, J., Zhu, J., Wang, M-X., Synthesis of diverse di- to
penta-substituted 1,2-dihydropyridine derivatives from gold(I)-catalyzed intramolecular addition of tertiary
enamides to alkynes, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.04.105
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Synthesis of Diverse Di- to Penta-Substituted 1,2-Dihydropyridine Derivatives from Gold(I)-
catalyzed Intramolecular Addition of Tertiary Enamides to Alkynes
Xingyi Zhang,† Xin-Ming Xu,‡ Liang Zhao,‡ Jingsong You,† Jieping Zhu,§ and Mei-Xiang Wang*,‡
† Key Laboratory of Green Chemistry and Technology (MOE), College of Chemistry, Sichuan Uni-
versity, Chengdu 610064, China
‡ Key Laboratory of Bioorganic Phosphorous and Chemical Biology (MOE), Tsinghua University,
Beijing 100184 China
§ Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-
SB-ISIC-LSPN, BCH 5304, 1015 Lausanne, Switzerland
ABSTRACT: As 3-aza-1,5-enynes, internal and terminal alkyne-bearing tertiary enamides underwent
an efficient Au(I)-catalyzed 6-endo-dig cyclization reaction to afford a variety of di- to penta-
substituted 1,2-dihydropyridine derivatives in high yields. The cyclization proceeds through a cas-
cade comprising of intramolecular nucleophilic addition of enaminic carbon to alkyne-gold(I) com-
plex, deprotonation and protodeauration steps. Au(I)-catalyzed tertiary enamide-alkyne cyclization
coupled with consecutive oxidative aromatization provided a straightforward route to polysubstituted
pyridines.
Keywords: tertiary enamide; 1,2-dihydropyridine; gold(I) catalysis; cyclization; pyridine
1,2-Dihydropyridines are versatile intermediates in the synthesis of various alkaloids and important
bioactive products such as azasugar derivatives and anti-influenza drug Tamiflu.1 Major synthetic
routes to 1,2-dihydropyridine derivatives include condensation reactions, reduction of and
nucleophilic addition to pyridines and pyridinium salts.2 Pericyclic reactions constitute other meth-
ods for the construction of 1,2-dihydropyridine structure.2 Formation of 1,2-dihydropyridines from
Rh(I)-catalyzed cycloisomerization of N-propargyl enamines under basic conditions has been report-

ed via a rhodium vinylidene intermediate.3 Recently, an efficient Au-catalyzed cycloisomerization of
N-propargyl enamines was also disclosed by Kozmin in the construction of fused N-heterocyclic
compounds.4 All methods suffer from at least one of the drawbacks ranging from poor reaction se-
lectivity, limited substrate scope and tedious preparation of reactants and harsh reaction conditions.
Development of general, efficient and diversity-orientated synthetic methodologies for 1,2-
dihydropyridines is highly desirable.2
As enamine variants, enamides have long been recognized as chemically stable species because of
the electron-withdrawing effect of N-acyl group.5 It has been shown recently that secondary
enamides act as aza-ene components to participate in aza-ene addition reactions with reactive
enophiles.6 However, no reactions occur when tertiary enamides are employed. Considering the cross
conjugation system within the molecules, we proposed a few years ago that enabled regulation of
delocalization of lone pair electrons on nitrogen into the carbon-carbon double bond would reinvig-
orate the nucleophilic activity of enamides. Guided by this working hypothesis, enaminic reactions
of tertiary enamides have been successfully established towards epoxides,7 carbonyls,8 imines9 and
nitriliums,10 providing unique and powerful methods for the synthesis of diverse heterocyclic com-
pounds.11 To further explore the reactivity and synthetic utility of tertiary enamides, we studied
intramolecular addition reaction of tertiary enamides to alkynes, envisioning the novel strategy to
construct N-heterocyclic rings. We report herein a highly efficient intramolecular addition of tertiary
enamides to various unactivated internal and terminal alkynes. The reaction proceeds through a
Au(I)-catalyzed 6-endo-dig cyclization to afford a variety of di- to penta-substituted 1,2-
dihydropyridine derivatives.12 A simple and straightforward method for the preparation of
polysubstituted pyridines is also demonstrated.
Table 1. Tertiary enamide-alkyne cyclization of 1a
entry
Cat. (mol %)
I2 (200)
solvent
DCM
DCE
temp. (oC)
time
10 h
8 h
2a (%)a
b
1
2
3
0 – rt
rt
-
b
ICl (100)
NBS (100)
-
b
DCE
rt
8 h
-

n.r.c
29d
n.r.c
80
4
5
Cat. A (5)
AuCl3 (5)
DMF
DCM
DCM
DCM
DCM
DCE
DCE
DCE
DCE
DCE
rt
rt
24 h
20 h
6
Cat. B (2.5)
Cat. C (2.5)
Cat. C (2.5)
Cat. C (2.5)
Cat. C (2.5)
Cat. C (2.5)
Cat. C (1.0)
rt
4 h
7
rt
10 min
10 min
4 h
8
40
rt
85
66e
87
9
10
11
12
13
40
80
80
80
10 min
10 min
2 h
98
72f
Cat. C (0.25)
20 h
trace
a
b
c
Isolated yield. An inseparable mixture of compounds was obtained. No reaction was observed,
e
and starting material was recovered in 98%. d Starting material was recovered in 43%. Starting ma-
terial was isolated in 15%. f A small amount of starting material was not converted.
We commenced our study by examining the reaction of N-(3-phenylprop-2-yn-1-yl)-substituted ter-
tiary enamide 1a with iodonium and bromonium. Unfortunately, treatment of 1a with iodine, iodine
chloride and NBS did not give any cyclization product. Instead, an inseparable mixture was obtained
(entries 1-3, Table 1). A rhodium(I) complex (Cat. A), which was reportedly able to catalyze
cycloisomerization of N-propargyl enamines,3 was also used. However, no reaction at all was ob-
served with the intact reactant 1a being recovered almost quantitatively (entry 4, Table 1). We then
turned our attention to cationic gold complexes, alkynophilic π-acid species that activate carbon-
carbon triple bond.4,12,13 Although AuCl3 was able to effect the cyclization of 1a, the catalytic activity
was appallingly low. In the presence of AuCl3 (5 mol %), for instance, 1,2-dihydropyridine product
2a was formed in only 29% yield in 20 h (entry 5, Table 1). While AuCl-phosphine complex (Cat. B)
exhibited no catalytic activity (entry 6, Table 1), AuSbF6-phosphine complex (Cat. C)14 catalyzed
the cyclization efficiently in dichloromethane (DCM) at ambient temperature to afford 2a in 80%
yield in 10 minutes (entry 7, Table 1). The chemical yield was improved to 85% when the reaction
was refluxed in DCM (entry 8, Table 1). Reaction proceeded analogously in dichloroethane (DCE)
(entries 9 and 10, Table 1). Pleasingly, an almost quantitative yield of 2a was yielded in 10 minutes
o
when the reaction was conducted at 80 C in DCE (entry 11, Table 1). Reaction was also effective
when catalyst loading was lowered to 1.0 mol % (entry 12, Table). No reaction took place in the ab-
sence of a catalyst or the catalyst loading was decreased to 0.25 mol % (entry 13, Table 1).

Table 2. Au(I)-catalyzed cyclization reaction of 1a-u
a
b
Cat. C (5 mol %) was used. Yield was obtained from the reaction using Cat. A (5 mol %) as a
catalyst. c Reported chemical yield using Cat. A (5 mol %) is 67%.
Under the optimized conditions, the scope of the reaction was scrutinized. Gratifyingly, the cationic
Au(I)-catalyzed tertiary enamide-alkyne cyclization appeared very general and highly efficient. As
summarized in Table 2, all substrates 1a-w, which were prepared conveniently following the estab-
lished procedures (see Supporting Information), were transformed into diverse 1,2-dihydropyridine
products in good to excellent yields irrespective of the substitution patterns and of the nature of the
substituents. For example, substrates 1a-c that contain a phenyl or an electron-rich aryl on acetylene
underwent cyclization reaction to afford 1-acetyl-4,6-diaryl-1,2-dihydropyridines 2a-c in high yields.
2-Cyanophenyl-bearing analog 1d was converted similarly into product 2d albeit an increased cata-
lyst loading (5 mol %) was required. Enaminic addition of tertiary enamide to methyl (1e) and even
trimethylsilyl (1f) capped acetylenes proceeded equally well to produce 4-alkylated and 4-silylated
1,2-dihydropyridine products 2e and 2f, in 85% and 76%, respectively.
In the case of N-(3-phenylprop-2-yn-1-yl)-tertiary enamides, substrates bearing a substituted phenyl
group (1g-j), 2-naphthyl (1k) and a hetereoaryl such as 2-furanyl (1l) underwent cyclization smooth-
ly to give high yields of the corresponding tri-substituted 1,2-dihydropyridine products 2g-l. When

2-thienyl-substituted tertiary enamide 1m was treated with the Au(I) catalyst, 4,6-di(2-thienyl)-1,2-
dihydropyridine 2m was produced in 43% yield. It is worth noting that tertiary enamides containing
hexenyl (1n) and hexyl (1o) underwent the Au(I)-catalyzed cyclization reaction identically, allowing
the synthesis of 6-alkenyl and 6-alkyl substituted 1,2-dihydropyridines efficiently. Interestingly, a
1,3-diyne-linked bis-tertiary enamide 1p, which was readily obtained from homo coupling of 1a (see
Supporting Information), underwent double cyclization reactions to furnish 1,1’,2,2’-tetrahydro-4,4’-
bipyridine derivative 2p although a slightly higher catalyst loading (5 mol %) was necessary. Varia-
tion of N-acetyl moiety to benzoyl (1q) and benzyloxycarbonyl (1r) group did not impose any unfa-
vorable effect on reaction as respective products 2q and 2r were yielded almost quantitatively.
In addition to tri-substituted 1,2-dihydropyridines, tetra- and penta-substituted 1,2-dihydropyridine
compounds were also easily synthesized by the Au(I)-catalyzed cyclization reaction. As exemplified
in Table 2, reaction employing tertiary enamide 1s gave rise to the formation of 1,2,4,6-tetra-
substututed 1,2-dihydropyridine 2s, while the use of cyclohexone-derived reactant 1t led to the gen-
eration of 1,4,5,6,-tetrasubstituted 1,2-dihydropyridine compound 2t. Remarkably, 1-acetyl-2-
methyl-4-phenyl-1,2,5,6,7,8-hexahydroqinoline 2u, a very rare 1,2,4,5,6-penta-substituted 1,2-
dihydropyridine species, was obtained nicely in 69%.
It was particularly worth noting that the Au(I) catalyst (Cat. C) was also able to catalyze perfectly
the intramolecular enaminic addition of tertiary enamides to a terminal alkyne moiety. This has been
evidenced convincingly by the high-yielding formation of 1,6-disubstituted 1,2-dihydropyridine
products 2v and 2w from the reactions of N-propargyl-substituted tertiary enamides 1v and 1w, re-
spectively. As we mentioned that the rhodium(I) complex (Cat. A) was inactive at all to substrates
1a-u that contain an internal alkyne.3 For a terminal alkyne substrate, we concurred with Lee’s work
that N-propargyl-N-benzoyl enamine 1v underwent the Rh-catalyzed reaction under basic conditions
to give 2v in 69% yield in 24 h. For a less reactive N-propargyl tertiary enamide 1w, however, the
Rh(I)-catalyzed reaction gave 30% of product 2w in 36 h along with the recovery of starting material
1w in 27% yield. It is obvious that the Au(I) catalysis is superior to Rh(I) catalysis in terms of sub-
strate scope and catalytic efficiency.
Extensive studies in the field of homogeneous gold catalysis have shown that 1,5-enynes undergo
invariably 5-endo-dig cycloisomerization reactions.13,15 These reactions have been reported to pro-
ceed through the cyclopropyl gold(I) carbene intermediates, which lead to the formation of different
five-membered ring products depending on the nature of ligands utilized.15 In contrast to these re-
ported examples, formation of 1,2-dihydropyridines from Au(I)-catalyzed reaction of 3-aza-1,5-
enynes, namely, both internal and terminal alkyne-bearing tertiary enamides 1 indicates undoubtedly
the operation of an entirely different reaction mechanism. While further studies are in progress to

elucidate the details of this cyclization reaction, we propose a most plausible reaction pathway. As
depicted in Scheme 1, interaction of Au(I) catalyst with reactants 1 would form a π-complex 3.
Intramolecular nucleophilic addition of the enaminic carbon of tertiary enamides to carbon-carbon
triple bond results in the formation of intermediates 4 which undergo deprotonation to give organo-
metallic species 5. Protodeauration of 5 furnishes the formation of final products 2. It is the
nucleophilic nature of tertiary enamides that lead to 6-endo-dig cyclization rather than always en-
countered 5-endo-dig one.
Scheme 1. Proposed mechanism
The resulting 1,2-dihydropyridines of various substituents and substitution patterns would serve as
valuable cyclic diene components in synthesis. Additionally, chemical manipulations of unsaturated
carbon-carbon bonds would provide diverse piperidine derivatives including alkaloids and their ana-
logs.1 To demonstrate the synthetic utility of Au(I)-catalyzed tertiary enamide-alkyne cyclization re-
action, preparation of substituted pyridine compounds was attempted.10a,16 As shown in Table 3,
without isolation and purification of 1,2-dihydropyridine products, Au(I)-catalyzed tertiary enamide-
alkyne cyclization reaction of 1a, 1o and 1u, and consecutive oxidative aromatization using MnO2
and oxygen as oxidants furnished 2,4-diphenylpyridine 3a, 2,4-di(2-thienyl)pyridine 3b and 2,2’-
diphenyl-4,4’-dipyridine 3c, respectively. While compound 3b has the potential application in ad-
vanced optoelectronic material science,17 4,4’-dipyridine 3c is a useful ligand in the construction of
coordination complexes.18 Starting from tertiary enamide 1t, the same Au(I)-catalyzed cyclization
reaction followed by the Cu(OAc)2-catalyzed auto-oxidation reaction19 produced directly 4-phenyl-
5,6,7,8-tetrahydroquinoline 3d, a privileged heterocyclic scaffold in medicinal chemistry.20
Table 3. Preparation of substituted pyridine derivatives

In summary, we have shown that tertiary enamides were able to act as nucleophiles to undergo
intramolecular addition to both internal and terminal alkynes under homogeneous gold catalysis. The
cationic Au(I)-catalyzed regiospecific 6-endo-dig cyclization of 3-aza-1,5-enynes constituted a high-
ly efficient and powerful method for the synthesis of diverse di- to penta-substituted 1,2-
dihydropyridine derivatives in high yields. Coupled with the subsequent oxidative aromatization, the
method provided a straightforward route to substituted pyridine compounds.
Supporting Information
Experimental procedures, compound characterization data and 1H and 13C NMR spectra.
ACKNOWLEDGMENT
We acknowledge NNSFC (21320102002) for financial support.
REFERENCES
1. For reviews, see: (a) Kumar, R.; Chandra, R. Adv. Heterocycl. Chem. 2001, 78, 269-313. (b)
Nakano, H.; Okuyama, Y.; Kwon, E. Heterocycles 2014, 89, 1-26. For recent examples, see: (c)
Mizoguchi, H.; Oikawa, H.; Oguri, H. Nat. Chem. 2014, 6, 57-64. (d) Duttwyler, S.; Chen, S.; Lu,
C.; Mercado, B. Q.; Bergaman, R. G.; Ellman, J. A. Angew. Chem. Int. Ed. 2014, 53, 3877-3880. (e)
Ishihara, K.; Yamada, H.; Akakura, M. Chem. Commun. 2014, 50, 6357-6360. (f) Pelletier, G.;
Constantineau-Forget, L.; Charette, A. B. Chem. Commun. 2014, 50, 6883-6885. (g) Satoh, N.;
Akiba, T.; Yokoshima, S.; Fukuyama, T. Angew. Chem. Int. Ed. 2007, 46, 5734-5736.
2. For a recent review, see: Silva, E. M. P.; Varandas, P. A. M. M.; Silva, A. M. S. Synthesis 2013,
45, 3035-3089. For recent examples, see: (b) Dudnik, A. S.; Weidner, V. L.; Motta, A.; Delferro, M.;
Marks, T. J. Nat. Chem. 2014, 6, 1100-1107. (c) Oshima, K.; Ohmura, T.; Suginome, M. J. Am.
Chem. Soc. 2012, 134, 3699-3702. (d) Tejedor, D.; Cotos, L.; Méndez-Abt, G.; García-Tellado, F. J.
Org. Chem. 2014, 79, 10655-10661. (e) Hoshimoto, Y.; Ohata, T.; Ohashi, M.; Ogoshi, S. Chem.

Eur. J. 2014, 20, 4105-4110. (f) Resende, D. I. S. P.; Guieu, S.; Oliva, C. G.; Silva, A. M. S. Tetra-
hedron Lett. 2014, 55, 6585-6588. (g) Wan, J.-P.; Lin, Y.; Jing, Y.; Xu, M.; Liu, Y. Tetrahedron
2014, 70, 7847-7880.
3. Kim, H.; Lee, C. J. Am. Chem. Soc. 2006, 128, 6336-6337.
4. Cui, J.; Chai, D. I.; Miller, C.; Hao, J.; Thomas, C.; Wang, J. Scheidt, K. A.; Kozmin, S. A. J. Org.
Chem. 2012, 77, 7435.
5. For reviews of enamides, see: (a) Carbery, D. R. Org. Biomol. Chem. 2008, 6, 3455. (b)
Gopalaiah, K.; Kagan, H. B. Chem. Rev. 2011, 111, 4599.
6. For reviews of secondary enamides, see: (a) Matsubara, R.; Kobayashi, S. Acc. Chem. Res. 2008,
41, 292-301. (b) Bernadat, Q.; Masson, G. Synlett 2014, 25, DOI: 10.1055/s-0034-1379166.
7. (a) Yang, L.; Deng, G.; Wang, D.-X.; Huang, Z.-T.; Zhu, J.; Wang, M.-X. Org. Lett. 2007, 9,
1387-1390. (b) Yang, L.; Zheng, Q.-Y.; Wang, D.-X.; Huang, Z.-T.; Wang, M.-X. Org. Lett. 2008,
10, 2461-2464. (c) Yang, L.; Wang, D.-X.; Pan, J.; Zheng, Q.-Y.; Huang, Z.-T.; Wang, M.-X. Org.
Biomol. Chem. 2009, 7, 2628-2634. (d) Yang, L.; Tong, S.; Wang, D.-X.; Huang, Z.-T.; Zhu, J.;
Wang, M.-X. Synlett 2011, 927-930.
8. Yang, L.; Wang, D.-X.; Huang, Z.-T.; Wang, M.-X. J. Am. Chem. Soc. 2009, 131, 10390-10391.
(b) Yang, L.; Lei, C.-H.; Wang, D.-X.; Huang, Z.-T.; Wang, M.-X. Org. Lett. 2010, 12, 3918-3921.
(c) Tong, S., Wang, D.-X.; Zhang, L.; Zhu, J.; Wang, M.-X. Angew. Chem. Int. Ed. 2012, 51, 4417-
4420.
9. Tong, S.; Xu, Y.; Wang, D.-X.; Zhao, L.; Zhu, J.; Wang, M.-X. Tetrahedron 2012, 68, 6492-
6497.
10. (a) Lei, C.-H.; Wang, D.-X.; Zhao, L.; Zhu, J.; Wang, M.-X. J. Am. Chem. Soc. 2013, 135, 4708-
4711. (b) Lei, C.-H.; Wang, D.-X.; Zhao, L.; Zhu, J.; Wang, M.-X. Chem. Eur. J. 2013, 19, 16981-
16987.
11. Wang, M.-X. Chem. Commun. 2015, 51, 6039-6049.
12. For the synthesis of pyridin-2-ones from Au-catalyzed cycloisomerization of N-
propargylcarbonyl enamines, see, Imase, H.; Noguchi, K.; Hirano, M.; Tanaka, K. Org. Lett. 2008,
16, 3563. For the synthesis tetrahydropyridin-2-ones from the Au-catalyzed cyclization of silyl ke-
tene amides and carbamates with alkynes, see, Minnihan, E. C.; Colletti, S. L.; Toste, F. D.; Shen, H.
C. J. Org. Chem. 2007, 72, 6287. For the synthesis of acyl-substituted 1,2-dihydropyridines from
Ag-catalyzed cyclization of N-propargyl enaminones, see, Martins, M. A. P.; Rossatto, M.; Frizzo, C.
P.; Scapin, E.; Buriol, L.; Zanatta, N.; Bonacorso, H. G. Tetrahedron Lett. 2013, 54, 847.

13. For reviews, see: (a) Obradors, C.; Echavarren, A. M. Acc. Chem. Res. 2014, 47, 902-912. (b)
Wang, Y.-M.; Lackner, A. D.; Toste, F. D. Acc. Chem. Res. 2014, 47, 889-901. (c) Fürstner, A. Acc.
Chem. Res. 2014, 47, 925-938. (d) Fensterbank, L.; Malacria, M. Acc. Chem. Res. 2014, 47, 953-
965. (e) Yeom, H.-S.; Shin, S. Acc. Chem. Res. 2014, 47, 966-977. (f) Zhang, L. Acc. Chem. Res.
2014, 47, 877-888. (g) Hashimi, A. S. Acc. Chem. Res. 2014, 47, 864-876. (h) Jiménez-Núñez, E.;
Echavarren, A. M. Chem. Rev. 2008, 108, 3326-3350. (i) Gorin, D. J.; Sherry, B. D.; Toste, F. D.
2008, 108, 3351-3378. (j) Li, Z.; Brouwer, C.; He, C. 2008, 108, 3239-3265. (k) Zhang, L.; Sun, J.;
Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271-2296. (l) Michelet, V.; Toullec, P. Y.; Genêt, J.-P.
Angew. Chem. Int. Ed. 2008, 47, 4268-4315.
14. (a) Ferrer, C.; Echavarren, A. M. Angew. Chem., Int. Ed. 2006, 45, 1105-1109. (b) Ferrer, C.;
Amijs, C. H. M.; Echavarren, A. M. Chem. Eur. J. 2007, 13, 1358-1373.
15. For a leading reference, see: López-Carrillo, V.; Huguet, N.; Mosquera Á.; Echavarren, A. M.
Chem. Eur. J. 2011, 17, 10972-10978 and references cited therein.
16. For recent strategies for the synthesis of pyridine derivatives, see: Hill, M. D. Chem. Eur. J.
2010, 16, 12052-12062 and references cited.
17. Bera, M. K.; Hommes, P.; Reissig, H.-U. Chem. Eur. J. 2011, 17, 11838-11843.
18. For recent reviews, see: (a) Adarsh, N. N.; Dastidar, P. Chem. Soc. Rev. 2012, 41, 3039-3060. (b)
Biradha, K.; Sarkar, M.; Rajput, L. Chem. Commun. 2006, 4169-4179.
19. Ding, D.; Lv, X.; Li, J.; Xu, G.; Ma, B.; Sun, J. Chem. Asian J. 2014, 9, 1539-1542 and refer-
ences cited therein.
20. For recent examples, see: (a) Hahn, M.; Follmann, M.; Huebsch, W.; Becker, E.; Stasch, J.;
Keldenich, J.; Delbeck, M.; Tinel, H.; Wunder, F.; Mittendorf, J.; Terebesi, I.; Lang, D.; Martin, R.
WO2014012934-A1. (b) Kanamoto, T.; Kodama, K.; Kuwata, K.; Nakajima, H.; Nakamura, H.;
Terakubo, S. JP2010059099-A.