A dynamic kinetic asymmetric transfer hydrogenation-cyclization tandem reaction: An easy access to chiral 3,4-dihydro-2: H -pyran-carbonitriles

Article abstract of DOI:10.1039/c7cc02156a

A chiral (mesitylene)RuCl(monosulfonated diamine) catalysed dynamic kinetic resolution (DKR)-asymmetric transfer hydrogenation (ATH) process is developed for highly enantio- (up to 99% ee) and diastereo- (up to 98:2 dr) selective reduction of challenging racemic α-aryl-γ-keto malononitriles. A spontaneous cyclization reaction of the hydrogenation products delivers a cascade process for efficient synthesis of useful enantioenriched 3,4-dihydro-2H-pyran-carbonitriles.

Full text of DOI:10.1039/c7cc02156a

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: D. Zheng, Q.
Zhao, X. Hu, T. Cheng, G. Liu and W. Wang, Chem. Commun., 2017, DOI: 10.1039/C7CC02156A.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Page 1 of 4
ChemComm
View Article Online
DOI: 10.1039/C7CC02156A
Journal Name
RSCPublishing
COMMUNICATION
Dynamic kinetic asymmetric transfer hydrogenation-cyclization
tandem reaction: an easy access to chiral 3,4-dihydro-2H-pyran-
carbonitriles
Cite this: DOI: 10.1039/x0xx00000x
Dongsong Zheng,a Qiankun Zhao,a Xiaoying Hu,a Tanyu Cheng,a Guohua
Liu,a,* and Wei Wanga,b,*
Received 00th January 2015,
Accepted 00th January 2015
DOI: 10.1039/x0xx00000x
www.rsc.org/
pyran-carbonitriles in a cascade manner. It should be noted that
commonly used approach to the molecular architectures relies on two
step transformations involved enantioselective conjugate addition of
malononitrile to chalcones, followed by the reduction of the chiral
adducts.7 However, generally moderate stereoselectivity is observed
due to the difficulty in the control of the remote 1,3-stereoselectivity.
A chiral (mesitylene)RuCl(monosulfonated diamine) catalysed
dynamic kinetic resolution (DKR)-asymmetric transfer
hydrogenation (ATH) process is developed for highly enantio-
(up to 99% ee) and diastereo- (up to 98:2 dr) selective reduction
of challenging racemic α-aryl-γ-keto malononitriles.
A
spontaneous cyclization reaction of the hydrogenation
products delivers a cascade process for efficient synthesis of
useful enantioenriched 3,4-dihydro-2H-pyran-carbonitriles.
Asymmetric transfer hydrogenation (ATH) has proved to be a viable
strategy for highly enantioselective reduction of prochiral ketones.1
Furthermore, implementation of dynamic kinetic resolution (DKR)
into the ATH has delivered a powerful approach to enantioenriched
1,2-diastereomeric functionalities, such as α-halo alcohols,2a α-
substituted β-hydroxy ketones/esters/amides,2b-k β-amino-α-hydroxy
esters,2l-m and others.2n-t Among them, notably, Johnson and
coworkers utilized this strategy to produce 3 stereogenic γ-
butyrolactones through a diastereoselective lactonization of in situ
formed optically active precursors.3 Despite these impressive
achievements, the DKR-ATH is restricted to construct adjacent 1,2-
stereogenic centers from racemic α-functionalized ketones. In contrast,
direct enantio- and stereo-selective formation of remote 1,3-
stereogenic structures using the strategy presents a daunting challenge.
To the best of our knowledge, only a biocatalytic process is recently
disclosed by Peng and colleagues (Scheme 1A).4 In conjunction of our
studies in the DKR-ATH5 and ATH,6 and organocatalytic
enantioselective conjugation addition of malononitrile to chalcones by
us and other groups,7 we proposed a new DKR-ATH process for ‘one-
pot’ synthesis of synthetically and biologically important 3,4-dihydro-
2H-pyran-carbonitriles, featured in numerous natural products,8 and
synthetic substances.9 The first DKR-ATH mediated highly enantio-
and diastereo-selective reduction of racemic α-aryl-γ-keto
malononitriles is developed by employing widely used chiral
(mesitylene)RuCl(monosulfonated diamine) as a catalyst (Scheme
1B). Furthermore, a spontaneous diastereoselective cyclization with
the hydrogenation products takes place to deliver 3,4-dihydro-2H-
Scheme 1. Catalytic Asymmetric Synthesis of 1,3-Diastereomerically
Centered Structures via DKR.
To test our working hypothesis, we chose the readily prepared
racemic
chalcones/malononitrile
adduct,
2-(3-oxo-1,3-
diphenylpropyl)malononitrile (1a) as a starting material (Table 1).10
Initially, the reaction was performed in the presence of commonly
used (S, S)-[(mesitylene)RuCl(TsDPEN)] (A, 2.0 mol%) as a catalyst
and HCO2Na as a hydrogen resource in H2O at 60 ºC (entry 1, for
details of optimization of reaction temperature, see SI in Table S1).
This journal is © The Royal Society of Chemistry 2015
J. Name., 2015, 00, 1‐3 | 1

ChemComm
Page 2 of 4
VJieowuArrtnicalelONnlainme e
COMMUNICATION
DOI: 10.1039/C7CC02156A
To our delight, the process proceeded smoothly to furnish the desired proposed based on our previous studies using chiral A catalyzed ATH
product 2a in 57% yield and with 93% ee. The absolute configuration reduction of ketones.5,6
for product 2a was determined to be S according to the known
Having established the efficiently enantioselective cascade
configuration reported in literature.1a It is noteworthy that due to the reactions for preparation of mono-stereo centered chiral 3,4-dihydro-
substrate’s poor solubility in water, which may be a factor for the low 2H-pyrans-carbonitriles over the ATH-cyclization sequence, we then
yield, alcohols as a co-solvent were used. It was found that all co- focused on the investigation of the application of A in the construction
solvents probed greatly increased the yield in markedly shortened of challenging remote 1,3-diastereomerically centered 3,4-dihydro-
reaction time (entries 2-4). Further optimization of volume ratio of 2H-pyrans-carbonitriles. However, under the optimized reaction
solvents led to the use of iPrOH/H2O (v:v = 3/1) to give the best yield conditions, we found that this DKR-ATH/cyclization process of 2-(3-
and enantioselectivity (entry 5 vs entries 4 and 6). In parallel, the oxo-1,3-diphenylpropyl)malononitrile only offered product of (2S,
result with A was better than those of other extensively studied 4S)-6-amino-2,4-diphenyl-3,4-dihydro-2H-pyran-5-carbonitrile with
(arene)RuCl(TsDPEN) catalysts (TsDPEN: N-(2-amino-1,2- a moderate diastereomeric ratio (89:11 dr). Inspired by the role of
diphenylethyl)-4-methyl benzene-sulfonamide, arene Ru-series: A-D) bases to enhance dr value during dynamic kinetic resolution processes,
and chiral Cp*MTsDPEN catalysts (Cp*M-series: E-F) under the several bases were probed (for details of screening of bases and
same reaction conditions (entry 5 vs entries 7-11).11
catalysts see SI in Table S2). The results revealed that NEt3 as a base
gave the dr value of 94/6 without deteriorating the ee value. To further
understanding the mechanistic aspect of the dynamic kinetic
resolution, we carried out the study of the racemization of (S)-3a in a
mixture of iPrOH and H2O (v/v = 3:1) in the presence of an equivalent
of NEt3. It was found that the complete racemization of (S)-3a
occurred within 7 h (Table S3, and Figures S1-2 in SI). These findings
indicated that the DKR-ATH-cyclization cascade proceeds via a retro-
Michael addition process,12 facilitated by NEt3 (Scheme 1B and S1 in
SI).
Table 1. Exploration of Chiral Diamine-based Catalysts for ATH/Cyclization of 2-
-(3-Oxo-3-phenylpropyl) Malononitrile.a
Table 2. Scope of ATH/Cyclization Enantioselective Cascade Reactions of γ-Keto
Malononitriles Catalyzed by Catalyst A.a
Entry
Cat.
Solvent (v/v)
t (h)
Yield (%)b
Ee (%)c
1
A
A
A
A
A
A
B
C
D
E
F
H2O
8
57
98
96
97
99
96
89
84
95
NDd
95
93
96
95
97
97
96
80
93
97
-
2
MeOH:H2O (1:1)
EtOH:H2O (1:1)
iPrOH:H2O (1:1)
iPrOH:H2O (3:1)
iPrOH:H2O (5:1)
iPrOH:H2O (3:1)
iPrOH:H2O (3:1)
iPrOH:H2O (3:1)
iPrOH:H2O (3:1)
iPrOH:H2O (3:1)
1
3
1
4
1
Entry
2
Ar
Yield (%)b
ee (%)c
5
1
6
1
1
2a
2b
2c
2d
2e
2f
Ph
99
97
95
83
96
95
91
92
89
94
91
91
90
97
97
95
90
97
91
94
97
90
92
97
96
95
7
5
2
4-FC6H4
3-FC6H4
2-FC6H4
4-ClC6H4
2-ClC6H4
3-BrC6H4
4-IC6H4
8
10
1
3
9
4
10
11
24
1
5
90
6
a To a solution of H2O and/or alcohol (4.0 mL) were added 1a (0.10 mmol), catalyst
(2.0 μmol) and HCO2Na (1.0 mmol) and the mixture was stirred at 60 °C for
7
2g
2h
2i
b
specified time. Yield was determined by 1H-NMR analysis. c Determined by
8
HPLC analysis using a chiral stationary phase. d Not detected.
9
4-NO2C6H4
4-CNC6H4
4-MeC6H4
3-MeOC6H4
2-naphthyl
10
11
12
13
2j
With the optimized reaction conditions in hand, we probed the
scope of A promoted this ATH/cyclization enantioselective cascade
reaction with a series of substituted substrates (Table 2). It was found
that the process serves as a general approach to enantioenriched 3,4-
dihydro-2H-pyran-carbonitriles 2. It seems that the electron- neutral
(2a), withdrawing (2b-2j), or donating (2k, and 2l) substituents on
aromatic ring have limited effect on reaction yields and
enantioselectivities. Moreover, fused aromatic naphthyl (2m) can be
applied by the protocol. Therefore, structurally diverse products 2 can
be synthesized. The absolute 2S configuration for products 2 is
2k
2l
2m
a To a solution of iPrOH and H2O (v/v = 3/1, 4.0 mL) were added 1 (0.10 mmol),
catalyst (2.0 μmol) and HCO2Na (1.0 mmol) and the mixture was stirred at 60 °C
for specified time. b Yield was determined by 1H-NMR analysis. c Determined by
HPLC analysis using a chiral stationary phase. d Not detected.
On the basis of the findings,
a series of 2-(3-oxo-1,3-
diarylpropyl)malononitriles were further tested to demonstrate its
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 2012

Page 3 of 4
Journal Name
ChemComm
View Article Online
COMMUNICATION
DOI: 10.1039/C7CC02156A
generality. As outlined in Table 3, this DKR-ATH/cyclization process
To demonstrate the synthetic utility of this approach, a gram-scale
is suitable for construction of structurally diverse 1,3- synthesis of chiral 4h as an example was carried out (Scheme 2).
diastereomerically centered 3,4-dihydro-2H-pyrans-carbonitriles 4a- Product 4h was obtained in a slightly improved yield (76%). The
4o in high yields with excellent enantioselectivities and good absolute 2S configuration of 4 is established from compound 2. The
diastereomeric ratios (up to 98/2 dr). Significant structural variation absolute 2S configuration of 4 is established analogously from
of Ar1 component in 1 can be tolerated. It appears that electronic compound 2. To determine the absolute configuration of position 4 in
properties of substituents have limited impact on enantio- and 4, we obtained both single crystal X-ray structures for chiral 4h and
diastereo-selectivities. Electron–neutral (4a, 4j-4p), withdrawing (4b- its 1:1 mixture of (S, S) and (S, R) epimeric forms for comparison. The
4e) and–donating (4f-4i) substituents can be tolerated. In addition to X-ray crystallographic analysis of chiral 4h reveals the two substitutes
aromatic structures, aliphatic one (4q) can participate in the process (eg, phenyl and 4-methoxyphenyl) have trans relationship (Scheme 2).
effectively. A similar trend is observed for Ar2 bearing various The six-member ring of dihydropyran moiety in 4h is a half-chair
functional groups including electron-neutral (4a-4i), withdrawing (4j conformation with out of plane CH2 group and two aromatic rings are
and 4k) and donating (4l-4n) substituents, and fused aromatic (4o) and stretching both sides with an edge-to-face structure, while its epimeric
heterocyclic (4p) structures.
form has cis geometry (see SI in Figure S3).13 Therefore, the absolute
configuration for chiral 4h is determined to be (2S, 4S).
Table 3. Scope DKR-ATH/Cyclization Cascade Reactions of α-Aryl-γ-Keto
Malononitriles Catalysed by Catalyst A.a-c
Ts
Ph
Ph
N
Ru
NH2
N
Cl
H2
NC CN
CN
Ar1
O
O
A (2.0 mol %)
Ar2
Ar1
Ar2
HCOONa,
iPrOH:H2O (3:1), Et3N, 60 o
3a-3o
C
4a-4o
Scheme 2. Gram Scale Synthesis of 4h and Its Single Crystal X-ray
Structure.
In conclusions, we have developed the first DKR-ATH
methodology for asymmetric reduction of challenging racemic α-aryl-
γ-keto malononitriles using chiral (mesitylene)RuCl(monosulfonated
diamine) as a promoter. A powerful DKR-ATH-cyclization cascade
process is accomplished with feedstock chemical HCO2Na as
i
hydrogen source in PrOH and H2O. The process delivers useful
enantioenriched 3,4-dihydro-2H-pyran-carbonitriles in an efficient
'one-pot' operation with high enantio- and diastereo-selectivity (up to
99% ee and up to 98:2 dr), whereas their synthesis generally relies on
two step transformations with generally moderate stereoselectivity
due to the difficulty in the remote 1,3-stereocontrol. The application
of the synthetic strategy for new transformations is under
investigation in our laboratories.
Acknowledgement
We are grateful to the National Natural Science Foundation of China
(21672149 and 21402120), the Shanghai Science and Technologies
Development Fund (13ZR1458700) for financial support.
Notes and references
a Laboratory of Resource Chemistry of Ministry of Education, Shanghai
Normal University, Shanghai 200234, China. E-mail: ghliu@shnu.edu.cn
b Department of Chemistry & Chemical Biology, University of New Mexico,
MSC 03 2060, Albuquerque, NM 87131, USA. E-mail: wwang@unm.edu
i
a To a solution of PrOH and H2O (v/v = 3 : 1, 4.0 mL) were added 3 (0.10
mmol), catalyst A (2.0 μmol), HCO2Na (1.0 mmol) and Et3N (0.1 mmol), and
the mixture was stirred at 60 °C for 5-12 h. b Isolated yield containing two
enantiomers. c Determined by HPLC analysis using a chiral stationary phase.
†
Electronic Supplementary Information (ESI) available: [Experimental
procedures and analytical data of chiral products]. See
DOI: 10.1039/c000000x/
1
(
a
) S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya, and R. Noyon, J.
Am. Chem. Soc., 1995, 117, 7562-7563. ( ) T. Ikariya and A. J.
Blacker, Acc. Chem. Res., 2007, 40, 1300−1308; ( ) S. E. Clapham, A.
Hadzovic, and R. H. Morris, Coordin. Chem. Rev., 2004, 248
b
c
,
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1‐3 | 3

ChemComm
Page 4 of 4
VJieowuArrtnicalelONnlainme e
COMMUNICATION
DOI: 10.1039/C7CC02156A
2201−2237; (
Rev., 2010, 254, 729−752.
) A. Ros, A. Magriz, H. Dietrich, R. Fernández, E. Alvarez, and J. 11 (
M. Lassaletta, Org. Lett., 2005, , 127−130; ( ) F. Eustache, P. I.
Dalko, and J. Cossy, Org. Lett., 2002, , 1263−1265; ( ) Y. Wu, Z.
Geng, J. Bai, and Y. Zhang, Chin. J. Chem., 2011, 29, 1467−1472; (
D. Cartigny, K. Püntener, T. Ayad, M. Scalone, and V.
Ratovelomanana-Vidal, Org. Lett., 2010, 12, 3788−3791; ( ) Z. Liu,
C. S. Shultz, C. A. Sherwood, S. Krska, P. G. Dormer, R. Desmond, 12 (a) J. Wang, H.-X. Xie, H. Li, L.-S. Zu, and W. Wang, Angew. Chem.
d
) R. Malacea, R. Poli, and E. Manoury, Coordin. Chem.
Hartog, K. Geurts, A. J. Minnaard, and B. L. Feringa, Chem. Rev.
2008, 108, 2824–2852.
,
2
(
a
a
) A. Fujii, S. Hashiguchi, N. Uematsu, T. Ikariya, and R. Noyori, J.
8
b
Am. Chem. Soc., 1996, 118, 2521−2522; (b) J. Sivamani, V.
4
c
Ashokkumar, V. Sadhasivam, K. Duraimurugan, and A. Siva, RSC
Adv., 2014, 60293–60299; ( ) M. Zahouily, B. Bahlaouan, M. Aadil,
A. Rayadh, and S. Sebti, Org. Process Res. Dev., 2004, , 275−278;
) M. Eylan and H. Gezegen, Turk. J. Chem., 2008, 32 55–61.
d
)
4
,
c
8
e
(
d
,
C. Lee, E. C. Sherer, J. Shpungin, J. Cuff, and F. Xu, Tetrahedron Lett.
2011, 52, 1685−1688; ( ) B. Seashore-Ludlow, F. Saint-Dizier, and P.
Somfai, Org. Lett., 2012, 14, 6334−6337; ( ) B. Seashore-Ludlow, P.
Villo, and P. Somfai, Chem. Eur. J., 2012, 18, 7219−7223; ( ) G.
,
Int. Ed., 2008, 47, 4177-4179; (b) F. Bravo, Z. Cimarosti, F. Tinazzi,
G. E. Smith, D. Castoldi, S. Provera, and P. Westerduin, Org. Process
Res. Dev. 2010, 14, 1162-1168; (c) W. Yang, Y. Yang, and D.-M. Du,
Org. Lett. 2013, 15, 1190-1193.
f
g
h
Kumaraswamy, A. N. Murthy, V. Narayanarao, S. P. B. Vemulapalli, 13 The structures of chiral and diastereoisomeric 4h are determined by X-
and J. Bharatam, Org. Biomol. Chem., 2013, 11, 6751−6765; (
Limanto, S. W. Krska, B. T. Dorner, E. Vazquez, N. Yoshikawa, and
L. Tan, Org. Lett., 2009, 12, 512−515; ( ) S.-M. Son and H.-K. Lee, J.
Org. Chem., 2013, 78, 8396−8404; ( ) A. Ros, A. Magriz, H. Dietrich,
J. M. Lassaletta, and R. Fernández, Tetrahedron 2007, 63
7532−7537; ( ) M. Villacrez and P. Somfai, Tetrahedron Lett., 2013,
54, 5266−5268; ( ) C. G. Goodman, D. T. Do, and J. S. Johnson, Org.
Lett., 2013, 15, 2446−2449; ( ) Z. Ding, J. Yang, T. Wang, Z. Shen,
and Y. Zhang, Chem. Commun., 2009, 571−573; ( ) S.-M. Son and H.-
K. Lee, J. Org. Chem., 2014, 79, 2666−2681; ( ) M. T. Corbett and J.
S. Johnson, J. Am. Chem. Soc., 2013, 135, 594−597; ( ) J. Han, S.
Kang, and H.-K. Lee, Chem. Commun., 2011, 47, 4004−4006; ( ) S.
Kang, J. Han, E. S. Lee, E. B. Choi, and H.-K. Lee, Org. Lett., 2010,
12, 4184−4187; ( ) J.-A. Kim, Y. J. Seo, S. Kang, J. Han, and H.-K.
Lee, Chem. Commun., 2014, 50, 13706−13709; ( ) H.-K. Lee, S. Kang,
and E. B. Choi, J. Org. Chem., 2012, 77, 5454−5460.
) K. M. Steward, M. T. Corbett, C. G. Goodman, and J. S. Johnson,
J. Am. Chem. Soc., 2012, 134, 20197−20206; ( ) K. M. Steward, E. C.
i
) J.
ray crystal analysis. CCDC-1512442 (chiral) and CCDC-1513095
(diastereoisomeric) contain the supplementary crystallographic data
for this paper.
j
k
,
,
l
m
n
o
p
q
r
s
t
3
(a
b
Gentry, and J. S. Johnson, J. Am. Chem. Soc., 2012, 134, 7329−7332.
Z. Peng, J. W. Wong, E. C. Hansen, and A. L. A. Puchlopek-Dermenci,
H. J. Clarke, Org. Lett., 2014, 16, 860−863.
4
5
6
T. Cheng, Q. Ye, Q. Zhao, and G. Liu, Org. Lett., 2015, 17
4972−4975.
,
(
a
) D. Zhang, T. Cheng, Q. Zhao, J. Xu, and G. Liu, Org. Lett., 2014,
16, 5764−5767; ( ) Q. Ye, T. Cheng, Y. Zhao, J. Zhao, R. Jin, and G.
Liu, ChemCatChem, 2015, , 1801−1805; ( ) M. Wu, T. Cheng, M. Ji,
and G. Liu, J. Org. Chem., 2015, 80, 3708−3713.
) L. Liu, D. Wu, X. Li, S. Wang, H. Li, J. Li, and W. Wang, Chem.
Commun., 2012, 48, 1692−1694; ( ) H. Zhao, Y.-B. Lan, Z.-M. Liu,
Y. Wang, X.-W. Wang, and J.-C. Tao, Eur. J. Org. Chem., 2012,
1935−1944; ( ) J. Shi, M. Wang, L. He, K. Zheng, X. Liu, L. Lin, and
X. Feng, Chem. Commun., 2009, 4711−4713; ( ) N. M. H. Elnagdi and
b
7
c
7
(a
b
c
d
N. S. Al-Hokbany, Molecules, 2012, 17, 4300−4312; (e) J.-S. Yu, F.-
M. Liao, W.-M. Gao, K. Liao, R.-L. Zuo, and J. Zhou, Angew. Chem.
Int. Ed., 2015, 54, 7381−7385; (
X.-J. Zhang, and M. Yan, Tetrahedron: Asymmetry, 2012, 23, 461-
467 ; ( ) K. Higashiyama and H. Otomasu, Chem. Pharm. Bull., 1980,
28, 1540−1545.
) M. Quinteiro, C. Seoane, and J. L. Soto, J. Heterocyclic Chem.
1978, 15, 57−61; ( ) D. Armesto, W. M. Horspool, N. Martin, A.
Ramos, and C. Seoane, J. Org. Chem., 1989, 54, 3069−3072; ( ) G.
Heinisch, W. Holzer, and G. M. Nawwar, Monatsh Chem., 1986, 117
247−253; ( ) M. Elmoghayer, M. E. Khalifa, M. Ahmed Ibraheim, and
M. Elnagdi, Monatsh Chem., 1982, 113, 53−57; ( ) X. Li, L. Song, C.
Xing, J. Zhao, and S. Zhu, Tetrahedron, 2006, 62, 2255−2263; ( ) D.
f) Z.-P. Hu, W.-J. Wang, X.-G. Yin,
g
8
(
a
,
b
c
,
d
e
f
V. Tyndall, T. Al Nakib, and M. J. Meegan, Tetrahedron Lett., 1988,
29, 2703−2706.
9
(
a
) A. S. Girgis, D. O. Saleh, R. F. George, A. M. Srour, G. G. Pillai,
C. S. Panda, and A. R. Katritzky, Eur. J. Med. Chem., 2015, 89
835−843; ( ) Y. Zheng, C. M. Tice, and S. B. Singh, Bioorg. Med.
Chem. Lett., 2014, 24, 3673−3682; ( ) I. Sharma and D. S. Tan, Nat.
Chem., 2013, , 157−158; ( ) J. Kaur, A. Kumari, and S. S. Chimni,
Tetrahedron, 2017, 73, 802−808; ( ) K. Higashiyama and H. Otomasu,
Chem. Pharm. Bull., 1980, 28, 1540−1545.
10 ( ) G. Casiraghi, L. Battistini, C. Curti, G. Rassu, and F. Zanardi,
,
b
c
5
d
e
a
Chem. Rev., 2011, 111, 3076–3154; (
4 | J. Name., 2012, 00, 1‐3
b) S. R. Harutyunyan, T. den
This journal is © The Royal Society of Chemistry 2012