Primary Aminothiourea-Catalyzed Enantioselective Synthesis of Rauhut-Currier Adducts of 3-Arylcyclohexenone with a Tethered Enone on the Aryl Moiety at the Ortho -Position

Article abstract of DOI:10.1021/acs.orglett.7b03959

An enantioselective synthesis of Rauhut-Currier (RC) adducts from 3-aryl cyclohexenone with a tethered enone moiety at the ortho-position on the aryl group is accomplished. This method provides a wide range of valuable synthetic building blocks having a unique [6-5-6] all-carbon-fused tricyclic skeleton. A primary amine-containing thiourea, a bifunctional organocatalyst, was found to be an efficient catalyst for this transformation. The primary amine counterpart of the catalyst possibly activates the aliphatic enone via dienamine formation (HOMO activation), whereas the thiourea counterpart activates the tethered enone (LUMO activation). Considering the difficulty in achieving an RC reaction of β,β-disubstituted (alkyl and aryl) enones, this method would be significantly rewarding.

Full text of DOI:10.1021/acs.orglett.7b03959

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Primary Aminothiourea-Catalyzed Enantioselective Synthesis of
Rauhut−Currier Adducts of 3‑Arylcyclohexenone with a Tethered
Enone on the Aryl Moiety at the Ortho-Position
Sanjay Maity, Suman Sar, and Prasanta Ghorai*
Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal By-pass Road, Bhauri, Bhopal-462066,
India
S
* Supporting Information
ABSTRACT: An enantioselective synthesis of Rauhut−
Currier (RC) adducts from 3-aryl cyclohexenone with a
tethered enone moiety at the ortho-position on the aryl group
is accomplished. This method provides a wide range of
valuable synthetic building blocks having a unique [6−5−6]
all-carbon-fused tricyclic skeleton. A primary amine-containing
thiourea, a bifunctional organocatalyst, was found to be an
efficient catalyst for this transformation. The primary amine
counterpart of the catalyst possibly activates the aliphatic enone via dienamine formation (HOMO activation), whereas the
thiourea counterpart activates the tethered enone (LUMO activation). Considering the difficulty in achieving an RC reaction of
β,β-disubstituted (alkyl and aryl) enones, this method would be significantly rewarding.
Scheme 1. Alternative Reaction Pathway for Enantioselective
he development of methods for the construction of the
and Regiospecific Rauhut−Currier Adduct
T
chiral C−C bond is an exciting and fascinating area of
research in organic chemistry. In this context, Morita−Baylis−
Hillman (MBH)1 and Rauhut−Currier (RC)2 reactions are
used for the synthesis of structurally complex natural products
and bioactive molecules.3 Traditionally, the reaction involves an
organocatalytic nucleophilic (e.g., PR3 or NR3) addition to an
enone (Scheme 1a) followed by enolate addition to another
carbonyl or enone moiety. Despite advances, the major
limitation in MBH and RC reactions is the substrates with
β,β-disubstituted enones. The steric crowding of such
substrates at the β-position makes the above nucleophilic
addition impossible, which is the bottleneck for this reaction.
Very recently, Ramasastry et al. disclosed the first asymmetric
MBH reaction of β,β-substituted enones with high enantiose-
lectivities using thiourea containing phosphine catalyst
(Scheme 1a),4 whereas the corresponding RC reactions are
not explored. Therefore, finding an alternative reaction pathway
to access such adducts with excellent enantio- and regiose-
lectivities would be significantly rewarding.
Over the past few decades, asymmetric amino catalysis has
become one of the most widespread and emerging areas of
research in organic chemistry. It activates the carbonyls
(HOMO) through enamine formation.5 Recently, this amino
catalysis has been further extended to activate the α,β-
unsaturated ketones via formation of a dienamine intermediate
that leads to a diverse range of chemical reactions to construct a
variety of complex chiral molecules. This dienamine provides
two reacting nucleophilic sites: the α- and γ-position of the
enone. The dienamine chemistry has been utilized in many
chemoselective reactions including MBH and RC reactions.6
The enantioselective intra- and intermolecular α-selective7 as
well as γ-selective8 functionalizations of α,β-unsaturated ketone
were well developed in MBH and RC reactions. However, as
mentioned above, such reactions on β,β-disubstituted enones as
nucleophiles remain a significant challenge.9,10 Moreover, in
Received: January 3, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03959
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
almost all of the previous reports for dienamine formation,9,10
a
a
Table 1. Optimization of the Reaction Conditions
secondary amine such as a proline or proline derivative is used
as the catalyst in the presence of additives.
Here, we investigate a primary aminothiourea/squaramide as
a bifunctional organocatalyst. The primary amine counterpart
of the catalyst would activate the aliphatic enone via the
formation of dienamine (HOMO); on the other hand, the
thiourea counterpart would activate the tethered enone
(LUMO) to provide a highly rigid platform for the generation
of the enantioselective Rauhut−Currier adduct (Scheme 1b).
Notably, [6−5−6] all-carbon tricyclic fused cores are present
in various natural products and drug molecules;11 in particular,
they are found in the taiwaniaquinoid and diterpenoid families
(Figure 1). Such unique [6−5−6]-abeo-abietane skeleton
family members have shown aromatase inhibitor activity and
are also used as drugs for the treatment of estrogen-dependent
cancers.12
b
c
entry
catalyst
solvent
t (h)
yield (%)
% ee
1
C1
C2
C3
C4
C5
C6
C5
C5
C5
C5
C5
C5
toluene
toluene
toluene
toluene
toluene
toluene
xylene
mesitylene
HFIP
72
72
72
72
96
96
96
96
96
96
96
96
38
35
33
20
51
2
3
16
4
ND
94
5
56
6
ND
93
7
82 (78)
8
84 (80)
90
9
ND
86
10
11
12
THF
10
18
80
DCM
94
benzene
74
a
Reaction conditions: 1 (0.05 mmol), C (0.005 mmol, 10 mol %) at rt.
b
Yields were determined from 1H NMR by using diphenyl acetonitrile
c
as an internal standard; isolated yields are shown in parentheses. The
enantiomeric excess was determined by HPLC analysis on a chiral
stationary phase. ND = not determined.
Figure 1. Natural products containing [6−5−6] all tricyclic carbon
skeleton.
Fascinated by these [6−5−6] all-carbon tricyclic skeletons,
we hypothesized that cyclohexenone tethered to another enone
at the β-position would chemoselectively participate in chiral
dienamine formation followed by a Michael addition to provide
the RC-type adduct in high enantioselectivity (as shown in
Scheme 1a).
To execute our hypothesis, we began our investigation by
using β-aryl-substituted cyclohexenone tethered with aromatic
enone as model substrate 1a. The major obstacles were the
inherent difficulties due to the multiple potential enolate sites
generated from dienamine, which may reduce the regioselectiv-
ities.
Despite these complexities, we strictly focused on over-
coming the challenges regarding enantio- and regioselectivity
issues. Various chiral primary amines derived from cinchona
alkaloid (C1−C3) were surveyed in toluene at room temper-
ature (Table 1). To our delight, all of the chiral amines afforded
the desired product with good regiospecificity but moderate
enantioselectivities (entries 1−3). Then we envisioned
engineering our catalyst design to improve the selectivity by
introducing the push−pull strategy where primary amine
activated the ketone (HOMO) and thiourea/squaramide
activated the enone moiety.13,14 As per the analysis, catalyst
C5 showed a sharp increase in enantioselectivity with 94% ee
and 56% yield (entry 5).
ature (see the Supporting Information) revealed that 10 mol %
catalyst C5 in xylene at room temperature were the optimum
conditions to furnish our desired product 3a with 93% ee and
82% NMR yield (Table 1, entry 7).
Using these optimized reaction conditions, we interested in
exploring the substrate scope on the tethered enone moiety,
which is summarized in Scheme 2. The generality of the
reaction was proved in terms of regio- and enantioselectivity.
The reactions with substrates having electron-donating groups
such as p-Me (3b), p-tBu (3c), p-OMe (3d), and p-Ph (3k) and
an electron-withdrawing group such as p-Cl (3e), p-Br (3f), p-F
(3h), p-NO2 (3i), and p-CF3 (3j) on the aryl moiety proceeded
smoothly to provide the [6−5−6] tricyclic skeleton in high
yields with excellent enantioselectivities. Moreover, irrespective
of the position of substitution on the aryl ring, such as o-Cl
(3n), o-Br (3o), 2,4-di-Cl (3p), or 3,4-di-OMe (3q), the
reaction proceeded well to afford the RC adduct with high
enantioselectivity. The heteroaryl moieties such as furyl (3l)
and thiophene-yl (3m) were well tolerated under these reaction
conditions. Even a difficult substrate such as aliphatic enone
also took part in these reaction conditions and led to the
desired product with high enantioselectivity. In some cases
(e.g., 3c, 3f, 3g, 3i, and 3m−p), the yields were good to
moderate. In such cases, no other products were obtained; only
the reactants were recovered. To show the synthetic utility of
this methodology, a gram-scale reaction was performed with
1d, and 3d was achieved with a very little decrease in
enantioselectivity (96% to 92% ee). However, after single
Next, arrays of bifunctional catalysts (see the Supporting
Information) were screened, and catalyst C5 was found to be
the best in terms of enantioselectivity. A quick study of all of
the parameters such as solvent, catalyst loading, and temper-
B
DOI: 10.1021/acs.orglett.7b03959
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Substrate Scope (Variation on Outer Aryl
Ring)
Scheme 3. Substrate Scope (Variation on Internal Aryl Ring)
a−d
a
b
Reaction conditions are the same as in Scheme 2. In the case of low-
yielding reactions, the starting substrates were recovered.
Scheme 4. Reaction of α-Methyl Enone
a
Reaction conditions: 1 (0.1 mmol), C5 (0.01 mmol, 10 mol %) in
b
xylene (2 mL) at rt. Yields shown are of isolated products.
c
Enantiomeric excess was determined by HPLC analysis on a chiral
d
stationary phase. Enantiomeric excess and yield on a 1.0 g scale
reaction. In the case of low-yielding reaction, the starting substrates
e
were recovered.
Scheme 5. Proposed Transition State
crystallization, the optically pure compound was obtained. The
absolute configuration (R) of the [6−5−6] core was confirmed
by X-ray analysis of 3g (see the SI).
Furthermore, the substitutions on the internal aryl moiety
were examined and the multisubstituted [6−5−6] tricyclic
skeleton was observed with good to excellent enantioselectiv-
ities (Scheme 3). A small decrease in enantioselectivity was
observed for the substrates with halogen substitution at the
meta-position, e.g., m-Cl (5g) and m-Br (5h). A combined
effect of electronic as well as steric conditions (less interaction
between substrate and catalyst in the transition state) could be
the reason for such moderate yields and selectivities. However,
the use of cyclopentenone instead of cyclohexenone did not
react to provide the desired product under these reaction
conditions. When the α-position was blocked by a methyl
group, interestingly, a γ-alkylation of the same was observed
with 2:1 diastereoselectivity (see Scheme 4).
Scheme 6. Synthetic Elaboration
The experimental results and stereochemical outcome of the
current reaction promoted us to propose a probable transition
state which is shown in Scheme 5.
To execute the synthetic utility of the current methodology,
an all-carbon quaternary center was installed (see Scheme 6) by
the treatment of 3d with methylmagnesium bromide in the
presence of copper(I) bromide to furnish 6 without loss of any
selectivity (>20:1 dr, 92% ee). The hydrogenation of the enone
was also carried out. However, a mixture of products was
obtained (see the SI).
C
DOI: 10.1021/acs.orglett.7b03959
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Soc. 2002, 124, 2402. (f) Frank, S. A.; Mergott, D. J.; Roush, W. R. J.
Am. Chem. Soc. 2002, 124, 2404. (g) Aroyan, C. E.; Miller, S. J. J. Am.
Chem. Soc. 2007, 129, 256. (h) Takizawa, S.; Nguyen, T. M.-N.;
Grossmann, A.; Enders, D.; Sasai, H. Angew. Chem., Int. Ed. 2012, 51,
5423. (i) Osuna, S.; Dermenci, A.; Miller, S. J.; Houk, K. N. Chem. -
Eur. J. 2013, 19, 14245. (j) Su, X.; Zhou, W.; Li, Y.; Zhang, J. Angew.
Chem., Int. Ed. 2015, 54, 6874. (k) Dong, X.; Liang, L.; Li, E.; Huang,
Y. Angew. Chem., Int. Ed. 2015, 54, 1621. (l) Zhou, W.; Su, X.; Tao, M.;
Zhu, C.; Zhao, Q.; Zhang, J. Angew. Chem., Int. Ed. 2015, 54, 14853.
(m) Yao, W.; Dou, X.; Wen, S.; Wu, J.; Vittal, J. J.; Lu, Y. Nat.
Commun. 2016, 7, 13024. (n) Li, S.; Liu, Y.; Huang, B.; Zhou, T.; Tao,
H.; Xiao, Y.; Liu, L.; Zhang, J. ACS Catal. 2017, 7, 2805. (o) Jin, H.;
Zhang, Q.; Li, E.; Jia, P.; Li, N.; Huang, Y. Org. Biomol. Chem. 2017,
15, 7097.
(3) Representative applications of intramolecular Rauhut−Currier
adducts in total synthesis: (a) Agapiou, K.; Krische, M. J. Org. Lett.
2003, 5, 1737. (b) Mergott, D. J.; Frank, S. A.; Roush, W. R. Proc. Natl.
Acad. Sci. U. S. A. 2004, 101, 11955. (c) Stark, L. M.; Pekari, K.;
Sorensen, E. J. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 12064.
(d) Dermenci, A.; Selig, P. S.; Domaoal, R. A.; Spasov, K. A.;
Anderson, K. S.; Miller, S. J. Chem. Sci. 2011, 2, 1568. (e) Jeon, S.;
Han, S. J. Am. Chem. Soc. 2017, 139, 6302.
(4) For asymmetric MBH reaction of β,β-disubstituted enone, see:
(a) Satpathi, B.; Ramasastry, S. S. V. Angew. Chem., Int. Ed. 2016, 55,
1777. (b) Satpathi, B.; Ramasastry, S. S. V. Synlett 2016, 27, 2178.
(c) Satpathi, B.; Wagulde, S. V.; Ramasastry, S. S. V. Chem. Commun.
2017, 53, 8042.
(5) For selected reviews on asymmetric amino catalysis, see:
(a) Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G. Angew.
Chem., Int. Ed. 2008, 47, 6138. (b) Melchiorre, P. Angew. Chem., Int.
Ed. 2009, 48, 1360. (c) Bertelsen, S.; Jørgensen, K. A. Chem. Soc. Rev.
2009, 38, 2178. (d) Ramachary, D. B.; Ramakumar, K. Eur. J. Org.
Chem. 2011, 2011, 2599. (e) Wei, Y.; Shi, M. Chem. Rev. 2013, 113,
6659.
In conclusion, we have developed a unique strategy for RC-
type reaction of 3-aryl cyclohexenone tethered to an enone
moiety at the ortho-position on the aryl moiety to provide an
uncommon [6−5−6] all-carbon tricyclic skeleton with excellent
enantioselectivity. This report may open a new era for primary
amines in dienamine catalysis for RC- and MBH-type reactions
in extremely sterically hindered substrates to obtain a critical
C−C bond in enantiomerically enriched form.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b03959.
Experimental procedures and characterization data
(PDF)
NMR spectra for all products (PDF)
Accession Codes
CCDC 1568745 and 1585234 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*pghorai@iiserb.ac.in
ORCID
(6) Recent articles on dienamine catalysis: (a) Ramachary, D. B.;
Reddy, Y. V. Eur. J. Org. Chem. 2012, 2012, 865. (b) Christmann, M.;
Prasanta Ghorai: 0000-0001-5120-2700
Notes
Brase, S. Asymmetric synthesis: More methods and applications, Eds.;
̈
Wiley-VCH: Weinheim, 2012; pp 43−48. (c) Silvi, M.; Cassani, C.;
Moran, A.; Melchiorre, P. Helv. Chim. Acta 2012, 95, 1985.
(d) Appayee, C.; Fraboni, A. J.; Brenner-Moyer, S. E. J. Org. Chem.
2012, 77, 8828. (e) Han, B.; He, Z.-Q.; Li, J.-L.; Li, R.; Jiang, K.; Liu,
T.-Y.; Chen, Y.-C. Angew. Chem., Int. Ed. 2009, 48, 5474. (f) Li, J.-L.;
Zhou, S.-L.; Han, B.; Wu, L.; Chen, Y.-C. Chem. Commun. 2010, 46,
2665. (g) Arimitsu, S.; Yonamine, T.; Higashi, M. ACS Catal. 2017, 7,
4736.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work has been funded by IISER Bhopal and CSIR, India.
S.M. and S.S. thank UGC and CSIR, New Delhi, India,
respectively, for fellowships. We thank Mr. Darpan Agarwal
(IISER Bhopal) for his help.
(7) α-Selective addition of enone via amine-based dienamine
activation: (a) Bencivenni, G.; Wu, L.-Y.; Mazzanti, A.; Giannichi,
B.; Pesciaioli, F.; Song, M.-P.; Bartoli, G.; Melchiorre, P. Angew. Chem.,
Int. Ed. 2009, 48, 7200. (b) Xu, D.-Q.; Xia, A.-B.; Luo, S.-P.; Tang, J.;
Zhang, S.; Jiang, J.-R.; Xu, Z.-Y. Angew. Chem., Int. Ed. 2009, 48, 3821.
(c) Han, B.; Xiao, Y.-C.; He, Z.-Q.; Chen, Y.-C. Org. Lett. 2009, 11,
4660. (d) Han, B.; Xiao, Y.-C.; Yao, Y.; Chen, Y.-C. Angew. Chem., Int.
REFERENCES
■
(1) (a) Morita, K.; Suzuki, Z.; Hirose, H. Bull. Chem. Soc. Jpn. 1968,
41, 2815. (b) Morita, K. Japan Patent 6803364, 1968. (c) Baylis, A. B.;
Hillman, M. E. D. German Patent 2155113, 1972. For reviews on
MBH reactions, see: (d) Huang, W.-Y.; Anwar, S.; Chen, K. Chem. Rec.
2017, 17, 363. (e) Pellissier, H. Tetrahedron 2017, 73, 2831.
(f) Basavaiah, D.; Veeraraghavaiah, G. Chem. Soc. Rev. 2012, 41, 68.
(g) Basavaiah, D.; Reddy, B. S.; Badsara, S. S. Chem. Rev. 2010, 110,
5447. (h) Declerck, V.; Martínez, J.; Lamaty, F. Chem. Rev. 2009, 109,
1. (i) Singh, V.; Batra, S. Tetrahedron 2008, 64, 4511. (j) Masson, G.;
Housseman, C.; Zhu, J. Angew. Chem., Int. Ed. 2007, 46, 4614. For
selected reports on MBH reactions, see: (k) McDougal, N. T.;
Trevellini, W. L.; Rodgen, S. A.; Kliman, L. T.; Schaus, S. E. Adv. Synth.
Catal. 2004, 346, 1231. (l) Lindner, C.; Liu, Y.; Karaghiosoff, K.;
Maryasin, B.; Zipse, H. Chem. - Eur. J. 2013, 19, 6429. (m) Yoshida, Y.;
Sako, M.; Kishi, K.; Sasai, H.; Hatakeyama, S.; Takizawa, S. Org.
Biomol. Chem. 2015, 13, 9022.
Ed. 2010, 49, 10189. (e) Stiller, J.; Marques
́
-Lop
́
ez, E.; Herrera, R. P.;
Frohlich, R.; Strohmann, C.; Christmann, M. Org. Lett. 2011, 13, 70.
̈
(f) Feng, X.; Zhou, Z.; Zhou, R.; Zhou, Q.-Q.; Dong, L.; Chen, Y.-C. J.
Am. Chem. Soc. 2012, 134, 19942. (g) Xia, A.-B.; Xu, D.-Q.; Wu, C.;
Zhao, L.; Xu, Z.-Y. Chem. - Eur. J. 2012, 18, 1055. (h) Lee, J. H.; Deng,
L. J. Am. Chem. Soc. 2012, 134, 18209. (i) Tian, X.; Melchiorre, P.
Angew. Chem., Int. Ed. 2013, 52, 5360. (j) Mose, R.; Jensen, M. E.;
Preegel, G.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2015, 54, 13630.
(8) γ-Selective addition of enone via amine-based dienamine
́
activation: (a) Bertelsen, S.; Marigo, M.; Brandes, S.; Diner, P.;
Jørgensen, K. A. J. Am. Chem. Soc. 2006, 128, 12973. (b) Bencivenni,
G.; Galzerano, P.; Mazzanti, A.; Bartoli, G.; Melchiorre, P. Proc. Natl.
Acad. Sci. U. S. A. 2010, 107, 20642. (c) Li, J.-L.; Kang, T.-R.; Zhou, S.-
L.; Li, R.; Wu, L.; Chen, Y.-C. Angew. Chem., Int. Ed. 2010, 49, 6418.
(d) Di Iorio, N.; Righi, P.; Mazzanti, A.; Mancinelli, M.; Ciogli, A.;
Bencivenni, G. J. Am. Chem. Soc. 2014, 136, 10250. (e) Yin, X.; Zheng,
Y.; Feng, X.; Jiang, K.; Wei, X.-Z.; Gao, N.; Chen, Y.-C. Angew. Chem.,
(2) For the intramolecular RC reaction, see reviews: (a) Chandra
Bharadwaj, K. RSC Adv. 2015, 5, 75923. (b) Xie, P.; Huang, Y. Eur. J.
Org. Chem. 2013, 2013, 6213. (c) Methot, J. L.; Roush, W. R. Adv.
Synth. Catal. 2004, 346, 1035. (d) Aroyan, C. E.; Dermenci, A.; Miller,
S. J. Tetrahedron 2009, 65, 4069. For selected reports, see: (e) Wang,
L.-C.; Luis, A. L.; Agapiou, K.; Jang, H.-Y.; Krische, M. J. J. Am. Chem.
D
DOI: 10.1021/acs.orglett.7b03959
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Int. Ed. 2014, 53, 6245. (f) Zou, C.; Zeng, C.; Liu, Z.; Lu, M.; Sun, X.;
Ye, J. Angew. Chem., Int. Ed. 2016, 55, 14257.
(9) Recent articles on MBH reaction via dienamine activation:
(a) Chen, S.-H.; Hong, B.-C.; Su, C. F.; Sarshar, S. Tetrahedron Lett.
2005, 46, 8899. (b) Utsumi, N.; Zhang, H.; Tanaka, F.; Barbas, C. F.,
III Angew. Chem., Int. Ed. 2007, 46, 1878. (c) Vesely, J.; Dziedzic, P.;
Cor
(10) Intramolecular Rauhut−Currier cyclizations of α,β-unsaturated
aldehydes based on dienamine activation: (a) Marques-Lopez, E.;
Herrera, R. P.; Marks, T.; Jacobs, W. C.; Konning, D.; de Figueiredo,
́
dova, A. Tetrahedron Lett. 2007, 48, 6900.
́
́
̈
́ ́
R. M.; Christmann, M. Org. Lett. 2009, 11, 4116. (b) Marques-Lopez,
E.; Herrera, R. P.; Marks, T.; Jacobs, W. C.; Christmann, M. Synthesis
2013, 45, 1016.
(11) (a) Ohtsu, H.; Iwamoto, M.; Ohishi, H.; Matsunaga, S.; Tanaka,
R. Tetrahedron Lett. 1999, 40, 6419. (b) Lin, W.-H.; Fang, J.-M.;
Cheng, Y.-S. Phytochemistry 1995, 40, 871. (c) Kawazoe, K.;
Yamamoto, M.; Takaishi, Y.; Honda, G.; Fujita, T.; Sezik, E.;
Yesilada, E. Phytochemistry 1999, 50, 493.
(12) (a) Minami, T.; Iwamoto, M.; Ohtsu, H.; Ohishi, H.; Tanaka,
R.; Yoshitake, A. Planta Med. 2002, 68, 742. (b) Iwamoto, M.; Ohtsu,
H.; Tokuda, H.; Nishino, H.; Matsunaga, S.; Tanaka, R. Bioorg. Med.
Chem. 2001, 9, 1911.
(13) For an asymmetric push−pull strategy, see: (a) Li, D. R.;
Murugan, A.; Falck, J. R. J. Am. Chem. Soc. 2008, 130, 46. (b) Asano,
K.; Matsubara, S. J. Am. Chem. Soc. 2011, 133, 16711. (c) Kobayashi,
Y.; Taniguchi, Y.; Hayama, N.; Inokuma, T.; Takemoto, Y. Angew.
Chem., Int. Ed. 2013, 52, 11114.
(14) Our contribution to asymmetric push−pull strategy: (a) Ravin-
dra, B.; Das, B. G.; Ghorai, P. Org. Lett. 2014, 16, 5580. (b) Maity, S.;
Parhi, B.; Ghorai, P. Angew. Chem., Int. Ed. 2016, 55, 7723. (c) Reddy,
R. R.; Gudup, S. S.; Ghorai, P. Angew. Chem., Int. Ed. 2016, 55, 15115.
(d) Hazra, G.; Maity, S.; Bhowmick, S.; Ghorai, P. Chem. Sci. 2017, 8,
3026. (e) Midya, A.; Maity, S.; Ghorai, P. Chem. - Eur. J. 2017, 23,
11216. (f) Maity, S.; Saha, M.; Hazra, G.; Ghorai, P. Org. Lett. 2017,
19, 5872.
E
DOI: 10.1021/acs.orglett.7b03959
Org. Lett. XXXX, XXX, XXX−XXX