Efficient synthesis of Xaa-Gly type (Z)-chloroalkene dipeptide isosteres via organocuprate mediated reduction

Article abstract of DOI:10.1016/j.tet.2016.06.080

A highly stereoselective synthesis of (Z)-chloroalkene dipeptide isosteres (CADIs) of the Xaa-Gly type has been achieved. Treatment of an allylic gem-dichloride with an organocuprate provided (Z)-chloroalkene formation corresponding to an Xaa-Gly type CAD

Full text of DOI:10.1016/j.tet.2016.06.080

Tetrahedron 72 (2016) 4968e4971
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Efficient synthesis of Xaa-Gly type (Z)-chloroalkene dipeptide
isosteres via organocuprate mediated reduction
*
Takuya Kobayakawa, Hirokazu Tamamura
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 June 2016
Received in revised form 29 June 2016
Accepted 30 June 2016
Available online 1 July 2016
A highly stereoselective synthesis of (Z)-chloroalkene dipeptide isosteres (CADIs) of the Xaa-Gly type has
been achieved. Treatment of an allylic gem-dichloride with an organocuprate provided (Z)-chloroalkene
formation corresponding to an Xaa-Gly type CADI through reductive dechlorination in high yield with
(Z)-selectivity.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Chloroalkene dipeptide isosteres
Organocuprate
Reductive dechlorination
1. Introduction
Replacement of an amide bond in biologically active peptides
with a non-hydrolyzable unit is a useful approach to solve the
disadvantages of peptides, e.g., their poor bioavailability and short
physiological half-lives due to proteolysis.1 Alkene-type dipeptide
isosteres (ADIs),2,3 which are designed as ground state mimics of
peptides, are considered to be ideal dipeptide mimetics for studies
of medicinal chemistry and chemical biology.2c,4
Native peptide bond
H
N
O
R2
H
O
R2
N
N
H
N
H
R1
O
R1
Cl R2
O
H
N
Our group has focused on synthetic studies of chloroalkene
structures,5 which are variable intermediates for synthetic strate-
gies6 and structural constituents of marine natural products.7 The
chloro-olefin conformation in particular could be expected to be
useful in an ADI (Fig. 1).8 In addition, replacement of an amide bond
in a peptide with a chloroalkene structure could be considered to be
more beneficial due to the mimicking of the steric restriction be-
tween the carbonyl oxygen and the side chain, a chlorine atom
being larger than an oxygen atom. Chlorine and oxygen have sim-
ilar electronegativity values and thus chloroalkene structures
might behave as steric and electronic mimics of peptide bonds.
Thus, we have expected that structures constrained by chlor-
oalkene and more steric restriction are introduced in overall
structures of peptides followed by possible improvement of phar-
macological activity.
R1
Chloroalkene type isosteres
H
O
Ground state
mimic
Fig. 1. Native peptide bonds and design of their isosteres.
Recently, we developed an efficient synthetic method for (Z)-
chloroalkene dipeptide isosteres (CADIs) via 1,4-asymmetric in-
duction in organocuprate-mediated allylic alkylation adjacent to
the chiral center of allylic gem-dichlorides.5,6d While reaction of (E)-
allylic gem-dichlorides with lower-order cyanocuprates affords (Z)-
CADIs in high yields with excellent (Z)-selectivity and diaster-
eoselectivity, reaction with a Gilman cuprate provides reduced
compounds by a carbone-chlorine bond cleavage via a single
electron transfer (SET) mechanism.3a,5,6d,9 It is noteworthy that this
SET reaction produces only the reductive dechlorinated com-
pounds, which correspond to Xaa-Gly type CADIs. In this paper, we
describe a useful method for the stereoselective synthesis of Bus-L-
Xaa-
reduction.
J[(Z)-CCl]CH]-Gly-OEt utilizing the organocuprate-mediated
* Corresponding author. Tel.: þ81 3 5280 8036; fax: þ81 3 5280 8039; e-mail
address: tamamura.mr@tmd.ac.jp (H. Tamamura).
http://dx.doi.org/10.1016/j.tet.2016.06.080
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

T. Kobayakawa, H. Tamamura / Tetrahedron 72 (2016) 4968e4971
4969
Table 2
2. Results and discussion
We prepared the -dichloro-
Scope of functional group tolerance
g,g
a,
b
-unsaturated ester 1a, which
has been reported as a precursor of the CADI synthesis,6d and in-
vestigated its reductive dechlorination. The reactivity of ester 1a
with a Gilman cuprate was examined as previously reported,6d
(Table 1). All of the reactions obtained (Z)-chloroalkene products
with undetectable levels of (E)-chloroalkene isomers (Z/E¼>20:1).
Reaction with a Gilman cuprate afforded the reductive dechlori-
nated compound (2a) in excellent yield (entry 1). The reaction with
both a higher order cuprate (Me3CuLi2$LiI$3LiBr) and the cyano
Gilman reagent (Me2CuLi2$LiCN$2LiBr) produced 2a in slightly
lower but still high yields (entries 2, 3). In addition, changing the
methyl group of alkyl ligands to n-butyl group resulted in a de-
creased yield (entry 4). On the other hand, Gilman cuprates with
additives such as TMSCl, BF3$OEt2, and HMPA did not lead to sig-
Entry
Substrate
2, Z/Eb
2, yield (%)c (product)
1
2
3
4
5
1a
1b
1c
1d
1e
>20:1
>20:1
>20:1
>20:1
>20:1
99 (2a)
98 (2b)
97 (2c)
84 (2d)
71 (2e)
aAll reactions were carried out at ꢀ78 ꢁC for 30 min on a 0.3 mmol scale with 4 equiv
nificant differences in chemical yields, but small amounts of
a-
of organocuprates in the presence of Li salts.
methylated compounds were observed (entries 5e7). Based on
these results, the Gilman reagent (entry 1) was adopted as the most
suitable.
b
Determined by 1H NMR with an unpurified reaction mixture.
Yields of isolated products.
c
Table 1
Reduction of a g,g-dichloro-a,b-enoate (1a) with organocopper reagents
Entry
Reagents
Additivesb
2a, Z/Ec
2a, yield (%)d
1
2
3
4
5
6
7
Me2CuLi$LiI$2LiBr
Me3CuLi2$LiI$3LiBr
Me2Cu(CN)$2LiBr
nBuCuLi$LiI
Me2CuLi$LiI$2LiBr
Me2CuLi$LiI$2LiBr
Me2CuLi$LiI$2LiBr
d
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
99
78
80
41
94
88
94
d
Scheme 1. Conversion from 2a to a Boc-protected L-Val-Gly type chloroalkene di-
peptide isostere 4a.
d
d
TMSCl
BF3$OEt2
HMPA
3. Conclusion
aAll reactions were carried out at ꢀ78 ꢁC for 30 min on a 0.1 mmol scale with 4 equiv
In conclusion, we have developed an efficient method for the
stereoselective synthesis of isosteres of the type Bus-L-Xaa-J[(Z)-
of organocuprates in the presence of Li salts.
b
4 equiv.
c
Determined by 1H NMR with an unpurified reaction mixture.
CCl]CH]-Gly-OEt using a organocuprate-mediated reduction. This
reaction forms the Z-chloroalkene in high yields with excellent Z-
selectivity. In addition, transformation of the protecting group of
the amine and hydrolysis of the ester can be performed. These
findings have shown a model of the efficient synthesis of Xaa-Gly
type isosteres. Currently, studies on the synthesis and evaluation
of bioactive peptides with CADIs are in progress.
d
Yields were determined by 1H NMR of unpurified reaction mixture using 1,4-
dinitrobenzene as an internal standard.
The optimal reduction condition is identified in Table 1 (entry 1),
and the substrate scope of this reductive dechlorination was ex-
plored next (Table 2). Treatment of various (E)-enoates (1aee) as
Xaa-Gly precursors, which were prepared as previously repor-
ted6d,10 with the optimized Gilman cuprates led to the reductive
products 2aee (entry 1e5). In all cases, the reductive products were
obtained with excellent Z-selectivity (>20:1). The substrates with
various sterically bulky alkyl groups gave reduced compounds in
excellent yields regardless of the steric factors of the alkyl side
chains (entries 1e3). The substrates, including an aromatic group
(entry 4) and an oxygen containing group (entry 5) gave high yields
with no decrease in Z-selectivity.
4. Experimental section
4.1. General methods
All reactions using air- or moisture-sensitive reagents were per-
formed in dried glassware under an atmosphere of nitrogen, with
commercially supplied solvents and reagents unless otherwise noted.
CH2Cl2 was distilled from CaH2 and stored over molecular sieves 4A.
Thin-layer chromatography (TLC) was performed on Merck 60F254
precoated silica gel plates and was visualized by fluorescence
quenching under UV light and by staining with phosphomolybdic
acid, p-anisaldehyde, or ninhydrin. Flash column chromatography
was carried out silica gel 60 N (Kanto Chemical Co., Inc.).
The substrate scope of the reductive dechlorination utilizing
Gilman cuprates was thus confirmed, and the reduced compound
2a was converted into a Boc-protected carboxylic acid 4a (Bus-L-
Xaa-J[(Z)-CCl]CH]-Gly-OH (Scheme 1), which can be used in
peptide chemistry. Deprotection of the Bus group in the presence of
AlCl3 and anisole11 followed by Boc protection gave the ester 3a
(Boc-L-Xaa-
hydrolyzed under basic condition to give the Boc-protected CADI 4a
(Boc-L-Xaa- [(Z)-CCl]CH]-Gly-OH) in 4 steps and 75% yield
without isomerization of the olefinic bond.
J
[(Z)-CCl]CH]-Gly-OEt). Finally, the ester of 3a was
4.2. Characterization
J
1H NMR (400 or 500 MHz) and 13C NMR (100 or 125 MHz)
spectra were recorded using a Bruker Avance II spectrometer.

4970
T. Kobayakawa, H. Tamamura / Tetrahedron 72 (2016) 4968e4971
Chemical shifts are reported in
d
(ppm) relative to Me4Si (in CDCl3)
(1.00 mL) at ꢀ78 ꢁC. After having been stirred at ꢀ78 ꢁC for 30 min,
the reaction was quenched by addition of a 3:2 saturated aqueous
NH4Cl-28% NH3 aqueous solution with additional stirring at room
temperature for 30 min. The mixture was extracted with Et2O, and
the extract was washed with brine and dried over MgSO4. Con-
centration under reduced pressure followed by flash chromatog-
raphy over silica gel with n-hexane-EtOAc (3:1) gave the title
as internal standard. Infrared (IR) spectra were recorded on a JASCO
FT/IR 4100, and are reported in wavenumbers (cmꢀ1). Low- and
high-resolution mass spectra were recorded on a Bruker Daltonics
micrOTOF focus (ESI-MS) spectrometers in positive and negative
detection modes. Optical rotations were measured on a JASCO DIP-
370 polarimeter operating at the sodium D line with a 100 mm path
length cell, and were reported as follows: [
100 mL), solvent).
a
]
(concentration (g/
compound 2d as a light yellow oil (97.4 mg, 84%): [
CHCl3); IR (ATR)
1721 (CO), 1369 (NHSO2), 1128 (NHSO2) cmꢀ1; 1H
NMR (500 MHz, CDCl3)
a
]D¼9.67 (c 1.11,
D
n
d
1.23 (t, J¼7.2 Hz, 3H), 1.28 (s, 9H), 3.14 (dd,
4.3. Experimental procedures for synthesis of compounds
J¼18.2, 6.7 Hz, 2H), 3.21 (dd, J¼18.2, 6.7 Hz, 2H), 3.21 (q, J¼7.2 Hz,
2H), 4.19e4.21 (m, 1H), 4.32e4.37 (m, 1H), 5.75 (t, J¼6.7 Hz, 1H),
4.3.1. (5S,3Z)-Ethyl 4-chloro-5-(1,1-dimethylethylsulfonamido)-7-
7.17e7.31 (m, 5H); 13C NMR (125 MHz, CDCl3)
d 14.3, 24.1 (3C), 34.0,
methyloct-3-enoate (2b). To
a
suspension of CuI (190 mg,
41.4, 60.2, 61.1, 62.0, 121.0, 127.0, 129.0 (2C), 130.0 (2C), 136.0, 137.0,
170.0; HRMS (ESI), m/z calcd for C18H27ClNO4S [MþH]þ 388.1344,
found 388.1345.
1.20 mmol) in THF (14.0 mL) was added dropwise a solution of
MeLi$LiBr complex in Et2O (1.18 M, 2.03 mL, 2.40 mmol) at ꢀ78 ꢁC
under nitrogen, and the mixture was stirred at 0 ꢁC for 10 min. To
the solution of the organocuprate was added dropwise a solution of
4.3.4. Ethyl
(5S,3Z)-6-((tert-butyldimethylsilyl)oxy)-4-chloro-5-
the
a
,
b
-unsaturated ester 1b (117 mg, 0.300 mmol) in THF (1.00 mL)
((1,1-dimethylethyl)sulfonamido)hex-3-enoate (2e). To a suspension
of CuI (190 mg, 1.20 mmol) in THF (14.0 mL) was added dropwise
a solution of MeLi$LiBr complex in Et2O (1.18 M, 2.03 mL,
2.40 mmol) at ꢀ78 ꢁC under nitrogen, and the mixture was stirred
at 0 ꢁC for 10 min. To the solution of the organocuprate was added
at ꢀ78 ꢁC. After having been stirred at ꢀ78 ꢁC for 30 min, the re-
action was quenched by addition of a 3:2 saturated aqueous NH4Cl-
28% NH3 aqueous solution with additional stirring at room tem-
perature for 30 min. The mixture was extracted with Et2O, and the
extract was washed with brine and dried over MgSO4. Concentra-
tion under reduced pressure followed by flash chromatography
over silica gel with n-hexane-EtOAc (3:1) gave the title compound
dropwise a solution of the
a,b-unsaturated ester 1e (142 mg,
0.300 mmol) in THF (1.00 mL) at ꢀ78 ꢁC. After having been stirred
at ꢀ78 ꢁC for 30 min, the reaction was quenched by addition of a 3:2
saturated aqueous NH4Cl-28% NH3 aqueous solution with addi-
tional stirring at room temperature for 30 min. The mixture was
extracted with Et2O, and the extract was washed with brine and
dried over MgSO4. Concentration under reduced pressure followed
by flash chromatography over silica gel with n-hexane-EtOAc (3:1)
gave the title compound (2e) as a light yellow oil (88.0 mg, 71%):
2b as a light yellow oil (104 mg, 98%): [
(ATR)
1733 (CO), 1368 (NHSO2), 1125 (NHSO2) cmꢀ1
(500 MHz, CDCl3)
a
]D¼ꢀ1.96 (c 0.98, CHCl3); IR
n
;
1H NMR
d
0.925e0.960 (m, 6H), 1.27 (t, J¼7.1 Hz, 3H), 1.37
(s, 9H), 1.52e1.65 (m, 3H), 3.24 (dd, J¼18.4, 6.8 Hz, 1H), 3.28 (dd,
J¼18.4, 6.8 Hz, 1H), 4.01e4.03 (m, 1H), 4.16 (q, J¼7.1 Hz, 2H),
4.22e4.27 (m, 1H), 5.98 (t, J¼6.8 Hz,1H); 13C NMR (125 MHz, CDCl3)
d
14.3, 22.1, 22.8, 24.3 (3C), 24.6, 34.0, 44.3, 58.7, 59.9, 61.2, 120.6,
[a
]D¼3.86 (c 1.09, CHCl3); IR (ATR)
n
1731 (CO), 1364 (NHSO2), 1132
0.0500e0.0580 (m,
138.0, 170.0; HRMS (ESI), m/z calcd for C15H29ClNO4S [MþH]þ
(NHSO2) cmꢀ1 1H NMR (500 MHz, CDCl3)
;
d
354.1500, found 354.1503.
6H), 0.872 (s, 9H), 1.25e1.28 (m, 3H), 1.40 (s, 9H), 3.27 (dd, J¼6.6,
2.1 Hz, 1H), 3.28 (dd, J¼6.6, 2.1 Hz, 1H), 3.73e3.77 (m, 1H),
3.85e3.88 (m, 1H), 4.14e4.18 (m, 3H), 4.52e4.54 (m, 1H), 6.10 (t,
4.3.2. Ethyl
(5S,3Z)-4-chloro-5-((1,1-dimethylethyl)sulfon-amido)
non-3-enoate (2c). To a suspension of CuI (190 mg, 1.20 mmol) in
THF (14.0 mL) was added dropwise a solution of MeLi$LiBr complex
in Et2O (1.18 M, 2.03 mL, 2.40 mmol) at ꢀ78 ꢁC under nitrogen, and
the mixture was stirred at 0 ꢁC for 10 min. To the solution of the
J¼6.6 Hz, 1H); 13C NMR (125 MHz, CDCl3)
ꢀ5.42, ꢀ5.34, 14.2, 14.3,
d
22.8, 24.3 (2C), 25.9 (3C), 31.7, 34.2, 60.2, 61.1, 64.1, 122.0, 135.0,
170.0; HRMS (ESI), m/z calcd for C18H37ClNO5SSi [MþH]þ 442.1845,
found 442.1848.
organocuprate was added dropwise a solution of the
a,b-un-
saturated ester 1c (117 mg, 0.300 mmol) in THF (1.00 mL) at ꢀ78 ꢁC.
After having been stirred at ꢀ78 ꢁC for 30 min, the reaction was
quenched by addition of a 3:2 saturated aqueous NH4Cl-28% NH3
aqueous solution with additional stirring at room temperature for
30 min. The mixture was extracted with Et2O, and the extract was
washed with brine and dried over MgSO4. Concentration under
reduced pressure followed by flash chromatography over silica gel
with n-hexane-EtOAc (3:1) gave the title compound 2c as a light
4.3.5. (5S,3Z)-5-((tert-Butoxycarbonyl)amino)-4-chloro-6-
methylhept-3-enoic acid (4a). To the solution of ester 2a6d (1.98 g,
5.00 mmol) in CH2Cl2 (50.0 mL) were added anisole (1.09 mL
10.0 mmol) and aluminum chloride (3.00 g, 22.5 mmol). After
having been stirred for 1 h at room temperature, the reaction
mixture was quenched with saturated aqueous NaHCO3 and
extracted with EtOAc. The extract was washed with brine and dried
over MgSO4. Concentration under reduced pressure gave the amine
as yellow oil, which was used immediately in the next step without
purification. The given amine in EtOH (10.0 mL) was added Boc2O
(1.20 g, 5.5 mmol). After stirring for 1 h at room temperature, the
reaction mixture was concentrated under reduced pressure. The
given ester 3a as yellow oil was used immediately in the next step
without purification. To the solution of ester 3a in THF (50.0 mL)
was added 1.00 M LiOH aq (25 mL, 25 mmol). After having been
stirred for 1 h at room temperature, the reaction mixture was
quenched with saturated aqueous NH4Cl and extracted with EtOAc.
The extract was washed with brine and dried over MgSO4. Con-
centration under reduced pressure followed by flash chromatog-
raphy over silica gel with n-hexane-EtOAc (2:1) gave the title
yellow oil (103 mg, 97%): [
(CO), 1370 (NHSO2), 1125 (NHSO2) cmꢀ1; 1H NMR (500 MHz, CDCl3)
0.869e0.917 (m, 3H), 1.25e1.37 (m, 16H) 1.65e1.73 (m, 2H), 3.24
a
]D¼5.13 (c 0.99, CHCl3); IR (ATR)
n 1730
d
(dd, J¼18.4, 6.8 Hz, 1H), 3.28 (dd, J¼18.4, 6.8 Hz, 1H), 4.10e4.18 (m,
4H), 5.96 (t, J¼6.8 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d 14.0, 14.3,
22.3, 22.8, 24.3, 28.0, 31.7, 34.0, 35.0, 59.9, 60.4, 61.1, 121.0, 138.0,
170.0; HRMS (ESI), m/z calcd for C15H29ClNO4S [MþH]þ 354.1500,
found 354.1505.
4.3.3. Ethyl (5S,3Z)-4-chloro-5-((1,1-dimethylethyl)sulfon-amido)-6-
phenylhex-3-enoate (2d). To
a suspension of CuI (190 mg,
1.20 mmol) in THF (14.0 mL) was added dropwise a solution of
MeLi$LiBr complex in Et2O (1.18 M, 2.03 mL, 2.40 mmol) at ꢀ78 ꢁC
under nitrogen, and the mixture was stirred at 0 ꢁC for 10 min. To
the solution of the organocuprate was added dropwise a solution of
compound 4a as a white solid (1.10 g, 75%): [
CHCl3); IR (ATR)
1733 (CO) cmꢀ1; 1H NMR (500 MHz, CDCl3)
¼0.905 (d, J¼6.5 Hz, 3H), 0.966 (d, J¼6.5 Hz, 3H), 1.44 (s, 9H),
1.85e1.92 (m, 1H), 3.26e3.37 (m, 2H), 3.98e4.01 (m, 1H), 4.78e4.80
a
]D¼ꢀ13.7 (c 1.00,
n
d
the
a,b-unsaturated ester 1d (126 mg, 0.300 mmol) in THF

T. Kobayakawa, H. Tamamura / Tetrahedron 72 (2016) 4968e4971
4971
(m, 1H), 5.93e5.96 (m, 1H); 13C NMR (125 MHz, CDCl3)
d 18.6, 19.8,
28.5 (2C), 29.9, 30.6, 33.5, 62.8, 80.0, 120.0, 138.0, 155.0, 175.0;
HRMS (ESI), m/z calcd for C13H23ClNO4 [MþH]þ 292.1310, found
292.1313.
3. For some recent examples of fluoroalkene dipeptide isosteres, see: (a) Narumi,
T.; Tomita, K.; Inokuchi, E.; Kobayashi, K.; Oishi, S.; Ohno, H.; Fujii, N. Tetrahe-
dron 2008, 64, 4332e4346; (b) Watanabe, D.; Koura, M.; Saito, A.; Yanai, H.;
Nakamura, Y.; Okada, M.; Sato, A.; Taguchi, T. J. Fluor. Chem. 2011, 132, 327e338;
(c) Villiers, E.; Couve-Bonnaire, S.; Cahard, D.; Pannecoucke, X. Tetrahedron
2015, 71, 7054e7062.
4. (a) Tamamura, H.; Hiramatsu, K.; Ueda, S.; Wang, Z.; Kusano, S.; Terakubo, S.;
Trent, J. O.; Peiper, S. C.; Yamamoto, N.; Nakashima, H.; Otaka, A.; Fujii, N. J. Med.
Chem. 2005, 48, 380e391; (b) Namanja, A. T.; Wang, X. J.; Xu, B.; Mercedes-
Camacho, A. Y.; Wilson, B. D.; Wilson, K. A.; Etzkorn, F. A.; Peng, J. W. J. Am.
Chem. Soc. 2010, 132, 5607e5609; (c) Narumi, T.; Hayashi, R.; Tomita, K.; Ko-
bayashi, K.; Tanahara, N.; Ohno, H.; Naito, T.; Kodama, E.; Matsuoka, M.; Oishi,
S.; Fujii, N. Org. Biomol. Chem. 2010, 8, 616e621; (d) Kobayashi, K.; Oishi, S.;
Hayashi, R.; Tomita, K.; Kubo, T.; Tanahara, N.; Ohno, H.; Yoshikawa, Y.; Furuya,
T.; Hoshino, M.; Fujii, N. J. Med. Chem. 2012, 55, 2746e2757 and references cited
therein.
Acknowledgements
This work was supported in part by KAKENHI, Grant-in-Aid for
Scientific Research (B) (15H04652 to H.T.); JSPS Core-to-Core Pro-
gram, A. Advanced Research Networks; and the Platform for Drug
Discovery, Informatics, and Structural Life Science of MEXT, Japan.
T.K. was supported by JSPS Research Fellowships for Young Scientists.
5. Narumi, T.; Kobayakawa, T.; Aikawa, H.; Seike, S.; Tamamura, H. Org. Lett. 2012,
14, 4490e4493.
6. (a) Tan, Z.; Negishi, E.-I. Angew. Chem., Int. Ed. 2006, 45, 762e765; (b) Geary, L.
M.; Hultin, P. G. J. Org. Chem. 2010, 75, 6354e6371; (c) Sawant, S. Y.; Somani, R.
S.; Cho, M. H.; Bajaj, H. C. RSC Adv. 2015, 5, 46589e46597; (d) Kobayakawa, T.;
Narumi, T.; Tamamura, H. Org. Lett. 2015, 17, 2302e2305.
Supplementary data
Supplementary data (This section presents the experimental
details, and 1H and 13C NMR spectra.) related to this article can be
found at http://dx.doi.org/10.1016/j.tet.2016.06.080.
7. (a) White, D. E.; Stewart, I. C.; Grubbs, R. H.; Stoltz, B. M. J. Am. Chem. Soc. 2008,
130, 810e811; (b) Guinchard, X.; Roulland, E. Synlett 2011, 2779e2788; (c)
ꢀ
Martín, M. J.; Coello, L.; Fernandez, R.; Reyes, F.; Rodríguez, A.; Murcia, C.;
ꢀ
Garranzo, M.; Mateo, C.; Sanchez-Sancho, F.; Bueno, S.; de Eguilior, C.; Fran-
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