Cu-catalyzed asymmetric conjugate addition of dialkylzincs to enones using a (±)- trans -1,2-cyclohexanediamine-based bis(NHC) derived from l -leucinol

Article abstract of DOI:10.1055/s-0034-1378916

A hydroxyamide-functionalized azolium salt as the precursor of a (±)-trans-1,2-cyclohexanediamine-based bis(NHC) ligand was designed and synthesized from readily accessible l-leucinol. The combination of a Cu salt with this chiral ligand precursor promote

Full text of DOI:10.1055/s-0034-1378916

LETTER
▌2933
lCettuer -Catalyzed Asymmetric Conjugate Addition of Dialkylzincs to Enones
Using a (±)-trans-1,2-Cyclohexanediamine-Based Bis(NHC) Derived from
L-Leucinol
Asymmetric Conjugate 1,4-Addition
Shun Kamihigashi, Naoatsu Shibata, Satoshi Sakaguchi*
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka
64-8680, Japan
5
Fax +81(6)63394026; E-mail: satoshi@kansai-u.ac.jp
Received: 25.08.2014; Accepted after revision: 08.10.2014
9
nocyclohexane. Recently, two additional examples of
metal complexes bearing chiral bis(NHC) ligands for
asymmetric catalytic transformations have appeared in
Abstract: A hydroxyamide-functionalized azolium salt as the pre-
cursor of a (±)-trans-1,2-cyclohexanediamine-based bis(NHC)
ligand was designed and synthesized from readily accessible L-leu-
cinol. The combination of a Cu salt with this chiral ligand precursor the literature (Figure 1). Herrmann and Kühn et al. devel-
promoted the asymmetric conjugate addition of Et Zn to 2-cyclo- oped cationic rhodium complexes bearing chiral
2
hexen-1-one at room temperature without the need for temperature bis(NHC)s based on 1,2,4-triazole derivatives and suc-
control to afford the corresponding 1,4-adduct with up to 95% ee.
cessfully demonstrated their use in the enantioselective
Key words: asymmetric catalysis, carbene complexes, copper, hydrogenation of dimethylitaconate and methyl-2-acet-
Michael addition, ligands
amidoacrylate to afford the desired reduced products with
enantioselectivities up to 61% ee. Zhang et al. reported
asymmetric catalytic Suzuki–Miyaura couplings of aryl
1
0
The development of improved catalysts for asymmetric bromides and arylboronic acids with moderate enantiose-
conjugate addition (ACA) reactions represents an ongo- lectivities (61% ee) by employing bis(NHC) complexes of
1
ing challenge in synthetic organic chemistry. Since palladium(II) derived from chiral 1,2-cyclohexanedi-
1
1
Woodward et al. first demonstrated that Arudengo-type amine. However, reports of efficient asymmetric cata-
N-heterocyclic carbenes (NHCs) accelerate the rate of lytic systems based on chiral bis(NHC) ligands remain
Cu-catalyzed 1,4-addition reactions of enones with dial- rare, although the tightly coordinating polydentate
kylzincs reagents, chiral NHC ligands have received con- bis(NHC) ligand system is expected to enhance catalyst
2,3
siderable attention. In addition to monodentate NHC stability and offer a key structure for the construction of
ligands,4 chelating polydentate NHCs have recently efficient stereodirecting elements.
5–8
emerged as promising chiral ligands for ACA reactions.
Recently, we reported the Cu-catalyzed ACA reaction of
enones with dialkylzinc reagents under the influence of a
functionalized azolium NHC ligand precursor. A combi-
A decisive breakthrough was achieved in 2005 by
Mauduit et al., who introduced a second coordination site
at the NHC ligand through incorporation of an alcohol
12
nation of the NHC unit and a second coordinating group,
such as a hydroxyamide group, on the side-arm of the
NHC, generates a strongly coordinating polydentate li-
gand that can lock the stereodirecting functional group in
a fixed conformation. The advantage of such chiral NHC
ligand precursors lies in their ease of preparation from
readily available naturally occurring α-amino acid deriva-
tives.
moiety to achieve highly enantioselective Cu-catalyzed
6
1,4-addition of dialkylzinc reagents to cyclic enones.
This report of a hydroxyalkyl-chelating NHC was soon
followed by the beautiful work of Alexakis and Mauduit
on the formation of enantioenriched all-carbon quaternary
7
centers with excellent stereoselectivities (up to 99% ee).
However, one major aspect of the study of the catalytic
ACA reactions is the development of an alternative cata-
lyst system that allows catalyst loading levels to be de-
creased.
During the course of an ongoing project focused on the
development of new catalysts for ACA reactions, we
elected to study the use of bis(NHC) ligands. We assumed
that the tightly coordinating bis(NHC) ligand system
might lead to improved catalyst turnover in ACA reac-
tions and allow significantly reduced catalyst loading for
efficient conversion of enones. Consequently, a new chi-
ral bis(NHC) ligand containing an hydroxyamide func-
tional group was designed and synthesized from (±)-
trans-1,2-diaminocyclohexane. Highly enantioselective
conjugate addition of dialkylzinc reagents to cyclic
enones was successfully achieved by employing a com-
bined catalytic system comprising a Cu salt and a
bis(NHC) azolium ligand precursor derived from L-leu-
cine.
There is growing interest in the synthesis and application
of bis(NHC) derivatives because polydentate bis(NHC)
ligands are expected to form stronger metal–ligand bonds,
and hence generate more stable and rigid complexes. Par-
ticularly, chiral bis(NHC) ligands are promising for asym-
metric applications. Pioneering work was performed by
Douthwaite et al., in which a chiral bis(NHC)–Pd(II) com-
plex was synthesized from optically pure trans-1,2-diami-
SYNLETT 2014, 25, 2933–2937
Advanced online publication: 29.10.2014
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DOI: 10.1055/s-0034-1378916; Art ID: st-2015-u0712-l
Georg Thieme Verlag Stuttgart · New York
©

2934
S. Kamihigashi et al.
LETTER
This study commenced with the synthesis of the chiral
azolium ligand precursor L1 (Scheme 1). The first step in-
volved formation of aryl amine derivative 2 through the
nucleophilic substitution reaction of 2-fluoronitrobenzene
and (±)-trans-1,2-diaminocyclohexane (1). Reduction of
R
R
N
N
N
N
Cl
N
N
R
N
N
2
Cl
2Cl
the nitro groups of 2 by using SnCl /EtOH followed by
2
R
condensation of the resulting primary amine with triethyl
orthoformate, yielded the corresponding dibenzimidazole
derivative 3. Finally, 3 was coupled with the α-chloroac-
etamide derived from chloroacetyl chloride and L-leucinol
to afford the desired hydroxyamide functionalized ben-
zimidazolium salt L1 as a 1:1 diastereoisomeric mixture.
N
L2
N
O
i-Bu
R
R =
OH
N
L4
H
L3
Figure 1 Chiral azolium salts
mono-NHC and bis(NHC) ligands, the results for the
same reaction using L2 (Figure 1) are also listed in Table
1.
NO2
N
NH2
NH2
NH
NH
N
N
(
i)
(ii)
iii)
(
±)-
(
Table 1 Initial Studies of the ACA Reaction using a Cu Precatalyst
N
and the Azolium Ligand Precursora
1
NO2
O
O
Cu salt (6 mol%)
2
3
azolium salt L1 or L2 (4.5 mol%)
+
Et2Zn
THF, r.t., 3 h
Et
4
5
i-Bu
Entry
Cu Salt
Ligand Product Yield ee
(%)b (%)c
OH
O
H
N
N
H
Cl
OH
N
1d,e
Cu(OTf)2
L2
L2
L1
L1
L1
(S)-5
(S)-5
(S)-5
(R)-5
(R)-5
99
31
61
92
90
81
8
N
N
O
i-Bu
3
2Cl
1,4-dioxane
2d,e
Cu(hfacac)(btmsa)f
r.t., 2 d
N
H
N
3d
4d
Cu(OTf)2
31
76
95
62%
O
OH
Cu(hfacac)(btmsa)f
Cu(hfacac)(btmsa)f
i-Bu
L1
5g
Scheme 1 Preparation of chiral bis(NHC) ligand precursor L1 from
±)-trans-1,2-diaminocyclohexane (1). Reagents and conditions: (i)
-fluoronitrobenzene, NaHCO , EtOH, reflux, 2 d, 85%; (ii) SnCl ,
a
Reaction conditions: 4 (1 mmol), Et Zn (3 mmol), Cu salt (6 mol%),
2
(
2
azolium salt (4.5 mol%), THF (9 mL), r.t., 3 h.
3
2
b
Determined by GC analysis using the internal standard technique.
Determined by GC analysis on a chiral stationary phase (see the Sup-
EtOH, NaHCO , reflux, 1 d, 99%; (iii) CH(OEt) , TsOH·H O, r.t.,
c
3
3
2
2
d, 78%.
porting Information).
d
To a solution of Cu precatalyst and azolium salt in THF, 4 was added
first, then Et Zn.
Note that the previously reported chiral bis(NHC) com-
pounds were synthesized from optically pure trans-1,2-di-
aminocyclohexane. In contrast, a racemic mixture of the
diamine was employed in this study. Our strategy was to
2
e
f
12b
Previously reported data.
Cu(hfacac)(btmsa): [bis(trimethylsilyl)acetylene](hexafluoroacetyl-
acetonato)copper(I).
g
To a solution of Cu precatalyst and azolium salt in THF, Et Zn was
2
introduce the chiral hydroxyamide side-arm into the added first, then 4.
dibenzimidazole derivative 3 as the final step in the syn-
thesis of the ligand precursor (Scheme 1). By using a sim-
ilar synthetic route, other bis(NHC) ligand precursors, L3
and L4, were synthesized from 1,2-ethanediamine and
Preliminary studies indicated that the choice of Cu precat-
alyst was an important factor. Whereas the combination of
Cu(OTf) and L2 gave (S)-5 with good enantioselectivity
2
1,3-diaminobenzene, respectively (Figure 1).
(81% ee), use of bis(NHC) L1 in place of L2 provided the
To test the possibility of achieving ACA reactions using
the chiral ligand precursor L1, the reaction of 2-cyclohex-
1,4-adduct with poor ee (Table 1, entry 1 vs. 3). In con-
trast, when the ACA reaction was performed with Cu(hfa-
cac)(btmsa) combined with L1, (R)-5 was obtained as the
major product with moderate stereoselectivity (76% ee;
entry 4). Furthermore, it was observed that the order of ad-
en-1-one (4) with Et Zn to generate 3-ethylcyclohexanone
2
(5) was selected as a model reaction; the results are pre-
sented in Table 1. To compare the relative abilities of
dition of enone and Et Zn affected the enantioselectivity
2
Synlett 2014, 25, 2933–2937
© Georg Thieme Verlag Stuttgart · New York

LETTER
Asymmetric Conjugate 1,4-Addition
2935
Table 2 Evaluation of Cu Precatalysts and the Effect of Catalyst
droxyquinolinato)copper(II) provided the desired product
with slightly lower enantioselectivity (entries 6 and 7).
Loading on the Cu-Catalyzed ACA Reaction of 4 with Et Zn under
2
a
the Influence of L1
In contrast, the combination of L1 with other Cu(I) and
Cu(II) complexes resulted in poor yield and ee for the 1,4-
adduct (Table 2, entries 8–11). These results indicate that
copper salts bearing anionic bidentate ligands, such as
acac or hfacac, are suitable for the present catalytic sys-
tem. It is speculated that the catalytically active Cu spe-
cies involves such a strongly coordinated anionic ligand.
Entry
Cu Salt
L1
(mol%)
Yield ee
b
b
(
mol%)
(%)
(%)
I
1
2
3
Cu (hfacac)(btmsa) (6.0)
4.5
4.5
4.5
4.5
4.5
4.5
4.5
4.5
4.5
4.5
4.5
3.0
1.5
1.0
1.5
90
89
89
93
78
86
83
56
85
73
37
94
92
68
79
95
97
93
95
88
89
88
0
I
c
Cu (hfacac)(cod) (6.0)
II
d
Cu (hfacac) (6.0)
2
The effect of catalyst loading on the ACA reaction was
then investigated (Table 2, entries 12–15). The reaction
was run using 3.0 mol% Cu precatalyst, and the amount of
L1 was reduced systematically. The best result was ob-
tained at a 1:0.5 ratio of Cu salt to bis(NHC) (entry 13),
suggesting that the catalytically active Cu species might
involve one NHC ligand, although further evidence is re-
quired to confirm this assumption. Additionally, it should
be noted that the amount of chiral ligand could be reduced
in the present catalyst system (entry 1 vs. 13).
4e
Cu (hfacac)(btmsa) (6.0)
I
5e
II
d
Cu (hfacac) (6.0)
2
II
6
7
8
9
Cu (acac) (6.0)
2
II
f
Cu salt (6.0)
II
Cu (OTf) (6.0)
2
II
Cu (NO ) (6.0)
68
70
50
93
97
96
92
3
2
I
1
1
1
1
1
0
1
2
3
4
5
[Cu (OTf)] ·C H (6.0)
2 6 6
An evaluation of hydroxyamide-functionalized bis(NHC)
ligands and conjugate enones in Cu-catalyzed ACA reac-
tion is summarized in Table 3.
I
[Cu (CH CN) ](OTf) (6.0)
3
4
I
Cu (hfacac)(btmsa) (3.0)
I
Table 3 Evaluation of Hydroxyamide-functionalized Bis(NHC) Li-
Cu (hfacac)(btmsa) (3.0)
gands and Conjugate Enones in the Cu-Catalyzed ACA Reactiona
I
Cu (hfacac)(btmsa) (3.0)
Entry Enone
Ligand
Product
Yield ee
I
1
Cu (hfacac)(btmsa) (1.5)
b
b
(%)
(%)
a
To a solution of Cu precatalyst and azolium salt in THF (9 mL),
1
2
3
4
4
4
4
4
L1
(R)-5
(S)-5
(R)-5
90
95
95
54
95
95
73
7
Et Zn (3 mmol) was added first, then 4 (1 mmol). The reaction mix-
2
ture was stirred at r.t. for 3 h.
ent-L1
L3
b
See Table 1 footnotes b and c.
Cu (hfacac)(cod): cyclooctadiene(hexafluoro-2,4-pentanedio-
c
I
nato)copper(I)
d
e
f
II
L4
(R)-5
Cu (hfacac) : bis(hexafluoroacetylacetonato)copper(II)
2
The reaction was conducted for 15 min.
O
O
Et
II
Cu salt: bis(8-hydroxyquinolinato)copper(II).
5
L1
L1
78c
39c
85
82
dramatically. Thus, (R)-5 could be obtained with excellent
enantioselectivity (95% ee) by adding 4 to a mixture of the
6
(R)-7
Cu salt, L1, and Et Zn.
O
O
Et
2
To obtain further information on the ACA reaction of 4 6d
with Et Zn using the Cu/L1 catalytic system, the influ-
2
8
(R)-9
ence of the Cu precatalyst and the catalyst loading were
then investigated (Table 2).1 The yield and ee of the
ACA reaction using Cu(hfacac)(btmsa) were comparable
to those obtained by using Cu(hfacac)(cod) (entries 1 and
O
O
Et
3,14
7
R
L1
L1
R
90
87
49
61
10 (R = C H )
(S)-11
(S)-11
5
11
2). Similarly, high stereoselectivity (93% ee) was ob-
8e
a
10
tained for the ACA reaction using Cu(hfacac) (entry 3).
2
I
To a solution of Cu(hfacac)(btmsa) (6.0 mol%) and azolium salt (4.5
mol%) in THF (9 mL), Et Zn (3 mmol) was added first, then enone (1
mmol). The reaction mixture was stirred at room temperature for 3 h.
However, a difference in the reactivity of Cu (hfa-
II
2
cac)(btmsa) and Cu (hfacac) was observed in the initial
2
stage of the ACA reaction. Whereas the reaction catalyzed
b
c
d
e
1
See Table footnotes b and c.
I
by the Cu (hfacac)(btmsa)/L1 system afforded (R)-5 in
Isolated yield.
9
3% yield and 95% ee after 15 min, a slightly lower yield
Reaction was conducted at 0 °C.
Cu(hfacac)(cod) was used instead of Cu(hfacac)(btmsa).
II
(78%) was obtained when Cu (hfacac) was used under
2
these conditions (entries 4 and 5). This difference in reac-
tivity may be due to the slow rate of Cu(II) → Cu(I) reduc-
tion under the reaction conditions. Moreover, the Cu(II)
salts such as bis(acetylacetonato)copper(II) and bis(8-hy-
The chiral ligand precursor ent-L1 was prepared from D-
leucinol by using the same synthetic route as that shown
in Scheme 1. As expected, treatment of 4 and Et Zn with
2
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2933–2937

2936
S. Kamihigashi et al.
LETTER
the Cu(hfacac)(btmsa)/ent-L1 catalytic system afforded
S)-5 in 95% yield and 95% ee (Table 3, entry 2). It is im-
(e) Alexakis, A.; Benhaim, C. Eur. J. Org. Chem. 2002,
221.
2) Fraser, P. K.; Woodward, S. Tetrahedron Lett. 2001, 42,
747.
3) For selected recent reviews, see: (a) N-Heterocyclic
Carbenes; Díez-González, S., Ed.; RSC-Publishing:
Cambridge, 2011. (b) Benhamou, L.; Chardon, E.; Lavigne,
G.; Bellemin-Laponnaz, S.; César, V. Chem. Rev. 2011, 111,
2705. (c) Kühl, O. Functionalised N-Heterocyclic Carbene
Complexes; Wiley-VCH: Weinheim, 2010. (d) Díez-
González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009,
3
(
(
(
portant to highlight the greater reactivity of 1,2-diamino-
cyclohexane-based bis(NHC) ligands such as L1
compared with that of chiral ligands based on other
bis(NHC) skeletons. Therefore, we synthesized the two
chiral ligands L3 and L4 from 1,3-diaminobenzene and
2
1,2-diaminoethane, respectively (Figure 1). When 4 was
allowed to react with Et Zn under the influence of a Cu
2
salt and L3, the desired 1,4-adduct was obtained in excel-
lent yield, but the enantioselectivity was somewhat lower
1
09, 3612. (e) Snead, D. R.; Seo, H.; Hong, S. Curr. Org.
Chem. 2008, 12, 1370. (f) N-Heterocyclic Carbenes in
Transition Metal Catalysis; Glorius, F., Ed.; Springer-
Verlag: Berlin/Heidelberg, 2007. (g) Douthwaite, R. E.
Coord. Chem. Rev. 2007, 251, 702. (h) N-Heterocyclic
Carbenes in Synthesis; Nolan, S. P., Ed.; Wiley-VCH:
Weinheim, 2006. (i) Kantchev, E. A. B.; O’Brien, C. J.;
Organ, M. G. Angew. Chem. Int. Ed. 2007, 46, 2768.
(entry 3). In contrast, the ACA reaction with L4 resulted
in formation of (R)-5 with only moderate yield (54%) and
poor stereoselectivity (7% ee; entry 4).
Reaction of 2-cyclohepten-1-one (6) proceeded with
slightly decreased enantioselectivity (85% ee) compared
with that of 4 (Table 3, entry 5). Furthermore, the reaction
(
j) Peris, E.; Crabtree, R. H. Coord. Chem. Rev. 2004, 248,
of 2-cyclopenten-1-one (8) with Et Zn using the present
2239. (k) César, V.; Bellemin-Laponnaz, S.; Gade, L. H.
Chem. Soc. Rev. 2004, 33, 619. (l) Herrmann, W. A. Angew.
Chem. Int. Ed. 2002, 41, 1290.
2
catalytic system occurred with difficulty, affording the
corresponding 1,4-adduct in poor yield, but with relative-
ly good enantioselectivity (82% ee; entry 6), along with
the formation of several undesired by-products. On the
other hand, the reaction of acyclic enone such as 3-nonen-
(
4) (a) Guillen, F.; Winn, C. L.; Alexakis, A. Tetrahedron:
Asymmetry 2001, 12, 2083. (b) Pytkowicz, J.; Roland, S.;
Mangeney, P. Tetrahedron: Asymmetry 2001, 12, 2087.
(c) Alexakis, A.; Winn, C. L.; Guillen, F.; Pytkowicz, J.;
2
-one (10) with Et Zn proceeded smoothly under these
Roland, S.; Mangeney, P. Adv. Synth. Catal. 2003, 345, 345.
(d) Winn, C. L.; Guillen, F.; Pytkowicz, J.; Roland, S.;
Mangeney, P.; Alexakis, A. J. Organomet. Chem. 2005, 690,
2
conditions to furnish (S)-4-ethylnonan-2-one in moderate
enantioselectivity (entry 7). Interestingly, replacement of
Cu(hfacac)(tmsa) with Cu(hfacac)(cod) improved the ste-
reoselectivity of the ACA reaction (entries 7 and 8).
5
672. (e) Matsumoto, Y.; Yamada, K.-i.; Tomioka, K.
J. Org. Chem. 2008, 73, 4578. (f) Lee, K.-s.; Hoveyda, A. H.
J. Org. Chem. 2009, 74, 4455.
In conclusion, we have developed a new 1,2-diaminocy-
(5) (a) Arnold, P. L.; Rodden, M.; Davis, K. M.; Scarisbrick, A.
C.; Blake, A. J.; Wilson, C. Chem. Commun. 2004, 1612.
(b) Uchida, T.; Katsuki, T. Tetrahedron Lett. 2009, 50,
clohexane-based bis(NHC) ligand derived from L-leuci-
nol. The highest ee reported to date (92% ee)6d for the
4
741.
NHC-Cu-catalyzed ACA reaction of 4 with Et Zn was im-
2
(
6) (a) Clavier, H.; Coutable, L.; Toupet, L.; Guillemin, J.-C.;
proved by using the present catalytic system. Synthesis of
the corresponding bis(NHC) ligand from a single enantio-
mer of trans-1,2-diaminocyclohexane and its utilization
in catalytic asymmetric transformations are underway in
our laboratory.
Mauduit, M. J. Organomet. Chem. 2005, 690, 5237.
(
b) Clavier, H.; Coutable, L.; Guillemin, J.-C.; Mauduit, M.
Tetrahedron: Asymmetry 2005, 16, 921. (c) Clavier, H.;
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(
d) Rix, D.; Labat, S.; Toupet, L.; Crévisy, C.; Mauduit, M.
Eur. J. Inorg. Chem. 2009, 1989.
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Acknowledgment
8
416. (b) Hénon, H.; Mauduit, M.; Alexakis, A. Angew.
This work was financially supported by a Grant-in-Aid for Scienti-
fic Research (C) (23550128) from Japan Society for the Promotion
of Science (JSPS). We thank Prof. Ryuichi Arakawa for the HRMS
analysis of compound L1.
Chem. Int. Ed. 2008, 47, 9122. (c) Kehrli, S.; Martin, D.;
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Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
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nr
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(10) (a) Riederer, S. K. U.; Bechlars, B.; Herrmann, W. A.; Kühn,
F. E. Dalton Trans. 2011, 41. (b) Gigler, P.; Bechlars, B.;
Synlett 2014, 25, 2933–2937
© Georg Thieme Verlag Stuttgart · New York

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Asymmetric Conjugate 1,4-Addition
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Herrmann, W. A.; Kühn, F. E. J. Am. Chem. Soc. 2011, 133,
589.
11) Shigeng, G.; Tang, J.; Zhang, D.; Wang, Q.; Chen, Z.; Weng,
L. J. Organomet. Chem. 2012, 700, 223.
2 H), 3.41–3.37 (m, 4 H), 2.58 (br, 2 H), 2.49–2.43 (m, 2 H),
2.05 (br, 2 H), 1.83 (br, 2 H), 1.66–1.58 (m, 2 H), 1.36 (t, J
= 6.9 Hz, 4 H), 0.89–0.86 (m, 6 H), 0.84–0.81 (m, 6 H).
1
(
2
+
2+
HRMS (ESI ): m/z calcd for C H N O : 316.2019;
3
6
52
6
4
(
12) (a) Okamoto, M.; Yamamoto, Y.; Sakaguchi, S. Chem.
Commun. 2009, 7363. (b) Shibata, N.; Okamoto, M.;
Yamamoto, Y.; Sakaguchi, S. J. Org. Chem. 2010, 16, 5707.
found: 316.2014.
(14) General Procedure for the ACA Reaction: To a solution
of azolium salt (0.045 mmol) in THF (9 mL) were added Cu
salt (0.06 mmol) and enone (1 mmol). After the mixture was
(c) Shibata, N.; Yoshimura, M.; Yamada, H.; Arakawa, R.;
Sakaguchi, S. J. Org. Chem. 2012, 77, 4079. (d) Dohi, K.;
Kondo, J.; Yamada, H.; Arakawa, R.; Sakaguchi, S. Eur. J.
Org. Chem. 2012, 7143.
cooled to 0 °C, Et Zn (1 M in hexanes, 3 mmol, 3 mL) was
added to the reaction vessel. The color immediately changed
from yellow to dark-brown. After stirring at room
2
1
(
13) Analytical and Spectral Data of L1: H NMR (400 MHz,
temperature for 3 h, the reaction was quenched with 10%
DMSO-d ): δ = 10.58 (br, 2 H), 8.54 (d, J = 8.2 Hz, 2 H),
HCl aq. The resulting mixture was extracted with i-Pr O
6
2
7.90 (br, 2 H), 7.68–7.66 (m, 2 H), 7.42–7.33 (m, 4 H), 5.76
(3 × 10 mL) and dried over Na SO . The product was
2
4
(br, 2 H), 5.30–5.18 (m, 4 H), 4.65–4.62 (m, 2 H), 3.81 (br,
purified by silica gel column chromatography (hexane–Et O).
2
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2933–2937

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