A trinuclear Zn3(OAc)4-3,3′-bis(aminoimino) binaphthoxide complex for highly efficient catalytic asymmetric iodolactonization

Article abstract of DOI:10.1039/c4cc02415j

A 3,3′-bis(aminoimino)BINOL ligand was newly designed and synthesized for the formation of a trinuclear Zn complex upon reaction with Zn(OAc) ₂. Using the harmony of the tri-zinc atoms, 1 mol% Zn ₃(OAc)₄-3,3′-bis(aminoimin

Full text of DOI:10.1039/c4cc02415j

Volume 50 Number 61 7 August 2014 Pages 8259–8430
ChemComm
Chemical Communications
www.rsc.org/chemcomm
ISSN 1359-7345
COMMUNICATION
Takayoshi Arai et al.
A trinuclear Zn (OAc) -3,3'-bis(aminoimino)binaphthoxide complex for
highly efficient3cataly4tic asymmetric iodolactonization

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
A trinuclear Zn3(OAc)4-3,30-bis(aminoimino)-
binaphthoxide complex for highly efficient
catalytic asymmetric iodolactonization†
Cite this: Chem. Commun., 2014,
50, 8287
Received 2nd April 2014,
Accepted 24th April 2014
Takayoshi Arai,*a Noriyuki Sugiyama,a Hyuma Masu,b Sayaka Kado,b
Shinnosuke Yabec and Masahiro Yamanakac
DOI: 10.1039/c4cc02415j
www.rsc.org/chemcomm
A 3,30-bis(aminoimino)BINOL ligand was newly designed and synthesized as in the production of biologically significant pharmaceutical
for the formation of a trinuclear Zn complex upon reaction with compounds and agricultural chemicals. Jacobsen pioneered an
Zn(OAc)2. Using the harmony of the tri-zinc atoms,
1 mol% organo-catalytic version of a useful asymmetric iodolactonization
Zn3(OAc)4-3,30-bis(aminoimino)binaphthoxide catalyzed asymmetric reaction using an urea catalyst.4 More recently, Johnston reported
iodolactonization in up to 99.9% ee.
an asymmetric iodolactonization catalyzed by a bis(amidine)
(BAM)-based Brønsted acid.5 Within the limited examples of
In nature, many metalloenzymes containing multiple metal centers metal-catalyzed asymmetric iodolactonization, Gao reported the
show remarkable catalytic activity not observed in non- or mono- use of a mononuclear Co-salen complex as a Lewis acid catalyst
metallic active sites. The multiple metal ions in the multinuclear for asymmetric iodolactonization.8,9 We have also reported an
metalloenzymes act cooperatively to produce maximum activity. asymmetric iodolactonization strategy using a newly developed
For example, phosphatidylcholine-preferring phospholipase C PyBidine(L1)-Ni(OAc)2 catalyst.10 The designer chiral ligands are
from Bacillus cereus (PC-PLCBc) catalyzes the hydrolysis of prepared to form a multinuclear metal catalyst for use in asymmetric
phospholipids. The active site of PC-PLCBc contains three Zn2+ iodolactonization, through the story described in Scheme 1.
ions, and the multiple zinc atoms are bridged by Asp122 and a
Based on the mononuclear L1–Ni(OAc)2 catalyst, the imidazolidine
water (or hydroxide) molecule.1 Employing multi-nuclear cooperative ligand L2, with a chiral BINOL-backbone, was designed for a dinuclear
effects also becomes an important concept for the design of artificial metal complex. 3,30-bis(imidazolidine)BINOL L2, prepared in situ by
‘‘catalysts’’,2 after pioneering works on the development of the condensation of monobenzyl (R,R)-diphenylethylenediamine with
lanthanide-containing heterobimetallic asymmetric catalysts.3 While (R)-3,30-formylbinaphthol, was applied to complex formation using
the bimetallic system in asymmetric catalyses has typically been 2 equiv. of metal acetate. In the asymmetric iodolactonization of
produced using the force of self-assembly, the rational design of
tri- or higher multinuclear complexes is still difficult even in
cutting-edge chemistry. Here, we report a designer multinuclear
metal catalyst for catalyzed asymmetric iodolactonization.
Iodolactonization,4–10 a type of halolactonization,11–13 represents
a powerful synthetic tool for generating iodine-functionalized cyclic
compounds in a single reaction. The resulting iodolactones are
both versatile and useful, and have applications as synthetic
intermediates in the total synthesis of natural products, as well
a Department of Chemistry, Graduate School of Science, Chiba University,
1-33 Yayoi, Inage-ku, Chiba, Japan. E-mail: tarai@faculty.chiba-u.jp;
Fax: +81 43 290 2889
b Center for Analytical Instrumentation, Chiba University, 1-33 Yayoi, Inage-ku,
Chiba, Japan
c Department of Chemistry, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku,
Tokyo, Japan
Scheme 1 The development of the chiral ligand of the multinuclear metal
catalyst for use in asymmetric iodolactonization, and preliminary results on
asymmetric iodolactonization using L1 and L2.
† Electronic supplementary information (ESI) available: Procedural and spectral
data. CCDC 956608. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c4cc02415j
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 8287--8290 | 8287

View Article Online
Communication
ChemComm
Table 1 The effect of the L3 :Zn(OAc)2 ratio and the analogs on catalytic
activity
5-phenylhex-5-enoic acid (1a), although the L2–Ni(OAc)2 1:2
complex gave iodolactone 2a with 41% ee, the L2–Zn(OAc)2 1:2
complex drastically improved the optical yield of 2a to 98% ee.
The diastereomeric 3,30-bis(imidazolidine)BINOL, derived from
(S,S)-diphenylethylenediamine with (R)-3,30-formylbinaphthol, gave
a 92% yield of 2a with 85% ee. The successful development of an
efficient asymmetric catalyst encouraged further study to determine
the structure of the L2–Zn(OAc)2 complex. The 1H-NMR study
revealed that both L2 and the L2–Zn(OAc)2 1:2 complex existed as
complex mixtures. The isolation of pure L2 required great effort, but
using the 1 : 2 Zn(OAc)2 catalyst with isolated L2 gave 2a with a
significantly lower selectivity of 62% ee compared to that obtained
using the catalyst generated in situ. The imidazolidine ring of L2
prepared in situ was hypothesized to be in equilibrium with the
opened aminoimino-form as shown in Scheme 2a, meaning that the
3,30-bis(aminoimino)BINOL is a promising candidate for providing
an effective Zn(OAc)2 catalyst.
Entry
Ligand
X (mol%)
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
L3
L3
L3
L4
L5
L6
1
2
3
3
2
1
2
2
2
2
24
24
19
64
69
9
34
Trace
99
99.6
99.6
68
89
––
To eliminate the cyclized imidazolidine from the equilibrium,
the 3,30-bis(tert-aminoimino)BINOL ligand (L3) in Scheme 2b was
redesigned. The newly designed L3 can capture two or three metals
in the flexible bis(aminoimino)binaphthol pocket.14 Reaction of
(R)-3,30-formylbinaphthol and (1R,2R)-2-(isoindolin-2-yl)-1,2-diphenyl-
ethan-1-amine (A)15 in ethanol proceeded smoothly at 80 1C to form
the imine, and a cold ethanol wash of the resulting precipitate gave
L3 as the sole product.16 The effect of changing the ratio of Zn(OAc)2
to L3 on catalyst performance was examined in Table 1. With an
L3 :Zn(OAc)2 ratio of 1 : 1 to 1 : 3, the iodolactone 2a was produced
with 99% ee (entries 1–3). However, stopping the reaction within 2 h
revealed that a 1 : 1 L3 :Zn(OAc)2 ratio resulted in a slower reaction
than using 1 : 2 or 1 : 3 ratios. The catalytic activity of several analogs
was also investigated in Table 1. The diastereomer of L3 (L4) only
gave 68% ee of 2a (entry 4). When one aminoimino functional group
was eliminated from L3, the L5–Zn(OAc)2 catalyst yielded a product
with 89% ee, although catalytic activity was significantly reduced
(entry 5). Removal of the axial chirality of the binaphthyl skeleton
resulted in a trace amount of 2a (entry 6). These results suggest that at
least one set of zinc atoms, existing at the appropriate position,
harmonizes cooperatively to produce iodolactones in a highly
enantioselective manner.
Table
2
Results for catalytic asymmetric iodolactonization using
a
L3–Zn3(OAc)4 catalyst
Entry
R1
R2
n
Time (h)
Yield (%)
ee (%)
1
C6H5
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
1
1
1
1
1
1
1
1
1
1
0
1
1
1
20
20
6
16
15
12
17.5
8
18
12
9
4
20
24
499
499
499
499
499
499
499
499
499
499
96
99.5
98
99.8
99.8
94
99.9
93
99.7
99.4
82
2a
3
p-BrC6H4
p-ClC6H4
p-FC6H4
p-CF3C6H4
p-MeC6H4
m-MeC6H4
o-MeC6H4
p-MeOC6H4
C6H5
4
5
6
7
8
9b
10
11c
12
13
14
87
99.3
94
c-C6H11
Me
C6H5
499
92
74
99
Results of investigations into the scope and generalization of
the catalytic asymmetric iodolactonization are shown in Table 2.
a
b
c
0.1 mol% catalyst was used. 5 mol% catalyst was used. The solvent
Using 1 mol% L3–Zn3(OAc)4 catalyst, a variety of 5-arylhex-5- was toluene : CH2Cl2 = 4 : 1.
enoic acid substrates were converted quantitatively to the corres-
ponding chiral gluconolactones with excellent enantioselectivity. For example, the p-trifluoromethyl-substituted compound was
obtained in 99.9% ee (entry 6). The relatively less reactive
substrate, having an o-substituent on the benzene ring, was used
with 5 mol% catalyst to give the product in 499% yield with
99.4% ee (entry 9). The reaction of 4-phenylpent-4-enoic acid gave
the g-butyrolactone with 87% ee (entry 11). 5-Cyclohexylhex-5-enoic
acid was also transformed successfully with 99.3% ee (entry 12). It
should be emphasized that only 0.1 mol% L3–Zn3(OAc)4 catalyst
gave 98% ee of 2a with a quantitative yield (entry 2).
For accessing the catalytic structure of the L3–Zn(OAc)2
complex, ESI-MS analysis of the catalyst solution suggested
Scheme 2 (a) The equilibrium of L2 between the imidazolidine and
aminoimino forms. (b) The design and synthesis of the 3,30-bis(tert-
aminoimino)BINOL ligand (L3).
the presence of a multi-nuclear zinc complex (Fig. 1). An ion
peak at m/z = 1028.3031 attributed to [L32–Zn3]2+ was observed,
8288 | Chem. Commun., 2014, 50, 8287--8290
This journal is ©The Royal Society of Chemistry 2014

View Article Online
ChemComm
Communication
Fig. 3 1H-NMR spectrum of the L3–Zn3(OAc)4 complex in toluene-d8
at ꢀ40 1C.
the central zinc and the end zinc atoms, which restricts the
conformation of the L3–Zn3 complex. The isolated crystalline
Zn3(OAc)4-3,30-bis(aminoimino)binaphthoxide produced a clean
1H-NMR spectrum at ꢀ40 1C (Fig. 3) and 1 mol% catalyst promoted
the asymmetric iodolactonization to give 2a with 99% ee.
Fig. 1 ESI-MS spectra of (a) L3 + Zn(OAc)2 (1 : 1), (b) L3 + Zn(OAc)2 (1 : 3),
and (c) L3–Zn3(OAc)4 + 1a (1 : 10).
Regarding the catalytic role of L3–Zn3(OAc)4, after mixing
L3–Zn3(OAc)4 and 10 equiv. of 1a, all acetoxy anions of L3–
Zn3(OAc)4 were replaced with 1a to give the ion peak at m/z =
1691.4724, corresponding to [L3–Zn3(CO2(CH2)3C(CH2)Ph)3]+
(Fig. 1c). This exchange suggests that the zinc-carboxylate of
1a is generated by the L3–Zn3(OAc)4 catalyst as a vital inter-
mediate in the highly enantioselective iodolactonization reac-
tion. However, two types of acetoxy anions were observed in the
1H-NMR spectrum of L3–Zn3(OAc)4, at 1.02 and 2.22 ppm. The
up-field peak was assigned by the DFT-GIAO calculation to the
outer acetoxy anions indicated in purple. Because the peak at
1.02 ppm becomes broader than the peak at 2.22 ppm, the
outer acetoxy anions would smoothly accept the exchange with
substrate 1a. Based on these experimental analyses on the
interaction of L3–Zn3(OAc)4 with 1a, a plausible transition state
for the L3–Zn3(OAc)4-catalyzed iodolactonization is proposed by
DFT computed molecular modeling (Fig. 4).17
The zinc-carboxylate of 1a is generated on the outer zinc
atom. In the cyclic transition state of the iodolactonization, the
benzene ring of 1a keeps away from the naphthyl ring of L3 to
avoid the steric repulsion observed in TS2 (the red curves in
Fig. 4). From the TS1 depicted in Fig. 4, the stereoselective
formation of (R)-iodolactone 2a is explained well. Because
multiple zinc atoms are important for getting high catalytic
even when mixing L3 and Zn(OAc)2 in a 1 : 1 ratio. When L3 and
Zn(OAc)2 were mixed in a 1 : 3 ratio, ESI-MS analysis showed a
new peak at m/z = 1301.2389, which suggested the formation of
a trinuclear zinc complex with L3.
A single crystal was obtained from the reaction of the 1 : 3
mixture of L3 and Zn(OAc)2 in methanol, and X-ray crystallographic
analysis revealed the structure of the complex to be trinuclear
Zn3(OAc)4-3,30-bis(aminoimino)binaphthoxide, as shown in Fig. 2.
In L3–Zn3(OAc)4, the two end zinc atoms make the complex
hexa-coordinated, and the central zinc atom is part of a tetrahedral
coordination sphere. For complex formation, one Zn(OAc)2 reacted
with L3 to give the central zinc binaphthoxide, and the two
remaining Zn(OAc)2 were coordinated, one at each end, by the
aminoimino functionality of L3. Alternatively, both end zinc atoms
formed a mixed acetoxy-binaphthoxide, and the central zinc
remained as Zn(OAc)2. Because X-ray crystallography and DFT
calculations of L3–Zn3(OAc)4 suggest s-bond characteristics of the
central zinc with phenolic oxygens, complex formation could
be explained via zinc-binaphenoxide [Zn–O: 1.949(3) or 1.962(3) Å].
In the L3–Zn3(OAc)4 complex, each of the acetoxy anions bridges
Fig. 2 X-ray crystallographic analysis of the trinuclear Zn3(OAc)4-3,30-
bis(aminoimino)binaphthoxide complex (L3–Zn3(OAc)4): (a) the side view,
and (b) the front view of the complex. Yellow and purple colored atoms are
coordinated acetyl carbons. Hydrogen atoms and solvent molecules are
omitted for clarity.
Fig. 4 A plausible transition state of L3–Zn3(OAc)4-catalyzed iodolacto-
nization: TS1 for (R)-iodolactone 2a, TS2 for (S)-2a.
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 8287--8290 | 8289

View Article Online
Communication
ChemComm
Chem. – Asian J., 2012, 7, 456; (e) S. E. Denmark, W. E. Kuester and
M. T. Burk, Angew. Chem., Int. Ed., 2012, 51, 10938.
activity as shown in Table 1, the central zinc atom would also
contribute to enhancing the zinc-carboxylate formation of 1a
and/or to accelerating the nucleophilic cyclization of the zinc-
carboxylate.
In conclusion, using a newly designed 3,30-bis(aminoimino)-
BINOL ligand, the trinuclear Zn3(OAc)4-3,30-bis(aminoimino)-
binaphthoxide complex (L3–Zn3(OAc)4) was prepared. The harmony
of the tri-Zn centers in L3–Zn3(OAc)4 showed outstanding catalytic
activity for the iodolactonization reaction to yield products in
quantitative yields with excellent enantioselectivity.18
This work was supported by a Grant-in Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology (Japan), by the Chiba University Iodine
Research Project and by the Workshop on Chirality in Chiba
University (WCCU).
12 Catalytic asymmetric bromolactonization: (a) K. Murai,
T. Matsushita, A. Nakamura, S. Fukushima, M. Shimura and
H. Fujioka, Angew. Chem., Int. Ed., 2010, 49, 9174; (b) K. Murai,
A. Nakamura, T. Matsushita, M. Shimura and H. Fujioka, Chem. –
Eur. J., 2012, 18, 8448; (c) D. H. Paull, C. Fang, J. R. Donald,
A. D. Pansick and S. F. Martin, J. Am. Chem. Soc., 2012,
134, 11128; (d) W. Zhang, S. Zheng, N. Liu, J. B. Werness,
I. A. Guzei and W. Tang, J. Am. Chem. Soc., 2010, 132, 3664;
(e) W. Zhang, N. Liu, C. M. Schienebeck, K. Decloux, S. Zheng,
J. B. Werness and W. Tang, Chem. – Eur. J., 2012, 18, 7296;
( f ) L. Zhou, C. K. Tan, X. Jiang, F. Chen and Y.-Y. Yeung, J. Am.
Chem. Soc., 2010, 132, 15474; (g) X. Jiang, C. K. Tan, L. Zhou and
Y.-Y. Yeung, Angew. Chem., Int. Ed., 2012, 51, 7771; (h) C. K. Tan,
L. Zhou and Y.-Y. Yeung, Org. Lett., 2011, 13, 2738; (i) H. J. Lee and
D. Y. Kim, Tetrahedron Lett., 2012, 53, 6984; ( j) C. K. Tan, C. Le and
Y.-Y. Yeung, Chem. Commun., 2012, 48, 5793.
13 Catalytic asymmetric chlorolactonization: (a) D. C. Whitehead,
R. Yousefi, A. Jaganathan and B. Borhan, J. Am. Chem. Soc., 2010,
132, 3298; (b) R. Yousefi, D. C. Whitehead, J. M. Mueller, R. J. Staples
and B. Borhan, Org. Lett., 2011, 13, 608; (c) and also see, ref. 12e.
14 Selected examples of multinuclear metal catalysts: (a) N. Kumagai,
S. Matsunaga, T. Kinoshita, S. Harada, S. Okada, S. Sakamoto,
K. Yamaguchi and M. Shibasaki, J. Am. Chem. Soc., 2003,
125, 2169; (b) B. M. Trost, H. Ito and E. R. Silcoff, J. Am. Chem.
Soc., 2001, 123, 3367; (c) Y. Xiao, Z. Wang and K. Ding, Chem. – Eur.
J., 2005, 11, 3668; (d) B. Y. Lee, H. Y. Kwon, S. Y. Lee, S. J. Na, S. Han,
H. Yun, H. Lee and Y.-W. Park, J. Am. Chem. Soc., 2005, 127, 3031;
(e) T. Ohshima, T. Iwasaki and K. Mashima, Chem. Commun., 2006,
2711; ( f ) R. M. Thomas, P. C. B. Widger, S. M. Ahmed, R. C. Jeske,
W. Hirahata, E. B. Lobkovsky and G. W. Coates, J. Am. Chem. Soc.,
2010, 132, 16520; (g) S. Takizawa, T. Katayama and H. Sasai, Chem.
Commun., 2008, 4113; (h) N. V. Kaminskaia, B. Spingler and
S. J. Lippard, J. Am. Chem. Soc., 2000, 122, 6411.
Notes and references
1 E. Hough, L. K. Hansen, B. Birknes, K. Jynge, S. Hansen, A. Hordvik,
C. Little, E. Dodson and Z. Derewenda, Nature, 1989, 338, 357.
2 Multimetallic Catalysts in Organic Synthesis, ed. M. Shibasaki and
Y. Yamamoto, Wiley-VCH, Weinheim, 2004.
3 M. Shibasaki, H. Sasai and T. Arai, Angew. Chem., Int. Ed. Engl., 1997,
36, 1236.
4 G. E. Veitch and E. N. Jacobsen, Angew. Chem., Int. Ed., 2010, 49, 7332.
5 M. C. Dobish and J. N. Johnston, J. Am. Chem. Soc., 2012, 134, 6068.
6 J. E. Tungen, J. M. J. Nolsøe and T. V. Hansen, Org. Lett., 2012,
14, 5884.
7 C. Fang, D. H. Paull, J. C. Hethcox, C. R. Shugrue and S. F. Martin,
Org. Lett., 2012, 14, 6290.
8 Z. Ning, R. Jin, J. Ding and L. Gao, Synlett, 2009, 2291.
15 T. Arai, M. Watanabe and A. Yanagisawa, Org. Lett., 2007, 9, 3595.
16 B. Saito and T. Katsuki, Angew. Chem., Int. Ed., 2005, 44, 4600.
9 L. Filippova, Y. Stenstrfm and T. V. Hansen, Tetrahedron Lett., 2014, 17 The transition structure was partially optimized with the B3LYP
55, 419.
method using 631LAN basis set consisting of LANL2DZ for Zn and
6-31G* for the rest. The L3–Zn3(OAc)3 moiety was only fully optimized
while the iodolactone 2a was frozen at the transition structure model
of the Zn cation catalyzed iodolactonization.
10 T. Arai, S. Kajikawa and E. Matsumura, Synlett, 2013, 2045.
11 Recent reviews on catalytic asymmetric halocyclization: (a) G. F. Chen
and S. M. Ma, Angew. Chem., Int. Ed., 2010, 49, 8306; (b) A. Castellanos
and S. P. Fletcher, Chem. – Eur. J., 2011, 17, 5766; (c) C. K. Tan, 18 H. Nakatsuji, Y. Sawamura, A. Sakakura and K. Ishihara, Angew.
L. Zhou and Y.-Y. Yeung, Synlett, 2011, 1335; (d) U. Hennecke, Chem., Int. Ed., DOI: 10.1002/anie.201400946.
8290 | Chem. Commun., 2014, 50, 8287--8290
This journal is ©The Royal Society of Chemistry 2014