Catalytic Asymmetric Iodoesterification of Simple Alkenes

Article abstract of DOI:10.1002/anie.202003886

Catalytic asymmetric iodoesterification of simple alkenes was achieved using a dinuclear zinc-3,3′-(R,S,S)-bis(aminoimino)binaphthoxide (di-Zn) complex. For iodoesterification using p-methoxybenzoic acid, the N-iodonaphthalenimide (NIN)-I₂ system was effective for producing iodoesters in a highly enantioselective manner. The synthetic utility of chiral iodo-p-methoxybenzoates was also demonstrated. The quartet of metal ionic bond, hydrogen bond, halogen bond, and π-π stacking is harmonized on the single reaction sphere of di-Zn catalyst for enabling the highly enantioselective catalytic asymmetric iodoesterification of simple alkenes for the first time.

Full text of DOI:10.1002/anie.202003886

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Accepted Article
Title: Catalytic Asymmetric Iodoesterification of Simple Alkenes
Authors: Takayoshi Arai, Kodai Horigane, Takumi K. Suzuki, Ryosuke
Itoh, and Masahiro Yamanaka
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202003886
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10.1002/anie.202003886
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Catalytic Asymmetric Iodoesterification of Simple Alkenes
Takayoshi Arai,*[a] Kodai Horigane,[a] Takumi K. Suzuki,[a] Ryosuke Itoh,[b] and Masahiro Yamanaka[b]
[a]
Prof. Dr. T. Arai, Mr. K. Horigane, Mr. T. K. Suzuki
Soft Molecular Activation Research Center (SMARC), Chiba Iodine Research Innovation Center (CIRIC), Molecular Chirality Research Center (MCRC),
and Department of Chemistry, Graduate School of Science
Chiba University
1-33 Yayoi, Inage, Chiba 263-8522, Japan
E-mail:
[b]
Mr. R. Itoh, Prof. Dr. M. Yamanaka
Department of Chemistry, and Research Center for Smart Molecules
Rikkyo University
3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8588, Japan
Supporting information for this article is given via a link at the end of the document
Abstract: Catalytic asymmetric iodoesterification of simple alkenes
Among the limited numbers of catalytic asymmetric
haloesterifications, Z. Tang and X. Zhang pioneered the
asymmetric bromoesterification of cyclic alkenes using chiral
phosphoric acid catalyst.[8] In the further study on the
was
bis(aminoimino)binaphthoxide
iodoesterification using
achieved
using
a
dinuclear
zinc-3,3’-(R,S,S)-
(di-Zn)
complex.
acid,
For
p-methoxybenzoic
the
N-
iodonaphthalenimide (NIN)-I2 system was effective for producing
iodoesters in a highly enantioselective manner. The synthetic utility
of the chiral iodo-p-methoxybenzoates was also demonstrated. The
quartet of metal ionic bond, hydrogen bond, halogen bond, and -
stacking is harmonized on the single reaction sphere of di-Zn
catalyst for enabling the highly enantioselective catalytic asymmetric
iodoesterification of simple alkenes in the first time.
haloesterifications,
(DHQD)2PHAL
(hydroquinidine
1,4-
phthalazinediyl diether) has been used as the organocatalyst. W.
Tang reported the (DHQD)2PHAL-(+)-CSA catalyst system for
the bromoesterification of allylic sulfonamides.[9] Y. Shi applied
the (DHQD)2PHAL catalyst for the bromoesterification of cyclic
alkenes.[10] In the paper, two examples of styrene derivatives
were examined to give the products in moderate enantiomeric
excesses. In 2015, Borhan also reported haloesterification of
allylic amides using (DHQD)2PHAL catalyst.[11] However, no
successful example of catalytic asymmetric haloesterification of
non-functionalized simple alkenes has been reported. A process
for catalytic asymmetric haloesterification of standard styrene
substrates was highly demanded. In 2014, highly efficient
catalytic asymmetric iodolactonization was developed using a
Halofunctionalization of alkenes using heteroatom nucleophiles
is important reactions for accessing novel sp3 stereogenic
centers together with the introduction of halo- and hetero-atom
functionalities in a single operation.[1] The fascination of the
halonium ion-mediated activations of alkenes has been also
documented as a powerful strategy for furnishing a ring-forming
reaction.[2] Among the wide range of halocyclizations,[3] the
3,3’-(R,R,R)-bis(aminoimino)binaphthol
Zn(OAc)2 (Scheme 1).[4i]
ligand
(L1)
and
intramolecular
iodo-,[4]
bromo-,[5]
chloro-,[6]
and
fluorolactonizations[7] have been well-studied in the catalytic
asymmetric manner. On the contrary, the intermolecular
“haloesterification” was hard to be conducted. Although the
haloesterification using easily obtainable alkenes and carboxylic
acids has a clear industrial advantage compared with the
intramolecular halolactonization requiring the preparation of
alkenoic acid substrates, the successful examples of catalytic
asymmetric haloesterification is limited due to the difficulty of
controlling the intermolecular reaction.
Scheme 1. Trinuclear Zn3(OAc)4-3,3’-bis(aminoimino)binaphthoxide (tri-Zn)
catalyzed asymmetric iodolactonization.
Recently, a detailed reaction mechanism of the tri-Zn-catalyzed
halolactonization was elucidated.[4k] In the reaction, carboxylic
acid substrates are converted to zinc carboxylates on the tri-Zn
complex, and the N-iodosuccinimide (NIS) is activated by
hydrogen bonding with the diamine unit of chiral ligand. The
catalytic amount of I2 mediates the alkene portion of the
substrates and NIS by forming a halogen bonding network.
Because the tri-Zn catalyst cooperatively manages the position
and reactivity of both the alkene unit and carboxylic acid, the
intermolecular haloesterification would also be catalyzed
effectively by the zinc complex.
Figure 1. From catalytic asymmetric iodolactonization to iodoesterification.
1
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10.1002/anie.202003886
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An efficient catalyst for the iodoesterification of -methyl styrene
(1a) was explored in Table 1.
methoxybenzoylation
of
-methylstyrene,
N-
iodonaphthalenimide (NIN) efficiently improved chemical yield
and enantioselectivity with up to 70% ee (entry 7), and the
reaction proceeded using 1.1 equiv of acid to the -
methylstyrene (entry 8). Interestingly, the catalyst prepared
Table 1. Exploration of catalyst for iodoesterification of -methylstyrene (1a)
using
improved the enantiomeric excess of 3c. However, even when
complexation was conducted using ratio of 1:3 for
3,3’-(R,S,S)-bis(aminoimino)binaphthol
ligand
(L2)
a
L2:Zn(O2CC6H4-p-OMe)2, a significant amount of dinuclear
complex (di-Zn) was suggested by ESI-MS analysis (see the
Supporting Information). The catalyst prepared in a 1:2 ratio
provided the best performance and gave 3c in 99% yield with
85% ee (entry 10).
Purification of the Zn(O2CC6H4-p-OMe)2-derived di-Zn complex
was difficult. Among the zinc carboxylates we examined,
although highly selective formation of the dinuclear complex was
achieved using Zn(O2CCH2C6H4-p-Me)2 (see the Supporting
Information), iodoesterification using p-MeC6H4CH2CO2H (2d)
resulted in low asymmetric induction of 3d with 25% ee (entry
12). When the Zn(O2CCH2C6H4-p-Me)2-derived di-Zn complex
was used for the iodo-p-methoxybezoylation of -methyl styrene,
the product 3c was obtained with 74% ee along with the
contaminated 3d. The simplicity of the experimental procedure
along with the prevention of contamination of 3c with 3d
indicated that the method used for entry 10 with Zn(O2CC6H4-p-
OMe)2-derived di-Zn complex was the best protocol. The mono-
nuclear zinc complex showed low catalytic activity (entry 11),
and the zinc salt without a ligand did not promote the reaction.
These features contribute to reliable high-level asymmetric
induction for iodoesterification using the Zn(O2CC6H4-p-OMe)2-
derived di-Zn catalyst prepared in situ. The requirement of I2 for
achieving high catalyst activity (entry 13) suggests the
cooperation of hydrogen bonding and halogen bonding with zinc
carboxylate would work also in the di-Zn-catalyzed
iodoesterification similar to Figure 2.
entry
L
3
L:Zn
I+ source
yield
(%)
ee
(%)
1
L1
L1
L1
L1
L1
L1
L1
L1
L2
L2
L2
L2
L2
3a
3b
3c
3c
3c
3c
3c
3c
3c
3c
3c
3d
3c
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:2
1:1
1:2
1:2
NIS
NIS
NIS
DIH
NISac
NIP
NIN
NIN
NIN
NIN
NIN
NIN
NIN
35
93
58
94
4
rac
25
56
61
4
2
3
4
Under optimal conditions, the scope and generality of the
5
Zn(O2CC6H4-p-OMe)2-derived
di-Zn-catalyzed
asymmetric
iodoesterification were examined in Scheme 2. The use of -
ethylstyrene resulted in product with up to 90% ee. For
heteroaromatic substrates, 3-isoproenylthiophene was smoothly
converted to the iodoester 3o in 99% yield with 90% ee. When
the Zn(O2CCH2C6H4-p-Me)2-derived di-Zn catalyst was applied
to iodoesterification using benzoic acids, 3p and 3q were
obtained with 65% ee and 72% ee, respectively. In the same
protocol, iodoesterification using cinnamic acid was achieved to
give 3r in 92% yield with 74% ee. Not only the -alkylstyrenes,
3s was obtained with 54% ee from a cyclic alkene, and 3t was
obtained with 68% ee from 1,1-dialkylalkene substrate.
6
86
91
99
97
99
88
56
2
49
70
67
79
85
83
25
87
7
8[a]
9[a]
10[a]
11[a]
12[a]
13[b]
[a] Reaction was conducted using 1.1 eq. of 2. [b] Reaction was examined
without I2.
When the original tri-Zn catalyst prepared from Zn(OAc)2 was
applied to the reaction of -methylstyrene with 2.0 equiv of
acetic acid (2a), the racemic iodoacetate product 3a was
obtained in 35% yield (Table 1, entry 1). The tri-Zn analog
prepared from Zn(OBz)2 promoted iodoesterification using
benzoic acid to give the iodobenzoate (3b) in 93% yield with
25% ee (entry 2). The p-methoxybenzoate version improved
selectivity
with
56%
ee
(entry
3).
For
iodo-p-
2
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Using a 1,4-bispropenylbenzene (4), double iodoesterification
proceeded smoothly to achieve up to 99% ee. In the double
iodoesterification, the di-Zn catalysts prepared from the other
carboxylic acids could function well. For example, reaction using
benzoic acid gave 5c with 96% ee.
The synthetic utility of the chiral iodoesters was demonstrated in
Scheme 4. Starting from 3l with 80% ee, after reduction of the
ester moiety using DIBAL-H, the resulting iodohydrin was
transformed further by K2CO3 to give the epoxide 6 with 78% ee
(Scheme 4a). From a comparison of the optical rotation of 6 with
the reported value,[13] the absolute configuration of iodoester 3l
obtained
using
the
dinuclear
zinc
(R,S,S)-
bis(aminoimino)binaphthoxide (di-Zn) catalyst was (S)-enriched.
Table 1 and Schemes 2–4 describe the absolute configuration of
the iodoesters by analogy. Direct treatment of 3i (82% ee) with
K2CO3 in DMF gave hydroxyester 7 in 83% yield (Scheme 4b).
The generation of 7 occurs via intramolecular cyclization of 3i,
followed by hydrolysis of the 1,3-dioxolium intermediate (int),
which was stabilized by the methoxy functionality. When NaN3
was used under similar conditions, nucleophilic addition reaction
of azide to the same intermediate occurred to give the chiral
azide 8 in 71% yield.[14]
Scheme 2. The di-Zn-catalyzed asymmetric iodoesterification.
To improve the enantiomeric excess of the iodoesters, a meso-
trick approach[12] was efficient (Scheme 3).
Scheme 4. Synthetic utility of chiral iodoesters.
The
bis(aminoimino)binaphthol ligand (L2) derived di-Zn-catalyzed
iodoesterification is proposed in Figure 2. Based on
reaction
mechanism
of
the
3,3’-(R,S,S)-
a
preliminary modeling study (see the Supporting Information) and
our previously reported transition state (TS) model in the tri-Zn-
catalyzed iodolactonization,[4k] we proposed a TS model of
concerted C-I/C-O bond formation including generation of the
zinc-carboxylate and formation of NIN-I2 complex via a halogen
bonding. In the major TS model (Figure 2a), the -methylstyrene
would be in the catalyst pocket from the CH2-functionality as a
Scheme 3. The di-Zn-catalyzed double iodoesterification.
3
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Figure 2. Presumed transition state model of di-Zn-catalyzed iodoesterification.
a) major TS. b) minor TS. (Zn: green, I: purple, N: blue, O: red, H: white. For
carbons, ligand: gray, substrate: light blue, NIN: pink, Nucleophilic carboxylate:
orange, Carboxylate stacking with NIN: yellow.)
For the major TS in Figure 2a, NIN shows a - stacking with
another zinc carboxylate (highlighted with yellow), and forms
hydrogen bonding network with the isoindoline of the chiral
ligand and the phenyl substituent of -methylstyrene. The p-
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would be helpful for avoiding the confusion caused by the
scrambling interaction of NIN with the other carboxylates.
In conclusion, the catalytic asymmetric iodoesterification of
simple alkenes was achieved using a newly identified dinuclear
zinc-3,3’-(R,S,S)-bis(aminoimino)binaphthoxide (di-Zn) complex.
This iodoesterification reaction provides a powerful synthetic tool
for producing valuable compounds from the easily obtainable
inexpensive alkenes.
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Acknowledgements
This research is supported by JSPS KAKENHI Grant Number
19H02709 in Grant-in-Aid for Scientific Research (B),
JP16H01004 and JP18H04237 in Precisely Designed Catalysts
with Customized Scaffolding, and 17KT0011 in Development of
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Keywords: haloesterification• metal catalyst• asymmetry•
halogen bonding• hydrogen bonding• - stacking
4
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Entry for the Table of Contents
A basis of organic chemistry is supplying valuable compounds from easily obtainable inexpensive materials. A dinuclear zinc-3,3’-(R,S,S)-
bis(aminoimino)binaphthoxide (di-Zn) complex enabled a first successful and general catalytic asymmetric iodoesterification of the simple
alkenes. The integrated fundamental forces of metal ionic bond, hydrogen bond, halogen bond, and - stacking play a quartet on the single
reaction sphere of di-Zn catalyst.
5
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