Synthesis of seven-membered lactones by regioselective and stereoselective iodolactonization of electron-deficient olefins

Article abstract of DOI:10.1039/c9cc10080f

A regio- A nd stereoselective iodolactonization of internal electron-deficient olefinic acids has been reported, which provides a straightforward access to a series of multi-functionalized seven-membered lactones containing two consecutive chiral centers. The ester substituents on the olefins played a key role in achieving high regioselectivity. This result was proved through experiments and DFT calculations.

Full text of DOI:10.1039/c9cc10080f

View Article Online
View Journal
ChemComm
Chemical Communications
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: P. Tang, L. Wang,
Y. Shao, Y. Wei, M. Li, N. Zhang, X. Luo, Z. Ke, Y. Liu and M. Zeng, Chem. Commun., 2020, DOI:
1
0.1039/C9CC10080F.
Volume 54
Number
January 2018
Pages 1-112
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
1
4
ChemComm
Chemical Communications
rsc.li/chemcomm
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
S. J. Connon, M. O. Senge et al.
Conformational control of nonplanar free base porphyrins:
towards bifunctional catalysts of tunable basicity
rsc.li/chemcomm

Page 1 of 5
Please d oC hn eo mt Ca do mj u ms t margins
View Article Online
DOI: 10.1039/C9CC10080F
Journal Name
COMMUNICATION
Synthesis of seven-membered lactones by regioselective and
stereoselective iodolactonization of electron-deficient olefins
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
b
a
a
a
Pan-Ting Tang, Liang-Neng Wang, You-Xiang Shao, Yi Wei, Ming Li, Ni-Juan Zhang, Xiao-Peng
a
b
a
a,c
Luo, Zhuofeng Ke, Yue-Jin Liu* and Ming-Hua Zeng*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A regio- and stereoselective iodolactonization of internal eletron- high efficiency. Thus, highly efficient and economical method
deficient olefinic acid has been reported, which provides a to prepare seven-membered lactones is in high demand.
straightforward access to a series of multi-functionalized seven-
a) Previous work on halolactonization reaction of terminal olefins
membered lactones containing consecutive two chiral centers. The
Rousseau, Yeung, and Kumar groups
O
ester substituents on olefins played key role in achieving high
regional selectivity. This result was proved through the
experiments and DFT calculation.
CO H
2
organic catalyst
X' source
X'
O
X

X' = C or O; X = Br or I
X
b) Challenges for internal olefins
Lactones are ubiquitous frameworks in a variety of natural
products and drug molecules. Among them, seven-membered
O
O
regioselectivity and stereoselectivity
1
O

O

X source


lactone has a special medium-ring structure and exhibits
numerous biological activities such as antitumor activity,
CO2H
+

R
R
R
exo
endo X
X
2
tyrosine kinase inhibitor and cytotoxic activity. In the light of
O
O
only three examples in Rousseau's work
this fact, there is a fundamental need for the development of
efficient methods to construct seven-membered lactone motif.
Traditional method for the synthesis of seven-member lactone
O
O
O
CO2H
X source
O
Me
+
Me

O


Me
low regioselectivity (exo/endo = 1:1)
3
4
I
via hydration reaction, Tishchenko reaction and oxidative
exo I
c) Seven-membered iodolactonization of internal alkenes
endo
5
lactonization of diols has been well-developed. High-dilution
O
and slow addition techniques are usually employed to avoid
intermolecular side reactions. However, various condensation
reagents and metal compounds are essential for high
efficiency. Moreover, most of these approaches are limited to
symmetrical substrates to avoid the chemical selectivity, which
lack of diversity in product structure. Recently, Shi et al.
reported a novel method for the preparation of seven-
membered lactones from benzoic acids and benzyl thioethers
via rhodium-catalyzed double C-H activation, which allows to
access to a series of seven-membered lactones with different
CO H
I
source
2
O

CO2R
this work

CO R
Ar
2
Ar
I
high regioselectivity (exo/endo > 20:1); high stereoselectivity (dr > 20:1)
Scheme 1 Approaches to access seven-membered lactones.
Halolactonization of olefin represents an important class of
reactions for the construction of lactones with halogen
functional group. Although great achievements have been
made on the synthesis of small halolactones, i.e. five- and six-
membered lactones, few methods have been developed for
7
6
functional groups. Unfortunately, harsh reaction conditions,
8
expensive rhodium catalyst and silver oxidant are required for
9
1
0
the synthesis of seven-membered lactone. Early in 1995,
Rousseau et al. disclosed a pioneering work on the synthesis of
a. Hubei Collaborative Innovation Center for Advanced Chemical Materials, Ministry
of Education Key Laboratory for the Synthesis and Application of Organic seven-membered lactone, in which oxygen-containing
Functional Molecules, and College of Chemistry and Chemical Engineering, Hubei
University, Wuhan, 430062, China. E-mail: liuyuejin@hubu.edu.cn
School of Materials Science and Engineering, PCFM Lab, Sun Yat-sen University,
Guangzhou 510275, China. E-mail: kezhf3@mail.sysu.edu.cn.
Department Key Laboratory for the Chemistry and Molecular Engineering of
Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi
Normal University, Guilin, 541004, China. E-mail: zmh@mailbox.gxnu.edu.cn
Footnotes relating to the title and/or authors should appear here. Electronic
10a
unsaturated acids were utilized as substrates (Scheme 1a).
b.
c.
In 2012, Yeung group reported a general and efficient
organicsulfur-catalyzed halolactonization reaction to prepare
the seven-membered lactones from long-chain olefinic acids
1
0e
(Scheme 1a).
Then, Kumar et al. developed an
†
organoselenium and DMAP co-catalyzed synthesis of seven-
Supplementary Information (ESI) available.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please d oC hn eo mt Ca do mj u ms t margins
Page 2 of 5
COMMUNICATION
Journal Name
membered lactones from unactivated alkenes.10g Despite reaction was obtained in 40% yield with high reVgieiowsAertlieclcetOivnliitnye
these advances, these reactions are limited to the terminal (exo/endo = 20:1) and low stereoselectivDiOtyI: (1d0.r10=391/.C39:1C)C1(T00a8b0leF
and electron-rich olefins. Moreover, these methods are not 1, entry 1). The structure of 2a was determined by single-
1
1
suitable for the synthesis of complex seven-membered crystal X-ray diffraction. Based on this encouraging finding, a
lactones with consecutive two chiral carbon centers. Only series of bases were screened (entries 2-8). Although most of
t
three substrates have been reported in Rousseau’s work, but bases had a promoting effect on the reaction, NaO Bu showed
poor regioselectivity were obtained (exo:endo = 1:1), giving a the highest activity, giving the product 2a in 58% yield and an
mixture of seven-membered and eight-membered products improved stereoselectivity (dr = 4:1) (entry 8). To further
Scheme 1b).1 Thus, developing novel methods for the enhance the stereoselectivity, we next investigated the
0a
(
synthesis of complex seven-membered lactones from internal reaction temperature (entries 10-12). When the reaction was
alkenes via halolactonization reaction is urgent but challenging conducted at room temperature, the diastereoselectivity of
(Scheme 1b). We envision that the incorporation of electron- reaction could be raised up to 18:1. However, the yield of
withdrawing group to olefin may promote the regioselectivity seven-membered lactone 2a was moderate. Finally, when N-
of the halolactonization reaction due to the different electron Iodosuccinimide (NIS) was used as iodinating reagent instead
density of the double bond. Herein, we present a general and of I , the yield of 2a could be imporved to 90% with high
2
efficient protocol for the construction of seven-membered stereoselectivity (dr > 20:1) and regioselectivity (exo/endo >
lactones with two chiral carbon centers from ester-substituted 20:1) (entry 13). The iodolactonization reaction could proceed
internal olefins via regioselective and stereoselective smoothly under argon atmosphere (entry 14). Weak base such
iodolactonization reaction (Scheme 1c).
as KHCO
5). The reaction afforded a low yield with 1.5 eq. of NIS and
no product was observed in the absence of NIS (entries 16-17).
3
could promote the reaction, giving a low yield (entry
1
Table 1 Optimization of the reaction conditionsa
O
O
O
Ar'
O
COOH
CO2Me
Ar'
I
reagent
base
O
+
NIS (3 equiv)
NaO Bu(1 equiv)
CO H
2
t
O
CO2Me
2
CO Me
MeCN, T(°C)
CO2R
I
I
MeCN, rt, air
Ar
CO2R
1a
2a exo
endo
2a CCDC 1918655
Ar
I
Entry
Base
I
reagent
T/°C
Yield of 2a
dr of 2a
exo/endo
20:1
1
2 (exo/endo > 20:1)
1
2
3
4
5
6
K2CO3
I2
I2
I2
I2
I2
I2
100
40%
1.3:1
1.7:1
2:1
O
O
2b, R = Et, 81%, dr > 20:1
c, R = nBu, 78%, dr > 20:1
2d, R = Bn, 73%, dr > 20:1
Cs2CO3
Li2CO3
KHCO3
KHSO4
K2HPO4
KOH
100
100
100
100
100
57%
65%
13%
51%
56%
> 20:1
> 20:1
13:1
2
O
O
O
O
i
2
2
f, R = Bu, 81%, dr > 20:1
g, R = Ph, 80%, dr > 20:1
CO2R
3:1
O
I
I
2
e, 85%, dr > 20:1
4:1
17:1
2
2
h, R' = 2-MOM, 41%, dr > 20:1
i, R' = 2-Me, 75%, dr > 20:1
2:1
18:1
O
2j, R' = 2-Cl, 71%, dr > 20:1
k, R' = 3-Me, 76%, dr > 20:1
2l, R' = 3,5-diMe, 93%, dr > 20:1
m, R' = 4-MeO, 83%, dr > 20:1
2n, R' = 4-F, 82%, dr > 20:1
o, R' = 4-CF3, 64%,dr > 20:1
7
8
9
I2
I2
I2
100
100
100
42%
58%
11%
1:1
4:1
1:1
> 20:1
19:1
6:1
2
t
O
NaO Bu
2
R'
CO2Me
none
2
i CCDC 1944537
2
I
10
11
12
NaO Bu
t
I2
I2
80
60
rt
63%
65%
70%
90%
10:1
15:1
13:1
14:1
t
NaO Bu
O
2p, R'' = H, 62%, dr > 20:1
q, R'' = 4-Cl, 52%, dr > 20:1
R''
2
t
I2
18:1
14:1
NaO Bu
O
2r, R'' = 3-Me, 70%, dr > 20:1
2s, R = 3-F, 62%, dr > 20:1
1
3b
NaO Bu
t
NIS
rt
> 20:1
> 20:1
CO2Me
2t, R = 3,4-diF, 83%, dr > 20:1
4c
t
2n CCDC 1973726
1
NaO Bu
NIS
NIS
rt
rt
88%
76%
> 20:1
> 20:1
> 20:1
> 20:1
I
15
KHCO3
Scheme 2 Synthesis of dibenzooxepinones. 1 (0.15 mmol),
NaO Bu (0.15 mmol), NIS (0.45 mmol), in 0.5 mL of MeCN at
6d
NaO Bu
t
NIS
---
rt
rt
81%
0%
> 20:1
---
> 20:1
---
1
t
17
NaO Bu
t
room temperature under air, 12 h, isolated yield.
aReaction conditions: 1a (0.1 mmol), base (1.0 eq.) iodine
reagent (3.0 eq.), in 0.5 mL of MeCN at room temperature
under air, 12 h. Yield, dr and exo/endo were determined by H
With the optimal conditions in hand, we next investigated
the generality of this protocol for the synthesis of
dibenzooxepinones and a range of multi-functionalized and
iododibenzooxepinones were synthesized with high
regioselectivity (exo/endo > 20:1) and stereoselectivity (dr >
1
b
c
d
NMR analysis. Isolated yield. In Ar condition. 1.5 eq. of NIS. Dr
=
diastereoselectivity.
Initially, we selected (E)-2'-(3-methoxy-3-oxoprop-1-en-1-
yl)-[1,1'-biphenyl]-2-carboxylic acid 1a as the model substrate
2
0:1) for the first time (Scheme 2). Olefins with various ester
groups such as, alkyl ester (2b-f) and aryl ester (2g) could give
the desired products in high yields (73-81%). Notably, ether
group is compatible in the reaction and gave the desired
product 2e in high yield. Substrates with electron-donating and
electron-withdrawing group on the biaryl motif could proceed
smoothly, generating the corresponding dibenzooxepinone
as the seven-membered lactone product belongs to an
2
important motif in natural products and bioactive molecules.
When the substrate 1a was treated with 3 equiv of I
equiv of K CO at 100°C under air condition in MeCN for 12 h,
the desired seven-membered lactone 2a via exo-cyclization
2
and 1
2
3
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 5
Please d oC hn eo mt Ca do mj u ms t margins
Journal Name
COMMUNICATION
products in moderate to excellent yields (2h-2o, 41-93%). The 4a). Furthermore, the iodolactone product 2a couVlidewbAerticfluerOtnhliener
substituents at ortho, meta, and para-position of the bottom converted into other seven-memberedDOlIa: 1c0t.o10n3e9/Cd9eCrCiv1a0t0iv8e0Fs
phenyl ring were all tolerated, even the ortho MOM- through deiodination reaction and allylation reaction (Scheme
substituted substrate 2h afforded the desired product in an 4b). Notably, the allylation reaction of 2a via radical process
acceptable yield. Moreover, substrates with naphthyl group had high stereoselectivity, giving the allylation product 2ab
were also suitable the reaction, providing the desired products with configuration retention, which may provide a significant
in moderate to good yields (2p-2t). The structures of 2e, 2i, 2n method for the synthesis of optically pure seven-membered
1
1
and 2o were characterized by X-ray crystallographic analyses.
lactones.
This protocol provides a powerful tool for the synthesis multi-
substituent benzooxepinones.
a) Gram scale reaction
O
O
O
t
CO2H
2
NaO Bu (1 equiv)
Ar
Ar
CO2H
CO2R
NIS (3 equiv)
NaOtBu (1 equiv)
CO Me
O
I
NIS (3 equiv)
MeCN, rt, 10 h
2
CO Me
Ar
Ar
CO2R
I
MeCN, rt, air
3
4
1a, 3 mmol
2a, 1.22 g, 85%
O
O
O
b) Diversification of product
O
Ph
Ph
Ph
Ph
O
O
O
O
O
Me
Bn
Et
3
Bu SnH
allySnBu3
AIBN
O
O
O
2a
I
I
AIBN
CO2Me
CO2Me
4
a, 78%, dr > 20:1
4a CCDC 1944536
4b, 62%, dr > 20:1
O
O
O
Me
O
Ph
Ph
Ph
2ac, 84%
2ab, 50%
O
O
O
O
O
O
nBu
Scheme 4 Synthetic application
O
O
O
I
I
I
4
c, 66%, dr > 20:1
4d, 93%, dr > 20:1
4e, 94%, dr > 20:1
Me
To evaluate the substituent effect of olefin on the
regioselectivity of iodolactonization reaction, olefins with
different functional groups, such as alkyl and aryl substituent
were subjected to the standard reaction conditions (Scheme
O
O
O
O
O
O
O
O
O
Me
iBu
O
Ph
O
O
I
I
I
Me
5
a). As expected, the alkyl-substituted substrate 1u gave a low
4
f, 96%, dr > 20:1
4g, 36%, dr > 20:1
4h, 89%, dr > 20:1
O
O
O
yield (73%) and regioselectivity (exo/endo = 6:1), while the
aryl-substituted olefin 1v could not generate the seven-
membered iodolactone product. Although substrate with
sulfonyl substituent 1w could react under reaction conditions,
it gave a low yield and regioselectivity. These experimental
results proved that the ester group played a significant role in
controlling the regioselectivity of iodolactonization reaction.
Me
Cl
CO2Me
F3C
CO2Me
O
O
O
CO2Me
I
I
I
Me
Cl
CF3
4k, 83%, dr > 20:1
4
i, 50%, dr > 20:1
4j, 96%, dr > 20:1
Scheme 3 Synthesis of α, β-unsaturated seven-membered
lactones. Reaction conditions: 3 (0.15 mmol), NIS (0.45 mmol),
t
a) Evaluate substituent effect on the regioselectivity
O
NaO Bu (0.15 mmol) in 0.5 mL of MeCN at room temperature
under air, 12 h, isolated yields.
2
a, R = MeO2C, 90% (exo:endo > 20:1,)
2u, R = nPr, 73% (exo:endo = 6:1)
2v
R
CO2H
standard
O
R
conditions
,
R = Ph, no product
Next, this protocol was applied to synthesis of α, β-
unsaturated seven-membered lactones from dienes via
iodolactonization reaction with high regioselectivity and
stereoselectivity (Scheme 3). The diene substrates with
different ester groups proceeded smoothly and generated the
desired α, β-unsaturated seven-membered iodolactones (4a-
g) in moderate to excellent yields (36-96%). The structure of
a was determined by single-crystal X-ray diffraction. Among
them, the reactivity of substrates with alkyl ester (4a-4f) is
higher than that with aryl ester (4g), probably due to weaken
electron-withdrawing effect of aryl ester group. The
unsaturated dienes with different substituents on aromatic
ring, such as Me (4h, 4i), Cl (4j) and CF (4k) were efficiently
3
converted into α, β-unsaturated products in moderate to
excellent yields (dr > 20:1).
To prove the applicability of this protocol, the substrate 1a
was performed on a gram scale reaction, affording the seven-
membered lactone product 2a in 85% yield (1.22 g) (Scheme
2w, R = SO2Ph, 34% (exo:endo = 1.4:1)
I
1
2
Scheme 5 Mechanistic studies.
Aiming to further elucidate the reaction mechanism,
density functional theory (DFT) calculations (for computational
details see Supporting information) were carried out by taking
4
4
1
1
1
a as representative substrate (Scheme S1). The reaction is
initiated by the electrophilic addition of NIS to the carbon-
carbon double bond of 1a, leading to the formation of C-C-I
three-membered ring intermediate A. After the formation of
A, it could transfer by intramolecular carboxylation and
deprotonation. However, the deprotonation leads to the
formation of stable lactone intermediate, which inhibit the
intramolecular carboxylation (see SI for details). On the other
hand, the reaction takes place through carboxylation following
by deprotonation is accessible. The carboxylate could achieve
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please d oC hn eo mt Ca do mj u ms t margins
Page 4 of 5
COMMUNICATION
Journal Name
by attacking the C-C-I moiety through both α-C and β-C.
Attributing to the iodolactonization of the C=C double bond,
the NPA charge of α-C changes from -0.169 to 0.055, while
that of β-C becomes more negative (see Figure S1). As a result,
the carboxylate of intermediate A prefers to take place on the
α-C rather than the β-C. This can be proved by the free energy
barriers of these two processes. As shown in Scheme S1, the
free energy barrier of the former (TS-AB) is 12.0 kcal/mol lower
than that of the latter (TS-AC). The attacking of α-C leads to the
formation of seven-membered ring intermediate B, which is
exothermic by 3.4 kcal/mol. On the other hand, the attacking
of β-C produces eight-membered ring intermediate C, which is
endothermic by 13.2 kcal/mol. It is obvious that the former is
favourable thermodynamically as well. The intermediate B will
be deprotonated with the formation of final iodolactonization
product 2a. It is in good accordance with the experimental
observed seven-membered lactones products.
Notes and references
View Article Online
DOI: 10.1039/C9CC10080F
1
(a) Y. Wache, M. Aguedo, J. M. Nicaud and J. M. Belin, Appl.
Microbiol. Biotechnol., 2003, 61, 393; (b) A. Parenty, X.
Moreau and J. M. Campagne, Chem. Rev., 2006, 106, 911; (c)
M. I. Konaklieva and B. J. Plotkin, Mini-Rev. Mrd. Chem., 2005,
5
, 73.
2
(a) H. Abe, K. Nishioka, S. Takeda, M. Arai, Y. Takeuchi and T.
Harayama, Tetrahedron Lett., 2005, 46, 3197; (b) M.
Altemçller, T. Gehring, J. Cudaj, J. Podlech, H. Goesmann, C.
Feldmann and A. Rothenberger, Eur. J. Org. Chem., 2009,
2009, 2130; (c) U. Hçller, G. Konig and A. D. Wright, Eur. J.
Org. Chem., 1999, 1999, 2949; (d) A. H. Aly, R. Edrada-Ebel, I.
D. Indriani, V. Wray, W. E. G. Mueller, F. Totzke, U. Zirrgiebel,
C. Schaechtele, M. H. G. Kubbutat, W. H. Lin, P. Proksch and
R. Ebel, J. Nat. Prod., 2008, 71, 972.
3
4
5
B. Liu, F. Hu and B.-F. Shi, ACS Catal., 2015, 5, 1863; (b) G.
Majji, S. K. Rout, S. Rajamanickam, S. Guin and B. K. Patel,
Org. Biomol. Chem., 2016, 14, 8178.
(a) M. Miyagawa and T. Akiyama, Chem. Lett., 2018, 47, 78;
(
b) Z. Shen, H. A. Khan and V. M. Dong, J. Am. Chem. Soc.,
O
2008, 130, 2916.
O
O
J. M. Schomaker, B. R. Travis and B. Borhan, Org. Lett., 2003,
5, 3089; (b) M. Ito, A. Osaku, A. Shiibashi and T. Ikariya, Org.
Lett., 2007, 9, 1821; (c) S. Seth, S. Jhulki and J. N. Moorthy,
Eur. J. Org. Chem., 2013, 12, 2445; (d) C. M. Nicklaus, P. H.
Phua, T. Buntara, S. Noel, H. J. Heeres and J. G. de Vries, Adv.
Synth. Catal., 2013, 355, 2839.
COOH
CO2Me
NIS
O
CO2Me
t
CO2Me
NaO Bu
I
MeCN, rt, 12 h
I
1a
2a-E
2a, anti product
O
O
O
H
N
H
I
OH
OH
O
t
t
NaO Bu
NaO Bu
CO2Me
NIS
CO2Me
O
I
6
7
X.-S. Zhang, Y.-F. Zhang, Z.-W. Li, F.-X. Luo and Z.-J. Shi,
Angew. Chem., Int. Ed., 2015, 54, 5478.
(a) A. N. French, S. Bissmire and T. Wirth, Chem. Soc. Rev.,
2004, 33, 354; (b) H. Fujioka and K. Murai, Heterocycles.,
I
O
OH
I
CO2Me TS-AC, G= 21.1 kcal/mol
COOH
TS-AB, G= 9.1 kcal/mol
OH
CO2Me
Trans-attack
CO2Me
I
I
C, G= 13.2 kcal/mol
A, G= 0.0 kcal/mol
B, G= -3.4 kcal/mol
2
013, 87, 763; (c) Y. Cheng, W. Yu and Y.-Y. Yeung, Org.
Scheme 6 Mechanism diagram.
Biomol. Chem., 2014, 12, 2333.
8
9
1
C. Fang, D. H. Paull, J. C. Hethcox, C. R. Shugrue and S. F.
Martin, Org. Lett., 2012, 14, 6290; (b) H. Paull, C. Fang, J. R.
Donald, C. R. Shugrue, A. D. Pansick and S. F.Martin, J. Org.
Chem., 2018, 83, 5954; (c) D. W. Klosowski and S. F. Martin,
Org. Lett., 2018, 20, 1269; (d) R. Yousefi, K. D. Ashtekar, D. C.
Whitehead, J. E. Jackson and B. Borhan, J. Am. Chem. Soc.,
In summary, we have disclosed a highly regioselective and
stereoselective iodolactonization reaction of electron-deficient
olefins via an electronic addition process, which rapidly
constructs divers seven-membered lactones with consecutive
two chiral carbon centers. By installing an ester group, we
changed the electronic density of double bond, and thus
controlled the regioselectivity of electronic addition step,
which was proved by experimental results and DFT calculation.
This methodology may serve as a powerful tool for the
synthesis of natural products and potentially active drug
molecules containing seven-membered lactone motif.
2
013, 135, 14524.
(a) G. E. Veitch and E. N. Jacobsen, Angew. Chem., Int. Ed.,
010, 49, 7332; (b) G. E. Veitch and E. N. Jacobsen, Angew.
2
Chem., Int. Ed., 2010, 49, 7332; (c) Y. Nishikawa, Y.
Hamamoto, R. Satoh, N. Akada, S. Kajita, M. Nomoto, M.
Miyata, M. Nakamura, C. Matsubara and O. Hara, Chem. Eur.
J., 2018, 24, 18880; (d) S. E. Denmark, P. Ryabchuk, M. T.
Burk and B. B. Gilbert, J. Org. Chem., 2016, 81, 10411.
0 (a) B. Simonot and G. Rousseau, J. Org. Chem., 1994, 59,
5
Moreover, the methodology may provide
a
general
912; (b) G. Burtin, H. Pellissier and M. Santelli,
introduction for regioselective and stereoselective
construction of medium and large sized lactones.
Tetrahedron., 1998, 54, 8065; (c) M. Srinivasan, S.
Sankararaman, H. Hopf, I. Dix and P. G. Jones, J. Org. Chem.,
2
001, 66, 4299; (d) T. Itoh, N. Yoshimoto and K. Yamamoto,
This work was supported by supported by the NSF of Hubei
Province (No. 2017CFA006, No. 2018CFB156), the National
Science Foundation for Distinguished Young Scholars of China
Heterocycles., 2010, 80, 689; (e) Y. A. Cheng, T. Chen, C. K.
Tan, J. J. Heng and Y.-Y. Yeung, J. Am. Chem. Soc., 2012, 134,
16492; (f) W.-Q. Zhang, L.-F. Cheng, J. Yu and L.-Z. Gong,
Angew. Chem. Int. Ed., 2012, 51, 4085; (g) A. Verma, S. Jana,
C. D. Prasad, A. Yadav and S. Kumar, Chem. Commun., 2016,
(No. 21525101), the Program of Ministry of Education Key
Laboratory for the Synthesis and Application of Organic
Functional Molecules (No. KLSAOFM1702), the NSF of Guangxi
Province (No. 2017GXNSFDA198040), the BAGUI talent
program and scholar program (No. 2014A001), National
Nature Science Foundation of China (No. 21973113).
5
2, 4179; (h) P. Finkbeiner, K. Murai, M. Röpke and R.
Sarpong, J. Am. Chem. Soc., 2017, 139, 11349.
1
1 For crystallographic data: 2a (CCDC 1918655), 2e (CCDC
1944538), 2o (CCDC 1973725), 2i (CCDC 1944537), 2n
(1974644) and 4a (CCDC 1944536) (CIF).
Conflicts of interest
There are no conflicts to declare.
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 5
ChemComm
View Article Online
DOI: 10.1039/C9CC10080F