Stereodivergent synthesis of β-iodoenol carbamates with CO2viaphotocatalysis

Article abstract of DOI:10.1039/d1sc03366b

Photocatalytic conversion of carbon dioxide (CO₂) into value-added chemicals is of great significance from the viewpoint of green chemistry and sustainable development. Here, we report a stereodivergent synthesis of β-iodoenol carbamates through a photocatalytic three-component coupling of ethynylbenziodoxolones, CO₂and amines. By choosing appropriate photocatalysts, bothZ- andE-isomers of β-iodoenol carbamates, which are difficult to prepare using existing methods, can be obtained stereoselectively. This transformation featured mild conditions, excellent functional group compatibility and broad substrate scope. The potential synthetic utility of this protocol was demonstrated by late-stage modification of bioactive molecules and pharmaceuticals as well as by elaborating the products to access a wide range of valuable compounds. More importantly, this strategy could provide a general and practical method for stereodivergent construction of trisubstituted alkenes such as triarylalkenes, which represents a fascinating challenge in the field of organic chemistry research. A series of mechanism investigations revealed that the transformation might proceed through a charge-transfer complex which might be formed through a halogen bond.

Full text of DOI:10.1039/d1sc03366b

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Stereodivergent synthesis of b-iodoenol
carbamates with CO2 via photocatalysis†
Cite this: DOI: 10.1039/d1sc03366b
a
Lu Wang,a Fuxing Shi,b Chaorong Qi,
Wenjie Xu,a Wenfang Xiong,a
*
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
a
Bangxiong Kanga and Huanfeng Jiang
*
Photocatalytic conversion of carbon dioxide (CO2) into value-added chemicals is of great significance from
the viewpoint of green chemistry and sustainable development. Here, we report a stereodivergent synthesis
of
b-iodoenol
carbamates
through
a
photocatalytic
three-component
coupling
of
ethynylbenziodoxolones, CO2 and amines. By choosing appropriate photocatalysts, both Z- and E-
isomers of b-iodoenol carbamates, which are difficult to prepare using existing methods, can be
obtained stereoselectively. This transformation featured mild conditions, excellent functional group
compatibility and broad substrate scope. The potential synthetic utility of this protocol was
demonstrated by late-stage modification of bioactive molecules and pharmaceuticals as well as by
elaborating the products to access a wide range of valuable compounds. More importantly, this strategy
could provide a general and practical method for stereodivergent construction of trisubstituted alkenes
such as triarylalkenes, which represents a fascinating challenge in the field of organic chemistry research.
A series of mechanism investigations revealed that the transformation might proceed through a charge-
transfer complex which might be formed through a halogen bond.
Received 21st June 2021
Accepted 2nd August 2021
DOI: 10.1039/d1sc03366b
rsc.li/chemical-science
Introduction
The development of new and efficient methodologies for the
conversion of carbon dioxide (CO2) into valuable chemicals is of
great signicance, because CO2 is considered as an ideal C1
feedstock in organic synthesis.1 Recently, visible-light photo-
catalysis has become a powerful strategy for CO2 transformation
and attracted ever-increasing attention from chemists.2 Many
elegant methods that cannot be achieved through conventional
thermal catalysis have been successfully developed to produce
various valued-added chemicals and fuels from CO2, such as
CO,3 CH3OH,4 CH4 (ref. 5) and carboxylic acids.6 Organic
carbamates constitute an important class of compounds, which
are widely used in agrochemicals,7 pharmaceuticals8 and as
intermediates in organic synthesis.9 Traditional methods for
the preparation of carbamates are mainly based on the use of
toxic phosgene and its derivatives, which are environmentally
unfriendly.10 In the past decades, many phosgene-free protocols
have been explored for the synthesis of carbamates.11 Among
aKey Laboratory of Functional Molecular Engineering of Guangdong Province, School
of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China. E-mail: crqi@scut.edu.cn; jianghf@scut.edu.cn
bState Key Laboratory of Chemical Resource Engineering, Institute of Computational
Chemistry, College of Chemistry, Beijing University of Chemical Technology, Beijing
100029, P. R. China
† Electronic supplementary information (ESI) available. CCDC 2041438, 2041439
and 2041440. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/d1sc03366b
Scheme
1 Synthesis and transformation of 1,2-difunctionalized
alkenes containing vinyl halide moiety.
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them, the methods using CO2 are appealing because CO2 is non- stereoselective synthesis of (Z)-2-iodovinyl phenyl ethers via
toxic, cheap, and readily available.12 In general, these methods a visible light-driven reaction of EBXs and phenols, which was
rely on the in situ formation of nucleophilic CO2-amine adduct proposed to proceed through the addition of phenols to EBXs to
followed by the interaction with electrophiles. However, some of form vinylbenziodoxolone intermediates, followed by light-
the methods still suffered from one or more drawbacks such as mediated fragmentation via phenolate electron donor–acceptor
the need for harsh reaction conditions, poor functional group (EDA) complexes (Scheme 1b).16c Although great achievement has
tolerance and limited substrate scope. Moreover, the stereo- been made in this eld, to our knowledge, the addition of amine-
selective addition of the CO2-amine adduct to carbon–carbon CO2 adduct to the highly electrophilic EBXs is unprecedented.
triple bond remain very rare, as the reversibility in the interac-
tion between CO2 and amine is usually a major issue.
Inspired by the excellent works mentioned above, and as part
of our continuous interest in the synthesis of organic carba-
On the other hand, 1,2-difunctionalized alkenes, especially mates with CO2 and amines,17 herein, we wish to report a visible
those containing vinyl halide moiety, are versatile and valuable light-mediated stereodivergent synthesis of b-iodoenol carba-
building blocks in organic synthesis, because they can be mates from ethynylbenziodoxolones, CO2 and amines under
further elaborated to access a variety of synthetically useful very mild reaction conditions (Scheme 1c). The transformation
multisubstituted alkenes and functional molecules through was proposed to proceed through a charge-transfer complex
transition metal-catalyzed cross-coupling reactions in a step- (CTC),18 which might be formed through a halogen bond.19 The
wise manner.13 Although many methods based on hal- obtained products that encompass the different reactivity of
ofunctionalization of alkynes or hydrofunctionalization of hal- enol carbamates and vinyl iodides have proven to be versatile
oalkynes have been established for producing these alkenyl bis-electrophiles to access
compounds, their stereodivergent synthesis and stereospecic compounds. More importantly, the strategy could provide
transformation still remain a great challenge (Scheme 1a).14
a general and practical method for stereodivergent construction
a range of valuable
Ethynylbenziodoxolones (EBXs), one of the most important of trisubstituted alkenes such as triarylalkenes, which repre-
classes of hypervalent iodine reagents, are versatile synthetic sents a great challenge in synthetic organic chemistry.
intermediates in organic chemistry.15 Especially, in the past six
years the addition of nucleophiles to EBXs to construct func-
tionalized vinylbenziodoxolones (VBXs) have been extensively
studied by the groups of Yoshikai, Waser and Miyake.16 Inter-
Results and discussion
We began our study by evaluating the three-component reaction
of phenyl-EBX (1a), diethylamine (2a) and CO2 (1 atm) under
estingly, in 2018, Miyake and co-workers reported the regio- and
Table 1 Optimization of reaction conditionsa
Entry
Catalyst
Base
Solvent
Yieldb (%)
Z/E
1
2
3
4
5
6
7
8
fac-Ir(ppy)3
Ir(ppy)2(dtbbpy)PF6
Ir[dF(CF3)ppy]2(dtbbpy)PF6
Ru(bpy)3Cl2
4CzIPN
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
—
Eosin Y
DBU
DBU
DBU
DBU
DBU
DBU
DBN
NEt3
Cs2CO3
tBuOK
DBU
DBU
DBU
DBU
DBU
DBU
—
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
CH3CN
DMF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
70
66
67
44
66
70
65
12
18
8
67
56
74
73
n.d.e
12
11
71
18 : 82
41 : 59
89 : 11
>99 : 1
98 : 2
>99 : 1
94 : 6
>99 : 1
>99 : 1
>99 : 1
>99 : 1
88 : 13
>99 : 1
>99 : 1
—
9
10
11
12
13
14c
15d
16
17
18f
>99 : 1
>99 : 1
46 : 54
Eosin Y
DBU
a
Reaction conditions: 1a (0.1 mmol), 2a (0.3 mmol), CO2 (1 atm), photocatalyst (1 mol%), base (0.2 mmol), solvent (1 mL), green LEDs irradiation
for 14 h, room temperature. b Yields and Z/E ratios were determined by 1H NMR analysis with CH2Br2 as internal standard. c Base (0.1 mmol), 0.5 h.
d
The reaction was performed in the dark. e n.d. ¼ not detected. f The reaction was conducted under blue LEDs irradiation.
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different conditions. To our delight, when the reaction was con- 14). Finally, control experiments demonstrated that no desired
ducted in ethyl acetate with fac-Ir(ppy)3 as the photocatalyst and product was formed in the absence of visible light (entry 15),
1,8- diazabicyclo[5.4.0]undec-7-ene (DBU) as the base, the desired while low yield was observed in the absence of photocatalyst or
product 3aa was obtained in 70% yield with a Z/E ratio of 18 : 82 base (entries 16 and 17). Moreover, when the reaction was per-
(Table 1, entry 1). Other catalysts including Ir(ppy)2(dtbbpy)PF6, Ir formed under blue LEDs irradiation conditions, low stereo-
[dF(CF3)ppy]2(dtbbpy)PF6, Ru(bpy)3Cl2, 4CzIPN and eosin Y were selectivity was observed albeit high yield was obtained (entry 18).
then examined for the reaction. It was shown that the catalyst We speculated that the product could undergo light-induced
employed has a great impact on the stereoselectivity of the isomerization due to the considerable UV-vis spectral overlap of
product and a reverse Z/E ratio could be achieved (entries 2–6). (Z)-3aa and (E)-3aa with the blue LEDs spectrum (for the UV-vis
Thus, by employing eosin Y as the photocatalyst, which possesses spectrum of 3aa see Fig. S1†).
lower triplet excited state energies, 3aa could be obtained in 70%
With the optimized reaction conditions in hand, we rst
yield with a Z/E ratio more than 99 : 1 (entry 6). Considering the examined the generality and robustness of the reaction with
important role of the base in CO2 conversion,20 we also investi- respect to the EBXs using eosin Y as the photocatalyst. As
gated other organic and inorganic bases. 1,5-Diazabicyclo[4.3.0] showed in Scheme 2, a wide range of aryl-EBXs could undergo
non-5-ene (DBN) could also give the desired product in 65% the reaction efficiently and gave the corresponding products (Z)-
yield with a Z/E ratio of 94 : 6 (entry 7), while the use of triethyl-
amine, Cs2CO3 or tBuOK led to low yields due to the formation of
large amounts of N,N-diethyl-2-iodobenzamide as the byproduct
(entries 8–10). Subsequent optimization revealed that the use of
dimethyl sulfoxide as the solvent led to higher yield (entries 11–
13). To our delight, decreasing the amount of the base to 1.0
equivalent relative to 1a and even shortening the reaction time to
0.5 h did not affect the reaction efficiency and selectivity (entry
Scheme 2 Synthesis of (Z)-b-iodoenol carbamates. Reaction condi- Scheme 3 Synthesis of (Z)-b-iodoenol carbamates. Reaction condi-
tions: 1 (0.1 mmol), 2a (0.3 mmol), eosin Y (1 mol%), DBU (0.1 mmol), tions: 1a (0.1 mmol), 2 (0.3 mmol), eosin Y (1 mol%), DBU (0.1 mmol),
DMSO (1 mL), CO2 (1 atm), green LEDs, rt, 0.5 h. Yields of the isolated DMSO (1 mL), CO2 (1 atm), green LEDs, rt, 0.5 h. Yields of the isolated
products are reported. All of the Z/E values are greater than 99 : 1 as products are reported. All of the Z/E values are greater than 99 : 1 as
determined by 1H NMR analysis of the crude reaction mixtures prior to determined by 1H NMR analysis of the crude reaction mixtures prior to
purification. aThe reaction was conducted on 1 mmol scale.
purification.
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3aa–(Z)-3na in moderate to good yields with excellent stereo- hinderance ((Z)-3ab–(Z)-3an). Moreover, the visible light-
selectivity. The Z-conguration of the carbamate products was promoted three-component reaction could be extended to
conrmed by X-ray crystallographic analysis of (Z)-3fa.21
A
various cyclic amines, affording the corresponding carbamates
variety of electron-donating and -withdrawing substituents at (Z)-3ao–(Z)-3ax in good yields. The substrate bearing a free
the para-, meta-, and ortho-positions of the benzene ring, hydroxyl group was also accommodated, providing the desired
including methyl, methoxyl, halogen (F, Cl and Br), cyano, nitro, product (Z)-3aw in 65% yield.
triuoromethyl and ester groups were well tolerated. The elec-
Remarkably, this method provides an efficient and conve-
tronic and steric properties of the substituents have no signif- nient approach for late-stage modication of bioactive mole-
icant effects on the reaction. Notably, EBXs derived from cules and pharmaceuticals containing free secondary amino
alkylacetylenes, alkynols and enynes were also suitable group (Scheme 4). For example, three simple amino acid esters
substrates for the reaction, providing the desired products (Z)- derived from glycine, L-valine and sarcosine, respectively, could
3oa–(Z)-3ra in moderate to high yields. Noted that the reaction readily undergo the reaction with 1a and CO2 under standard
of 1a on 1 mmol scale proceeded smoothly to give the desired conditions and gave the carbamate products (Z)-3ay–(Z)-3aaa.
product (Z)-3aa in 62% yield, demonstrating the scalability of Both antidepressant drugs Fluoxetine22a (marketed as Prozac)
the reaction.
and Amoxapine22b were suitable coupling partners to give the
Encouraged by these results, we continued to investigate the corresponding products (Z)-3aba and (Z)-3aca in moderate
substrate scope with respect to amines under the standard yields. The late-stage modications of Sitagliptin22c and Cyti-
conditions (Scheme 3). A series of structurally diverse acyclic sine,22d which are used for treating diabetes and smoking
dialkylamines, including symmetric and unsymmetric ones, cessation, respectively, were successful to afford the products
could be applied to the transformation with good to high effi- (Z)-3ada and (Z)-3aea. Furthermore, the antihistamine drug
ciency regardless of their alkyl chain length and steric Desloratadine,22e the potent bruton tyrosine kinase (BTK)
inhibitor Ibrutinib N-1,22f and the antimigraine drug Lomer-
izine22g could undergo the modication process without diffi-
culty ((Z)-3afa–(Z)-3aha).
Subsequently, the substrate scope of the three-component
reaction catalyzed by fac-Ir(ppy)3 was explored to assemble (E)-
Scheme 5 Synthesis of (E)-b-iodoenol carbamates. Reaction condi-
tions: 1 (0.1 mmol), 2a (0.3 mmol), fac-Ir(ppy)3 (1 mol%), DBU (0.2
Scheme 4 Synthesis of (Z)-b-iodoenol carbamates. Reaction condi- mmol), EtOAc (1 mL), CO2 (1 atm), green LEDs, rt, 14 h. Yields of the
tions: 1a (0.1 mmol), 2 (0.3 mmol), eosin Y (1 mol%), DBU (0.1 mmol), isolated products are reported. Compounds isolated as pure stereo-
DMSO (1 mL), CO2 (1 atm), green LEDs, rt, 0.5 h. Yields of the isolated isomers contained <1% of the alternative geometrical isomer. The E/Z
products are reported. All of the Z/E values are greater than 99 : 1 as values reported in parentheses were determined by 1H NMR analysis of
determined by 1H NMR analysis of the crude reaction mixtures prior to the crude reaction mixtures prior to purification. aThe reaction was
purification.
conducted on 1 mmol scale.
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b-iodoenol carbamates (Scheme 5). Pleasingly, a variety of aryl-
A series of secondary amines could be converted to the cor-
EBXs bearing electron-withdrawing or electron-donating groups responding products (E)-3ab–(E)-3af, (E)-3ah, (E)-3ak, (E)-3ao–
on the benzene rings could enter into the reaction and gave the (E)-3ar in 48–73% yield with good stereoselectivities (Scheme 6).
anticipated products (E)-3aa–(E)-3fa, (E)-3ia, (E)-3ka and (E)-3sa Moreover, the Ir-catalyzed three-component reaction could be
in moderate to good yields. Although the catalyst fac-Ir(ppy)3 applied to amino acid esters and drugs, as exemplied by
gave the adducts as a mixture of stereoisomers in these cases, glycine ester and Amoxapine, which gave the desired products
the minor (Z)- isomers were easily separated from the major (E)- (E)-3ay and (E)-3aca in 61% and 53% yields, respectively. The
isomers by column chromatography. Moreover, the reaction of geometry of the product (E)-3aca was also conrmed by the X-
1a could be performed on a 1 mmol scale to give the desired ray diffraction analysis.24
product in moderate yield. The electronic effect of substituents
To unravel the underlying synthetic value of the protocol,
on the aromatic rings has an obvious inuence on the stereo- a series of subsequent transformations of the newly formed
selectivity. The EBX reagents bearing a strong electron- product (Z)-3aa was performed. As can be seen from Scheme 7A,
withdrawing group on the aryl ring delivered the products (Z)-3aa could take part in a range of Cu- or Pd-catalyzed cross-
with lower stereoselectivities than those with weak electron- coupling reactions via C(sp2)–I bond cleavage, including thio-
withdrawing or electron-donating groups. However, alkyl- lization (4), methoxycarbonylation (5), Sonogashira (6) and
substituted EBXs could not give the desired (E)-b-iodoenol Suzuki cross-coupling reactions (7 and 8). In addition, the
carbamate products. For example, the reaction of EBX 1p under palladium-catalyzed [2 + 2 + 1] cycloaddition reaction of (Z)-3aa
the same conditions only afforded (Z)-3pa in 45% yield (not with diphenylacetylene could also proceed smoothly, affording
shown), indicating that (Z)-3pa could not undergo photo- a structurally intriguing pentasubstituted fulvene derivative 9 in
catalytic Z to E isomerization under these conditions, which 62% yield.25 The structure of compound 9 was conrmed by X-
might be due to the absence of a conjugated p system in such ray crystallographic analysis.26
a molecule.23
Stereodivergent synthesis of triarylalkenes represents a long-
standing challenge because of the small energy difference
between E and Z isomers of triarylalkenes. With the visible light-
mediated stereodivergent synthesis of b-iodoenol carbamates in
hand, we hypothesized whether this transformation would
provide a general method for stereodivergent synthesis of tri-
arylalkenes, since both iodine atom and carbamate group might
serve as convenient handles for cross-coupling to form C–C
bonds. With this goal in mind, we attempted to synthesize 1-
uoro-4-(2-(4-methoxyphenyl)-1 phenylvinyl)benzene (11), an
alkene with three different aryl groups. As can be seen in
Scheme 7B, both (Z)-3aa and (E)-3aa could undergo the Pd-
catalyzed Suzuki cross-coupling with (4-methoxyphenyl)
boronic acid to give the desired products (Z)-10 and (E)-10 in
72% and 84% yields, respectively. Subsequent Pd-catalyzed
Kumada–Corriu cross-coupling with Grignard reagent (4-uo-
rophenyl)magnesium bromide would afforded the desired
products (Z)-11 and (E)-11 in high yields with excellent stereo-
selectivities. Notably, these types of complementary pairs of
alkenes would otherwise be difficult to prepare through classic
Wittig olenation reaction.
To gain some insight into the mechanism, we conducted
a series of control experiments and spectroscopic investiga-
tions. Firstly, it was found that 1a could react with CO2 and 2a in
the absence of visible light and photosensitizer to form a stable
vinylbenziodoxolone product 12 in excellent yield, and irradia-
tion of 12 with green LEDs in the presence of eosin Y and DBU
led to the formation of (Z)-3aa, indicating compound 12 was the
key intermediate for the transformation. Control experiments
showed that light, eosin Y and DBU are all essential for the
Scheme 6 Synthesis of (E)-b-iodoenol carbamates. Reaction condi- formation of (Z)-3aa from 12 (Scheme 8A).
tions: 1a (0.1 mmol), 2 (0.3 mmol), fac-Ir(ppy)3 (1 mol%), DBU (0.2
Next, we tried to explore the role of the photocatalyst eosin Y
mmol), EtOAc (1 mL), CO2 (1 atm), green LEDs, rt, 14 h. Yields of the
isolated products are reported. Compounds isolated as pure stereo-
isomers contained <1% of the alternative geometrical isomer. The E/Z
values reported in parentheses were determined by 1H NMR analysis of
the crude reaction mixtures prior to purification.
in this transformation. Stern–Volmer quenching studies
showed that the excited eosin Y was effectively quenched by the
addition of a mixture of 12 and DBU (1 : 1 molar ratio) rather
than by 12 alone (Fig. S2†), indicating that DBU might be
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Scheme 7 Versatile transformations of the b-iodoenol carbamates.
capable of interacting with 12 to accelerate the quenching of for more details). These results suggested that a thermody-
ox
red
eosin Y*. The redox potential of 12 (E ¼ +1.05 V vs. SCE, E
¼
namical activation of 12-DBU complex by eosin Y (ET
¼
p/2
p/2
ꢀ1.22 V vs. SCE; Fig. S4 and S5†) were also measured by cyclic 44.0 kcal molꢀ1) via energy transfer might be feasible, while the
voltammetry experiments, which demonstrated that the redox thermodynamical activation of 12 by eosin Y via energy transfer
ox
1/2
potential of 12 is outside the redox range of eosin Y (E
¼
is rather difficult.27
red
1/2
+0.83 V vs. SCE, E ¼ ꢀ1.11 V vs. SCE).27 Moreover, the reaction
To further conrm the role of DBU, the UV-vis absorption
was signicantly inhibited by addition of 1.0 equivalent of 2,5- spectra tests were conducted on 12 and DBU in DMSO at 0.1 M
dimethylhexa-2,4-diene, which is
a
well-known triplet concentration for each species. A signicant bathochromic shi
quencher.28 In this case, only little amount of (Z)-3aa was was observed when mixing 12 and DBU in a 1 : 1 ratio (Scheme
formed along with intermediate 12 in 35% yield (Scheme 8B). 8D(i)). The Job's plot further conrmed a 1 : 1 binding stoichi-
The above results suggested that electron transfer between 12 ometry for 12 and DBU (Scheme 8D(ii)). 1H NMR analysis
and eosin Y might not be involved in the reaction, precluding showed that all the proton signals of DBU in CDCl3 were
a photoinduced redox process. In support of the energy transfer signicantly shied to lower eld when 1 equivalent of 12 was
catalysis, we observed that irradiation of a mixture of 12 and added, also indicating that DBU would interact with 12 directly
DBU (1 : 1, molar ratio) in DMSO with blue LEDs in the absence (Scheme 8D(iii)). Moreover, the DFT studies revealed that the
of any photocatalysts would give 3aa in 52% yield with a Z/E calculated N/I distance of the 1 : 1 complex of DBU and 12 is
˚
ratio of 36 : 64 (Scheme 8C). Furthermore, the density func- 3.15 A in singlet ground state, which is signicantly smaller
˚
tional theory (DFT) calculations showed that the triplet excited than the sum of the van der Waals radii of N and I atoms (3.7 A),
state energies of 12 and complex 12-DBU were computed to be and the atomic polar tensors (APT) charges29 on the N and I
endergonic by 89.7 and 41.6 kcal molꢀ1, respectively (see ESI† atom are ꢀ0.43 and +0.88 eꢀ, respectively. However, in the
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Scheme 8 Mechanistic studies.
˚
excited triplet state the N/I distance will be shorten to 2.83 A, used for the reaction under standard reaction conditions,
and the APT charges on the N and I atom are changed to ꢀ0.39 products (Z)- and (E)-3aa were obtained with 83% and 71% of D-
and +0.57 eꢀ, respectively (Scheme 9, and see ESI† for more form, respectively, indicating that amines are the major proton
details). All these results suggested that 12 and DBU might form source for the carbamate products (see ESI† for more details).
a charge-transfer complex (CTC) through an attractive non-
covalent halogen bond.
Although the mechanism of the visible light-mediated three-
component reaction has not yet been fully elucidated, on the
Then, the time course of the reaction catalyzed by fac-Ir(ppy)3 basis of the above-described observations and previous litera-
under green LEDs irradiation was studied. It was shown that the ture, a plausible mechanism is proposed in Scheme 9. Initially,
yield of (Z)-3aa increased rapidly at the early stage of the reac- CO2 reacts with ethylamine (2a) in the presence of DBU to give
tion and reached a maximal value of about 50% aer 0.5 h, and carbamate salt I,17 which will nucleophilically attack the C–C
then decreased gradually while the yield of its E-isomer triple bond of EBX 1a to form a vinyl carbanion intermediate II.
increased (Scheme 8E), indicating (Z)-3aa was rst generated Subsequent protonation of intermediate II will lead to the
and then isomerized to (E)-3aa under the visible light irradia- formation of vinylbenziodoxolone 12.16a,c–e Then, interaction
tion conditions. This could be conrmed by irradiation of pure between 12 and DBU via a halogen bond forms a charge-transfer
(Z)-3aa with green LEDs in the presence of fac-Ir(ppy)3, which complex III. Under the irradiation of green LEDs, a triplet triplet
gave (E)-3aa with high efficiency. It is also found that (Z)-3aa energy transfer (TTEnT) between complex III and excited state
could also undergo the isomerization under blue LEDs irradi- PC* occurs to generate an excited charge-transfer complex III*,
ation in the absence of any photocatalysts albeit with low effi- which will undergo a rapid intermolecular single-electron
ciency (Scheme 8F), revealing the importance of photocatalyst transfer (SET) process to give the product (Z)-3aa, along with
in controlling the stereoselectivity of the transformation.
the formation of aryl radical IV and radical cation V. Subsequent
Finally, the source of the vinylic hydrogens in the nal hydrogen atom transfer (HAT) from V to IV will generate
product 3aa was investigated. When diethylamine-N-D1 was benzoate VI and VII. In the case of eosin Y as the photocatalyst,
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Scheme 9 Proposed mechanism.
the resulting (Z)-3aa cannot further undergo photoinduced a charge-transfer complex which might be formed through
isomeriation to yield its isomer (E)-3aa due to the low ET of eosin a halogen bond.
Y. However, when photocatalysts with higher ET, such as fac-
Ir(ppy)3 is employed,30 a contra-thermodynamic, photocatalytic
Z to E isomerization of (Z)-3aa will proceed via an energy
transfer process,31 furnishing the (E)-3aa product. Additionally,
Data availability
All data supporting the ndings of this study are available
within the paper and its ESI,† include experimental details, the
results of the DFT calculations, characterization data, and H
in
ðE
this
case,
since
photoexcited
fac-Ir(ppy)3
*III=IV
1=2
30
1
¼ ꢀ1:73 V vs: SCEÞ might be responsible for the
and 13C NMR spectra of all new compounds. Crystallographic
data for the crystal structures has been deposited at the CCDC
under CCDC 2041438 for (Z)-3fa, 2041439 for (E)-3aca and
2041440 for 9.
single-electron reduction of 12 on the basis of the Stern–Volmer
quenching results (Fig. S3†), an alternative reaction pathway for
the formation of (Z)-3aa that involves direct electron transfer
between 12 and fac-Ir(ppy)3 cannot be excluded at present
(Fig. S9†).
Author contributions
Conclusions
L. W., H. J. and C. Q. designed the research and
experiments; L. W., W. X. (Wenjie Xu), W. X. (Wenfang Xiong)
and B. K. contributed to the experiment work and F. S.
contributed to the DFT calculations; L. W. and C. Q. wrote the
manuscript; all authors discussed the results and commented
on the manuscript.
We have reported a visible light-mediated stereodivergent
synthesis of b-iodoenol carbamates from ethynylbenziodox-
olones, CO2 and amines for the rst time. By choosing appro-
priate photocatalysts, both Z- and E-isomers of b-iodoenol
carbamates, which are difficult to prepare using existing
methods, can be obtained stereoselectively. The mild reaction
conditions allowed excellent functional group compatibility
and broad substrate scope. The potential utility of this protocol
was demonstrated by late-stage modication of second amino
group-containing bioactive molecules and drugs as well as by
elaborating the products to access a wide range of synthetically
valuable compounds. More importantly, this strategy could
Conflicts of interest
The authors declare no competing nancial interest.
Acknowledgements
provide a general and practical method for stereodivergent This work was nancially supported by the Ministry of Science
synthesis of trisubstituted alkenes such as triarylalkenes, which and Technology of the People’s Republic of China
represents a fascinating challenge in the eld of organic (2016YFA0602900), the National Natural Science Foundation of
chemistry research. A series of mechanism investigations China (21971073 and 22001075) and the Natural Science
revealed that the transformation might proceed through Foundation of Guangdong Province (2019A1515011468). We
Chem. Sci.
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also thank Professor Jiarong Chen (Central China Normal
University) for his helpful discussion.
143, 2200; (e) L.-L. Liao, G.-M. Cao, Y.-X. Jiang, X.-H. Jin,
X.-L. Hu, J. J. Chruma, G.-Q. Sun, Y.-Y. Gui and D.-G. Yu, J.
Am. Chem. Soc., 2021, 143, 2812; (f) Y. Gao, H. Wang,
Z. Chi, L. Yang, C. Zhou and G. Li, CCS Chem., 2021, 3, 1848.
7 (a) Y. Zhou, Z. Ke, H. Ye, M. Hong, Y. Xu, M. Zhang, W. Jiang
and Q. Hong, J. Agric. Food Chem., 2020, 68, 14739; (b)
V. Mariyappan, M. Keerthi and S.-M. Chen, J. Agric. Food
Chem., 2021, 69, 2679.
Notes and references
1 For selected reviews, see: (a) M. He, Y. Sun and B. Han,
Angew. Chem., Int. Ed., 2013, 52, 9620; (b) M. Aresta,
A. Dibenedetto and A. Angelini, Chem. Rev., 2014, 114,
´
´
¨
´
1709; (c) A. Tortajada, F. Julia-Hernandez, M. Borjesson,
T. Moragas and R. Martin, Angew. Chem., Int. Ed., 2018, 57,
15948; (d) V. A. Peshkov, O. P. Pereshivko, A. A. Nechaev,
A. A. Peshkov and E. V. Van der Eycken, Chem. Soc. Rev.,
2018, 47, 3861; (e) X. Li, J. Yu, M. Jaroniec and X. Chen,
Chem. Rev., 2019, 119, 3962; (f) S. Wang and C. Xi, Chem.
Soc. Rev., 2019, 48, 382; (g) Y. Yang and J.-W. Lee, Chem.
Sci., 2019, 10, 3905; (h) L. Song, Y.-X. Jiang, Z. Zhang,
Y.-Y. Gui, X.-Y. Zhou and D.-G. Yu, Chem. Commun., 2020,
56, 8355; (i) H.-R. Li and L.-N. He, Organometallics, 2020,
39, 1461.
2 For selected reviews, see: (a) Y.-Y. Gui, W.-J. Zhou, J.-H. Ye
and D.-G. Yu, ChemSusChem, 2017, 10, 1337; (b) Y. Cao,
X. He, N. Wang, H.-R. Li and L.-N. He, Chin. J. Chem., 2018,
36, 644; (c) J. Hou, J.-S. Li and J. Wu, Asian J. Org. Chem.,
2018, 7, 1439; (d) C. S. Yeung, Angew. Chem., Int. Ed., 2019,
58, 5492; (e) X. He, L.-Q. Qiu, W.-J. Wang, K.-H. Chen and
8 (a) J. Skacel, B. S. Slusher and T. Tsukamoto, J. Med. Chem.,
2021, 64, 279; (b) P. Bhutani, G. Joshi, N. Raja, N. Bachhav,
P. K. Rajanna, H. Bhutani, A. T. Paul and R. Kumar, J. Med.
Chem., 2021, 64, 2339; (c) Y. Wu, B. Wang, H. Lu, H. Zhao,
B. Yang, L. Li, Y. Lu, D. Zhang, N. Sun and H. Huang, J.
Med. Chem., 2021, 64, 3234.
9 (a) M. R. Harris, L. E. Hanna, M. A. Greene, C. E. Moore and
E. R. Jarvo, J. Am. Chem. Soc., 2013, 135, 3303; (b) D. Holt and
M. J. Gaunt, Angew. Chem., Int. Ed., 2015, 54, 7857; (c)
A. C. P. Rivera, R. Still and D. E. Frantz, Angew. Chem., Int.
Ed., 2016, 55, 6689; (d) A. Nishizawa, T. Takahira, K. Yasui,
H. Fujimoto, T. Iwai, M. Sawamura, N. Chatani and
M. Tobisu, J. Am. Chem. Soc., 2019, 141, 7261; (e)
M. Wilkovitsch, M. Haider, B. Sohr, B. Herrmann,
J. Klubnick, R. Weissleder, J. C. T. Carlson and H. Mikula,
J. Am. Chem. Soc., 2020, 142, 19132; (f) C. Wata and
T. Hashimoto, J. Am. Chem. Soc., 2021, 143, 1745.
L.-N. He, Green Chem., 2020, 22, 7301; (f) C. Xi, Z. Fan and 10 (a) S. Ozaki, Chem. Rev., 1972, 72, 457; (b) H. Babad and
Z. Zhang, ChemSusChem, 2020, 13, 6201; (g) Z. Zhang,
A. G. Zeiler, Chem. Rev., 1973, 73, 75.
J.-H. Ye, T. Ju, L.-L. Liao, H. Huang, Y.-Y. Gui, W.-J. Zhou 11 (a) A. M. Tafesh and J. Weiguny, Chem. Rev., 1996, 96, 2035;
and D.-G. Yu, ACS Catal., 2020, 10, 10871; (h) B. Cai,
H. W. Cheo, T. Liu and J. Wu, Angew. Chem., Int. Ed., 2021,
DOI: 10.1002/anie.202010710; (i) G. Zhang, Y. Cheng,
M. Beller and F. Chen, Adv. Synth. Catal., 2021, 363, 1583.
3 (a) Z. Jiang, W. Wan, H. Li, S. Yuan, H. Zhao and P. K. Wong,
Adv. Mater., 2018, 30, 1706; (b) Z. Jiang, X. Xu, Y. Ma,
(b) D. Chaturvedi, Tetrahedron, 2012, 68, 15; (c) G. S. Kumar,
C. U. Maheswari, R. A. Kumar, M. L. Kantam and
K. R. Reddy, Angew. Chem., Int. Ed., 2011, 50, 11748.
12 For selected reviews, see: (a) Z. Zhang, J.-H. Ye, D.-S. Wu,
Y.-Q. Zhou and D.-G. Yu, Chem.–Asian J., 2018, 13, 2292; (b)
W. Schilling and S. Das, ChemSusChem, 2020, 13, 6246.
H. S. Cho, D. Ding, C. Wang, J. Wu, P. Oleynikov, M. Jia, 13 (a) N. T. Barczak, D. A. Rooke, Z. A. Menard and
J. Cheng, Y. Zhou, O. Terasaki, T. Peng, L. Zan and
H. Deng, Nature, 2020, 586, 549; (c) D. Saito, Y. Yamazaki,
Y. Tamaki and O. Ishitani, J. Am. Chem. Soc., 2020, 142,
19249; (d) H. Zhang, Y. Wang, S. Zuo, W. Zhou, J. Zhang
and X. W. D. Lou, J. Am. Chem. Soc., 2021, 143, 2173.
E. M. Ferreira, Angew. Chem., Int. Ed., 2013, 52, 7579; (b)
J. R. Lawson, E. R. Clark, I. A. Cade, S. A. Solomon and
M. J. Ingleson, Angew. Chem., Int. Ed., 2013, 52, 7518; (c)
M. J. Koh, T. T. Nguyen, H. Zhang, R. R. Schrock and
A. H. Hoveyda, Nature, 2016, 531, 459; (d) T. T. Nguyen,
M. J. Koh, T. J. Mann, R. R. Schrock and A. H. Hoveyda,
Nature, 2017, 552, 347.
4 (a) R. K. Yadav, G. H. Oh, N.-J. Park, A. Kumar, K.-j. Kong and
J.-O. Baeg, J. Am. Chem. Soc., 2014, 136, 16728; (b) Y. A. Wu,
I. McNulty, C. Liu, K. C. Lau, Q. Liu, A. P. Paulikas, 14 (a) T. Xu, C. W. Cheung and X. Hu, Angew. Chem., Int. Ed.,
C. J. Sun, Z. Cai, J. R. Guest, Y. Ren, V. Stamenkovic,
L. A. Curtiss, Y. Liu and T. Rajh, Nat. Energy, 2019, 4, 957.
5 (a) G. Gao, Y. Jiao, E. R. Waclawik and A. Du, J. Am. Chem.
Soc., 2016, 138, 6292; (b) H. Rao, L. C. Schmidt, J. Bonin
and M. Robert, Nature, 2017, 548, 74; (c) L.-Y. Wu,
2014, 53, 4910; (b) L. Wang, J. M. Lear, S. M. Rafferty,
S. C. Fosu and D. A. Nagib, Science, 2018, 362, 225; (c)
X. Zeng, S. Liu, G. B. Hammond and B. Xu, ACS Catal.,
2018, 8, 904; (d) X. Zeng, S. Liu, Y. Yang, Y. Yang,
G. B. Hammond and B. Xu, Chem, 2020, 6, 1018.
´
Y.-F. Mu, X.-X. Guo, W. Zhang, Z.-M. Zhang, M. Zhang and 15 For selected reviews, see: (a) J. P. Brand, D. F. Gonzalez,
T.-B. Lu, Angew. Chem., Int. Ed., 2019, 58, 9491.
S. Nicolai and J. Waser, Chem. Commun., 2011, 47, 102; (b)
A. Yoshimura and V. V. Zhdankin, Chem. Rev., 2016, 116,
3328; (c) Y. Li, D. P. Hari, M. V. Vita and J. Waser, Angew.
Chem., Int. Ed., 2016, 55, 4436; (d) D. P. Hari, P. Caramenti
and J. Waser, Acc. Chem. Res., 2018, 51, 3212.
ˇ
¨
6 (a) S. Wang, B.-Y. Cheng, M. Srsen and B. Konig, J. Am. Chem.
Soc., 2020, 142, 7524; (b) H. Wang, Y. Gao, C. Zhou and G. Li,
J. Am. Chem. Soc., 2020, 142, 8122; (c) H. Huang, J.-H. Ye,
L. Zhu, C.-K. Ran, M. Miao, W. Wang, H. Chen, W.-J. Zhou,
Y. Lan, B. Yu and D.-G. Yu, CCS Chem., 2020, 2, 1746; (d) 16 For selected recent examples, see: (a) J. Wu, X. Deng,
D. Kong, M. Munch, Q. Qiqige, C. J. C. Cooze,
B. H. Rotstein and R. J. Lundgren, J. Am. Chem. Soc., 2021,
H. Hirao and N. Yoshikai, J. Am. Chem. Soc., 2016, 138,
9105; (b) J. Wu, K. Xu, H. Hirao and N. Yoshikai, Chem.–
© 2021 The Author(s). Published by the Royal Society of Chemistry
Chem. Sci.

View Article Online
Chemical Science
Edge Article
Eur. J., 2017, 23, 1521; (c) B. Liu, C.-H. Lim and G. M. Miyake,
J. Am. Chem. Soc., 2018, 140, 12829; (d) P. Caramenti,
N. Declas, R. Tessier, M. D. Wodrich and J. Waser, Chem.
Sci., 2019, 10, 3223; (e) R. Tessier, J. Ceballos, N. Guidotti,
R. Simonet-Davin, B. Fierz and J. Waser, Chem, 2019, 5,
2243; (f) W. Ding, J. Chai, C. Wang, J. Wu and N. Yoshikai,
J. Am. Chem. Soc., 2020, 142, 8619; (g) B. Liu, J. V. Alegre-
Requena, R. S. Paton and G. M. Miyake, Chem.–Eur. J.,
2020, 26, 2386.
A. Clausen, M. Kubryk, S. Krska, T. Rosner, B. Simmons,
J. Balsells, N. Ikemoto, Y. Sun, F. Spindler, C. Malan,
E. J. J. Grabowski and J. D. Armstrong, J. Am. Chem. Soc.,
2009, 131, 8798; (d) A. E. M. Blom, H. R. Campello,
H. A. Lester, T. Gallagher and D. A. Dougherty, J. Am.
Chem. Soc., 2019, 141, 15840; (e) E. A. Stone, K. J. Cutrona
and S. J. Miller, J. Am. Chem. Soc., 2020, 142, 12690; (f)
S. v. Hoppe, J. J. M. Rood, L. Buil, E. Wagenaar,
R. W. Sparidans, J. H. Beijnen and A. H. Schinkel, Mol.
Pharmaceutics, 2018, 15, 5124; (g) M. Thevis, K. Walpurgis
and A. Thomas, Anal. Chem., 2020, 92, 506.
17 (a) W. Xiong, C. Qi, H. He, L. Ouyang, M. Zhang and H. Jiang,
Angew. Chem., Int. Ed., 2015, 54, 3084; (b) Y. Peng, J. Liu,
C. Qi, G. Yuan, J. Li and H. Jiang, Chem. Commun., 2017, 23 (a) J. L. Magee, W. Shand Jr and H. Eyring, J. Am. Chem. Soc.,
53, 2665; (c) W. Xiong, C. Qi, R. Cheng, H. Zhang, L. Wang,
D. Yan and H. Jiang, Chem. Commun., 2018, 54, 5835; (d)
L. Wang, C. Qi, R. Cheng, H. Liu, W. Xiong and H. Jiang,
Org. Lett., 2019, 21, 7386; (e) W. Xiong, R. Cheng, B. Wu,
W. Wu, C. Qi and H. Jiang, Sci. China: Chem., 2020, 63,
1941, 63, 677; (b) A. Singh, C. J. Fennell and J. D. Weaver,
Chem. Sci., 2016, 7, 6796; (c) J. J. Molloy, T. Morack and
R. Gilmour, Angew. Chem., Int. Ed., 2019, 58, 13654; (d)
¨
J. J. Molloy, M. Schafer, M. Wienhold, T. Morack,
C. G. Daniliuc and R. Gilmour, Science, 2020, 368, 302.
331; (f) R. Cheng, C. Qi, L. Wang, W. Xiong, H. Liu and 24 CCDC 2041439 ((E)-3aca) contains the supplementary
H. Jiang, Green Chem., 2020, 22, 4890; (g) L. Wang, crystallographic data for this paper.†
P. Wang, T. Guo, W. Xiong, B. Kang, C. Qi, G. Luo, Y. Luo 25 (a) A. D. Finke, O. Dumele, M. Zalibera, D. Confortin, P. Cias,
and H. Jiang, Org. Chem. Front., 2021, 8, 1851.
18 (a) C. G. S. Lima, T. d. M. Lima, M. Duarte, I. D. Jurberg and
G. Jayamurugan, J.-P. Gisselbrecht, C. Boudon,
W. B. Schweizer, G. Gescheidt and F. Diederich, J. Am.
Chem. Soc., 2012, 134, 18139; (b) A. D. Finke, S. Haberland,
W. B. Schweizer, P. Chen and F. Diederich, Angew. Chem.,
Int. Ed., 2013, 52, 9827; (c) P. Preethalayam, K. S. Krishnan,
S. Thulasi, S. S. Chand, J. Joseph, V. Nair, F. Jaroschik and
K. V. Radhakrishnan, Chem. Rev., 2017, 117, 3930.
˜
M. W. Paixao, ACS Catal., 2016, 6, 1389; (b) B. Liu, C.-H. Lim
and G. M. Miyake, J. Am. Chem. Soc., 2017, 139, 13616; (c)
G. E. M. Crisenza, D. Mazzarella and P. Melchiorre, J. Am.
Chem. Soc., 2020, 142, 5461; (d) C. Wang, R. Qi, H. Xue,
Y. Shen, M. Chang, Y. Chen, R. Wang and Z. Xu, Angew.
Chem., Int. Ed., 2020, 59, 7461; (e) B. Sun, X. Shi, 26 CCDC 2041440 (9) contains the supplementary
X. Zhuang, P. Huang, R. Shi, R. Zhu and C. Jin, Org. Lett.,
2021, 23, 1862.
crystallographic data for this paper.†
¨
27 D. P. Hari and B. Konig, Chem. Commun., 2014, 50, 6688.
19 For selected reviews, see: (a) P. Metrangolo, H. Neukirch, 28 (a) M. Zhu, C. Zheng, X. Zhang and S.-L. You, J. Am. Chem.
T. Pilati and G. Resnati, Acc. Chem. Res., 2005, 38, 386; (b)
G. Cavallo, P. Metrangolo, T. Pilati, G. Resnati,
M. Sansotera and G. Terraneo, Chem. Soc. Rev., 2010, 39,
Soc., 2019, 141, 2636; (b) Z. Zhang, D. Yi, M. Zhang, J. Wei,
J. Lu, L. Yang, J. Wang, N. Hao, X. Pan, S. Zhang, S. Wei
and Q. Fu, ACS Catal., 2020, 10, 10149.
3772; (c) G. Cavallo, P. Metrangolo, R. Milani, T. Pilati, 29 J. Cioslowsk, J. Am. Chem. Soc., 1989, 111, 8336.
A. Priimagi, G. Resnati and G. Terraneo, Chem. Rev., 2016, 30 K. Teegardin, J. I. Day, J. Chan and J. Weaver, Org. Process
116, 2478.
Res. Dev., 2016, 20, 1156.
20 M. Hulla and P. J. Dyson, Angew. Chem., Int. Ed., 2020, 59, 31 (a) J. B. Metternich and R. Gilmour, J. Am. Chem. Soc., 2015,
1002.
137, 11254; (b) J. B. Metternich and R. Gilmour, J. Am. Chem.
Soc., 2016, 138, 1040; (c) C. Zhu, H. Yue, B. Maity,
I. Atodiresei, L. Cavallo and M. Rueping, Nat. Catal., 2019,
2, 678; (d) C. Onneken, K. Bussmann and R. Gilmour,
Angew. Chem., Int. Ed., 2020, 59, 330; (e) J. J. Molloy,
21 CCDC 2041438 ((Z)-3fa) contains the supplementary
crystallographic data for this paper.†
22 (a) C. J. Wenthur, M. R. Bennett and C. W. Lindsley, ACS
Chem. Neurosci., 2014, 5, 14; (b) B. M. Cohen, P. Q. Harris,
R. I. Altesman and J. O. Cole, Am. J. Psychiatry, 1982, 139,
1165; (c) K. B. Hansen, Y. Hsiao, F. Xu, N. Rivera,
¨
M. Schafer, M. Wienhold, T. Morack, C. G. Daniliuc and
R. Gilmour, Science, 2020, 368, 302.
Chem. Sci.
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