λ3-Iodanes as Visible Light Photocatalyst in Thioacetalization of Aldehydes

Article abstract of DOI:10.1002/ejoc.201900753

Introduction of an iodine(III) reagent as visible-light photocatalyst for chemoselective dithioacetalization has been the limelight of the current methodology. The mechanistic investigations reveal that the reactions proceeded via radical pathway upon lig

Full text of DOI:10.1002/ejoc.201900753

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Accepted Article
Title: λ3-Iodanes as Visible Light Photocatalyst in Thioacetalization of
Aldehydes
Authors: Khokan Choudhuri, MILAN PRAMANIK, and Prasenjit Mal
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10.1002/ejoc.201900753
European Journal of Organic Chemistry
COMMUNICATION
λ3-Iodanes as Visible Light Photocatalyst in Thioacetalization of
Aldehydes
Khokan Choudhuri,[a] Milan Pramanik,[a] and Prasenjit Mal*[a]
Abstract: Introduction of an iodine(III) reagent as visible-light
photocatalyst for chemoselective dithioacetalization has been the
limelight of the current methodology. The mechanistic investigations
reveal that the reactions proceeded via radical pathway upon light
induced hemolytic cleavage of C-I bond of the catalyst. Several
dithioacetals were easily accessible at room temperature and
environmentally benign condition.
photocatalyst.[20]{Ji, 2016 #11838} Herein, we demonstrate a mild
and facile method for a chemoselective dithioacetalization
reaction of several aromatic and aliphatic aldehydes using
iodine(III) reagent as a visible light photocatalyst.
Introduction
Many organosulfur compounds[1] are biologically and
pharmaceutically active, and ubiquitously found in many natural
products. Dithioacetals serve as key intermediates[2] in many
natural products synthesis like jatrophone, (-) bertyadionol,
rapamycin, discodermolide, etc.[3] In particular, dithioacetals are
commonly used as protecting group of carbonyls as well as
directing groups for C-H activation reactions.[4] The dithioacetals
are also known to be used as important precursors for alkylation,[5]
fluorination,[6] hydrogenolysis,[7] olefination[8] and autooxidation[9]
reaction, etc. The known approaches for the synthesis of
dithioacetals include the use of metal catalysts,[10] metal free
catalyst,[11] Lewis acid catalysts,[12] resin bound solid phase
synthesis[13] and phase transfer catalysts.[14] However in most
cases, these methods have limitation due to the use of hazardous
chemicals, formation of undesired side products and lack of
chemoselectivity. Therefore, chemo selective synthesis of
dithioacetal under mild conditions are highly desirable.
Figure 1. List of the iodine(III) derivatives used herein as visible light
photocatalyst.
Figure 1 enlists the iodine(III) reagents used for present study.
We have anticipated that the presence of nitro groups at aryl
moiety of 4d is expected to have strong absorption at visible
region. Therefore 4d is expected to respond better as visible light
photocatalyst than 4a, 4b and 4c.
Over past decade, the research area under visible light
photocatalyst has become one of the powerful techniques in
organic synthesis.[15] Interestingly, the photoredox catalysts are
mild in nature, have high functional group tolerance ability which
make them popular in organic synthesis. Moreover, the commonly
used visible light photocatalysts are either pollutant organic
dyes[16] or expensive metal complexes of Ru- and Ir- metals.[17] So,
their use in industrial, medicinal and pharmaceutical applications
are commonly restricted. Recently, the use of iodine based
reagent as photocatalyst is getting popular.[18] Nevertheless, this
research field needs significant improvement and very few reports
are available for the use of hypervalent iodine reagents[19] as
Results and Discussion
Maruoka’s group have developed hydroacylation of branched
aldehydes using λ3-iodane reagent as visible light photocatalyst
via generating of acyl radical from aldehyde (Figure 2a).[18c, 21]
Similarly, upon irradiation at 400 nm, synthesis of ester directly
from alkyl benzene using bis(trifluoroacetoxy)iodo]benzene
(PIFA) could be achieved as shown in Figure 2b.[18b] Recently,
Lee group has reported Eosin Y catalyzed thioacetalization of
aldehyde under visible light.[22] Our chemoselective approach on
dithioacetylation of aldehyde under photolytic condition using
iodine(III) reagent is depicted in Figure 2d.
The reaction condition was optimized using 4-bromo
benzaldehyde (1a) and thiophenol (2a) as model substrates
(Table 1). The reaction mixture was taken in appropriate solvents
under inert condition and exposed to visible light obtained from
3W LED bulb at room temperature. Among the iodine(III) catalysts
examined (entries 1-4), 4d was found to be superior and yielded
3aa with 94% yield (entry 4). The decrement of catalyst loading to
10 mol % led to lesser amount of product formation (entry 5). Poor
yield (ca. 10%) of 3aa was obtained when the reaction was carried
[a]
Mr. K. Choudhuri, Mr. M. Pramanik, Dr. P. Mal
School of Chemical Sciences, National Institute of Science
Education and Research (NISER), HBNI, Bhubaneswar, PO
Bhimpur-Padanpur, Via Jatni, District Khurda, Odisha 752050, India
E-mail: pmal@niser.ac.in; homepage:
https://www.niser.ac.in/users/pmal#profile-main
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201900753
European Journal of Organic Chemistry
COMMUNICATION
Table 1. Condition Optimization.
out under open atmosphere (entry 6). However, the reaction
completely failed either at dark condition (entry 7) or in absence
of any catalyst (entry 8). No significant improvement of results
were obtained when the solvents were changed to DMSO, DCE,
THF and EtOH (entries 9-12). Use of other light sources than 3W
blue LED did not lead to any encouraging results (entries 13-16).
entry
1
catalyst
4a
solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMSO
DCE
Light Source
3aa (%)a
27
3W Blue LED
3W Blue LED
3W Blue LED
3W Blue LED
3W Blue LED
3W Blue LED
under dark condition
3W Blue LED
3W Blue LED
3W Blue LED
3W Blue LED
3W Blue LED
10W Blue LED
15W Green LED
10W White LED
15W CFL
2
4b
35
3
4c
72
4
4d
94
5
4d
75b
10c
NRd
NRd
NRd
30
6
4d
7
4d
8
none
4d
9
10
11
12
13
14
15
16
4d
4d
THF
10
4d
EtOH
21
4d
CH3CN
CH3CN
CH3CN
CH3CN
94
4d
85
4d
65
4d
77
aReaction condition: 1a (0.324 mmol), 2a (0.648 mmol), and 4d (20 mol %), in
dry CH3CN, irradiation with 3W blue LED for 18 h. b4d was used as 10 mol %.
cat open air. dno conclusive results.
Figure 2. a) Hypervalent iodine catalyzed C-C bond formation reactions using
UV light.[21a] b) Visible light mediated C-O bond formation using iodine(III)
reagent.[18b] c) Dithioacetalization of aldehydes using Eosin Y.[22] d) Our
thioacetalization approach based on λ3-iodanes as visible light photocatalyst.
Under optimized condition,
a variety of thioacetals were
synthesized using thiophenols and 4-bromobenzaldehyde (Figure
3). Electron donating group (-Me, -OMe) at the thiophenol ring
provided excellent yield of the products (3ac, 3ah). However,
relatively poor yield was obtained when electron withdrawing
group -CF3 was attached (3af). Aliphatic thiols i.e.,
phenylmethanethiol and propane-1,3-dithiol led to give excellent
yield 3ai and 3aj respectively. Halogenated thiophenols were well
tolerated under the optimized reaction condition and
corresponding products 3ab, 3ae and 3ag were obtained in good
to excellent yield with -Br, -F and -Cl derivatives, respectively.
Figure 3. Results of thioacetalization reaction (isolated yield); Conditions: 1a
(0.324 mmol), 2a (0.648 mmol), and 4d (0.064 mmol), in 2.0 mL CH3CN; a) C-
S coupled product using different kind of thiophenol.
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10.1002/ejoc.201900753
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COMMUNICATION
We have also established the chemoselectivity and functional
group tolerance of the reaction (Figure 5). Delightfully, when both
keto and aldehyde groups were reacted under the standard
condition only thioacetylation product from the aldehyde
functionality were formed (3pa, 3na, 3oa, 3qi). Similarly,
aldehyde group selectively reacted in presence of ester group to
produce 3ma.
The optimized reaction condition was further extended to various
aldehydes (3b to 3s) to verify the significance of the methodology
(Figure 4). In presence of 20 mol % of catalyst 4d and under inert
atmosphere, structurally diverse thioacetalization products were
isolated in good yields. Aromatic aldehydes with electron donating
groups led to formation of products in high yields (3bb, 3cb, 3db,
3eb, 3fc). However, relatively poor yields were obtained for the
aldehydes with electron withdrawing substituents (3gc, 3hc, 3ia,
3ja). Heteroaromatic thiophene-2-carbaldehyde reacted smoothly
to afford the desired product 3la in 87% yield. It is noteworthy to
mention that, 3-phenylbutanal and 2-phenylacetaldehyde also
served to afford the desired product (3rb, 3sb) in very good yields,
respectively. Our methodology was unsuccessful for the aliphatic
aldehydes with aliphatic thiols. However, very poor yield was
observed with acetophenone (~5%, Figure 6).
To get insight into the mechanism of the reaction, control
experiments were performed shown in Figure 6. When 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO) was employed under
optimized condition (Figure 6a), the reaction was completely
inhibited. This fact suggested that the radical pathway could be
operative for the photo-transformation. Similarly, under standard
condition any thioacetylated product 3aa was not obtained from
the disulfide 5 (Figure 6b). This observation ruled out the
possibility for the involvement of any disulfide intermediate. The
chemoselectivity experiment (Figure 6c) was performed using 1.0
equiv of both 1a and 4-bromoacetaphenone under optimized
condition and 3aa was isolated in 91 % yield as the single product.
This was possible due to formation of a sterically crowded
tetrahedral intermediate 6 generated from acetophenone (Figure
6e) which dictates the origin of chemoselectivity. This statement
was further supported, when acetophenone was treated under
standard condition and the product 7 was detected ca. 5% (NMR
analysis, Figure 6d).
Figure 4. Scope of thioacetalization reaction using different benzaldehyde
derivatives; Conditions: 1a (0.324 mmol), 2a (0.648 mmol), and 4d (0.064 mmol),
in 2.0 mL CH3CN.
Figure 6. Control experiments.
Based on the control experiment and literature reports,[18c, 21-23]
a
plausible chain mechanism is proposed in Figure 7. By
photochemical initiation of the reaction, iodine(III) reagent 4d led
to the formation of acyloxy radical intermediate 8. Following, the
radical intermediate 8 might have helped to generate thiyl radical
9 from thiophenol. The thiyl radical 9 upon reaction with the
aldehydes formed the intermediate 10. Now during the
propagation of the chain reaction, we anticipate that the
intermediate 10 abstracted the hydrogen from thiophenol to
generate the hemithioacetal 11.[22] Thus it is expected that the
Figure 5. Chemoselective thioacetalization reaction.
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European Journal of Organic Chemistry
COMMUNICATION
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product 3 with the reaction from thiophenol via intermediate 12 in
presence of 2,4-dinitrobenzoic acid.[22]
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Figure 7. A generalized mechanism for the thioacetalization is proposed which
works under visible light photocatalyst via radical mechanism.
Conclusions
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In summary, herein we report a dithioacetalization of aldehydes
using an iodine(III) reagent as visible-light photocatalyst. The
developed method is chemoselective, mild, atom-economical and
operationally simple. Several dithioacetals could be easily
accessed at room temperature and under environmentally benign
condition from a variety of aliphatic and aromatic aldehydes in
good to excellent yields. This facile and mild condition also
tolerated several functional groups. Overall, this methodology is
utilized to construct C-S bonds, which might have a wide
application in synthesizing complex molecules.
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Acknowledgments
We thank Debasis Sahoo for helping us to optimize the conditions.
M.P. and K. C. thank NISER for fellowships. We thank CSIR for
funding (Project No. 02(0338)/18/EMR-II dated 24-04-2018).
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Keywords: C-S Coupling • λ3-Iodanes • Iodine(III) • Organo-
photocatalyst • Visible Light
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10.1002/ejoc.201900753
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Introducing iodine(III) reagent as
visible-light photo-catalyst for the
chemoselective thioacetalization of
aldehydes. Mechanistically shown that
the reactions proceeded via radical
pathway upon light induced hemolytic
cleavage of C-I bond of the catalyst.
Iodine(III) Photocatalyst*
Khokan Choudhuri, Milan Pramanik and
Prasenjit Mal*
Page No. – Page No.
λ3-Iodanes as Visible Light
Photocatalyst in Thioacetalization of
Aldehydes
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