Iodothiocyanation/Nitration of Allenes with Potassium Thiocyanate/Silver Nitrite and Iodine

Article abstract of DOI:10.1002/adsc.201600304

Direct strategies for the iodothiocyanation and iodonitration of allenes have been developed. In this process, potassium thiocyanate/silver nitrite and molecular iodine are used as the source of SCN, ONO₂and iodine to provide the desired products in moderate to good yields with high stereoselectivity. (Figure presented.).

Full text of DOI:10.1002/adsc.201600304

UPDATES
DOI: 10.1002/adsc.201600304
Iodothiocyanation/Nitration of Allenes with Potassium
Thiocyanate/Silver Nitrite and Iodine
Xiaodong Yang,a Yue She,a Ya Chong,a Huichun Zhai,a He Zhu,a Baohua Chen,a
Guosheng Huang,a and Rulong Yana,*
a
State Key Laboratory of Applied Organic Chemistry, Key laboratory of Nonferrous Metal Chemistry and Resources
Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou, Gansu 730000, Peopleꢀs Republic
of China
Fax : (+86)-0931-891-2596; e-mail: yanrl@lzu.edu.cn
Received: March 19, 2016; Revised: July 8, 2016; Published online: && &&, 0000
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/adsc.201600304.
Abstract: Direct strategies for the iodothiocyana-
tion and iodonitration of allenes have been devel-
oped. In this process, potassium thiocyanate/silver
nitrite and molecular iodine are used as the source
of SCN, ONO2 and iodine to provide the desired
products in moderate to good yields with high ste-
reoselectivity.
in a one-pot process. In the light of sustainable
chemistry, the development of a strategy for the di-
functionalization of allenes with readily accessible re-
agents to achieve the transformations of iodothiocya-
nation and iodonitration is highly desirable.
Keywords: allenes; iodonitration; iodothiocyanation
Modern synthetic organic chemistry benefits tremen-
dously from the advances in the difunctionalization of
allenes providing for the rapid and straight-forward
access to synthetically complex molecules in a single
procedure.[1] A variety of different difunctional strat-
egies have been elegantly demonstrated on olefins,
such as diamination, aminooxygenation, dioxygena-
tion, cyanotrifluoromethylation, fluoroamination,
phosphonofluorination and oxysulfonylation.[2] With
the development of difunctionalization, allene as
a special and potential substrate had received much
attention in difunctionalization for its unique chemi-
cal property.[3] In the past years, some excellent and
significant works on the difunctionalization of allenes
were reported by the group of Ma.[4] In 2013, the
group of Che reported a new approach for the selec-
tive difunctionalization of cysteine-containing pep-
tides through a gold-mediated oxidative allene-thiol
coupling reaction (Scheme 1).[5] Recently, Laali re-
ported a selectfluor-mediated difunctionalization of
allenes with TMSX and NH4SCN.[6] Although signifi-
cant progress has been reported in the difunctionali-
zation of allenes, the scope was mainly restricted to
hydroxythiolation and dithiocyanation simultaneously Scheme 1. The difunctionalization of allenes.
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Organosulfur compounds have served as building ously with NOE experiments. To further improve the
blocks to generate bioactive and pharmaceutical yield, various solvents were tested and these studies
molecules.[7] Especially, the iodothiocyanted allene demonstrated that the reaction could be performed
has found ready use in the synthesis of macromolecu- most efficently in 1,4-dioxane (Table 1, entries 2–9).
lar organosulfur compounds by way of the Negishi By optimizing the reaction temperature, we found
cross-coupling reaction.[8]
that the reaction at 608C led to an improvement in
Commerically available potassium thiocyanate, as yield (Table 1, entries 10–12). On extensive evaluating
an ideal thiolating reagent, has been widely used to of additives such as AgF, CuI, ZnCl2 and trifluoroace-
construct the C–S bond for its stability.[9] Similarly, tic acid (TFA), only lower yields of 3aa were ob-
simple iodine is also widely used in organic synthesis tained. The optimized conditions were thus estab-
and iodo-organic compounds have a broad transfor- lished as 1a (0.5 mmol), 2a (0.75 mmol) and iodine
mation ability to other functional groups.[10] As part (0.6 mmol) in 1,4-dioxane at 608C.
of our investigations on the utilization of iodine in or-
ganic chemistry, herein, we report an iodine-promoted
iodothiocyanation and iodonitration of allene with po-
tassium thiocyanate/silver nitrite.
Table 2. The reactions of substituted allenes and potassium
thiocyanate.
Firstly, buta-2,3-dien-2-ylbenzene (1a) and potassi-
um thiocyanate (2a) were chosen as model substrates
to perform test the reaction in the presence of iodine
in 1,4-dioxane at 608C. To our delight, the reaction
occurred and the product (Z)-(3-iodo-4-thiocyanato-
but-2-en-2-yl) benzene (3aa) was isolated in 86%
yield. The structure of 3aa was confirmed unambigu-
Table 1. Optimization of the reaction conditions.[a]
Entry Additive (mol%) T [oC] Solvent
Yields [%][b]
1
2
3
4
5
6
7
8
none
none
none
none
none
none
none
none
none
none
none
none
60
60
60
60
60
60
60
60
60
r.t.
80
100
60
60
60
60
60
1,4-dioxane 86
DMF
DMSO
NMP
35
26
–
DCE
EtOH
THF
toluene
MeCN
1,4-dioxane
53
47
61
22
36
–
9
10
11
12
13c
14
15
16
17
1,4-dioxane 75
1,4-dioxane 68
1,4-dioxane 85
1,4-dioxane 71
1,4-dioxane 77
1,4-dioxane 66
1,4-dioxane 43
none
ZnCl2 (10)
TFA (10)
AgF (10)
CuI (10)
[a]
Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol),
iodine (0.6 mmol) solvent (2 mL), 608C.
Yields of isolated products.
Under N2. The entry in bold type highlights the opti-
mized reaction conditions, and the reaction time was
monitored by TLC. DMF=N,N-dimethylformamide,
DMSO=dimethyl sulfoxide, NMP=N-methylpyrroli-
done.
[b]
[c]
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With the optimized conditions in hand, the scope of substituted allenes, such as 1t and 1u, were trans-
the substrate allenes was examined and the results are formed under the standard conditions and the target
shown in Table 2. A number of allenes smoothly un- products 3ta and 3ua were isolated in 68% and 56%
derwent this iodothiocyanation and the desired prod- yield, respectively [Scheme 2, Eqs. (3) and (4)]. The
ucts were afforded in moderate to excellent yields substrate 1v with only alkyl substituents was also tol-
with high regioselectivity. As shown in Table 2, the re- erated in this process, the total yield of 3va and 3va’
actions were less affected by the nature of the groups was 55% and the molar ratio of isolated 3va:3va’ was
on the aromatic ring of allenes. The substrates 3h and approximately 1:1 [Scheme 2, Eq. (5)].
3i were employed for this transformation, and the de-
In order to enlarge the scope of this transformation,
sired products 3ha and 3ia were obtained in 56% and further experiments were conducted with more sub-
55% yields. Even on changing R1 from alkyl to aryl, strates, such as AgNO2, AgNO3, NaSO2Ph, AgOTf,
the desired products 3oa and 3pa were also generated NaNO2, AgF. It was gratifying to find that AgNO2
in excellent yields. Nevertheless, the reaction was in- was compatible with this process and gave the prod-
compatible with 1-vinylidene-1,2,3,4-tetrahydronaph- uct (E)-2-iodo-3-phenylbut-2-en-1-yl nitrate 4ab in
thalene, and failed to give the desired product 3qa.
45% yield. After screening the parameters of temper-
It is worth mentioning that when propa-1,2-dien-1- ature, acids and solvents, no better results were ach-
ylbenzene 1r and KSCN were subjected to the opti- ieved. However, it is a facial method for the iodoni-
mized conditions, the products 3ra and 3ra’ were ob- tration of allenes.[12] The scope of this reaction was
tained in 55% and 34% yields [Scheme 2, Eq. (1)]. In- further investigated and the results are illustrated in
terestingly, an unexpected product 3sa was isolated in Table 3. Generally, the reaction between substituted
81% yield when (1-cyclopropylpropa-1,2-dien-1-yl)- allenes and AgNO2 proceeded smoothly and afforded
benzene 1s was employed as the substrate [Scheme 2, the corresponding products in moderate yields. Simi-
Eq. (2)].[11] Further investigation disclosed that poly- larly, the nature of the substituent on the aromatic
Scheme 2. The reactions of substituted allenes and potassium thiocyanate.
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Table 3. The reaction of substituted allenes and AgNO2.
Scheme 4. Proposed mechanism.
the central carbon of allene to form iodonium inter-
mediate I. For the trasformation of 1a and 2a, SCNÀ
quickly combines with I to form 3aa via nucleophilic
addition. For 1a and 2b, similarly, 4ab is generated by
oxidation and nucleophilic addition with AgNO2.
In summary, we have successfully developed an ef-
ficient method for iodothiocyanation and iodonitra-
tion of allenes. The procedure, using iodine and
KSCN/AgNO2, provides a simple and practical ap-
proach to generate the desired products in moderate
to high yields.
Experimental Section
rings of the allenes again did not significantly affect General Procedure for Iodothiocyanation of Allenes
the yields in this reaction.
with Iodine and Potassium Thiocyanate
The versatility of the product 3ba is shown in
Scheme 3 by further transformations into a valuable
product. The product 3ba reacted with phenylmagne-
sium bromide smoothly under mild conditions, thus
yielding (Z)-1-methyl-4-(3-phenyl-4-thiocyanatobut-2-
en-2-yl)benzene 5 in good yield.
To gain insight into the reaction mechanism, several
mechanistic experiments were carried out. The radical
scavengers TEMPO (2,2,6,6,-tetramethylpiperidine 1-
oxyl) and BHT (butylated hydroxytoluene) were also
employed in this transformation, but no influence was
detected. This result suggests that this reaction does
not follow a radical pathway. On the basis of the
above results, a plausible mechanism is depicted in
Scheme 4. The transformation of substrates 1a and 2a/
2b occurs by similar pathways. firstly, iodine attacks
The allene (1a, 0.5 mmol), potassium thiocyanate (2a,
0.75 mmol), and iodine (0.6 mmol) were mixed in 1,4-diox-
ane (2 mL) and this mixture was heated under air at 608C
for 3 h. The reaction mixture was cooled to room tempera-
ture and quenched with water. Then the mixture was
washed with saturated Na2S2O4 solution and extracted with
ethyl acetate (15 mLꢂ3). The combined organic phase was
dried with anhydrous Na2SO4. The solvent was evaporated
under vacuum and the crude product was purified by
column chromatography, eluting with petroleum ether/
EtOAc (20:1) to afford the desired product (Z)-(3-iodo-4-
thiocyanatobut-2-en-2-yl)benzene (3aa).
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21672086, 21403256) and the Funda-
mental Research Funds for the Central Universities (lzujbky-
2016-39).
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6 Iodothiocyanation/Nitration of Allenes with Potassium
Thiocyanate/Silver Nitrite and Iodine
Adv. Synth. Catal. 2016, 358, 1 – 6
Xiaodong Yang, Yue She, Ya Chong, Huichun Zhai,
He Zhu, Baohua Chen, Guosheng Huang, Rulong Yan*
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