Facile Syntheses of N-Heterocyclic Carbene Precursors through I2- or NIS-Promoted Amidiniumation of N-Alkenyl Formamidines

Article abstract of DOI:10.1002/asia.201600182

We have developed I₂- or N-iodosuccinimide (NIS)-mediated amidiniumation of N-alkenyl formamidines for the syntheses of cyclic formamidinium salts, some of which could be directly used as N-heterocyclic carbene (NHC) precursors. Treatment of io

Full text of DOI:10.1002/asia.201600182

DOI: 10.1002/asia.201600182
Communication
Iodoamination
Facile Syntheses of N-Heterocyclic Carbene Precursors through I2-
or NIS-Promoted Amidiniumation of N-Alkenyl Formamidines
Jing Li,[a] Jiajun Jiao,[a] Caiyun Zhang,[a] Min Shi,[a, b] and Jun Zhang*[a]
mamidine salts, which are potentially direct precursors of
Abstract: We have developed I2- or N-iodosuccinimide
(NIS)-mediated amidiniumation of N-alkenyl formamidines
NHCs (Scheme 1a).[9] Very recently, we found an efficient N-io-
dosuccinimide (NIS) mediated aminoamidiniumation of N-al-
for the syntheses of cyclic formamidinium salts, some of
kenyl formamidines for the synthesis of bicyclic imidazolidini-
which could be directly used as N-heterocyclic carbene
um salts (Scheme 1b).[10] Herein, we report I2- or NIS-mediated
(NHC) precursors. Treatment of iodine-containing forma-
amidiniumation of N-alkene formamidines for the syntheses of
midinium salts with Al2O3 led to the formation of cyclic
cyclic formamidinium salts, some of which were previously un-
formamidinium salts with an unsaturated backbone. A
known and which could be used directly as NHC precursors
rhodium(I) complex ligated by a representative NHC was
(Scheme 1c). Treatment of iodine-containing formamidinium
prepared by the reaction of [Rh(cod)Cl]2 (cod=1,5-cyclo-
octadiene) with the free carbene obtained in situ from de-
protonation of the corresponding formamidinium salts.
The NHCs prepared in situ can also react with S8 to afford
the corresponding thiones.
Over the last decade, N-heterocyclic carbenes (NHCs) have
been paid much attention due to their widespread and spec-
tacular applications as ligands for organometallic catalysis and
as organocatalysts.[1] Since the steric and electronic properties
of NHCs play a prominent role in catalysis, a variety of fascinat-
ing new NHCs with different scaffolds have been developed, in
which of special interest are electronic and steric variations re-
sulting from different backbone structures and substituents on
the NHCs.[1h,2] The deprotonation of the heterocyclic ring pre-
cursor is by far the most commonly used method to obtain
a free or ligated NHC, and the most frequently used precursor
of NHC is cyclic formamidinium salt.[2b]
We have developed several synthetic strategies for the syn-
thesis of various NHC precursor salts through cyclization of
functionalized formamidines, such as N-alcohol,[3–5] N-carbon-
yl,[6,7] and N-alkynyl formamidines.[8] Bertrand and co-workers
Scheme 1. Synthetic strategies for the synthesis of various NHC precursor
salts through cyclization of N-alkenyl formamidines.
reported that protonated N-alkenyl formamidines could under-
go cyclization under gentle heating, resulting in the cyclic for-
salts with Al2O3 led to the formation of cyclic formamidinium
salts with an unsaturated backbone. The synthetic methodolo-
gy was applied to synthesize a novel bisimidazolidinium salt. A
rhodium(I) complex ligated by a representative NHC can be
prepared by the reaction of [Rh(cod)Cl]2 (cod=1,5-cycloocta-
diene) with the free carbene obtained in situ. The transforma-
tion of the resulting NHCs into the corresponding thiones is
also presented.
[a] J. Li, J. Jiao, C. Zhang, Prof. Dr. M. Shi, Dr. J. Zhang
Key Laboratory for Advanced Materials and Institute of Fine Chemicals
School of Chemistry&Molecular Engineering
East China University of Science and Technology
130 Mei Long Road, Shanghai 200237 (China)
E-mail: zhangj@ecust.edu.cn
[b] Prof. Dr. M. Shi
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
Iodine reagents are often used to activate and oxidize al-
kenes through the formation of halonium ions and have been
successfully applied in the aminohalogenation of alkenes.[11]
We started our investigation by allowing I2 to react with N-
354 Fenglin Road, Shanghai 200032 (China)
Supporting information for this article can be found under http://
dx.doi.org/10.1002/asia.201600182.
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alkene formamidines 1a–1j, which were synthesized through
alkylation or acylation of the N,N’-diarylformamidines (Scheme
S1, see the Supporting Information). I2 (1.2 equiv) efficiently
promoted the iodoamination cyclization of N-alkenyl formami-
dines to afford iodine-containing formamidinium salts. Forma-
midines with sterically demanding aryl N substituents, such as
mesityl (Mes) and 2,6-diisopropylphenyl (Dipp) groups, were
reactive under the applied conditions (Entries 1 and 2, Table 1).
Formamidine 1c having an ortho-monosubstituted aryl group
at the nitrogen atom also underwent cyclization to afford the
corresponding five-membered imidazolinium salt 2c in moder-
ate yield (Entry 3, Table 1). Besides aryl groups, an alkyl group
at the nitrogen atom was also tolerated (Entry 4, Table 1). Fur-
ther study revealed the methodology also allowed access to
six-membered 3,4,5,6-tetrahydropyrimidinium salts 2e and 2 f
with sterically demanding aryl N substituents (Entries 5 and 6,
Table 1). Six-membered formamidinium salts 2g with a carbon-
yl-containing backbone and 2h with a fused benzene ring at
the backbone also could be obtained by the method in mod-
erate yield (Entries 7 and 8, Table 1). Iodoamination cyclization
of N-2-allylphenyl 1i afforded seven-membered formamidini-
um salt 2i (Entry 9, Table 1), while 1j, the isomer of 1i, under-
went cyclization to give an acyclic formamidinium salt 2j
(Entry 10, Table 1). The X-ray crystal structures of 2h, 2i, and 2j
confirmed their constitutions (Figure 1–3).
Table 1. I2-mediated amidiniumation of N-alkene formamidines.[a]
Entry
1
Starting Material
Product (Yield)[b]
Figure 1. Molecular structure of 2h with ellipsoids set at 20% probability.
The counterion (IÀ) and H atoms in aryl rings have been omitted for clarity.
(69%)
(67%)
2
3
4
5
(51%)
(64%)
(85%)
Figure 2. Molecular structure of 2i.C6H5CH3 with ellipsoids set at 20% proba-
bility. The counterion (IÀ), C6H5CH3, and H atoms in aryl rings have been
omitted for clarity.
6
7
(85%)
(67%)
8
(73%)
(43%)
(68%)
Figure 3. Molecular structure of 2j with ellipsoids set at 20% probability.
The counterion (IÀ) and H atoms in aryl rings have been omitted for clarity.
9
Next, NIS was examined in the iodoamination cyclization of
N-alkene formamidines (Table 2). In contrast to the I2-mediated
iodoamination cyclization, under activation of NIS, N,N’-diaryl
formamidines 1a or 1b underwent cyclization to afford 2-iodo
imidazolium salts 4 or 5, respectively (Entries 1 and 2, Table 2).
Treatment of N-3-butenyl formamidine 1c and 1d with NIS led
to the formation of six-membered formamidinium salt 6 and 7,
10
[a] Reaction conditions: 1.2 equiv I2, toluene, 258C, 2–5 h. Cy=cyclohexyl,
Bn=benzyl. [b] Isolated yields.
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Table 2. NIS-mediated amidiniumation of N-alkene formamidines.[a]
Table 3. Synthesis of various unsaturated NHC precursors through HI
elimination of iodine-containing NHC precursors.[a]
Entry
1[c]
Starting Material
Product (Yield)[b]
Entry
1
Starting Material
Product (Yield)[b]
(72%)
(35%)
2[c]
(82%)
2
3
(90%)
(70%)
3
4
(46%)
(92%)
4
5
6
(97%)
(95%)
(74%)
5
6
(47%)
(32%)
[a] Reaction conditions: 2.0 equiv of NIS, toluene, 258C, 8 h. [b] Isolated
yields. [c] 608C
[a] Reaction conditions: Al2O3, CH2Cl2, 258C, 3 h. [b] Isolated yields.
respectively, having an exomethylene group (Entries 3 and 4,
Table 2). Cyclization products 4–7 probably resulted from the
HI elimination of the corresponding iodine-containing cyclic
formamidinium salts 2a, 2b, 2e, and 2 f. The HI elimination
may be promoted by succinimide, a byproduct often released
from NIS-mediated reactions. NIS-mediated iodoamination of
1i and 1j resulted in the same cyclization products 2i and 2j
as in I2-mediated cyclization (Entries 5 and 6, Table 2). The
structure of 4 was confirmed by the X-ray crystallography (Fig-
ure S1 in the Supporting Information).
tion by KN(SiMe3)2 (KHMDS) and after reaction with S8 afforded
a dithione compound 13, the structure of which has been con-
1
firmed by NMR and HRMS analyses [Eq. (1)]. H NMR analysis of
13 exhibits only one set of proton signals in the aliphatic re-
gions, indicating a symmetric structure of 13. The 13C NMR sig-
nals for C=S appear at d=181.7 ppm for 13. Imidazolidine-2-
thiones are important vicinal diamine derivatives, which exhibit
a wide range of biological and pharmaceutical activities,[13] rep-
resent supported ligands in bioactive coinage metal com-
plexes,[14 ]and serve as important precursors for the preparation
of guanidines.[15]
With iodine-containing cyclic formamidinium salts in hand,
we further evaluated their reactivity. Recently, Diaba and Bon-
joch et al. reported an Al2O3-promoted transformation of g-io-
doamines, iodoaminocyclization products of b-aminoalkenes,
into b-aminoalcohols.[12] Interestingly, under treatment of alu-
mina (Al2O3), instead of alcohol-containing product, five-mem-
bered imidazolinium salts 2a, 2b and 2d smoothly underwent
HI elimination, leading to the formation of the corresponding
imidazolium salts 8–10 through HI elimination (Entries 1–3,
Table 3). Six-membered formamidinium salts 6, 7, and 11
having an exomethylene group were obtained through HI
elimination of 2e, 2 f, and 2h, respectively (Entries 4–6,
Table 3).
Using the established iodoamination cyclization method, we
could also synthesize a kind of novel bisimidazolinium salt.
Treatment of vinylene-bridged N-Mes bisformamidine 1k with
I2 resulted in the formation of a bisimidazolinium salt 12. The
in situ prepared 12 subsequently underwent the deprotona-
We further attempted to synthesize an N-Dipp counterpart
of bisimidazolinium salt 12. Disappointingly, when we treated
N-Dipp bisformamidine 1l with I2, we obtained only a mixture
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of several cyclization products which were difficult to separate.
All attempts to purify the products failed. NIS was then exam-
ined in the transformation. Treatment of 1l with three equiva-
lents of NIS afforded a new kind of cyclization product 14
[Eq. (2)]. X-ray crystallography reveals there is only one five-
membered formamidine salt formed in 14 (Figure 4), probably
due to the presence of the two bulkier N-Dipp substituents in
1l, preventing the second cyclization process.
NHC precursors. Treatment of iodine-containing formamidini-
um salts with Al2O3 led to the formation of cyclic formamidini-
um salts with unsaturated backbones. Rhodium(I) complex li-
gated by a representative NHC was prepared by the reaction
of [Rh(cod)Cl]2 with the free carbene obtained in situ from the
deprotonation of the corresponding formamidinium salts. The
NHCs prepared in situ can also react with S8 to afford the cor-
responding thiones.
Acknowledgements
Financial support from Shanghai Pujiang Talent Program
(11J1402500) and the National Natural Science Foundation of
China (21171056) is gratefully acknowledged.
Figure 4. Molecular structure of 14 with ellipsoids set at 20% probability.
The counterion (IÀ) and H atoms in aryl rings have been omitted for clarity.
Keywords: alkenes · iodine · iodoamination · N-heterocyclic
carbenes · N-iodosuccinimide
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Manuscript received: February 14, 2016
Accepted Article published: March 9, 2016
Final Article published: March 30, 2016
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