Rhodium-Catalyzed Generation of Anhydrous Hydrogen Iodide: An Effective Method for the Preparation of Iodoalkanes

Article abstract of DOI:10.1021/acs.orglett.8b02980

The preparation of anhydrous hydrogen iodide directly from molecular hydrogen and iodine using a rhodium catalyst is reported for the first time. The anhydrous hydrogen iodide generated was proven to be highly active in the transformations of alkenes, phenyl aldehydes, alcohols, and cyclic ethers to the corresponding iodoalkanes. Therefore, the present methodology not only has provided convenient access to anhydrous hydrogen iodide but also offers a practical preparation method for various iodoalkanes in excellent atom economy.

Full text of DOI:10.1021/acs.orglett.8b02980

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Rhodium-Catalyzed Generation of Anhydrous Hydrogen Iodide: An
Effective Method for the Preparation of Iodoalkanes
Chaoyuan Zeng,† Guoli Shen,† Fan Yang,† Jingchao Chen,*,† Xuexin Zhang,† Cuiping Gu,†
Yongyun Zhou,† and Baomin Fan*,†,‡
†YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming 650500, China
‡Key Laboratory of Chemistry in Ethnic Medicinal Resources, Yunnan Minzu University, Kunming 650500, China
S
* Supporting Information
ABSTRACT: The preparation of anhydrous hydrogen iodide
directly from molecular hydrogen and iodine using a rhodium
catalyst is reported for the first time. The anhydrous hydrogen
iodide generated was proven to be highly active in the
transformations of alkenes, phenyl aldehydes, alcohols, and
cyclic ethers to the corresponding iodoalkanes. Therefore, the
present methodology not only has provided convenient access
to anhydrous hydrogen iodide but also offers a practical
preparation method for various iodoalkanes in excellent atom
economy.
Table 2. Optimization of Reaction Conditions
odoalkanes, also known as alkyl iodides, are versatile
Ibuilding blocks in organic synthesis due to their outstanding
Table 1. Screening of Ligands and Transition-Metal
a
Precursors
entry
solvent
pressure
yield (%)
1
2
3
4
5
6
7
8
9
toluene
DCE
DCM
DMF
MTBE
DME
toluene
toluene
toluene
40 bar
40 bar
40 bar
40 bar
40 bar
40 bar
10 bar
2 bar
92
84
50
NR
NR
trace
92
92
40
entry
metal
ligand
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Rh(COD)2BF4
Rh(COD)2BF4
Rh(COD)2BF4
Rh(COD)2BF4
Rh(COD)2BF4
Rh(COD)2BF4
Rh(COD)2BF4
[Rh(COD)Cl]2
Rh(CO)2(C5H7O2)
Rh(COD)2SbF6
Rh(COD)2OTf
RhCl3·3H2O
PPh3
75
84
80
72
79
70
77
53
61
72
47
trace
NR
58
56
trace
( )-Binap
Dppe
Dppb
Dppf
atmospheric pressure
a
Reaction conditions: Rh(COD)BF4 (0.01 mmol) and ( )-Binap
xantphos
(0.012 mol) in solvent (2 mL) were stirred at room temperature for
30 min under Ar, and then 1a (0.2 mmol) and I2 (0.2 mmol) were
added. The reaction mixture was stirred in a hydrogen atmosphere.
tricyclohexylphosphine
( )-Binap
( )-Binap
( )-Binap
( )-Binap
( )-Binap
( )-Binap
( )-Binap
( )-Binap
( )-Binap
reaction activities in various reactions such as alkylation,1 cross
coupling,2 reduction,3 addition,4 esterification,5 and the
organometallic transformations.6 The common present meth-
ods for the preparation of iodoalkanes rely on the Finkelstein
reaction7 or iodination8 of the corresponding alcohols.
Although the direct addition of hydrogen iodide to alkenes
has provided an atom-economic strategy for the facile synthesis
of iodoalkanes and has been introduced in many textbooks,9
relevant reports are quite few in the literature due to the low
[Rh(C5Me5)Cl2]2
[Ir(COD)Cl]2
Ru(COD)Cl2
Pd(OAc)2
a
Reaction conditions: Metal (0.01 mmol) and ligand (M:P = 1:1.2)
in toluene (2 mL) was stirred at room temperature for 30 min under
Ar, and then 1a (0.2 mmol) and I2 (0.2 mmol) were added. The
reaction mixture was stirred in a hydrogen atmosphere of 40 bar.
Note: COD = 1,5-cyclooctadiene; [Rh(C5Me5)Cl2]2 = pentamethyl-
cyclopentadienylrhodium(III) chloride dimer.
Received: September 18, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02980
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 3. Scope Exploring of Alkenes
a
Reaction conditions: Rh(COD)BF4 (0.01 mmol) and ( )-Binap (0.012 mol) in toluene (2 mL) were stirred at room temperature for 30 min
b
under Ar, and then 1 (0.2 mmol) and I2 (0.2 mmol) were added. The reaction mixture was stirred in a hydrogen atmosphere of 2 bar. Reacted
under a hydrogen atmosphere of 10 bar.
reaction activity of aqueous hydrogen iodide in the reactions
with alkenes and the uncontrollable iodine liberation of the
gaseous hydrogen iodide.10 Thus, methods have been
developed to obviate this drawback by allowing for the in
situ HI generation via a combination of reagents. The reaction
of silanes and iodine has provided a method for the generation
of anhydrous hydrogen iodide, and its application in
hydroiodination reactions has been reported.11 However, the
unavoidable byproduct iodosilane has weakened its utility,
especially in the chemical industry. Alternative reagents such as
Et3N·HI,12 Al2O3·I2,13 TiI4,14 I2/thiol,15 and Me3SiCl/NaI16
were also developed. Clearly, the development of a practical,
effective, atom-economic, and inexpensive iodination feedstock
is still urgent and is met with broad interest. To the best of our
knowledge, there has been no example of generating
anhydrous hydrogen iodide directly from molecular hydrogen
and iodine.
metal catalyst. The reaction mechanism of hydrogenation
reactions was known as the Horiuti−Polanyi mechanism,18
which describes hydrogen molecule dissociation followed by
the sequential addition of atomic hydrogen to the alkenes. We
envisioned that using iodine as an atomic hydrogen acceptor
might result in the generation of anhydrous hydrogen iodide.
Herein, we report the unprecedented rhodium-catalyzed
preparation of anhydrous hydrogen iodide from hydrogen
and iodine. This robust reagent was successfully applied to the
reaction of alkenes, aldehydes, alcohols, and ethers, affording
various iodoalkanes in one-pot reaction.
Our study commenced with the hydroiodination reaction of
alkenes, carried out by the reaction of hydrogen gas and iodine
with the complex of Rh(COD)BF4 and PPh3 as catalyst and
DCE as solvent, performed under a hydrogen atmosphere of
40 bar (Table 1). To our delight, we have observed the fading
of reddish brown iodine solution, and finally a light yellow
solution resulted after 3 h. After the addition of styrene 1a, the
addition product 1-iodo-1-phenylethane 2a was obtained as
expected in 75% yield over 4 h (Table 1, entry 1). To improve
The hydrogenation reaction of alkenes, which is the most
widely used reaction in the organic chemistry industry,17
represents an example of hydrogen activation by a transition
B
DOI: 10.1021/acs.orglett.8b02980
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
screening results show that the hydroiodination reaction can
proceed in toluene, DCE, and DCM (Table 2, entries 1−3).
Other solvents, including DMF, MTBE, and DME, were not
suitable (Table 2, entries 4−6). The following pressure
experiments indicated that a hydroiodination reaction took
place smoothly at 10 and 2 bar (Table 2, entries 7 and 8).
However, the reaction under atmospheric pressure which was
carried out by using a hydrogen balloon reacted slowly, giving
the desired product only in 40% yield with the majority of 1a
unreacted after 72 h (Table 2, entry 9).
Scheme 1. Reaction of Anhydrous Hydrogen Iodide with
Other Substrates
a
With the optimized reaction conditions in hand [5 mol % of
Rh(COD)2BF4, 6 mol % of Binap, toluene as solvent and
performed at room temperature under 2 bar], the scope and
limitations for this hydroiodination reaction of various alkenes
were investigated. The experimental results are presented in
Table 3. In general, most of the alkene hydroiodination
reactions proceed smoothly to afford the corresponding
iodoalkanes as Markovnikov addition products. Notably, high
reaction yields were achieved by using halogenated styrenes
(Table 3, entries 2−6) and diphenylethenes (Table 3, entries
10−11) with halogen groups kept intact in the products. In
contrast, electron-rich styrenes were less reactive than electron-
poor substrates. For example, the hydroiodination reaction of
para-methyl-styrene 1g only afforded the desired product in a
trace amount under an enhanced pressure of 10 bar (Table 3,
entry 7); trimethyl-2-vinylbenzene 1h and para-methoxyl-
styrene 1i failed to produce any hydroiodination products
(Table 3, entries 8−9). We were delighted to notice the
aliphatic alkenes reacted efficiently to give the corresponding
iodoalkanes (Table 3, entries 12−16). In addition, internal
alkenes also performed well; the reaction of cyclooctene almost
gave quantitative yield (Table 3, entry 17). cis-4-Octene gave a
moderate yield, probably because of its unfavorable electronic
property (Table 3, entry 18). Conjugated alkene, such as
methyl cinnamate, also participated readily in this hydro-
iodination protocol to give the Michael addition product 2s
(Table 3, entry 19).
To our delight, the current methodology was suitable for the
hydroiodination of various phenyl aldehydes by switching the
rhodium precursor and phosphine ligand (Scheme 1a).
Benzaldehyde was converted to benzyl iodide 4a under the
standard conditions, and its derivatives with methyl or
methoxyl substitutions were also applicable to give the benzyl
iodide derivatives 4b−d. Substrates with halogen substitutions
on the phenyl ring were also compatible and afforded benzyl
iodide derivatives 4e−g. Nevertheless, no iodoproduct 4h was
detected by using 3-phenylpropanal, indicating that the
aliphatic aldehyde may not applicable.
a
Reaction conditions: Rhodium catalyst (0.01 mmol) and phosphine
ligand (M:P = 1:1.2) in DCE (2 mL) were stirred at room
temperature for 30 min under Ar, and then 3 or 5 (0.2 mmol) and I2
(0.2 mmol) were added. The reaction mixture was stirred in a
*
hydrogen atmosphere. Rhodium catalyst (0.01 mmol) and
phosphine ligand (0.012 mol) in 6 (2 mL) were stirred at room
temperature for 30 min under Ar, and then I2 (0.2 mmol) was added.
The reaction mixture was stirred in a hydrogen atmosphere, and the
reaction yields were calculated by the amount of I2 used.
Furthermore, the current preparation method of anhydrous
hydrogen iodide has provided access to benzyl iodides from
benzyl alcohols. As it was summarized in Scheme 1b, most of
the halogenated benzyl alcohols and the alkyl-substituted
benzyl alcohols were transformed to the corresponding benzyl
iodides in excellent yield; benzyl alcohol and 4-nitrobenzyl
alcohol also reacted well. Notably, the aliphatic alcohols such
as 4n and 4o were also applicable.
In addition, anhydrous hydrogen iodide successfully
participated in the ring-opening reactions of cyclic ethers to
afford various iodohydrins (Scheme 1c). Epoxides such as
cyclopentene oxide and 1,2-epoxycyclohexane were efficiently
transformed to the vicinal iodohydrins 7a and 7b. 4-Membered
cyclic ether, together with 5- and 6-membered cyclic ethers, all
have reacted smoothly and afforded the corresponding ring-
the reaction yield, alternative phosphine ligands were screened.
It was found that all of the tested phosphine ligands can
promote the present hydroiodination reaction (Table 1, entries
2−7), but all less effective than ( )-Binap in terms of the
reaction yield (Table 1, entry 2). With ( )-Binap as ligand,
various transition metal catalysts including rhodium, iridium,
ruthenium, and palladium precursors were next tested. The
results indicate that except for RhCl3·3H20 and [Rh(C5Me5)-
Cl2]2 all of the tested rhodium precursors showed moderate
catalytic abilities (Table 1, entries 8−11). Iridium and
ruthenium catalysts were also effective (Table 1, entries 14−
15), but Pd(OAc)2 failed to promote the current reaction
(Table 1, entry 16).
Other reaction parameters including solvent, temperature,
and the hydrogen pressure were next investigated. The solvent
C
DOI: 10.1021/acs.orglett.8b02980
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Letter
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In summary, we have realized the first catalytic preparation
method for anhydrous hydrogen iodide from iodine and
hydrogen. By employing this technology, various substrates
including alkenes, phenyl aldehydes, alcohols, and cyclic ethers
were transformed into the corresponding iodoalkanes. Notably,
the present catalytic method has not only provided a practical
preparation method for anhydrous hydrogen iodide and
iodoalkanes but also offered a promising future for other
hydrogen iodide participating reactions. Further investigations
of other organic reactions using anhydrous hydrogen iodide are
underway in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b02980.
Experimental procedures and characterization data
(PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: chenjingchao84@163.com.
*E-mail: adams.bmf@hotmail.com.
ORCID
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Tetrahedron Lett. 1987, 28, 4497−4498.
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2518.
Chaoyuan Zeng: 0000-0001-7032-6004
Baomin Fan: 0000-0003-1789-3741
Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
We gratefully thank the National Natural Science Foundation
of China (21572198), the Applied Basic Research Project of
Yunnan Province (2018FB021, 2017FA004), and the Depart-
ment of Education of Yunnan Province (2017ZDX046) for
their financial support.
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DOI: 10.1021/acs.orglett.8b02980
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