Structure and reactivity of bis(iodozincio)methane solution

Article abstract of DOI:10.1016/j.jorganchem.2005.06.046

Bis(iodozincio)methane, which has been shown to be an efficient reagent for organic synthesis, is obtained as THF solution. The structural information about the reagent as THF solution was corrected by small angle neutron scattering and by anomalous X-ray scattering. Those scattering experiments implied that the prepared bis(iodozincio)methane exists without forming any oligomer or aggregate. A coordination of tetrahydrothiophene to bis(iodozincio)methane enhances the nucleophilicity of the reagent and stabilizes its monomeric structure in the solution.

Full text of DOI:10.1016/j.jorganchem.2005.06.046

Journal of Organometallic Chemistry 690 (2005) 5546–5551
www.elsevier.com/locate/jorganchem
q
Structure and reactivity of bis(iodozincio)methane solution
a,
a
a
a
Seijiro Matsubara *, Hideaki Yoshino , Yuhei Yamamoto , Koichiro Oshima ,
b
b
c
c,d
Hideki Matsuoka , Kozo Matsumoto , Kazuhiko Ishikawa , Eiichiro Matsubara
a
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoudai-Katsura, Nishikyo, Kyoto 615-8501, Japan
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoudai-Katsura, Nishikyo, Kyoto 615-8501, Japan
b
c
Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan
Department of Material Science and Technology, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo, Kyoto 606-8501, Japan
d
Received 16 May 2005; accepted 30 June 2005
Available online 22 August 2005
Abstract
Bis(iodozincio)methane, which has been shown to be an efficient reagent for organic synthesis, is obtained as THF solution. The
structural information about the reagent as THF solution was corrected by small angle neutron scattering and by anomalous X-ray
scattering. Those scattering experiments implied that the prepared bis(iodozincio)methane exists without forming any oligomer or
aggregate. A coordination of tetrahydrothiophene to bis(iodozincio)methane enhances the nucleophilicity of the reagent and stabi-
lizes its monomeric structure in the solution.
Ó 2005 Elsevier B.V. All rights reserved.
Keywords: SANS; AXS; Zinc; Dimetal; Solution; Structural study
1. Introduction
that treatment of diiodomethane with excess zinc gives
gem-dizinc species in their Wittig-type methylenation
reaction. Since then, the reduction of dihalomethane
with zinc has been investigated by Nysted, [8] Takai,
Oshima, Nozaki, [9,10] Eische and Piotrowski [11] and
Lombardo, [12] from a view point of methylenation of
carbonyl compounds. These researchers concluded that
methylene dizinc species is a reactive species. While these
procedures had used in situ formation of methylene di-
zinc species during methylenation reaction, we showed
the preparation of methylene dizinc as THF solution
from diiodomethane and zinc dust in the presence of
lead catalyst [13]; we analyzed its structure by 1H
NMR (Fig. 1) [14,15]. We then performed several types
of molecular transformations using this THF solution of
methylene dizinc [16].
Methylene dimetal reagents have been developed as
carbonyl methylenation reagents to compensate for
some drawbacks of Wittig reagents [1,2]. The ylide nat-
urally exhibits a strong basicity, which often leads to an
enolization of the starting carbonyl compound. At the
same time, the ylid often suffers from a lack of nucleo-
philicity. These points can be overcome by use of a
gem-dimetal compound or a metal carbene complex
[3,4]. Cainelli and co-workers [5] had reported methyle-
nation of ketones and aldehydes with gem-dimagnesium
reagent which was prepared from diiodomethane and
Mg/Hg in ether. More conveniently, Fried and co-work-
ers [6] and Miyano and co-workers [7] demonstrated
q
COE 21 for a United Approach to New Material Science.
Corresponding author. Tel.: +81 75 383 2441; fax: +81 75 383
The broad signal at higher field (À1.1 ppm) in Fig. 1
was understood as a signal of a methylene which is
substituted with two electropositive zinc atoms. How-
ever, it is impossible to tell from this 1H NMR spectrum,
*
2438.
E-mail address: matsubar@orgrxn.mbox.media.kyoto-u.ac.jp (S.
Matsubara).
0022-328X/$ - see front matter Ó 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.06.046

S. Matsubara et al. / Journal of Organometallic Chemistry 690 (2005) 5546–5551
5547
should be determined. The former reflects their aggrega-
tion including Schlenk equilibrium and the latter is a sin-
gle molecular structure of the corresponding reagent
(Fig. 2). We tried to determine the sizes of 1 in THF
solution by small angle neutron scattering (SANS)
[20], and the distances between atoms by anomalous
X-ray scatterings by synchrotron radiation [21]. The
method will be available not only for this specific case
but also for many structural studies concerning organo-
metallic reagents in solution [22].
Fig. 1. 1H NMR of the dizinc reagent in THF-d8 (0.45 M), which was
prepared from diiodomethane, zinc powder, and a catalytic amount of
PbCl2in THF-d8.
what is the other substituent on the zinc atoms. The
structure of the zinc reagent in THF should be deter-
mined considering equilibrate transmetallation between
the molecules of 1, that is, Schlenk equilibrium. [17]
The equilibrium in this case would be discussed not only
by Eq. (1) but also by Eq. (2) in Scheme 1. Schlenk equi-
librium of 1 may induce a polymeric structure such as a
linear compound 3 or cyclic compound 4. We tried to
determine the structure of 1 in solution by direct X-
ray and neutron scattering technique [18].
In general, structural studies of organometallics in
solution have not progressed so well [18,19]. For this
purpose, both macroscopic and microscopic structural
information should be obtained. In other words, the size
of a solute and the distance between atoms in the solute
2. Results and discussion
We tried to determine the size of the solute in the pre-
pared solution of gem-dizinc prepared from diiodome-
thane and zinc in the presence of lead catalyst. Such
information will also tell us about the homogeneity of
the solution. Small-angle neutron scattering (SANS) will
give information concerning the sizes of the aggregate of
the solute [19,20]. The result is shown in Fig. 3. Most of
the SANS profile, where q > 0.07 AÀ1 was well identified
with the simulated scattering curve of the sphere parti-
cles which have the radius of gyration (Rg) of 9.2 A.
At the smaller angle regions, those where q is less than
˚
˚
˚
0.07, two components with Rg = 15 and 60 A can be rec-
ognized, although the data are scattered due to weak
scattering intensity. However, the contributions from
both of these components with larger Rg can be said
to be very small. The results show that only small parti-
(1)
(2)
IZnCH ZnCH ZnI
+ ZnI
2
2 CH (ZnI)
1
2
2
2
2
2
˚
cles (Rg: about 9.2 A) exist with high homogeneity in a
IZn–CH Zn–CH ZnI + ZnI
2
IZnCH ZnCH ZnI
2
2
2
2
3
THF solution of dizinc species. This means that the
Schlenk equilibrium in Scheme 1 stays with bis(iodozin-
cio)methane molecules 1 which do not aggregate with
each other so much. To investigate the inside of the
small particles, we used X-ray scattering technique.
To obtain a good scattering of the solute, one needs a
strong X-ray beam. Although X-ray scattering by white
X-rays of synchrotron radiation give the radial distribu-
tion function of the solute in large region, a difficulty
2
IZn–CH Zn–CH ZnI + n ZnI
2
2
2
n
3
CH Zn
2
n
4
Scheme 1.
Preparation
in solvent
Macroscopic
Information
Aggregation
(or Schlenk equilibrium)
Aggregates
Organometalic
molecule
Microscopic Information
Fig. 2. Structural study of an organometallic reagent in a solution.

5548
S. Matsubara et al. / Journal of Organometallic Chemistry 690 (2005) 5546–5551
C-C
I-Zn
I-C
O-C
Zn-O
Zn-C
I-C
(a)
I-C
I-I
I-O
Total pair distribution function
0
(b)
Environmental pair distribution
function aound I
0
0
(c)
Environmental pair distribution
function aound Zn
Å
10
0
1
2
3
4
5
6
7
8
9
Fig. 4. (a) Pair distribution function of bis(iodozincio)methane (1). (b)
Pair distribution function based on AXS at Zn-atm K-edge. (c) Pair
distribution function based on AXS at I-atm K-edge. The data
collected by Photon Factory of the Institute of Material Structure
Science, High Energy Accelerator Research Organization, Tsukuba,
Ibaraki.
Fig. 3. SANS profile for bis(iodozincio)methane (0.4 M) in THF-d8.
The two data sets plotted by dots were obtained at two different
camera lengths (the sample-detector distance, d: 1 m, large angle
region, s: 4 m, small angle region). These camera lengths cover
different scattering vector, q, range (q = 4psin h/k, where 2h is the
scattering angle and k is the wavelength of neutron). Three lines are
simulated scattering curves. The data was collected by SANS-U of the
Institute for Solid State Physics, University of Tokyo, Tokai, Ibaraki.
˚
solution has atoms within 6–7 A. This means the reduc-
tion of diiodomethane with zinc in THF (Scheme 1)
gave monomeric bis(iodozincio)methane (1). In other
words, under the conditions of bis(iodozincio)methane
preparation, it is not necessary to consider the contribu-
tions of the Schlenk equilibrium which form polymeth-
ylene zinc.
arises to assign each peaks of the radial distribution
function to the corresponding atoms in the solution.
To solve this problem, we applied anomalous X-ray
scattering (AXS) [21]. After we obtained the normal
X-ray scattering in the area from small to large angle
at 32.867 keV, anomalous X-ray scatterings around hea-
vy atoms were measured to identify the peaks of the
radial distribution function. The AXS was measured un-
der irradiation of X-rays near the K-edge of zinc atom
(9.961 keV) at 9.661 and 9.931 keV and near the K-edge
of iodine atom (33.167 keV) at 33.117 and 32.867 keV.
In Fig. 4, the total pair distribution function (a) is shown
in comparison with the Zn (zinc) environmental pair dis-
tribution function (b) and the I (iodine) environmental
pair distribution function (c). Comparing these func-
tions, one can easily assign the peaks in (a) to distances
between each pair of atoms.
Removal of the solvent from the THF solution of
dizinc 1 in vacuo gave a white solid 5. The solid 5 would
not dissolve into THF. This fact means that the
structure had changed during the concentration process.
Various other solvents: DMI (1,3-dimethyl-2-imidazo-
lidinone), CS2, 1,2-dichloroethane, pyridine, DMF,
and DMSO, were examined in attempts to dissolve the
solid 5. Among them, DMSO showed reasonable solu-
bility. The solid was considered to be a polymeric dizinc
species (3 or 4). An addition of tetrahydrothiophene
(THT) changed the situation dramatically. After an
addition of the same volume of THT to the THF solu-
tion of the dizinc which was prepared from diiodome-
thane and zinc, the solvent was removed in vacuo.
This procedure also gave a white solid 6. The solid 6
was soluble in THF or THT. Extended X-ray absorp-
tion fine structure (EXAFS) gives us new information
about a solution at the atomic level around the selected
center atom [17,18c]. EXAFS spectroscopy of these
solutions (Fig. 5, (a) the THF solution of 1, (b) 5 in
DMSO, and (c) 6 in THT) was used to get some infor-
mation regarding the structure. The comparison of (a)
Thus, two scattering measurements of the dizinc spe-
cies in THF will tell us the detailed structure in solution.
Before these scattering analyses, we cannot tell the struc-
ture of gem-dizinc species which was prepared as shown
in Eq. (1) (Scheme 1), as the Schlenk equilibrium may
change the structure of 1 into 2, 3, or 4. The SANS
experiment (Fig. 3) concluded that the solution of the di-
zinc consisted of small homogeneous particles. That is, it
is not necessary to consider the possibility of polymeric
structure via Schlenk equilibrium. The radius of gyra-
˚
and (b) results showed that signals beyond 3.5 A were
stronger in (b) than in (a). This result implies that the
solution in (b) has the larger molecules that may be
the polymeric species such as 3 or 4. It is notable that
the spectrum in (c) has very weak signals beyond
˚
tion of these small homogeneous particles was 9.2 A,
as shown in Fig. 3, and it is hard to decide if the struc-
ture of the particle is monomeric 1 or dimeric 2. The
AXS data in Fig. 4 showed that the molecule in the
˚
3.5 A. This fact means that the dimetal species in (c)
remained as small molecules in solution, that is, 1 in a

S. Matsubara et al. / Journal of Organometallic Chemistry 690 (2005) 5546–5551
5549
O
O
O
THF–THT
I
CH (ZnI) + RCOCl
+
2
2
25 ˚C, 2 h
R
R
R
O
10a-c
9a-c
10a-c
9a-c
R = Ph
= 2-Thiophenyl
= 2-Furanyl
98%
82%
96%
<1%
<1%
<1%
Scheme 4.
the formation of 2, 3, or 4 via Schlenk equilibrium,
[25] the function of tetrahydrothiophene is very unique.
A coordinated solvent such as tetrahydrothiophene
(THT) may strengthen the nucleophilicity of bis(iodo-
zincio)methane. The effect was obvious in the reaction
with acyl chloride [17,26]. Treatment of acyl chloride
with bis(iodozincio)methane (1) in THF led to the direct
reaction of acyl chloride with THF (Scheme 3). A Lewis
acid existing in a THF solution of 1, such as zinc(II) io-
dide or 1 itself mediated the formation of 9a. To the re-
agent 1 in THF (0.5 M, 4 mL, 2.0 mmol), which was
prepared from diiodomethane and zinc in THF, 5 ml
of tetrahydrothiophene (THT) was added at 25 °C.
The mixture was stirred for 10 min. At the same temper-
ature, benzoyl chloride (2.0 mmol) in THF (1.0 ml) was
added dropwise. The resulting solution was stirred for
2 h at the same temperature. An aqueous work-up affor-
ded 1,3-diketone 10a in 98% yield, and no formation of
9a was observed (Scheme 4). Other examples are also
shown in Scheme 4.
Fig. 5. Fourier transform of the EXAFS spectra at Zn K-edge: (a) the
THF solution of dizinc from diiodomethane (0.1 M), (b) 5 in DMSO
(0.1 M), and (c) 6 in THT (0.1 M). The data were collected at Spring 8,
Sayo, Hyogo.
3. Conclusion
monomeric form with having some THT as a ligand,
even after concentration procedure. An addition of
THT inhibits the formation of any polymeric species
such as 3 or 4. The effect of THT can be understood
as follows. As shown in Scheme 2, Schlenk equilibrium
[23] may proceed via aggregation [24]. A strongly coor-
dinated solvent like THT, however, may inhibit the
formation of aggregation. As some solvent may form
stable ZnI2–solvent complexes, which would benefit
The information obtained about the structure of 1 in
solution will be useful for the design of the reaction. At
the same time, the profiling of the reaction pathway
using 1 by ab initio calculation requires such information
[27]. The activation of 1 with tetrahydrothiophene arises
not only from an electrodonating effect to zinc atom via
coordination but also from the stabilization of mono-
meric form of 1. Thus, the structural studies of bis(iodo-
zincio)methane help the deeper understanding of the
I
I
ZnI
Zn
ZnI
Zn
I
Zn
I
Zn
1
3, 4
CH
CH
2
aggregation
CH
2
transmetallation
CH
2
2
IZn
ZnI
7
8
Scheme 2. Possible pathway for Schlenk equilibrium.
O
O
O
THF
I
+
CH (ZnI) in THF (1) + PhCOCl
Ph
Ph
10a < 1 %
2
2
Ph
O
25 ˚C, 2 h
9a 99 %
Scheme 3. Reaction of benzoyl chloride with tetrahydrofuran in the presence of 1.

5550
S. Matsubara et al. / Journal of Organometallic Chemistry 690 (2005) 5546–5551
reaction. The method is useful not only for the analysis
of 1 but also for the general organometallics studies,
although the measurements require neutron and syn-
chrotron beam lines [28].
financial support provided by Chugai Pharmaceutical
Co., Ltd. and that from Takahashi Industrial and Eco-
nomical Research Foundation are also acknowledged.
References
4. Experimental
[1] G. Wittig, G. Geissler, Liebigs. Ann. Chem. 80 (1953) 44.
[2] (a) M. Schlosser, Top. Stereochem. 5 (1970) 1;
(b) B. Schaub, T. Jenny, M. Schlosser, Tetrahedron Lett. 25
(1984) 4097;
The SANS measurements were performed by SANS-
U of Institute for Solid State Physics, The University of
Tokyo, at the research reactor JRR-3, Tokai, Japan.
(c) A. Maercker, Org. React. 14 (1965) 270;
˚
(d) B.E. Maryanoff, A.B. Reits, Chem. Rev. 89 (1989) 863.
[3] (a) I. Marek, J.F. Normant, Chem. Rev. 96 (1996) 3241;
(b) I. Marek, Chem. Rev. 100 (2000) 2887;
(c) J.F. Normant, Acc. Chem. Res. 34 (2001) 640.
[4] F.Z. Do¨rwart, in: Metal Carbenes in Organic Synthesis, Wiley–
VCH, Weinheim, 1999.
[5] (a) F. Bertini, P. Grasselli, G. Zubiani, G. Cainelli, Tetrahedron
26 (1970) 1281;
(b) D.A. Fidler, J.R. Jones, S.L. Clark, H. Stange, J. Am. Chem.
Soc. 77 (1955) 6634.
[6] P. Turnbell, K. Syoro, J.H. Fried, J. Am. Chem. Soc. 88 (1966)
4764.
[7] H. Hashimoto, M. Hida, S. Miyano, J. Organomet. Chem. 10
(1967) 518.
[8] The Nysted reagent (L.N. Nysted, US Patent 3 865 848 (1975);
Chem. Abstr. 83 (1975) 10406q) is commercially available from
Aldrich Co.
The wavelength of neutron beam was 7 A. Solutions
were measured in quartz cells with a pass length of
4 mm at 25 °C [29]. The AXS experiments under irradi-
ation of X-rays were carried out on the BL-9C at Pho-
ton Factory of the Institute of Material Structure
Science, High Energy Accelerator Research Organiza-
tion, Tsukuba, Ibaragi. Solutions were measured in
quartz cells (0.05 mm) with a pass length of 1 mm at
25 °C [30]. The EXAFS at Zn K-edge experiments was
carried out on the BL-01B1 at Spring 8 (Hyogo, Japan)
operated at 8 GeV, stored current 70–100 mA. Solutions
were measured in polypropylene bag at 25 °C [31].
5. Preparation of bis(Iodozincio)methane (1)
[9] K. Takai, Y. Hotta, K. Oshima, H. Nozaki, Tetrahedron Lett. 27
(1978) 2417.
[10] J.-I. Hibino, T. Okazoe, K. Takai, H. Nozaki, Tetrahedron Lett.
26 (1986) 5579.
[11] J.J. Eisch, A. Piotrowski, Tetrahedron Lett. 24 (1983) 2043.
[12] (a) L. Lombardo, Tetrahedron Lett. 23 (1982) 4293;
(b) L. Lombardo, Org. Synth. 65 (1987) 81.
[13] K. Takai, T. Kakiuchi, Y. Kataoka, K. Utimoto, J. Org. Chem.
59 (1994) 2668.
[14] S. Matsubara, T. Mizuno, T. Otake, M. Kobata, K. Utimoto, K.
Takai, Synlett (1998) 1369.
A
mixture of Zn (25 mmol), diiodomethane
(1.0 mmol), and PbCl2 (0.005 mmol) in THF (2.0 ml)
was sonicated for 1 h in an ultrasonic cleaner bath under
Ar. To the mixture, diiodomethane (10 mmol) in THF
(20 ml) was added dropwise over 15 min at 10 °C with
vigorous stirring. The mixture was stirred for 2 h at
25 °C. After the stirring was stopped, the reaction vessel
was stood undisturbed for several hours. Excess zinc
[15] S. Matsubara, D. Arioka, K. Utimoto, Synlett (1999) 1411.
[16] (a) S. Matsubara, K. Oshima, K. Utimoto, J. Organomet. Chem.
617–618 (2001) 39;
1
was separated by sedimentation. H NMR spectra of
the obtained supernatant showed a broad singlet at
(b) S. Matsubara, K. Oshima, Proc. Jpn. Ac. 79 (2003) 71;
(c) S. Matsubara, K. Oshima, in: T. Takeda (Ed.), Modern
Carbonyl Olefination, Wiley–VCH, Weinheim, 2004, p. 200.
[17] S. Matsubara, Y. Yamamoto, K. Utimoto, Synlett (1998) 1471.
[18] (a) A.E.H. Wheatly, New J. Chem. 28 (2004) 435;
(b) H. Otake, Pure Appl. Chem. 59 (1987) 1143;
(c) M. Uchiyama, M. Kameda, O. Mishima, N. Yokoyama, M.
Koike, Y. Kondo, T. Sakamoto, J. Am. Chem. Soc. 120 (1998)
4943.
À1.1 ppm at 0 °C, which corresponded to the methylene
1
proton of 1. The concentration was determined by H
NMR using 2,2,3,3-tetramethylbutane as an internal
standard. The supernatant was used for the further reac-
tion as a solution of 1 in THF (0.4–0.5 M). In a sealed
vessel, a solution of 1 can be stored at room temperature
at least for two months.
[19] (a) Y. Hashimoto, U. Mizuno, H. Matsuoka, T. Miyahara, M.
Takakura, M. Yoshimoto, K. Oshima, K. Utimoto, S. Matsu-
bara, J. Am. Chem. Soc. 123 (2001) 1503;
Acknowledgments
(b) S. Matsubara, K. Oshima, E. Matsubara, J. Syn. Soc. Jpn. 60
(2002) 383.
Helpful advice for SANS-U by Prof. Dr. Mitsuhiro
Shibayama, Tokyo University is acknowledged. We also
thank Prof. Dr. Tsunehiro Tanaka, and Dr. Takashi
Yamamoto, Kyoto University, for the EXAFS measure-
ment at Spring 8 and helpful discussions. This work was
supported financially by the Japanese Ministry of Edu-
cation, Science, Sports, and Culture through COE 21
for a United Approach to New Material Science. The
[20] (a) N. Ise, T. Okubo, S. Kunugi, H. Matsuoka, K. Yamamoto,
Y. Ishii, J. Chem. Phys. 81 (1984) 3294;
(b) H. Matsuoka, T. Ikeda, H. Yamaoka, M. Hashimoto, T.
Tahakashi, M. Agamalian, G.D. Wignall, Langmuir 15 (1999) 293.
[21] M. Saito, C.Y. Park, K. Omote, K. Sugiyama, Y. Waseda, J.
Phys. Soc. Jpn. 66 (1997) 633.
[22] (a) Structural studies for polymer supported catalysts in solvent,
see: J. Stein, L.N. Lewis, Y. Gao, R.A. Scott, J. Am. Chem. Soc.
121 (1999) 3693;

S. Matsubara et al. / Journal of Organometallic Chemistry 690 (2005) 5546–5551
5551
(b) Z.M. Michalska, K. Strzelec, J. Mol. Catal. A: Chem. 177
(2001) 89.
[23] W. Schlenk, W. Schlenk, Chem. Ber. 62 (1929) 920.
[24] S. Matsubara, T. Ikeda, K. Oshima, K. Utimoto, Chem. Lett. 30
(2001) 1226.
[25] A. Hirai, M. Nakamura, E. Nakamura, J. Am. Chem. Soc. 121
(1999) 8665.
[26] S. Matsubara, K. Kawamoto, K. Utimoto, Synlett (1998) 267.
[27] S. Matsubara, K. Ukai, H. Fushimi, Y. Yokota, H. Yoshino, K.
Oshima, K. Omoto, A. Ogawa, Y. Hioki, H. Fujimoto, Tetrahe-
dron 58 (2002) 8255.
[28] S. Matsubara, K. Oshima, H. Matsuoka, K. Matsumoto, K.
Ishikawa, E. Matsubara, Chem. Lett. 34 (2005) 952.
[29] K. Matsumoto, H. Mazaki, H. Matsuoka, Macromolecules 37
(2004) 2256.
[30] S. Sato, M. Imafuku, E. Matsubara, A. Inoue, Y. Waseda,
Mater. Trans., JIM (2001) 1977.
[31] T. Uruga, H. Tanida, Y. Yoneda, K. Takeshita, S. Emura, M.
Takahashi, M. Harada, Y. Nishihata, Y. Kubozono, T. Tanaka,
T. Yamamoto, H. Maeda, O. Kamishima, Y. Takabayashi, Y.
Nakata, H. Kimura, S. Goto, T. Ishikawa, I. Synchrotron Radiat.
6 (1999) 143.