Preparation, solid-state structure, and synthetic applications of isolable and storable haloalkylzinc reagents [1]

Full text of DOI:10.1021/ja994371v

4508
J. Am. Chem. Soc. 2000, 122, 4508-4509
Communications to the Editor
characteristic resonance by H and 13C NMR (Table 1).9 The
iodomethylzinc resonance appearing at 1.49 ppm (and -12.2 ppm
by 13C NMR) is consistent with the values reported for the related
ether complexes. The elemental analysis is also consistent with
the proposed structural formula. The stability of this complex was
further confirmed when the elemental analysis of an 8 month-
old sample kept in the freezer indicated that very little (if any)
decomposition had occurred. Furthermore, this 8 month-old
powder was still a very effective cyclopropanating reagent (vide
infra). Several other highly colored complexes derived from
bipyridine were prepared (2-6) and they displayed similar spectral
properties10 and reactivities. The relevant 1H and 13C NMR
resonances for the complex are shown in Table 1. The bipyridine
complex of IZnCH2I is less soluble in CH2Cl2 than the Zn(CH2I)2
complex, but both complexes are readily soluble in THF. The
bipyridine complex of bis(iodoethyl)zinc (4) exists as a 1:1
diastereomeric mixture. We were also able to generate the
bipyridine complex of Shi’s reagent11 (CF3CO2ZnCH2I), but it
appeared to be slightly less stable than those derived from the
traditional reagents.
1
Preparation, Solid-State Structure, and Synthetic
Applications of Isolable and Storable Haloalkylzinc
Reagents
Andre´ B. Charette,* Jean-Franc¸ois Marcoux,
Carmela Molinaro, Andre´ Beauchemin, Christian Brochu, and
EÄ lise Isabel
De´partement de Chimie, UniVersite´ de Montre´al
P.O. Box 6128, Station Downtown
Montre´al, Que´bec, Canada H3C 3J7
ReceiVed December 15, 1999
Haloalkylzinc reagents are widely used as cyclopropanating,1
homologating2 and alkylating reagents.3 Recently, ether complexes
of these reagents (Zn(CH2I)2 and IZnCH2I) have been character-
ized in solution by NMR and in solid-state by X-ray crystal-
lography.4 These ether complexes are quite weak as they readily
dissociate in solution to liberate the electrophilic reagents. Our
ongoing interest in this area prompted us to generate more stable
complexes that could be isolated and stored but that would also
release the electrophilic methylene moiety under specific condi-
tions. Hence, it is well-known that the amine complexes of
dialkylzinc are quite stable, but the analogous bipyridine com-
plexes display unique properties.5 More specifically, the dissocia-
tion constant for TMEDA‚Zn(t-Bu)2 is higher than that measured
for TMEDA‚ZnMe2.6 Quite unexpectedly, this trend is oppositive
for the related bipy‚ZnR2 complexes and the dissociation constant
is higher for bipy‚ZnMe2 than for bipy‚Zn(t-Bu)2.6 The unique
stabilizing feature imparted by the bipyridine ligand prompted
us to synthesize and study the stability of the complexes generated
from bipyridine and haloalkylmetal reagents even though it has
been previously reported that amines are generally alkylated by
these highly electrophilic reagents.7 In this contribution, we report
the first synthesis, structure determination, and synthetic applica-
tions of isolable and storable zinc carbenoid reagents.
After numerous attempts to get suitable crystals of one of the
bipyridine complex for X-ray analysis, we eventually succeeded
in generating suitable crystals of the 2,2′-biquinoline complex of
Wittig’s [Zn(CH2I)2]12 7 and of the highly reactive Denmark’s
[Zn(CH2Cl)2] reagent 8, which had never been characterized by
X-ray crystallography (Figure 1).13 In these structures, the zinc
center displays a distorted tetrahedral geometry. The observed
bond lengths and bond angles are consistent with most of those
observed for the diether complexes of iodomethylzinc carbenoids.4
For example, the typical I-CH2-Zn bond angles for analogous
diether complexes range from 106.9 to 119.4° depending upon
which ligand is used and the typical bond lengths Zn-C is
between 1.995 and 2.04 Å for the zinc carbenoids (Table 2).
As expected, these complexes are not good cyclopropanating
reagents since their electrophilic character is seriously hampered
by the highly basic character of the ligand. For example, if 2
equiv of bipy‚Zn(CH2I)2 (1) is added to a solution of cinnamyl
alcohol in CH2Cl2, a 10% yield of the cyclopropane derivative is
A nice and clear dark orange solution was obtained when a
1,1′-bipyridine solution was added to a milky suspension of bis-
(iodomethyl)zinc in CH2Cl2 at -40 °C.8 A stable, non-pyrophoric
yellow solid could be precipitated upon slow addition of hexane,
and filtration produced the desired complex in 90% yield. This
complex, assigned as bipy‚Zn(CH2I)2 (1), showed all of the
(1) (a) Simmons, H. E.; Cairns, T. L.; Vladuchick, S. A.; Hoiness, C. M.
Org. React. (N.Y.) 1973, 20, 1-131. (b) Charette, A. B. Cyclopropanation
mediated by zinc organometallics; Knochel, P., Jones, P., Eds.; Oxford
University Press: Oxford, 1999; pp 263-283.
(2) Sidduri, A.; Rozema, M. J.; Knochel, P. J. Org. Chem. 1993, 58, 2694-
2713.
(3) For an excellent review on zinc carbenoids, see: Motherwell, W. B.;
Nutley, C. J. Contemp. Org. Synth. 1994, 1, 219-241.
(9) Although it has been reported that basic nitrogen atoms are readily
alkylated by the zinc reagent to generate quaternary ammonium salts, we have
not detected any traces of these products. For the synthesis and characterization
of N-methylbipyridinium iodide and N,N-dimethylbipyridinum diiodide, see:
Tabushi, I.; Yazaki, A. Tetrahedron 1981, 37, 4185-4188.
(10) See Supporting Information for complete characterization data.
(11) Yang, Z. Q.; Lorenz, J. C.; Shi, Y. Tetrahedron Lett. 1998, 39, 8621-
8624.
(12) The complex decomposed to the related IZnCH2I complex upon data
collection. See Supporting Information for the X-ray crystal structure and
crystallographic data for this complex.
(13) The complex crystallizes as a monomer with two independent
conformers in the unit cell. See Supporting Information for the structure of
the other conformer.
(4) (a) Denmark, S. E.; Edwards, J. P.; Wilson, S. R. J. Am. Chem. Soc.
1991, 113, 723-725. (b) Denmark, S. E.; Edwards, J. P.; Wilson, S. R. J.
Am. Chem. Soc. 1992, 114, 2592-2602. (c) Charette, A. B.; Marcoux, J. F.;
Be´langer-Garie´py, F. J. Am. Chem. Soc. 1996, 118, 6792-6793. (d) Charette,
A. B.; Marcoux, J.-F. J. Am. Chem. Soc. 1996, 118, 4539-49. (e) Denmark,
S. E.; Oconnor, S. P. J. Org. Chem. 1997, 62, 3390-3401.
(5) Noltes, J. G.; Van Den Hurk, J. W. G. J. Organomet. Chem. 1965, 3,
222-228.
(6) Noltes, J. G.; Boersma, J. J. Organomet. Chem. 1967, 9, 1-4.
(7) Wittig, G.; Schwarzenbach, K. Justus Liebigs Ann. Chem. 1961, 650,
1-21.
(8) Denmark, S. E.; Edwards, J. P. J. Org. Chem. 1991, 56, 6974-6981.
10.1021/ja994371v CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/19/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 18, 2000 4509
1
Table 1. Selected H and 13C Chemical Shifts for Complexes 1-6
Table 2. Selected Bond Lengths (Å) and Angles (deg) for
Complex 7 and 8
ZnCH(R)X
bond lengths
7
8
complex
1H
1.49
2.71
1.64
3.40, 3.38
3.33
1.61
13C
Zn-C(21)
Zn-C(23)
Zn-Cl(1)
Zn-Cl(2)
Zn-I
Zn-I
Zn-N(1)
Zn-N(12)
2.015(8)
2.082(9)
2.013(5)
2.054(6)
3.222(2)
3.168(2)
1
2
3
4
5
6
-12.2
32.9
-14.6
23.94, 23.76
19.48
-20.5
3.477(4)
3.551(7)
2.135(7)
2.141(6)
2.117(4)
2.137(4)
bond angles
7
8
C(22)-Zn-C(21)
Zn-C(21)-I(1)
Zn-C(23)-I(2)
Cl(1)-C(21)-Zn
Cl(2)-C(22)-Zn
N(12)-Zn-N(1)
125.5(3)
113.5(3)
116.0(5)
127.7(3)
115.8(3)
115.3(4)
77.02(15)
76.8(2)
The complex bipy‚IZnCH2I (3) can also be used in methylation
reactions. One example is to use it as a sulfur alkylating agent
for the synthesis of the precursor in the [2,3]-sigmatropic
rearrangement of sulfonium ylides. Treatment of thioether 10 with
2 equiv of bipy‚IZnCH2I produced the desired [2,3]-sigmatropic
rearrangement product 11 in 84% yield (eq 3).16
Figure 1. ORTEP drawing of complex 8. Ellipsoids are drawn at at the
40% probability level.
observed after 6 h at room temperature (eq 1). The yield of
In conclusion, we have shown that the bipyridine complexes
of haloalkylzinc reagents are fully characterized and quite stable
reagents that can be stored and used in haloalkylzinc mediated
processes. The use of these reagents in catalytic asymmetric
processes will be reported in due course.
cyclopropanation is increased to 75% if the more basic zinc
alkoxide is used. Conversely, we found that it is possible to release
or activate the reagent by adding freshly prepared ZnI2.14 The
reaction of the benzyl ether proceeded in very good yield (>95%)
with only 1 equiv of the reagent and 1 equiv of ZnI2.
Reagent 1 is also quite effective in stereoselective processes.
For example, the cyclopropanation of the cyclohexene acetal 9
proceeded in 88% and produced a 96:4 diastereomeric mixture
with complex 1 (eq 2). These results are comparable to those
Acknowledgment. This research was supported by the NSERC
(Canada), Merck Frosst Canada, F.C.A.R. (Que´bec), and the Universite´
de Montre´al. J.-F. M, A.B., E.I. would like to thank NSERC for a
Postgraduate Scholarship (PGS A and/or B). C.M. and C.B. thank
Biome´ga for a postgraduate fellowship.
Supporting Information Available: 1H and 13C NMR spectra of all
the complexes. Description of the structure determination and tables of
X-ray crystallographic data for the various complexes including atomic
coordinates, anisotropic thermal parameters, and fixed atom coordinates;
listing of observed and calculated structure factors for the various
complexes (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
JA994371V
(14) Several Lewis acids were tested and ZnI2 is by far superior to others.
At this time, it is not clear what is the exact mechanism by which the reagent
is released. For a theoretical study on the Lewis acid activation of halometh-
ylzinc reagents, see: Nakamura, E.; Hirai, A.; Nakamura, M. J. Am. Chem.
Soc. 1998, 120, 5844-5845.
(15) Mash, E. A.; Hemperly, S. B.; Nelson, K. A.; Heidt, P. C.; Van Deusen,
S. J. Org. Chem. 1990, 55, 2045-2055.
(16) Kosarych, Z.; Cohen, T. Tetrahedron Lett. 1982, 23, 3019-3022.
reported by Mash using the zinc-copper couple and di-
iodomethane.15