Formation of transition metal carbenes using haloalkylzinc reagents

Article abstract of DOI:10.1039/b705459a

A new reaction of haloalkylzinc compounds, leading to transition metal carbenes, is described; halomethylzinc and halobenzylzinc compounds react with ruthenium and iridium complexes to form methylene and benzylidene complexes, including the Grubbs catalyst. The Royal Society of Chemistry.

Full text of DOI:10.1039/b705459a

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Formation of transition metal carbenes using haloalkylzinc reagents
Elena Poverenov and David Milstein*
Received (in Cambridge, UK) 11th April 2007, Accepted 15th May 2007
First published as an Advance Article on the web 1st June 2007
DOI: 10.1039/b705459a
A new reaction of haloalkylzinc compounds, leading to
transition metal carbenes, is described; halomethylzinc and
halobenzylzinc compounds react with ruthenium and iridium
complexes to form methylene and benzylidene complexes,
including the Grubbs catalyst.
2 2
(2 equivalents) to a dichloromethane solution of CH I (4.4
equivalents) at 230 uC followed by warming to 0 uC resulted in
formation the iodomethylzinc complex 1 (Scheme 1). To this
reaction mixture was added a methylene chloride solution of
(
PPh ) RuCl 2 (one equivalent) at 230 uC, followed by
3 3
2
substitution of the triphenylphosphine ligands by tricyclohexylpho-
Haloalkylzinc reagents are useful reagents in organic synthesis. For
example, bis(iodomethyl)zinc and iodomethylzinc iodide, pro-
duced in situ from diiodomethane and diethylzinc, are used in the
Simmons–Smith cyclopropanation reaction, which has been a
sphine (2.5 equivalents), for stabilization of the resulting carbene
1
0
31
complex. After 2 h at room temperature, P and H NMR
1
1
2
spectra revealed formation of the previously reported complex
(
PCy ) Cl RuLCH (3) in 80% yield.{ The synthesis of this
3
2
2
2
1
subject of intensive investigations over the past five decades. They
compound by the sulfur ylide method resulted in a low yield, due
2
are also used in homologation and alkylation. Haloalkylzinc
3
1
0
to the instability of the methylene sulfur ylide. To our knowledge,
this is the first example of the use of haloalkyl zinc reagents (or, to
our knowledge, metal carbenoid precursors in general) for the
preparation of a metal alkylidene complex.
compounds, stabilized by coordination of bipyridine, were
4
isolated.
We were intrigued by the possibility of employing haloalkylzinc
compounds as reagents for the formation of transition metal
Schrock-type carbene (alkylidene) complexes, which are widely
Studying the applicability of the reaction for the formation of
alkylidene complexes beyond methylidenes, we applied it to
formation of the widely used Grubbs ruthenium benzylidene
catalyst. Indeed, the reaction proceeded smoothly with the benzal
5
used in synthetic chemistry. For instance, catalysis of alkene
6
metathesis reactions by Schrock molybdenum alkylidenes and
7
Grubbs ruthenium alkylidenes has resulted in a multitude of
2
chloride-derived zinc reagent. Thus, addition of Et Zn to a
8
synthetic applications.
methylene chloride solution of benzal chloride at 230 uC led to
formation of a yellow precipitate, presumably the bis(chloroben-
Several useful methods for the synthesis of alkylidene complexes
9
have been described, perhaps the most common one being based
zyl)zinc complex 4, which was reacted in situ with (PPh
3 3 2
) RuCl .
on diazoalkane precursors. However, this method suffers from
thermal instability of the diazo precursors and in many cases,
metal diazo adducts are formed rather than carbene complexes.
Recently, we have developed a general method for the preparation
of carbene complexes based on the use of sulfur ylides, which are
Following substitution of the triphenylphosphine ligands by
12
tricyclohexylphosphine, complex (PCy
3
)
2
RuCl
2
(LCHPh) 5 was
31
formed in 81% yield, as indicated by P NMR. Following
workup, this complex was isolated in 63% yield (Scheme 2).{
The reaction of haloalkyl zinc reagents with transition metal
complexes is not limited to ruthenium complexes. For instance,
this reaction can be utilized for formation of an iridium
benzylidene complex. While disubstituted alkylidene iridium
10
prepared in situ from simple sulfonium salts.
We have now discovered a new reaction, involving haloalkyl
zinc compounds, which upon reaction with transition metal
complexes lead to metal alkylidenes. Using halomethylzinc and
halobenzylzinc reagents, Grubbs-type ruthenium methylidene and
benzylidene complexes and an Ir-based benzylidene complex were
formed.
1
3
complexes, trans-[(PR
3
)
2
IrCl(LCR9R0)] were synthesized, and
14 15
iridium methylene complexes were also reported, stable mono-
substituted alkylidene iridium complexes were unknown until,
i
recently, trans-[(P Pr ) ClIrLCHPh] 7 was prepared by utilizing the
3
2
First, we have examined the reaction of the common
cyclopropanation reagent, bis(iodomethyl)zinc, with Ru(II). A
10
sulfur ylide-based method. We have now found that the zinc-
reagent based reaction is also capable of direct formation of
complex 7. Thus, when the chlorobenzyl zinc reagent, generated
1
1
slightly modified literature procedure was used for the in situ
formation of this reagent. Addition of a hexane solution of Et Zn
2
2
in situ from Et Zn and benzal chloride, was reacted with the in situ
i
10
prepared [(P Pr ) IrCl] complex 6 at 230 uC, complex 7 was
Department of Organic Chemistry, The Weizmann Institute of Science
Rehovot, 76100, Israel. E-mail: david.milstein@weizmann.ac.il
3 2
2
formed in 60% isolated yield (Scheme 2).{
Scheme 1
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Scheme 2
i
Synthesis of (P Pr
2
To a pentane (7 ml) suspension of [(COE) IrCl]
was added 58 mg (0.364 mmol) of PPr
for 20 min at r.t. to give an orange solution of [(P Pr
then its volume was reduced to 2 ml. Prepared in situ as described in
preparation of 5 (benzal chloride 52 ml, 0.405 mmol and Et Zn 235 ml,
.235 mmol), chlorobenzylzinc complex 4 in 2 ml of CH Cl was treated
3 2
) ClIrLCHPh 7.
2
(82 mg, 0.091 mmol)
3
. The reaction mixture was stirred
i
i
3 2 2
) IrCl] complex 6,
2
Scheme 3
0
2
2
with a solution of 6 pre-cooled to 230 uC. After 30 min at 230 uC, 5 ml of
cold pentane were added and a light-green precipitate was obtained. After
decantation of the liquid, the precipitate was washed with pentane and the
product complex 7 was extracted with toluene. Removal of solvent by
vacuum, gave 69 mg (0.109 mmol, 60% yield) of the known complex 7.
Spectral data were identical to those reported in the literature.
Theoretical studies showed that haloalkyl zinc reagents undergo
the cyclopropanation reaction through a methylene transfer
mechanism, in which the methylene unit (with no participation
10
16
of Zn) interacts directly with the olefin. In the present case, most
probably, the metal center of the transition metal complex behaves
as a nucleophile and attacks the methylene (or benzylidene) group,
with concomitant transfer of the halide to zinc, resulting in
1
A. B. Charette and A. Beauchemin, Simmons–Smith cyclopropanation
reaction, Organic Reactions, J. Wiley & Sons, New York, 2001, vol. 58,
pp. 1–415; A. F. Noels and A. Demonceau, Catalytic Cyclopropanation.
Applied Homogeneous Catalysis with Organometallic Compounds, ed. B.
Cornils and W. A Herrmann, Wiley-VCH Verlag GmbH, Weinheim,
formation of ZnX and the carbene complex (Scheme 3).
2
To summarize, a new reaction, involving haloorganozinc
carbenoid donors and transition metal complexes, leading to
alkylidene complexes, has been discovered. While the scope of this
reaction has not been fully explored yet, we have already observed
that this facile and synthetically simple reaction can be utilized for
formation of methylene and benzylidene complexes of ruthenium
and iridium, including the Grubbs catalyst.
2nd edn, 2002, vol. 2, pp. 793–808; S. E. Denmark and G. Beutner,
Enantioselective [2 + 1] Cycloaddition: Cyclopropanation with Zinc
Carbenoids. Cycloaddition Reactions in Organic Synthesis, ed. S.
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2
3
4
5
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2
Notes and references
A. B. Charette, J.-F. Marcoux, C. Molinaro, A. Beaychemin, C. Brochu
and E. Isabel, J. Am. Chem. Soc., 2000, 122, 4508–4509.
{
Synthesis of (PCy
A pre-cooled to 230 uC methylene chloride solution (3 ml) of benzal
chloride (20 ml, 0.157 mmol) was treated with a 230 uC 1 M hexane
solution of Et Zn (91 ml, 0.091 mmol). After 30 min, the solution was
warmed to 0 uC and stirred until a yellow–brown precipitate of the complex
appeared. Then 1.5 ml of a cold dichloromethane solution of
PPh RuCl (35 mg, 0.037 mmol) were added. After 1 h at 230 uC,
cold PCy (25 mg, 0.091 mmol) in 1 ml of CH Cl was added and the
3 2 2
) (Cl) RuLCHPh 5.
G. Maas, Chem. Soc. Rev., 2004, 33, 183–190; H. M. L. Davies and
S. A. Panaro, Tetrahedron, 2000, 56, 4871–4880; M. P. Doyle and D. C.
Forbes, Chem. Rev., 1998, 98, 911–935; H. M. L. Davies and O. Loe,
Synthesis, 2004, 2595–2608; G. C. Bazan, R. R. Schrock and M. B.
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Stille, D. Straus and R. H. Grubbs, Pure Appl. Chem., 1983, 55,
2
4
(
3
)
3
2
3
2
2
1733–1744.
reaction was warmed to room temperature and stirred for 1 h. The solvent
was evaporated, the purple solid was washed with methanol (3 6 5 ml) and
dried under vacuum to give 19 mg (0.023 mmol, 63% yield) of complex 5,
6
7
R. R. Schrock, J. S. Murdzek, G. C. Bazan, J. Robbins, M. DiMare
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P. Schwab, R. H. Grubbs and J. W. Ziller, J. Am. Chem. Soc., 1996,
1
2
(
PCy
the literature.
Synthesis of (PCy
To a methylene chloride (1.5 ml) solution of methylene iodide (11 ml,
.137 mmol) at 230 uC was added a 1 M solution of Et Zn in hexane (62 ml,
.062 mmol) pre-cooled to 230 uC. After 15 min at 230 uC, the reaction
3 2 2
) RuCl (LCHPh). Spectral data were identical to those reported in
118, 100–110; M. Ulman, T. R. Belderrain and R. H. Grubbs,
Tetrahedron Lett., 2000, 4689–4693.
For recent reviews, see: A. F u¨ rstner, Angew. Chem., Int. Ed., 2000, 39,
3
)
2
Cl
2
2
RuLCH 3.
8
3
1
9
012–3043; T. M. Trnka and R. H. Grubbs, Acc. Chem. Res., 2001, 34,
8–29; A. H. Hoveyda and R. R. Schrock, Chem.–Eur. J., 2001, 7,
45–950.
0
0
2
vessel was warmed to 0 uC and a white precipitate of iodomethylzinc
complex 1 appeared. The mixture was cooled again to 230 uC and 1.5 ml
9 F. Zaragoza Dorwald, Metal Carbenes in Organic Synthesis, Wiley-
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was added. After 30 min at 230 uC, PCy (21 mg, 0.078 mmol) in 1 ml of
CH Cl was added and the reaction was kept for an additional 10 min at
30 uC, followed by warming up to room temperature. After 2 h, P and
3 3 2
) RuCl (30 mg, 0.031 mmol)
3
2
2
31
2
1
12
H NMR spectra revealed formation of the known complex
PCy (Cl) 3 in 80% yield. Due to the instability of complex 3,
RuLCH
its isolation in pure form was not possible, and the yield was determined by
(
3
)
3
2
2
3
1
P NMR using triphenylphosphine oxide as an internal standard. Spectral
data were identical to those reported in the literature.
3
190 | Chem. Commun., 2007, 3189–3191
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