Functional-group chemistry of organolithium compounds: Photochemical [2+2] cycloaddition of alkenyl-substituted lithium cyclopentadienides

Article abstract of DOI:10.1002/anie.200503726

(Chemical Equation Presented) Li and light: Alkenyl-substituted lithium cyclopentadienides, which are in equilibrium with the substituted lithocene anion structure 1, undergo a photochemical [2+2] cycloaddition to yield selectively the carbon-carbon coupling product 2. This is a rare case of organic functional-group chemistry for a reactive organolithium compound.

Full text of DOI:10.1002/anie.200503726

Angewandte
Chemie
chemistry at the stage of the active organolithium nucleo-
[
2]
philes is virtually nonexistent. All the desired structural and
functional-group variations, therefore, need to be made in
synthetic sequences either before or after the organolithium
[
3]
stage. This is also true for syntheses that involve substituted
or functionalized lithium cyclopentadienide reagents. Deri-
vatization of cyclopentadienyl (Cp) ligand frameworks in
metallocene syntheses, for example, practically never takes
place at the stage of the cyclopentadienyllithium reagent; it is
mostly done prior to the actual lithiation step or in some rarer
[
4]
cases after the final transmetalation. We have now found a
useful method for carrying out organic functional-group
chemistry at the stage of suitably substituted lithium cyclo-
pentadienides. This method demonstrates the principal fea-
sibility of utilizing organic functional-group transformations
at active organolithium nucleophiles and at the same time
provides a new entry to the synthesis of very useful organic
ligand systems.
In our work we focused on the photochemical [2+2]
cycloaddition reaction between alkenyl substituents attached
to the lithium cyclopentadienides. We had previously shown
that the intramolecular [2+2] cycloaddition reaction of
bis(alkenylcyclopentadienyl) ligands complexed to Group 4
metals constitutes a viable synthetic pathway to ansa metal-
[
5]
locenes. It had been demonstrated that this reaction could
even be extended to the construction of ansa calcocenes and
[
6,7]
related systems (Scheme 1).
Since it was known that
Organolithium Compounds
DOI: 10.1002/anie.200503726
Scheme 1.
Functional-Group Chemistry of Organolithium
Compounds: Photochemical [2+2] Cycloaddition
of Alkenyl-Substituted Lithium
lithium cyclopentadienides undergo facile ligand dispropor-
tionation of the donor-ligand-stabilized monomer to give the
corresponding anionic lithiocene structures (Scheme 2),
Cyclopentadienides**
[
8,9]
Jan Paradies, Gerhard Erker,* and Roland Fröhlich
Organolithium compounds are among the most important
[
1]
reagents in organic and organometallic synthesis. Because
of their high reactivity and sensitivity, functional-group
Scheme 2.
[
+]
[*] Dr. J. Paradies, Prof. Dr. G. Erker, Dr. R. Fröhlich
Organisch-Chemisches Institut
Universität Münster
Corrensstrasse 40, 48149 Münster (Germany)
Fax: (+49)251-833-36503
we decided to use this feature to extend the typical metal-
locene photocycloaddition reaction to the corresponding
alkenyl-functionalized lithiocenes.
E-mail: erker@uni-muenster.de
+
We synthesized a series of lithium (alkenyl)cyclopenta-
[
] Röntgenstrukturanalyse
[
10]
dienides by means of the fulvene route.
As a typical
[
**] Financial support from the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie is gratefully acknowledged.
example tert-butylcyclopentadiene (5e) was treated with
acetone in the presence of pyrrolidine to yield the 3-tert-
butyl-substituted 6,6-dimethylpentafulvene 6e, which was
[
11]
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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then treated with lithium diisopropylamide (LDA) in diethyl
ether to cleanly yield 7e in 78% yield (Scheme 3). The
alkenyl-Cp)–Li compound 7e was characterized spectro-
broad resonances of almost equal intensity at d = ꢀ12.2 and
ꢀ12.3 ppm (at 168 K), which we attribute to a mixture of the
diastereomeric lithiocenes rac-9e and meso-9e. The very
broad low-field signal stays broad for a much larger temper-
ature range. It decreases in intensity with decreasing temper-
ature and shifts its maximum continuously to lower field. At
(
scopically and by C,H elemental analysis. Treatment with
7
the lowest temperature (168 K) a single slightly broadened Li
NMR resonance remains at d = ꢀ1.1 ppm which is approx-
imately equal in intensity to the pair of signals at d = ꢀ12.2/
1
2.3 ppm (see Figure 2). The interpretation of this typical
Scheme 3.
tetramethylethylenediamine (tmeda) gave [{(H C=C-
2
Me)C H (tBu)}Li(tmeda)] (8e), which was characterized by
5
3
an X-ray crystal structure analysis (see Figure 1, for details
7
Figure 2. Temperature-dependent Li NMRspectra (233.1 MHz,
[
D ]THF) of the 7e/meso-9e/rac-9e equilibrium.
8
NMR behavior is straightforward: we have most likely
monitored the consequences of a rapid equilibration between
the THF-stabilized monomer [7e(thf) ] with the correspond-
n
+
+
ing lithiocene anion 9e and its [Li(thf) ] ion. The [Li(thf) ]
m
m
ion equilibrates with the 7e monomer under our NMR
+
conditions, and the equilibration 27eÐ9e + [Li(thf) ] is
m
strongly temperature dependent and shifted almost com-
pletely to the right at low temperature (Scheme 4; for further
details see the Supporting Information).
Figure 1. X-ray crystal structure of 8e.
see the Supporting Information). It features a monomeric
structure in which the C=C bond of the alkenyl substituent
We have made use of these characteristic equilibrium
features for the photochemical [2+2] cycloaddition at the
stage of the functionalized lithiocene. A solution of 7e in
(
d(C6ꢀC7) = 1.332(4) Š) is coplanar with the central 1,3-
disubstituted Cp ring. The electrostatic LiꢀCp interaction
[D ]THF in a quartz NMR tube was placed in a Schlenk tube
8
5
1
2
results in uniform (h -C H R R )Li coordination with LiꢀC
(2 cm i.d.) that was filled with acetone. This was placed in a
5
3
distances being in a narrow range between
.257(5) Š and 2.299(5) Š. The LiꢀN
bond lengths are slightly shorter at
2
2
N1).
.125(5) Š (LiꢀN2) and 2.155(4) Š (Liꢀ
[12]
The lithiocene equilibration can best
be monitored by temperature-dependent
7
[8]
Li NMR spectroscopy. A solution of 7e
in [D ]THF at ambient temperature fea-
8
tures a single sharp resonance at d =
ꢀ
7.5 ppm. Upon cooling the sample, the
signal rapidly broadens and splits into two
Scheme 4.
3
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cooling bath (THF) and irradiated at ꢀ908C with a water-
cooled HPK125 lamp (quartz filter) from a distance of 3 cm.
Under these specific conditions a slow [2+2] cycloaddition
reaction took place that in the course of two days resulted in
the clean formation of the cyclized product 10e (95% yield
along with 5% starting material; Scheme 5). The obtained
shifting the 27Ð9 equilibrium to the monomer side increases
steadily with decreasing steric bulk of the substituent R
attached to the Cp ring (for details see the Supporting
Information).
We have used this method for the preparation of a new
ansa titanocene system. The (alkenyl)Cp–lithium reagent 7e
was irradiated under our typical reaction conditions (see
above) and the resulting cyclobutylene-linked biscyclopenta-
dienide reagent 10e was transmetalated by treatment with
[
TiCl (thf) ]. Subsequent oxidative chlorination by treatment
3 3
[
13]
with PbCl2 eventually gave the ansa titanocene complex
1
1e in 82% yield as a 6:1 mixture of the rac isomer with one
[
14]
of the two possible meso diastereomers (Scheme 5).
Single crystals were obtained of the minor compound of
the mixture, namely meso-11e. The X-ray crystal structure
analysis shows the presence of the cyclobutylene-bridged
ansa-metallocene framework (Figure 3). The CꢀC s bonds of
the bridging four-membered carbocycle amount to 1.584(5) Š
(
C10AꢀC10B) and 1.529(5) Š (C11AꢀC11B); d(C10Aꢀ
C11A) = 1.543(5) Š, d(C10BꢀC11B) = 1.550(5) Š (for fur-
ther details see the Supporting Information).
Scheme 5.
mixture seems to represent the photostationary equilibrium
under these specific conditions. Further irradiation at ꢀ908C
through a THF filter instead of the acetone filter led to a slow
conversion to a 70:30 mixture of 7e and 10e, similar to the
mixture found upon direct irradiation of pure 7e at ꢀ908C
under these conditions with purely THF-filtered light. Pho-
tolysis of the reaction mixture after cyclization (95% 10e) at
room temperature with pyrex-filtered UV light converted it
cleanly back to 7e. Complex 10e was isolated from several
experiments and characterized spectroscopically (see the
Experimental Section) and by a transmetalation reaction
(
see below).
The photochemical [2+2] cycloaddition of the lithiocene
is not limited to the example 7e!10e but has been observed
with other substituted lithium (alkenyl)cyclopentadienides as
well. Thus the low-temperature irradiation of the trimethyl-
silyl-substituted (methylethenyl)Cp–lithium derivative 7d
Figure 3. X-ray crystal structure of the meso-titanocene dichloride 11e.
(
HPK125, quartz, acetone filter, ꢀ908C) gave 83% yield of
the cyclized product 10d after 3 days. The isopropyl deriva- Experimental Section
tive 7c cyclized similarly to give 61% yield of 10c after 3 days,
whereas the methyl-substituted system 7b was much less
efficient in this reaction. The cyclized product 10b was
obtained in a yield of only 39% of after 4 days of irradiation
at ꢀ908C under our typical conditions, and the parent
compound (7a) did not cyclize at all.
10e: A Philipps HPK lamp (125 W) placed in a water-cooled vacuum-
jacketed quartz vessel was used for UV irradiation. A 0.26m solution
of 7e (prepared by deprotonation of 6e with LDA in diethyl ether)
[
15]
in [D ]THF in a 5-mm quartz NMR tube and was placed in a 2-cm i.d.
8
Schlenk tube filled with acetone (10 mL) serving as a filter and for
heat transfer. The Schlenk tube was placed at a distance of 3 cm from
the light source. The sample was irradiated in a THF-filled cooling
bath at ꢀ908C for 2 days. For a preparative reaction 7e (300 mg,
1.78 mmol) was dissolved in THF (20 mL) (2-cm i.d. Schlenk tube)
and photolyzed under similar conditions as described above for
Qualitatively, the observed efficiencies for the [2+2]
cycloadditions seem to parallel the 7Ð9 equilibrium reached
at low temperature. Whereas formation of the lithiocene
anion seems to be close to complete at 168 K in the case of the
tert-butyl derivative 27e!9e, a substantial quantity (ca.
2
days. The solvent was removed in vacuo to give a white solid. The
solid was suspended in diethyl ether and the supernatant liquid
removed by syringe to separate unreacted starting material. This
procedure was repeated twice (2 ” 10 mL diethyl ether). The remain-
5
0%) of the isopropyl-substituted monomer is present under
the same conditions in the equilibrium as judged by its
1
ing solid was dried in vacuo to yield 211 mg (71%) of 10e. H NMR
7
prominent Li NMR feature at d = ꢀ6.8 ppm (9d lithiocene
(
599.8 MHz, [D ]THF), 758C): d = 5.23 (m, 2H), 5.17 (m, 2H), and
8
+
signal observed at d = ꢀ12.2/ꢀ12.3 ppm, [Li(thf) ] reso-
5.15 (m, 2H; C H ), 2.49 (m, 2H), and 1.83 (m, 2H; CH ), 1.47 (s, 6H;
5 3 2
m
1
3
nance at d = ꢀ1.2 ppm in [D ]THF at 168 K). This trend of
CH ), 1.09 ppm (s, 18H; CH ); C NMR (150.8 MHz, [D ]THF,
8
3
3
8
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3081

Communications
7
58C): d = 129.4 (C-q), 127.1 (C-q), 102.9 (CH), 101.3 (CH), 97.6
[7] For a recent review on organometallic photochemistry see T. E.
Bitterwolf, J. Organomet. Chem. 2004, 689, 3939 – 3952; see also
Q. Chu, D. C. Swenson, L. R. MacGillivray, Angew. Chem. 2005,
117, 3635 – 3638; Angew. Chem. Int. Ed. 2005, 44, 3569 – 3572,
and references therein.
[8] L. A. Paquette, W. Bauer, M. R. Sivik, M. Bühl, M. Feigel,
P. von R. Schleyer, J. Am. Chem. Soc. 1990, 112, 8776 – 8789; K.
Kunz, J. Pflug, A. Bertuleit, R. Fröhlich, E. Wegelius, G. Erker,
E.-U. Würthwein, Organometallics 2000, 19, 4208 – 4216; K.
Kunz, G. Erker, G. Kehr, R. Fröhlich, Organometallics 2001, 20,
392 – 400.
[9] Reviews: P. Jutzi, J. Organomet. Chem. 1990, 400, 1 – 17; P. Jutzi,
Pure Appl. Chem. 1990, 62, 1035 – 1038; P. Jutzi, Pure Appl.
Chem. 1989, 61, 1731 – 1736; P. Jutzi, Adv. Organomet. Chem.
1986, 26, 217 – 295; E. Weiss, Angew. Chem. 1993, 105, 1565 –
1587; Angew. Chem. Int. Ed. Engl. 1993, 32, 1501 – 1523; D.
Stahlke, Angew. Chem. 1994, 106, 2256 – 2259; Angew. Chem.
Int. Ed. Engl. 1994, 33, 2168 – 2171; P. Jutzi, N. Burford, Chem.
Rev. 1999, 99, 969 – 990; P. Jutzi, G. Reumann, Dalton Trans.
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van Lenthe, Organometallics 2003, 22, 1562 – 1576.
[10] K. Ziegler, W. Schꢀfer, Justus Liebigs Ann. Chem. 1934, 511,
101 – 109; K. Ziegler, H.-G. Gellert, H. Martin, K. Nagel, J.
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Sullivan, W. F. Little, J. Organomet. Chem. 1967, 8, 277 – 285; P.
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642 – 644; Angew. Chem. Int. Ed. Engl. 1989, 28, 628 – 629; G.
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(CH), 48.3 (C-q), 33.3 (CH ), 32.1 (C-q), 31.3 (CH ), 25.9 ppm (CH ).
3
2
3
1
1e: A mixture of [TiCl (THF) ] (232 mg) and 10e (211 mg,
3 3
0
.63 mmol) was dissolved in 15 mL of precooled THF at ꢀ788C. The
solution was stirred overnight and then warmed to room temperature.
The vigorously stirred solution was treated with solid anhydrous lead
dichloride (105 mg, 0.38 mmol, 0.6 equiv). The reaction mixture was
stirred for an additional 4 h before the solvent was removed in vacuo.
The residue was suspended in pentane and the insoluble material
removed by filtration through a plug of celite. The solid was washed
with pentane until the filtrate was colorless, and the combined
filtrates were concentrated in vacuo at ꢀ508C to give a red
precipitate. The supernatent solution was removed by syringe and
the solid dried in vacuo. The solution was further concentrated to
yield a second fraction of the product (total yield: 227 mg, 82%, rac/
meso-A/meso-B: 6/1/–); m.p. 2028C (decomp 3198C); meso-11e:
1
H NMR (599.8 MHz, [D ]benzene, 258C): d = 6.78 (m, 2H), 6.20 (m,
6
2
1
H) and 5.90 (m, 2H, C H ), 2.11 (m, 2H) and 1.54 (m, 2H; CH ),
5
3
2
1
3
3 3
.54 (s, 18H; CH ), 0.99 ppm (s, 6H; CH ); C NMR (150.8 MHz,
[
D ]benzene, 258C): d = 143.3 (C-q), 140.5 (C-q), 130.6 (CH), 117.1
6
CH), 108.0 (CH), 50.4 (C-q), 34.5 (C-q), 31.6 (CH ), 30.0 (CH ),
2
d = 6.60 (m, 1H), 6.39 (m, 1H), 6.37 (m, 1H), 6.28 (m, 1H), 6.07 (m,
1
1
3
2
1
5.8 ppm (CH ); rac-11e: H NMR (599.8 MHz, [D ]benzene, 258C):
3
6
H), and 6.02 (m, 1H; C H ), 2.11 (m, 2H), and 1.54 (m, 2H; CH ),
5
3
2
1
3
.53 (s, 9H) and 1.32 (s, 9H; CH ), 1.01 ppm (s, 6H; CH ); C NMR
3
3
(
(
150.8 MHz, [D ]benzene, 258C): d = 155.8 (C-q), 144.4 (C-q), 143.3
C-q), 140.7 (C-q), 127.9 (CH), 120.2 (CH), 117.1 (CH), 116.2 (CH),
6
1
3
09.7 (CH), 106.7 (CH), 50.5 (C-q), 49.8 (C-q), 34.8 (C-q), 34.6 (C-q),
1.5 (CH ), 30.4 (CH ), 29.9 (CH ), 29.9 (CH ), 25.6 (CH ), 25.3 ppm
3
3
2
2
3
(CH ); elemental analysis: calcd (%) for C H TiCl : C 65.32, H 7.77;
3
2
4
3
4
2
found: C 64.93, H 7.73. Slow concentration of a solution of rac/meso-
1e in diethyl ether gave red crystals of meso-11e suitable for the X-
1
ray crystal structure analysis.
[11] K. J. Stone, R. D. Little, J. Org. Chem. 1984, 49, 1849 – 1853.
[
[
[
12] See for a comparison: A. Hammel, W. Schwarz, J. Weidlein, Acta
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13] G. A. Luinstra, J. H. Teuben, J. Chem. Soc. Chem. Commun.
Received: October 20, 2005
Published online: March 29, 2006
1990, 1470 – 1471.
14] This synthesis is especially useful since we could not prepare
Keywords: cycloaddition · lithium · metallocenes ·
[
5]
.
complex 11e in analogy to the zirconium analogue by photo-
chemical [2+2] cycloaddition of the corresponding (alke-
nylCp) TiCl system.
photochemistry
2
2
[
15] T. J. Clark, T. A. Nile, Synlett 1990, 589 – 590.
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[
[
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3
082 www.angewandte.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 3079 –3082