New approach to the stereoselective synthesis of metalated dienes via an isomerization-elimination sequence

Article abstract of DOI:10.1021/ja027027y

Treatment of Cp₂ZrBu₂ with enol ether containing a remote double bond lead to conjugated metalated diene as single isomer via a tandem isomerization-elimination sequence. 2-Arylsulfonyl 1,3-dienes can also be used as a source of dienyl zirconocene derivatives, and the stereochemistry of the diene is dependent on the transmetalation reaction. Copyright

Full text of DOI:10.1021/ja027027y

Published on Web 08/08/2002
New Approach to the Stereoselective Synthesis of Metalated Dienes via an
Isomerization-Elimination Sequence
Nicka Chinkov, Swapan Majumdar, and Ilan Marek*
Department of Chemistry and Institute of Catalysis Science and Technology, Technion-Israel Institute of
Technology, Technion City, 32000 Haifa, Israel
Received May 24, 2002
Scheme 1. Synthesis of Conjugated Dienyl Zirconocene
Derivatives
The carbometalation of a carbon-carbon multiple bond is one
of the most fundamental and straightforward methodologies for the
preparation of new organometallics.1 Particularly interesting, the
carbometalation of unactivated alkynes is a practical method for
the preparation of vinylmetals, which have great versatility as
building blocks in organic synthesis.2 However, despite these
extensive investigations, there are very few reports on vinylmeta-
lation of alkynes since it gives new vinyl organometallics,3 which
may exhibit a reactivity similar to that of the starting vinyl
organometallic compounds. This type of carbometalation results
in oligomerization or polymerization reactions. Several pathway
alternatives have been recently described in the literature, but the
stereoselectivity for the preparation of these metalated dienes is
the major problem.4
We have recently reported that vinyl enol ethers,5 vinyl alkyl-
(aryl) sulfides, vinyl sulfoxides, and vinyl sulfones6 smoothly react
with the zirconocene derivative 17 to give stereoselectively the
corresponding vinylic organometallic derivatives. Moreover, it has
also been described that 1 can induce in some cases, multipositional
regioisomerization of unconjugated dienes.8
So, we reasoned that unconjugated dienes bearing an enol ether
moiety such as 3-8 should undergo a new tandem isomerization-
elimination reaction to give, in a single-pot operation, the corre-
sponding metalated dienyl zirconocene derivatives 9 (Scheme 1).
All the starting materials 3-8 either of E or Z stereochemistry
were easily prepared in a single-pot operation by carbocupration
reaction9 of alkoxyallene10 (as the unique common starting material)
followed by reaction with the appropriate electrophiles.2 When 3Z
is treated with 1 in THF for 15 min at +50 °C, the corresponding
E conjugated diene 10 is isolated in 80% yield after hydrolysis
(entry 1, Table 1). The formation of a discrete organometallic
species was checked by iodinolysis (entry 2, Table 1), but the
resulting iodo diene 11 was found to be unstable and rapidly
isomerized to a mixture of (E)- and (Z)-isomers. Thus, the presence
of the organometallic was classically checked by reaction with
allylic halide after transmetalation of the dienyl zirconocene 9 into
organocopper reagent11 (entry 3). An (E,Z)-triene 12 is obtained in
good overall yield with an isomeric ratio always higher than 95 to
5 as determined by NMR and gas chromatography analyses of the
crude reaction mixture. When the reaction is performed on the enol
ether 3E, the same (E,Z)-dienylmetal is obtained as determined after
reaction with allyl chloride (entry 4, Table 1). In both cases, the
stereochemistry was determined on the basis of differential nuclear
Overhauser effect spectra. Thus, whatever the stereochemistry of
the starting enol ether, the reaction is stereoselective and leads to
the (E,Z)-dienyl zirconium derivative 9 (Scheme 1). The diene
isomerization-elimination is not limited to those dienes with a one-
Table 1. Preparation of Isomerically Pure Dienes and Trienes
+
entry
comp
n
R
E
pdts
yielda (%)
1
2
3
4
5
6
7
8
3Z
3Z
3Z
3E
4
5
6
7
1
1
1
1
2
3
6
1
1
/
/
/
/
/
/
/
H
H3O+
I2
10
11
12
12
13
14
15
16
17
24E
25
26
27
28
29
30
80
75
70
72
70
71
70
80
75
70
61
61
59
75
76
59
b
H
H
H
H
H
H
Me
/
/
/
/
/
allylClc
allylClc
allylClc
allylClc
H
allylClc
H3O+
H3O+
NBS
9
8
10
11
12
13
14
15
16
23cCu
23cCu
23cCu
23cCu
23cCu
23cCu
23cCu
1-iodohexynec,d
p-iodotoluenec,d
methylvinyl ketonee
allylClc
/
/
/
cyclohexenonee
a Isolated yield after purification by chromatography on silica gel.
b Iododiene is unstable at room temperature and isomerized with time.
c Obtained after a transmetalation step with 10% CuCl‚2LiCl. d Obtained
after a transmetalation step with 5% Pd(PPh3)4. e In the presence of 1 equiv
of TMSCl.
carbon tether. Thus 4, 5, and 6 (with 2, 3, and 6 carbon tethers
respectively) also underwent this tandem reaction (Table 1, entries
5-7). Moreover, the migrating group can be a 1,2-disubstituted
alkenyl group since 7 (entry 8, R ) Me, Table 1) undergoes
similarly the isomerization-elimination process to give the corre-
sponding (E,Z)-dienyl zirconocene derivative.
Finally, we were also interested to investigate the effect of the
position of the unsaturated chain on the isomerization-elimination
reaction. For this purpose 89 was submitted to our isomerization-
elimination conditions as described in Scheme 1. After hydrolysis
of the dienyl zirconocene complex, 17 was isolated as unique (E,Z)-
isomer in 75% yield. To gain more insight into the reaction
mechanism, we have repeated this isomerization-elimination
reaction on the dideuterated enol ether 18.
When 18 was treated with 1 for 15 min at +55 °C, 19 was
obtained in 62% yield after hydrolysis. The examination of the 1H-
and 13C NMR of 19 indicates that the two deuterium atoms are
* To whom correspondence should be addressed. E-mail: chilanm@
tx.technion.ac.il.
9
10282
J. AM. CHEM. SOC. 2002, 124, 10282-10283
10.1021/ja027027y CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Mechanistic Hypotheses for the
Isomerization-Elimination Sequence
rearrangement. To further increase the scope of the reaction,
transmetalation of vinyl zirconiums 23a-c into several different
vinylic organometallic derivatives was performed.11 To our surprise,
when these metalated dienes were transmetalated to copper deriva-
tive by addition of CuCl‚2LiCl for 1 h at +45 °C, a complete
isomerization of the dienyl system was found; that is, trans-23cZr
is transmetalated into cis-23cCu, and then after hydrolysis, only
the (E)-isomer of 24 is formed in 70% yield.16
Although we must await further investigations to elucidate
completely the mechanism of this transmetalation, the synthetic use
of this reaction is underlined in Table 1 (entries 10-16). For
example, 23cCu reacts either via a SN2′ process with allyl chloride
(Table 1, entry 15) or in a 1,4-addition manner with methyl vinyl
ketone and cyclohexenone in the presence of TMSCl in 75 and
59% yields, respectively (Table 1, entries 14 and 16). Finally, the
palladium-catalyzed cross-coupling reaction of 23cCu with iodo-
alkyne or p-tolyl iodide, opens new routes for further functional-
ization as shown by the formation of 26 and 27 in Table 1 (entries
12 and 13).17 In summary, we have reported an easy and
straightforward new preparation of various metalated dienes in only
two chemical steps from common starting materials. The study of
the scope of this new methodology is underway and will be reported
in due course.
Scheme 3. Preparation and Reactivity of Dienylzirconocene
Complexes from 2-Arylsulfonyl-1,3-dienes
Acknowledgment. This research was supported by the Israel
Science Foundation administrated by the Israel Academy of
Sciences and Humanities (79/01-1) and by the Fund for the
Promotion of Research at the Technion
now at the vinylic and allylic positions (Scheme 2). This migration-
elimination reaction can be explained by the following mechanism
(Scheme 2): 1 reacts first with the remote double bond of 18 to
form a zirconacyclopropane derivative 18a. Then, via a C-H allylic
activation,12 the η3-allyl intermediate 18b is formed, and after
hydrogen migration, the new zirconacyclopropane 18c is produced.
By the same sequence, but with the deuterium atom instead of the
hydrogen (18c into 18d), the zirconacyclopropane 18e is finally
obtained before its rearrangement into the zirconacyclopentene
intermediate 18f. Then, by an elimination reaction, the metalated
dideuteriodiene 18g is obtained as determined by its hydrolyzed
product 19.
From this mechanistic pathway, we can rationalize not only the
stereochemistry of the (E,Z)-dienyl zirconocene derivative but also
that the stereochemistry of the initial enol ether has no effect on
the stereochemical outcome of the reaction since the carbon-
heteroatom bond of the sp3-metalated center 18f is free to isomerize
before the elimination.
When the migrating group is now geminated to the leaving group
such as in 8, the isomerization reaction occurs similarly to give
the zirconacyclopropane 20a but is followed by a â-elimination
reaction to lead to the â-metalated allenyl intermediate 20b (Scheme
2). Then, 20b is isomerized into its more stable dienyl form 20c,13
in which the alkyl and the organometallic groups are anti to each
other. After hydrolysis, a unique isomer is observed (determined
by NOE effects). This last approach where the leaving group is
geminated to the zirconacyclopropane led us also to investigate the
case of sulfonyl 1,3-dienyls derivatives 21a-c.14 As for the enol
ether methodology, the major advantage of this approach is the
very easy preparation of acyclic 2-arylsulfonyl 1,3-dienes from
allylic sulfones and aldehydes in a one-pot procedure.15 Then, the
treatment of 21a-c with 1.5 equiv of 1 at room temperature lead
to the cis isomer 24a-c (cis/trans > 95/5), whatever the stereo-
chemistry of the starting material (Scheme 3). By analogy with
the mechanistic pathway described for the enol ether 8, we believe
that the transformation of 21a-c also occurs via the formation of
the â-metalated allenyl intermediate generated from the â-elimina-
tion of the corresponding zirconacyclopropane and subsequent
Supporting Information Available: Experimental procedures and
spectra data of selected compounds are available (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
References
(1) Marek, I. J. Chem. Soc., Perkin Trans. 1 1999, 535.
(2) (a) Normant, J. F.; Alexakis, A. Synthesis 1981, 841 (b) Marek, I.;
Normant, J. F. In Metal-Catalyzed Cross-Coupling Reactions; Diederich,
F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998; p 271.
(3) (a) Alexakis, A.; Normant, J. F. Tetrahedron Lett. 1982, 23, 5151. (b)
Furber, M.; Taylor, R. J. K.; Burford, S. C. J. Chem. Soc., Perkin Trans.
1 1986, 1809.
(4) (a) Hara, R.; Nishihara, Y.; Landre, P. D.; Takahashi, T. Tetrahedron
Lett. 1997, 38, 447. (b) Takahashi, T.; Hara, R.; Huo, S.; Ura, Y.; Leese,
M. P.; Suzuki, N. Tetrahedron Lett. 1997, 38, 4857. (c) Kasatkin, A.;
Whitby, R. J. J. Am. Chem. Soc. 1999, 121, 7039. (d) Ganchegui, B.;
Bertus, P.; Szymoniak, J. Synlett 2001, 123.
(5) (a) Liard, A.; Marek. I. J. Org. Chem. 2000, 65, 7518. (b) Liard, A.;
Chechik, C.; Farhat, S.; Morlender-Vais, N.; Averbuj, C.; Marek, I. J.
Organomet. Chem. 2001, 624, 26.
(6) Farhat, S.; Marek, I. Angew. Chem., Int. Ed. 2002, 41, 1410.
(7) Negishi, E.; Huo, S. In Titanium and Zirconium in Organic Synthesis;
Marek, I., Ed.; Wiley-VCH: Weinheim, Germany, 2002; p 1.
(8) Negishi, E.; Maye, J. P.; Choueiry, D. Tetrahedron 1995, 51, 4447.
(9) Alexakis, A.; Normant, J. F. Isr. J. Chem. 1984, 24, 113.
(10) Hoff, S.; Brandsma, L.; Arens, J. F. Rec. TraV. Chim. Pays-Bas 1968,
87, 916.
(11) (a) Wipf, P.; Jahn, H. Tetrahedron 1996, 52, 12853. (b) Takahashi, T.;
Kotora, M.; Kasai, K.; Suzuki, N. Tetrahedron Lett. 1994, 35, 5685.
(12) (a) Resconi, L. J. Mol. Catal. 1999, 146, 167. (b) Cohen, S. A.; Auburn,
P. R.; Bercaw, J. E. J. Am. Chem. Soc. 1983, 105, 1136. (c) Akita, M.;
Yasuda, H.; Nagusuna, K.; Nakamura, A. Bull. Chem. Soc. Jpn. 1983,
56, 554.
(13) Rozema, M. J.; Knochel, P. Tetrahedron Lett. 1991, 32, 1855.
(14) Backvall, J.-E.; Chinchilla, R.; Najera, C.; Yus, M. Chem. ReV. 1998, 98,
2291.
(15) Cuvigny, T.; Herve du Penhoat, C.; Julia, M. Tetrahedron 1986, 42, 5329.
(16) Heating the dienyl zirconocene 23cZr at +50 °C with or without LiCl
does not isomerize the metalated diene.
(17) (a) Negishi, E.; Van Horn, D. E. J. Am. Chem. Soc. 1977, 99, 3168. (b)
Negishi, E.; Okukado, N.; King, A. O.; Van Horn, D. E.; Spiegel, B. J.
Am. Chem. Soc. 1978, 100, 2254.
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