Titanocene(II)-promoted cross-coupling of unsaturated compounds

Article abstract of DOI:10.1002/ejoc.200500976

Vinyl pivalate in the presence of the titanocene(II) reagent Cp ₂Ti[P(OEt)₃]₂ reacts both with nonpolar C≡C triple bonds and with polar C=O double bonds, to produce conjugated dienes and allylic alcohols, respectively. Similar alkenylation also takes place when (Z)-alkenyl sulfones are treated with alkynes and carbonyl compounds. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500976

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200500976
Titanocene(II)-Promoted Cross-Coupling of Unsaturated Compounds
Akitoshi Ogata,[a] Masami Nemoto,[a] Koutarou Arai,[a] Kenji Kobayashi,[a]
Akira Tsubouchi,[a] and Takeshi Takeda*[a]
Keywords: Allylic alcohols / Cross-coupling / Conjugated dienes / Metallacycles / Titanium
Vinyl pivalate in the presence of the titanocene(II) reagent
Cp2Ti[P(OEt)3]2 reacts both with nonpolar CϵC triple bonds
and with polar C=O double bonds, to produce conjugated
dienes and allylic alcohols, respectively. Similar alkenylation
also takes place when (Z)-alkenyl sulfones are treated with
alkynes and carbonyl compounds.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
We recently reported two methods for the transformation Suzuki coupling,[3] Stille coupling,[4] and Hiyama coup-
of thioacetals into cyclopropanes. Alkyl-substituted cyclo- ling[5] – are frequently employed for carbon–carbon bond
propanes are produced through reactions between thioacet- formation between two sp2 carbon atoms. A major syn-
als and vinyl pivalate (2) promoted by the titanocene() rea- thetic route to the alkenylmetal compounds used in these
gent Cp2Ti[P(OEt)3]2 (1), whilst vinylcyclopropanes are ob- reactions is hydrometallation of alkynes. Direct cross-coup-
tained by treatment of thioacetals with the titanocene() ling between alkenes containing a leaving group and al-
reagent 1 and buta-1,3-dienes.[1] During this study we found kynes, promoted by a low-valent metal species 1 as depicted
that the vinylcyclopropane 3 was produced when the pival- in Scheme 3, would therefore be advantageous: the pro-
ate 2 (3 equiv.) was treated successively with excess quanti- cedure should give conjugated dienes, the products of the
ties of 1 (7 equiv.) and the thioacetal 4 at 25 °C for 2 h above conventional cross-couplings, without the need for
(Scheme 1). The formation of 3 indicates that buta-1,3- prior transformation of alkynes into any alkenylmetal spe-
diene is formed by the self-coupling of 2, probably via the cies. Another advantage of this methodology is that it
titanacyclopentane intermediate 5, in which equilibrium of should also be applicable to reactions of compounds pos-
the formation of titanacycle 5 would be favored by elimi- sessing a carbon–heteroatom multiple bond.
nation of titanocene dipivalate (Scheme 2). This result
prompted us to investigate a new titanocene()-promoted
intermolecular cross-coupling of unsaturated compounds
via a similar titanacycle intermediate.
Scheme 3. Titanocene()-promoted cross-coupling of unsaturated
compounds.
In this context, we have studied titanocene()-promoted
Scheme 1. Formation of vinylcyclopropanes.
cross-couplings between vinyl pivalate (2) and unsaturated
compounds, and here we describe the preparation of conju-
gated dienes 6 and allylic alcohols 7 through reactions be-
tween 2 and alkynes 8 or carbonyl compounds 9, via the
titanacycle intermediates 10 and 11 (Scheme 4). These reac-
tions are useful in that vinyl pivalate (2), a poor substrate
Scheme 2. Self-coupling of vinyl pivalate (2).
for transition-metal-catalyzed cross-couplings, is available
as a coupling component.
Transition-metal-catalyzed reactions between alkenyl ha-
lides or sulfonates and alkenylmetal compounds[2] – such as
Treatment of alkynes 8 with vinyl pivalate (2) (3 equiv.)
in the presence of titanocene() reagent 1 (3 equiv.) at 0–
25 °C for 2.5 h produced the conjugated dienes 6 in good
yields (Table 1). Although the reactions of unsymmetrical
alkynes generally proceeded with mixed regioselectivity,
high selectivity was observed when phenylacetylene deriva-
[a] Department of Applied Chemistry, Graduate School of Engi-
neering, Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
Fax: +81-42-388-7034,
E-mail: takeda-t@cc.tuat.ac.jp
878
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 878–880

Titanocene()-Promoted Cross-Coupling of Unsaturated Compounds
SHORT COMMUNICATION
Table 1. Reactions between unsaturated compounds and vinyl piv-
alate (2).
Scheme 4. Titanocene()-promoted vinylation of alkynes and car-
bonyl compounds.
tives were employed; only the regioisomers in which a vinyl
group was attached at the carbon atom β to the phenyl
group were produced (Entries 2 and 3). The formation of
the vinylallene 12 (Entry 5) supports the hypothetical reac-
tion pathway depicted in Scheme 4 because it is reasonable
to assume that β-elimination of the initially produced dien-
yltitanium intermediate 13 affords the allene 12 (Scheme 5).
Aliphatic aldehydes 9 also reacted with vinyl pivalate (2)
under the same reaction conditions to produce allylic
alcohols
7 (Entries 6–8). Reactions between aliphatic
ketones and 2 also produced the alcohols 7 at lower reac-
tion temperatures (Entries 9–11). It was found, however,
that aromatic and α,β-unsaturated carbonyl compounds
were inappropriate substrates for this reaction; treatment of
these compounds with the pivalate 2 and titanocene() rea-
gent 1 resulted in the formation of complex mixtures.
Some synthetic reactions that involve the formation of
five-membered titana-[6] and zirconacycles[7] and their sub-
sequent β-elimination have been investigated. The diethyl-
zirconocene-promoted intermolecular reactions between
ethyl vinyl ether and alkynes proceed through the formation
of zirconacyclopentenes and subsequent elimination of an
ethoxy group, similarly to the present reaction.[8] Couplings
of unsaturated compounds via three-membered titanacycles
have been reported; in the presence of the divalent titanium
alkoxide complex, alkynes react with allyl[9] and propar-
gyl[10] carbonates intermolecularly.
[a] Contaminated with 8a. Yield was determined by NMR analysis.
[b] Carried out at –10 °C overnight.
It is noteworthy that this reaction is a versatile method
for the intermolecular vinylation of both polar and nonpo-
lar multiple bonds, and this methodology could be extend-
able to alkenylation of multiple bonds. Such idea has been
partly substantiated with the (Z)-alkenyl sulfone (Z)-14
(Scheme 6). Treatment of diphenylacetylene (8a) with (Z)-
14 (2 equiv.) in the presence of 1 (2 equiv.) at 0–25 °C for
Scheme 5. Formation of vinylallenes.
2.5 h gave the diene 15, while a similar reaction between The formation of these compounds is attributable to the
(Z)-14 and the aldehyde 9a produced the allylic alcohol 16. reaction of the unsaturated compounds with the titano-
It was of great interest that the reduction products 17 and cene() reagent 1, without involvement of the (E)-alkenyl
18, rather than the alkenylation products, were isolated sulfone. These results imply that the cross-coupling pro-
when the corresponding (E) isomer (E)-14 was employed. ceeds through a cyclic transition state similar to 10 and 11,
Eur. J. Org. Chem. 2006, 878–880
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
879

A. Ogata, M. Nemoto, K. Arai, K. Kobayashi, A. Tsubouchi, T. Takeda
SHORT COMMUNICATION
associated with titanocene(), alkenyl sulfone, and alkyne
or carbonyl group, in which the (E) isomer may suffer steric
hindrance much more than the (Z) isomer.
Experimental Section
Typical Experimental Procedure: Finely powdered molecular sieves
(4 Å, 90 mg), magnesium turnings (24 mg, 0.99 mmol), and
Cp2TiCl2 (224 mg, 0.9 mmol) were placed in a flask and dried by
heating with a heat gun in vacuo (2–3 Torr). After the system had
cooled, THF (1.5 mL) and P(OEt)3 (0.31 mL, 1.8 mmol) were
added successively with stirring under argon at 25 °C. After 3 h,
the reaction mixture was cooled to 0 °C. A THF (1 mL) solution
of 2 (115 mg, 0.9 mmol) was added dropwise over 5 min to the
mixture, which was then stirred for 30 min. After a THF (1 mL)
solution of 8b (66 mg, 0.3 mmol) had been added dropwise over
10 min, stirring was continued at 0 °C for 30 min and then at 25 °C
for 2 h. The reaction was quenched by addition of 1  NaOH. The
usual workup and purification by column chromatography on silica
gel (hexane) gave 6d (62 mg, 83%).
Acknowledgments
This work was carried out under the 21th Century COE “Future
Nanomaterials” program at Tokyo University of Agriculture and
Technology.
Scheme 6. Alkenylation of alkynes and carbonyl compounds.
[1] T. Takeda, K. Arai, H. Shimokawa, A. Tsubouchi, Tetrahedron
Lett. 2005, 46, 775–778.
The stereochemistry of these reactions is also fascinating;
the configuration of the double bond originating from (Z)-
alkenyl sulfone is (E). The observed stereospecificity is com-
pletely different from that of the alkenylation of carbonyl
compounds with alkenyl halides through the formation of
alkenylmetal compounds such as Nozaki–Hiyama–Kishi
reaction,[11] which generally proceeds with retention of con-
figuration. The stereospecificity is interpreted in terms of
the formation of the titanacycle 19 with retention of config-
uration and subsequent syn elimination as shown in
Scheme 7.
[2] Metal-catalyzed Cross-coupling Reactions, 2nd ed. (Eds.: A.
de Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004.
[3] a) A. Suzuki, Pure Appl. Chem. 1985, 57, 1749–1758; b) F.
Bellina, R. Carpita, R. Rossi, Synthesis 2004, 2419–2440; c) F.
Robert, X. Youjun, Can. J. Chem. 2005, 83, 266–272; d) A.
Suzuki, Chem. Commun. 2005, 4759–4763.
[4] a) J. K. Stille, Pure Appl. Chem. 1985, 57, 1771–1780; b) E.
Pablo, E. M. Antonio, Angew. Chem. Int. Ed. 2004, 43, 4704–
4734; c) A. M. Echararren, Angew. Chem. Int. Ed. 2005, 44,
3962–3965.
[5] a) T. Hiyama, Y. Hatanaka, Pure Appl. Chem. 1994, 66, 1471–
1478; b) T. Hiyama, J. Organomet. Chem. 2002, 653, 58–61.
[6] a) Y. Takayama, S. Okamoto, F. Sato, J. Am. Chem. Soc. 1999,
121, 3559–3560; b) R. Nakajima, H. Urabe, F. Sato, Chem.
Lett. 2002, 4–5; c) Y. Song, S. Okamoto, F. Sato, Tetrahedron
Lett. 2002, 43, 6511–6514; d) Y. Song, Y. Takayama, S. Okam-
oto, F. Sato, Tetrahedron Lett. 2003, 44, 653–657.
[7] a) T. Takahashi, D. Y. Kondakov, N. Suzuki, Chem. Lett. 1994,
259–262; b) T. Takahashi, R. Hara, S. Huo, Y. Ura, M. P.
Leese, N. Suzuki, Tetrahedron Lett. 1997, 38, 8723–8726; c)
D. B. Millward, R. M. Waymouth, Organometallics 1997, 16,
1153–1158; d) A. Ligard, J. Kaftanov, H. Chechik, S. Farhat,
N. Morlender-Vais, C. Averbuj, I. Marek, J. Organomet. Chem.
2001, 624, 26–33; e) S. Farhat, I. Marek, Angew. Chem. Int.
Ed. 2002, 41, 1410–1413; f) J. Barluenga, L. Álvarez-Rodrigo,
F. Rodríguez, F. J. Fañanás, Angew. Chem. Int. Ed. 2004, 43,
3932–3935; g) J. Barluenga, F. Rodríguez, L. Álvarez-Rodrigo,
F. J. Fañanás, Chem. Eur. J. 2004, 10, 101–108; h) J. Barluenga,
F. Rodríguez, L. Álvarez-Rodrigo, J. M. Zapico, F. J. Fañanás,
Chem. Eur. J. 2004, 10, 109–116; i) S. Farhat, I. Zouev, I. Ma-
rek, Tetrahedron 2004, 60, 1329–1337.
Scheme 7. Stereochemical course of alkenylation.
In conclusion, we have established a novel vinylation,
promoted by the titanocene() reagent, of compounds con-
[8] T. Takahashi, D. Y. Kondakov, Z. Xi, N. Suzuki, J. Am. Chem.
Soc. 1995, 117, 5871–5872.
taining multiple bonds with vinyl pivalate (2). As implied [9] Y. Takayama, Y. Gao, F. Sato, Angew. Chem. Int. Ed. Engl.
1997, 36, 851–853.
in the reaction of alkenyl sulfones, the concept of this cross-
coupling could be applicable to the stereoselective alkenyl-
ation of a variety of unsaturated compounds and could pro-
[10] C. Delas, H. Urabe, F. Sato, J. Am. Chem. Soc. 2001, 123,
7938–7973.
[11] a) K. Takai, K. Kimura, T. Kuroda, T. Hiyama, H. Nozaki,
vide a comprehensive approach for the construction of car-
bon frameworks. Study along these lines is currently un-
derway.
Tetrahedron Lett. 1983, 24, 5281–5284; b) Y. Kishi, Pure Appl.
Chem. 1992, 64, 343–350.
Received: December 14, 2005
Published Online: January 5, 2006
880
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Eur. J. Org. Chem. 2006, 878–880