Metalative reppe reaction. Organized assembly of acetylene molecules on titanium template leading to a new style of acetylene cyclotrimerization

Full text of DOI:10.1021/ja0161913

J. Am. Chem. Soc. 2001, 123, 7925-7926
Scheme 1. Conventional and New Styles of the Reppe
7925
Metalative Reppe Reaction. Organized Assembly of
Reaction
Acetylene Molecules on Titanium Template Leading
to a New Style of Acetylene Cyclotrimerization
Daisuke Suzuki,† Hirokazu Urabe,‡ and Fumie Sato*,†
Departments of Biomolecular Engineering and Biological
Information, Graduate School of Bioscience and
Biotechnology, Tokyo Institute of Technology
4259 Nagatsuta-cho, Midori-ku, Yokohama
Kanagawa 226-8501, Japan
Scheme 2. The Metalative Reppe Reaction
ReceiVed May 14, 2001
ReVised Manuscript ReceiVed June 18, 2001
Cyclotrimerization of acetylenes as illustrated in the upper
equation of Scheme 1, which was first developed by Reppe et al.
in 1948,1 has recently attracted much attention as a method for
the preparation of aromatic compounds.2 However, in practice,
when this method is to be applied to the preparation of substituted
aromatic compounds from three different, unsymmetrical acetyl-
enes, 38 homo- and cross-coupling products possibly may be
produced. Thus, the assembly of such acetylenes to strictly one
single aromatic compound is a formidable challenge.3
Considering the importance of organometallic compounds in
organic synthesis together with the aforementioned Reppe-type
reactions, we show herein a new and perfect style of acetylene
cyclotrimerization. Thus, three different, unsymmetrical acetylenes
and one molecule of a certain metallic species, which is a titanium
in the present case, are combined together in a highly controlled
manner to giVe directly aromatic organometallic compounds as
a single isomer. As this new cyclotrimerization of acetylenes
affords arylmetal compounds, it should be called the metalative
Reppe reaction as shown in the lower equation of Scheme 1.
Experimental operation of the metalative Reppe reaction, which
can be carried out in one pot, is very simple as illustrated in
Scheme 2 and entries 1-3 of Table 1.4 Dialkoxytitanacyclopen-
tadiene 45 was first prepared from two different, unsymmetrical
acetylenes 1 and 2 (as the first and second acetylenes) and a
divalent titanium alkoxide reagent, (η2-propene)Ti(O-i-Pr)2 (3),6
at -50 °C. Ethynyl tolyl sulfone (5)7,8 was then added as the
third acetylene and the reaction temperature was raised to room
temperature to give a single aryltitanium compound 6, the
presence of which was confirmed by the subsequent reactions
with electrophiles to give single adducts 7-9. Thus, simple
hydrolysis afforded the aromatic product 7, the structure of which
was unambiguously assigned by standard analyses and comparison
with an authentic sample prepared independently by a different
route. More importantly, deuteriolysis gave the single deuterated
aromatic compound 7-d. Moreover, the treatment of the arylti-
tanium compound 6 with iodine or an aldehyde furnished an
aromatic iodide 8 or a homologated aromatic compound 9,
demonstrating the advantageous feature of the metalative Reppe
reaction over the conventional version. It should be emphasized
that the asymmetry of the third acetylene 5 was preserved in the
products 7-d, 8, and 9 through the regioselective generation of
the carbon-titanium bond in 6.
† Department of Biomolecular Engineering.
‡ Department of Biological Information.
(1) Reppe, W.; Schweckendiek, W. J. Justus Liebigs Ann. Chem. 1948,
560, 104-116.
(2) Saito, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901-2915. Lautens,
M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49-92. Trost, B. M. Angew.
Chem., Int. Ed. Engl. 1995, 34, 259-281. Grotjahn, D. B. In ComprehensiVe
Organometallic Chemistry II; Hegedus, L. S., Abel, E. W., Stone, F. G. A.,
Wilkinson, G., Eds.; Pergamon Press: Oxford, 1995; Vol. 12, pp 741-770.
Schore, N. E. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, pp 1129-1162. Vollhardt,
K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539-556. Mu¨ller, E. Synthesis
1974, 761-774.
(3) A portion of this work was orally presented at the 79th Annual Meeting
of the Chemical Society of Japan, March 29, 2001, Kobe; Abstract 2H405.
Quite recently, after we completed the preparation of this manuscript, the
following report on the selective cyclotrimerization of three different,
unsymmetrical acetylenes by taking advantage of palladium catalysis appeared.
(a) Gevorgyan, V.; Radhakrishnan, U.; Takeda, A.; Rubina, M.; Rubin, M.;
Yamamoto, Y. J. Org. Chem. 2001, 66, 2835-2841. Other cyclotrimerization
methods of acetylenes to aromatic compounds reported recently are so far
limited to the homo-coupling of an acetylene (ref 3b-h), cross-coupling
involving at least one symmetrical acetylene (ref 3i-l), or cross-coupling of
tethered acetylenes (i.e., diynes or triynes) (ref 3m-r). (b) Saito, S.; Kawasaki,
T.; Tsuboya, N.; Yamamoto, Y. J. Org. Chem. 2001, 66, 796-802. (c) Ozerov,
O. V.; Patrick, B. O.; Ladipo, F. T. J. Am. Chem. Soc. 2000, 122, 6423-
6431. (d) Ozerov, O. V.; Ladipo, F. T.; Patrick, B. O. J. Am. Chem. Soc.
1999, 121, 7941-7942. (e) Chio, K. S.; Park, M. K.; Han, B. H. J. Chem.
Res. (S) 1998, 518-519. (f) Hill, J. E.; Balaich, G.; Fanwick, P. E.; Rothwell,
I. P. Organometallics 1993, 12, 2911-2924. (g) Kataoka, Y.; Takai, K.;
Oshima, K.; Utimoto, K. J. Org. Chem. 1992, 57, 1615-1618. (h) Jhingan,
A. K.; Maier, W. F. J. Org. Chem. 1987, 52, 1161-1165. (i) Mori, N.; Ikeda,
S.; Odashima, K. Chem. Commun. 2001, 181-182. (j) Sato, Y.; Ohashi, K.;
Mori, M. Tetrahedron Lett. 1999, 40, 5231-5234. (k) Takahashi, T.; Tsai,
F.-Y.; Li, Y.; Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 1999, 121, 11093-
11100. (l) Takahashi, T.; Xi, Z.; Yamazaki, A.; Liu, Y.; Nakajima, K.; Kotora,
M. J. Am. Chem. Soc. 1998, 120, 1672-1680. (m) Kotha, S.; Mohanraja, K.;
Durani, S. Chem. Commun. 2000, 1909-1910. (n) Witulski, B.; Stengel, T.;
Ferna´ndez-Herna´ndez, J. M. Chem. Commun. 2000, 1965-1966. (o) Yama-
moto, Y.; Ogawa, R.; Itoh, K. Chem. Commun. 2000, 549-550. (p) Witulski,
B.; Stengel, T. Angew. Chem., Int. Ed. 1999, 38, 2426-2430. (q) Yamamoto,
Y.; Nagata, A.; Itoh, K. Tetrahedron Lett. 1999, 40, 5035-5038. (r) Negishi,
E.; Harring, L. S.; Owczarczyk, Z.; Mohamud, M. M.; Ay, M. Tetrahedron
Lett. 1992, 33, 3253-3256.
(4) For the details of experimental procedures and physical properties of
products, see the Supporting Information.
(5) Urabe, H.; Sato, F. J. Am. Chem. Soc. 1999, 121, 1245-1255. Hamada,
T.; Suzuki, D.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 1999, 121, 7342-
7344. Urabe, H.; Nakajima, R.; Sato, F. Org. Lett. 2000, 2, 3481-3484.
(6) Sato, F.; Urabe, H.; Okamoto, S. Pure Appl. Chem. 1999, 71, 1511-
1519. Sato, F.; Urabe, H.; Okamoto, S. Synlett 2000, 753-775. Sato, F.; Urabe,
H.; Okamoto, S. Chem. ReV. 2000, 100, 2835-2886. Kulinkovich, O. G.; de
Meijere, A. Chem. ReV. 2000, 100, 2789-2834.
(7) Commercially available ethynyl tolyl sulfone (5) is the reagent of choice
in laboratories due to its easy handling and storage. While the corresponding
sulfoxide also underwent the same reaction, but with lower efficiency (17%
yield of 7), ethynyl sulfide or ethynyl ethyl ether did not afford the aromatic
compound. Both the strong electron-withdrawing nature of the sulfonyl group,
which should promote the [4+2] addition or insertion in Scheme 3, and its
character as a good leaving group appear essential for the success of this
transformation.
(8) For a review on synthetic application of sulfones, see: Simpkins, N.
S. Sulphones in Organic Synthesis; Pergamon Press: Oxford, 1993.
10.1021/ja0161913 CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/19/2001

7926 J. Am. Chem. Soc., Vol. 123, No. 32, 2001
Communications to the Editor
Table 1. Preparation of Various Aromatic Compounds by the
Metalative Reppe Reaction
Scheme 3. Proposed Reaction Course for the Final Step of
the Metalative Reppe Reaction
rearranges to a suitable position such as 11 where the 1,2-
elimination of the sulfonyl group is feasible. Finally, the sulfonyl
group was eliminated to shift the equilibrium to the formation of
the aryltitanium compound 6. Alternatively, path b involves
regioselective insertion of the third acetylene 5 to the titanacycle
4 followed by the elimination of the sulfonyl group at the sp2
carbon with inversion of configuration to give 6. However, in
any event, as we could not so far identify any of the important
intermediates in Scheme 3, a conclusion on the exact reaction
path should await further study.
The above preparation of aromatic compounds appears reason-
ably general in that the alkyl and ester groups in the first acetylene,
the alkyl group in the second acetylene, and the electrophiles are
arbitrarily selected depending upon the synthetic purpose. Another
example to substantiate this point is shown in entry 4 in Table 1.
Needless to say, two of the three acetylenes may be of the same
kind as the reactions which are listed in entries 5-7. Even though
two molecules of the sulfonyl acetylene were employed as the
second and third acetylenes in entries 5 and 6, they behaved as
quite different acetylenes, because one molecule was incorporated
as such to form a sulfonyl substituent, while the other molecule
was transformed to the titanated CdC unit in a regioselective
manner. The issue, namely, which sulfonyl group of the two in
the intermediate (such as 10 in Scheme 3) is preferably eliminated
in entry 6, may be highly dependent on the structure of titanacycle,
but the single aromatic product was obtained in this case. The
metalative Reppe reaction could also be applied to the generation
of various bicyclic aromatic titanium compounds from tethered
diynes as shown in entries 8-10. In general, it should also be
noted that functional groups such as an ester, amide, sulfonyl, or
alkoxide groups in the starting acetylenes survive the reaction
conditions to permit the preparation of functionalized aryltitanium
compounds. In summary, we have reported herein the first
metalative Reppe reaction, which realized the direct preparation
of aryltitanium compounds10 from three acetylenes in a highly
organized manner.
a Based on the results of deuteriolysis in the right column. For entries
8 and 9, the structures are tentatively shown. X refers to O-i-Pr, Cl,
and/or SO2Tol. b Lower incorporation of deuterium as compared to other
entries should be attributable to the use of a larger amount of the
sulfonylacetylene, as its acidic acetylenic proton may protonate the
aryltitanium compound during the reaction. c Only protonation is shown,
1
because H NMR analysis hardly determined the position and/or the
degree of the deuteration.
Acknowledgment. We are grateful to the Japan Society for the
Promotion of Science for financial support. D.S. thanks the same
organization for a Research Fellowship of the Japan Society for the
Promotion of Science for Young Scientists.
Path a or b in Scheme 3 most likely accounts for the
incorporation of the third acetylene.9 Thus, in path a, the [4+2]
cycloaddition of the titanacyclopentadiene 4 and the sulfonyl-
acetylene 5 took place to furnish the bicyclic titanacycle 10, at
least in an equilibrium concentration. The regioselection as well
as the high regioselectivity of this cycloaddition is the key to the
later formation of the aryl-titanium bond of 6 at the defined
position. Then, the carbon-titanium bond of the titanacycle 10
Supporting Information Available: Experimental procedures and
physical properties of products (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JA0161913
(9) The mechanism of metal-catalyzed cyclotrimerization of acetylenes has
been explained in terms of [4+2] cycloaddition or insertion of the third
acetylene to the metallacyclopentadiene, followed by the reductive elimination
of the metal (refs 2, 3c, 3f, 3l). However, the present case apparently consists
of the elimination of the sulfonyl group rather than the reductive elimination
of the metal at the final step.
(10) For synthetic application of organotitanium compounds, see: Reetz,
M. T. Organotitanium Reagents in Organic Synthesis; Springer-Verlag: Berlin,
1986. Ferreri, C.; Palumbo, G.; Caputo, R. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991;
Vol. 1, pp 139-172. Reetz, M. T. In Organometallics in Synthesis; Schlosser,
M., Ed.; Wiley: Chichester, 1994; pp 195-282.