Dodecamethoxy- and hexaoxotricyclobutabenzene: Synthesis and characterization

Article abstract of DOI:10.1021/ja064063e

We report herein the syntheses of dodecamethoxytricyclobutabenzene (TCBB) 1 and hexaoxo-TCBB 2, a class of molecules with structural and theoretical interest. The preparation is based on the 3-fold [2 + 2] cycloadditions of benzyne and ketene silyl acetal

Full text of DOI:10.1021/ja064063e

Published on Web 07/15/2006
Dodecamethoxy- and Hexaoxotricyclobutabenzene: Synthesis and
Characterization
Toshiyuki Hamura, Yousuke Ibusuki, Hidehiro Uekusa, Takashi Matsumoto, Jay S. Siegel,†
Kim K. Baldridge, and Keisuke Suzuki*
InteractiVe Research Center of Science, Department of Chemistry, Tokyo Institute of Technology, SORST, Japan
Science and Technology Corporation (JST), O-okayama, Meguro-ku, Tokyo 152-8551, Japan, and the Institute of
Organic Chemistry, UniVersity of Zu¨rich, Winterthurerstrasse 190, Zu¨rich CH-8057, Switzerland
Received June 9, 2006; E-mail: ksuzuki@chem.titech.ac.jp
Scheme 1a
The idea that annulation of a small ring onto benzene would
induce bond-length alternation by trapping out one Kekule´ reso-
nance structure is a provocative concept for chemists.1 Tricyclo-
butabenzene (TCBB) Ia2 serves as a key model compound in this
discussion, to which cognates, such as halo-substituted derivatives
Ib, Ic,3,4 hexamethylene derivative II,5 and triangular [4]phenylene
derivative III,6 are compared.
a Reagents and conditions: (a) 4a, n-BuLi, Et2O, -78 °C, 5 min; (b)
aq. KF, n-Bu4NCl, CH3CN, 0 f 25 °C, 5 h; (c) NBS, i-Pr2NEt, CH2Cl2,
-78 °C, 1 h; (d) TsCl, K2CO3, acetone, 25 °C, 10 h (5: 48%, 4 steps); (e)
4a, n-BuLi, Et2O, 0 °C (6: 54%, syn/anti ) 1.5:1); (f) H2, Pd/C, EtOAC,
25 °C; (g) TsCl, K2CO3, acetone, 25 °C, 10 h (7-syn: 83%, 2 steps,
We report the syntheses of two new cognates, dodecamethoxy-
TCBB 1 and hexaoxo-TCBB 2, via 3-fold [2 + 2] cycloadditions
of benzyne and ketene silyl acetals (KSAs).7 The present synthesis
overcomes numerous issues in previously reported synthesis of
TCBBs8 and uses the selectively protected 2-iodophloroglucinol
derivative 3 as a novel synthetic equivalent of benztriyne IV. Inter-
mediate 3 has advantages for the rapid and regioselective annulation
of three fully functionalized four-membered rings as in 1 and 2.
7-anti: 81%, 2 steps).
groups. To address this, the structure of 6 was determined by X-ray
analysis after converting to the bromotosylate 7, confirming that
the directing ability of the benzyloxy group overrides that of the
four-membered ring.
Figure 1. Regioselectivity of substituted benzynes.
Bromotosylate 7 was subjected to the third [2 + 2] cycloaddition
with KSA 4b, furnishing fully oxygenated tricyclobutabenzene 8
in 51% yield (Scheme 2). Amazingly, the cycloaddition was highly
regioselective, giving cycloadduct 8a as the major regioisomer,
along with a small amount of minor regioisomer 8b. The structure
The first cycloaddition occurred by treatment of iodotriflate 39
with n-BuLi in the presence of KSA 4a to give a single cycloadduct,
which was converted to bromotosylate 5 by selective hydrolysis
of the aryl silyl ether followed by the dibromination and tosylation
(Scheme 1). The high regioselectivity of this first [2 + 2]
cycloaddition could be rationalized by the directing effect of the
siloxy group as described before.7
Scheme 2a
Benzyne A, generated from 5, cleanly underwent the second [2
+ 2] cycloaddition with KSA 4a to give cycloadduct 6 in 54%
yield.10 Key features of this process include the following: (1)
halogen-lithium exchange of 5 exclusively occurred at the bromine
atom between the electron-withdrawing toluenesulfonate and the
benzyloxy group, generating benzyne A selectively without losing
the C4 bromide;11 (2) highly regioselective cycloaddition gave 6
exclusively, which was interesting in its own right, as we recently
reported that a four-membered ring also has a powerful directing
effect in the benzyne cycloaddition (Figure 1).12 The regioselectivity
issues raised a question of which is the more influential directing
a Reagents and conditions: (a) 4b, n-BuLi, Et2O, 0 °C (8: 51% from
7-syn, 8a/8b ) 6:1); (b) (MeO)3CH, TsOH, MeOH, 60 °C (1: 51% from
7-syn, 56% from 7-anti, 2 steps).
† Visiting professor (Jan. 1-Mar. 31, 2005) on leave from University of Zu¨rich.
9
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J. AM. CHEM. SOC. 2006, 128, 10032-10033
10.1021/ja064063e CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Acknowledgment. We thank Prof. Yves Rubin, UCLA, for
helpful discussions. This research was partially supported by the
21st Century COE program, a Grant-in-Aid for Young Scientists
(B), and the Swiss National Fund.
Supporting Information Available: General procedures, spectral
data for compounds 1, 3, and 5-9. This material is available free of
charge via the Internet at http://pubs.acs.org.
Figure 2. Molecular structure of 1. Selected exptl13 [calcd14] distances
(Å) and angles (°): C1-C2 1.389(2) [1.390], C1-C6 1.396(2) [1.399], C1-
C1A 1.523(2) [1.530], C6-C6A 1.529(2) [1.530], C1A-C6A 1.614(2) [1.623];
References
C6-C1-C2 120.2(1) [120.0], C1-C2-C3 119.8(1) [120.0], C1-C6-C6A
94.0(1) [94.2], C6-C1-C1A 94.1(1) [94.2], C1-C1A-C6A 86.0(1) [85.8],
C6-C6A-C1A 85.7(1) [85.8].
(1) (a) Siegel, J. S. Angew. Chem., Int. Ed. Engl. 1994, 33, 1721-1723. (b)
Frank, N. L.; Siegel, J. S. In AdVances in Theoretically Interesting
Molecules; Thummel, R. P., Ed.; JAI Press: Greenwich, CT, 1995; Vol.
3, pp 209-260.
(2) (a) Nutakul, W.; Thummel, R. P.; Taggart, A. D. J. Am. Chem. Soc. 1979,
101, 770-771. (b) Doecke, C. W.; Garratt, P. J.; Shahriari-Zavareh, H.;
Zahler, R. J. Org. Chem. 1984, 49, 1412-1417. (c) Boese, R.; Bla¨ser,
D.; Billups, W. E.; Haley, M. M.; Maulitz, A. H.; Mohler, D. L.; Vollhardt,
K. P. C. Angew. Chem., Int. Ed. Engl. 1994, 33, 313-317.
(3) Camaggi, G. J. Chem. Soc. C 1971, 2382-2388. (b) Thummel, R. P.;
Korp, J. D.; Bernal, I.; Harlow, R. L.; Soulen, R. L. J. Am. Chem. Soc.
1977, 99, 6916-6918.
(4) Stanger, A.; Ashkenazi, N.; Boese, R.; Bla¨ser, D.; Stellberg, P. Chem.s
Eur. J. 1997, 3, 208-211.
(5) Kawase, T.; Minami, Y.; Nishigaki, N.; Okano, S.; Kurata, H.; Oda, M.
Angew. Chem., Int. Ed. 2005, 44, 316-319.
(6) (a) Diercks, R.; Vollhardt, K. P. C. J. Am. Chem. Soc. 1986, 108, 3150-
3152. (b) Mohler, D. L.; Vollhardt, K. P. C.; Wolff, S. Angew. Chem.,
Int. Ed. Engl. 1990, 29, 1151-1153. (c) Boese, R.; Matzger, A. J.; Mohler,
D. L.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1995, 34, 1478-
1481.
(7) (a) Hosoya, T.; Hamura, T.; Kuriyama, Y.; Matsumoto, M.; Suzuki, K.
Synlett 2000, 520-522. (b) Hamura, T.; Hosoya, T.; Yamaguchi, H.;
Kuriyama, Y.; Tanabe, M.; Miyamoto, M.; Yasui, Y.; Matsumoto, T.;
Suzuki, K. HelV. Chim. Acta 2002, 85, 3589-3604.
(8) Hamura, T.; Ibusuki, Y.; Uekusa, H.; Matsumoto, T.; Suzuki, K. J. Am.
Chem. Soc. 2006, 128, 3534-3535.
(9) For details, see Supporting Information.
(10) The reaction was performed in dilute solution because of the poor solubility
of bromotosylate 5 in Et2O. Choice of the leaving group was also
important. For example, the reaction of the corresponding bromotriflate
gave low yield of the cycloadduct 6. The same situation was observed
for the third [2 + 2] cycloaddition of 7.
Figure 3. 13C NMR spectra of 2 (125 MHz, D2SO4, TMS as reference).
of 8a (syn/anti stereoisomers) was unequivocally assigned through
derivatization to the corresponding triketone 9 by two-step hy-
drolysis [(i) TsOH, CH2Cl2, MeOH, 25 °C; (ii) BF3‚Et2O, H2O,
-78 f 25 °C].9 This high regioselectivity (8a/8b ) 6:1) is striking
in view of the pseudo-symmetric oxygenation pattern of benzyne
B having two four-membered rings with high symmetry, where
the difference in both rings appears to be small. Cycloadduct 8
could also be converted to the symmetrical hexakis(dimethyl)acetal
1 under acidic conditions.
(11) Recently, related chemoselective generation of polyfunctionalized arynes
by I/Mg exchange of 2-iodophenyl sulfonates was reported. See: Sa-
pountzis, I.; Lin, W.; Fisher, M.; Knochel, P. Angew. Chem., Int. Ed. 2004,
43, 4364-4366.
Acetal 1 gave single crystals suitable for X-ray analysis (slow
crystallization, hexane, EtOAc, -15 °C). The central benzene ring
of 1 is planar, and the all internal angles are almost 120° (Figure
2).13 The average C-C bond length in the central benzene ring Q
) 1.394 Å (exptl) [1.395 Å (calcd)], and the endo/exo bond lengths
were essentially the same (endo 1.396 Å/exo 1.392 Å exptl) [endo
1.399 Å/exo 1.390 Å (calcd)]; δendo-exo ) 0.004 Å [0.009 Å].14
Experimental/computational structures show a decrease in Q and
δ as a function of the electronegativity of rim atoms in Ia-1-Ib:
Q ) 1.401, 1.394, 1.389 Å; δ ) 0.023, 0.004, -0.006 Å. Various
explanations exist for this effect.15 NMR computations for 1 (146.8,
114.6, 56.3 ppm) match well the observed 13C spectrum (141.0,
111.0, 51.7 ppm). Thus, structures and properties of these com-
pounds are well predicted computationally.
Hexaoxo-TCBB 2 was observed for the first time by cleavage
of hexaacetal 1 with concentrated sulfuric acid.16 The 13C NMR in
D2SO4 showed that all acetal functionalities were cleanly removed
to give quantitatively the characteristic peaks of the 1,2-dione
moiety (189 and 173 ppm) expected for ketone 2 [194.2 and 179.1
(calcd)]14 (Figure 3). Methanol (62 ppm) was generated during the
deprotection of 1.
The computationally predicted structure of 2 is planar with an
average benzene bond length Q ) 1.402 Å and a bond alternation
δ ) 0.0023 Å (exo ) 1.401(4) Å; endo ) 1.403(7) Å).14,17 Although
the related II with exo methylene groups displays essentially the
same average bond length Q ) 1.405 Å, the bond alternation δ )
0.045(8) Å (exo ) 1.382(1) Å; endo ) 1.427(9) Å) is much larger.
Notable also is the longer C-C bond length between the carbonyls
of 2 (1.592 Å) versus that between the methylenes of II (1.513 Å).
These trends are already seen in the simple cyclobutenes and will
form the basis for a future paper.
(12) Hamura, T.; Ibusuki, Y.; Sato, K.; Matsumoto, T.; Osamura, Y.; Suzuki,
K. Org. Lett. 2003, 5, 3551-3554.
(13) Crystallographic data for 1: C24H36O12, MW ) 516.53, colorless crystal,
0.38 × 0.20 × 0.08 mm, monoclinic, space group P21/c, Z ) 4, T )
93(2) K, a ) 12.3650(13), b ) 10.4112(7), c ) 22.0747(16) Å, â )
115.171(6)°, V ) 2571.9(4) Å3, λ(Mo KR) ) 0.71073 Å, µ ) 0.107 mm-1
.
Intensity data were collected on a Bruker SMART 1000 diffractometer.
The structure was solved by direct methods and refined by the full-matrix
least-squares on F2 (SHELXL97). A total of 45 417 reflections were
measured and 5897 were independent. Final R1 ) 0.0472, wR2 ) 0.1170
(4999 refs; I > 2σ(I)), and GOF ) 1.055 (for all data, R1 ) 0.0570, wR2
) 0.1218).
(14) Computations: B3LYP14a DFT and MP214b methods were employed, using
GAMESS14c and GAUSSIAN.14d As substantiated, previously optimized
geometries were obtained with B3LYP/cc-pVDZ.14e Subsequent single
point GIAO chemical shielding computations14f relative to TMS were
performed using the DZ(2d,p) basis set.14g Since B3LYP is known to
overestimate the deshielding contributions to the chemical shielding tensor
in cases when electron correlation is important, MP2 was also used. (a)
Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. 1988, B37, 785-789. (b) Moller,
C.; Plesset, M. S. Phys. ReV. 1934, 46, 618. (c) Schmidt, M. W.; Baldridge,
K. K.; Boatz, J. A.; Elbert, S. T.; Gordon, M. S.; Jensen, J. H.; Koseki,
S.; Matsunaga, N.; Nguyen, K. A.; Su, S.; Windus, T. L.; Elbert, S. T. J.
Comput. Chem. 1993, 14, 1347. (d) Frisch, M. J.; et al. GAUSSIAN 03;
Gaussian, Inc.: Pittsburgh, PA, 2003. (e) Dunning, T. H., Jr.; Hay, P. J.
In Modern Theoretical Chemistry; Schaefer, H. F., III, Ed.; Plenum: New
York, 1976; Vol. 3, p 1. (f) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-
5652. (g) Gauss, J. Chem. Phys. 1993, 99, 3629.
(15) (a) Baldridge, K. K.; Siegel, J. S. J. Am. Chem. Soc. 1992, 114, 9583-
9587. (b) Baldridge, K. K.; Siegel, J. S. J. Am. Chem. Soc. 2002, 124,
5514-5517. For another explanation, see: (c) Stanger, A. J. Am. Chem.
Soc. 1998, 120, 12034-12040.
(16) Rubin, Y.; Knobler, C. B.; Diederich, F. J. Am. Chem. Soc. 1990, 112,
1607-1617. Protonation of 2 has little effect on the chemical shift,
compared to the previously reported tetraketone derivative; see ref 8.
(17) Selected geometries for 2: C-Cendo 1.403(7) Å, C-Cexo 1.401(4) Å, Car-
CCO 1.519(3) Å, CCO-CCO 1.592(9) Å, CdO 1.188(5) Å; Car-Car-Car
120.0°, Car-Car-Cco 93.57°, Car-CCO-CCO 86.43°, CCO-CCO-OCO
136.69°.
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