Synthesis of [6.6]Metacyclophane via the Suzuki Coupling

Full text of DOI:10.1021/jo971334i

J . Org. Chem. 1997, 62, 8589-8590
8589
Sch em e 1
Syn th esis of [6.6]Meta cyclop h a n e via th e
Su zu k i Cou p lin g
Beverly B. Smith and William R. Kwochka*
Department of Chemistry and Physics,
Western Carolina University,
Cullowhee, North Carolina 28723
Robert Damrauer
Department of Chemistry, University of Colorado at Denver,
P.O. Box 173364, Denver, Colorado 80217-3364
R. J effrey Swope and J oseph R. Smyth
Department of Geological Sciences,
University of Colorado at Boulder,
Boulder, Colorado 80309
Received J uly 22, 1997
Cyclophane chemistry has contributed greatly to the
understanding of fields as varied as molecular and
cationic recognition to fundamental principles of NMR.2
To date, the largest all-carbon [n.n]metacyclophane
prepared is [5.5]metacyclophane, which was synthesized
by the acid-catalyzed dimerization of δ-2-methoxyphen-
ylvaleric acid, yet no conformational information is
available about this system.3 [4.4]Metacyclophane has
been prepared by a combination of an intramolecular
photocycloaddition followed by Birch reduction,4 and
molecular mechanics calculations predict that the anti
conformer is energetically preferred.5 The most in-depth
study of an [n.n]metacyclophane was performed on [3.3]-
metacyclophane, which was synthesized by the chromium
hexacarbonyl complex method.6 Variable-temperature
NMR studies and X-ray crystallography revealed that
[3.3]metacyclophane has a thermodynamic preference for
the syn conformation rather than the anti conformation
of [2.2]metacyclophane.7 While the Wurtz coupling was
the first method employed to make [2.2]metacyclophane,8
the most common procedure for preparing the smaller
[n.n]metacyclophanes and their derivatives has been the
oxidation of the sulfide precursor to the corresponding
sulfone, followed by flash vacuum thermolysis, or pho-
tolysis, to extrude SO2 in the ring contraction.9 Addition-
ally, a highly strained mono(Dewar benzene) isomer of
[1.1]metacyclophane has been prepared, possibly paving
the way to the fully aromatic system.10
Recently, we demonstrated that the palladium-cata-
lyzed coupling of an alkyl-9-borabicyclononane (alkyl-9-
BBN) derivative with an aryl bromide (the Suzuki
coupling) could be used to prepare a silicon-containing
cage system.11 As an extension of this work, we have
also been examining a general synthesis of all-carbon [n]-
and [n.n]metacyclophanes. We report here the synthesis
and structure determination of [6.6]metacyclophane (1),
which is formed according to Scheme 1 in a single
reaction vessel.
The bis-9-BBN adduct 2 was formed at room temper-
ature by adding 1,5-hexadiene to a solution of 2.05 equiv
of 9-BBN in THF (Scheme 1). The reaction mixture
containing 2 was then added to a solution of 1,3-
dibromobenzene, NaOH, and Pd(PPh3)4 in THF. This
mixture was refluxed overnight under an inert atmo-
sphere to provide 1 in 6% isolated yield. No [6]metacy-
clophane was detected by GC/MS.
The efficiency for this cyclization process is relatively
low because the conditions are not entropically favor-
able: we have formed an 18-membered ring in which the
four carbon-carbon bonds are created sequentially.
Consequently, formation of the acyclic systems 3 (5%) and
4 (7%) effectively compete with the cyclization process.
It is also likely that large amounts of polymeric material
were formed in the reaction, but no effort was made to
identify these. No 1,3-dibromobenzene or other starting
materials were detected in the reaction mixture. When
the coupling was carried out using different Suzuki
conditions12 (a 3 M aqueous NaOH solution) a similar
yield of 1 was obtained.
Compound 1 was crystallized from pentane and gave
clear, colorless crystals suitable for X-ray study.13 One
ORTEP view of [6.6]metacyclophane, 1a shows the sym-
metry in the molecule as well as a cavity that measures
6.6 Å in length by 5.3 Å in width. Another ORTEP
representation, 1b, clearly shows the anti conformation
of the 18-membered ring in which the benzene rings are
nearly perpendicular to the plane of the methylene
bridges (Figure 1). Thermodynamic preference for the
* To whom correspondence should be addressed. Phone: (704) 227-
7260. Fax: (704) 227-7647. E-mail: kwochka@wcu.edu.
(1) To whom inquiries regarding the X-ray analysis should be
addressed.
(2) (a) Vo¨gtle, F. Cyclophane Chemistry: Synthesis, Structures and
Reactions; J ohn Wiley and Sons: Chichester, 1993. (b) Diederich, F.
Cyclophanes; Royal Society of Chemistry: Cambridge, 1991. (c) Keehn,
P. M.; Rosenfeld, S. M. Cyclophanes; Academic Press: New York, 1983;
Vols. 1 and 2.
(3) Bien, S. J . Chem. Soc. 1960, 4015.
(4) Nishimura, J .; Ohbayashi, A.; Ueda, E.; Oku, A. Chem. Ber. 1988,
121, 2025.
(5) Fukazawa, Y.; Usui, S.; Tanimoto, K.; Hirai, Y. J . Am. Chem.
Soc. 1994, 116, 8169.
(6) Semmelhack, M. F.; Harrison, J . J .; Young, D. C.; Gutierrez, A.;
Rafii, S.; Clardy, J . J . Am. Chem. Soc. 1985, 107, 7508.
(7) a) Wilson, D. J .; Boekelheide, V.; Griffin, R. W., J r. J . Am. Chem.
Soc. 1960, 82, 2, 6302. (b) Sato, T.; Akabori, S.; Kainosho, M.; Hata,
K. Bull. Chem. Soc. J pn. 1968, 41, 218.
(10) Wijsman, G. W.; van Es, D. S.; de Wolf, W. H.; Bickelhaupt, F.
Angew. Chem., Int. Ed. Engl. 1993, 32, 726.
(11) Kwochka, W. R.; Damrauer, R.; Schmidt, M. W.; Gordon, M. S.
Organometallics 1994, 13, 3728.
(12) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh, M.;
Suzuki, A. J . Am. Chem. Soc. 1989, 111, 314.
(8) Vo¨gtle, F.; Neumann, P. Synthesis 1973, 85 and references
therein.
(9) a) For simple metacyclophanes see ref 2. (b) For cagelike
cyclophanes see: West, A. P., J r.; Smyth, N.; Kraml, C. M.; Ho, D. M.;
Pascal, R. A., J r. J . Org. Chem., 1993, 58, 3502.
S0022-3263(97)01334-0 CCC: $14.00 © 1997 American Chemical Society

8590 J . Org. Chem., Vol. 62, No. 24, 1997
Notes
F igu r e 1. ORTEP representations showing the cavity of the macroring 1a and the anti conformation 1b. The crystallographic
numbering is not the same as the systematic numbering scheme.
was stirred for a short time before 2.17 mL of 1,5-hexadiene
(18.26 mmol, 1 equiv) was rapidly added. The reaction mixture
was stirred at room temperature for 3 h to form the bis-9-BBN
adduct 2. The borane intermediate 2 was then cannulated to a
previously flame-dried 500 mL, two-necked round-bottom flask
equipped with a condenser that contained 2.21 mL of 1,3-
dibromobenzene (18.26 mmol, 1 equiv), 633 mg of Pd(PPh3)4 (0.55
mmol, 0.03 equiv), and 3.84 g of dry NaOH pellets (95.88 mmol,
5.25 equiv) in 100 mL of THF and refluxed for 12 h under
nitrogen. The reaction mixture was then poured into 100 mL
of hexanes and extracted with 1 M HCl (50 mL), saturated
aqueous NaHCO3 (50 mL), and brine (50 mL). Following drying
(MgSO4) and solvent removal, the crude material was filtered
through a plug of silica gel with hexanes. The product was
isolated by flash column chromatography on silica gel with 0.5%
Et2O/hexanes as a crystalline solid in 6% (167 mg) yield: mp
(uncorrected) 92-93 °C. Evaporative recrystallization of 1 from
pentane gave crystals suitable for X-ray analysis: 1H NMR (400
MHz, CDCl3) δ 7.16 (m, 2H), 6.97 (s, 2H), 6.96 (d, J ) 7.2 Hz,
4H), 2.57 (t, J ) 7.14 Hz, 8H), 1.60 (m, 8H), 1.29 (m, 8H); 13C
NMR (100 MHz, benzene-d6)16 δ 142.7, 128.4, 128.3, 126.5, 35.3,
30.8, 27.6; IR (KBr) 759 cm-1; MS (70 eV), m/z 321 (M + 1, 27),
anti conformation over the syn was predicted by molec-
ular mechanics calculations.14 In the anti conformation,
the methylene bridges of both the [2.2]metacyclophane
and 1 are nicely staggered and show no sign of Pitzer
strain, which is present in the syn conformers of both of
these ring systems.5 In addition, the [4.4]metacyclo-
phane, which belongs to the same C2v point group, also
appears to adopt the anti conformation.
Exp er im en ta l Section 15
[6.6]Meta cyclop h a n e (1). To a flame-dried 250 mL round-
bottom flask under a nitrogen atmosphere was added 127.8 mL
of 0.3 M 9-BBN (37.52 mmol, 2.05 equiv) in THF. The solution
(13) Crystal structure analysis of 2: crystal dimensions 0.40 × 0.20
× 0.21 mm; crystal system, orthorhombic; space group, Pbcm; unit cell
dimensions and volume, a ) 7.085(2) Å, b ) 15.978(3) Å, c ) 17.349-
(3) Å, V ) 1964.0(8) Å3, Z ) 4, R ) 0.0775 (wR ) 0.0551), rcalcd ) 1.084
g/cm3, 2 < 2q < 51, l (Mo KR) ) 0.710 73 Å, 26 °C, ω data collection,
2059 w/1796 unique of which 570 > 4I/σ and used for least-squares
refinement. Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK (fax: Int. code
+ (1223) 336-033; e-mail: teched@chemcrys.cam.ac.uk).
320 (M+, 100). Anal. Calcd for C24H32
Found: C, 89.96; H, 10.02.
: C, 89.93; H, 10.07.
Ack n ow led gm en t. This research was supported by
a Scholar/Fellow grant (R.D.) and supplemental funding
(W.R.K.) from the Camille and Henry Dreyfus Founda-
tion. R.D. and W.R.K. were supported by the National
Science Foundation, CHE-9223037. W.R.K. also ac-
knowledges Western Carolina University for financial
support. Finally, the investigators greatly appreciate
the use of NMR facilities at both the University of
Colorado at Boulder and the University of North
Carolina at Asheville.
(14) CSC’s Chem3D Pro, Version 3.1 makes use of Allinger’s MM2
force field approach to energy minimization. Cambridge Scientific
Computing, 875 Massachusetts Ave., Sixth Floor, Cambridge, MA
02139. Internet: support@camsci.com.
(15) All reagents were purified prior to use. Anhydrous THF was
obtained by distillation from Na/benzophenone. The 9-BBN was
titrated using Brown’s method (see: Brown, H. C. Organic Synthesis
via Boranes; Wiley-Interscience: New York, 1975). All reactions were
performed in flame-dried glassware under an inert atmosphere of
argon. 1H and 13C NMR were obtained on either a Bruker 400 MHz
NMR or a Varian 200 MHz NMR. Infrared spectra were obtained on
a Beckman IR-33. Ultraviolet spectra were recorded on a Perkin-Elmer
Model 552A UV-vis spectrophotometer. Gas chromatography was
performed on a Hewlett-Packard 5890 gas chromatograph using a 30
Su p p or tin g In for m a tion Ava ila ble: 1H NMR and 13C
NMR for compound 1 (2 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
m
J + W Scientific SE-30 fused silica capillary column. GC/MS
analyses were carried out on a Hewlett-Packard 5895B GC/MS system.
Flash chromatography was performed on silica gel 60, 230-400 mesh
ASTM, obtained from Baxter Scientific. The aluminum-backed TLC
plates used were cut from sheets of Whatman AL AIL G/UV plates.
Visualization of the TLC plates was done by dipping the plate in 10%
phosphomolybdic acid/ethanol and heating with a heat gun. Melting
points were taken using a Laboratory Devices MEL-TEMP apparatus
and are uncorrected. Elemental analyses were performed by Atlantic
Microlab Inc., Atlanta, GA.
J O971334I
(16) The signals due to C-9/12 and C-10/11 were coincident when
this spectrum was recorded in CDCl3.