Syntheses of syn and anti doublebent [5]phenylene

Article abstract of DOI:10.1021/ol049225v

The parent and dipropyl-substituted anti (1a,b) and syn doublebent (2a,b) [5]phenylenes have been assembled by CpCo-catalyzed double cyclization of regiospecifically constructed appropriate hexaynes. ¹H NMR, NICS, and an X-ray structural analys

Full text of DOI:10.1021/ol049225v

ORGANIC
LETTERS
2004
Vol. 6, No. 13
2249-2252
Syntheses of Syn and Anti Doublebent
[5]Phenylene†
Dennis T.-Y. Bong, Eugene W. L. Chan, Rainer Diercks, Peter I. Dosa,
Michael M. Haley, Adam J. Matzger, Ognjen Sˇ. Miljanic´, and
K. Peter C. Vollhardt*
Center for New Directions in Organic Synthesis, Department of Chemistry,
UniVersity of California at Berkeley, and the Chemical Sciences DiVision,
Lawrence Berkeley National Laboratory, Berkeley, California 94720-1460
Andrew D. Bond‡
UniVersity of Cambridge, Department of Chemistry, Lensfield Road,
Cambridge, CB2 1EW, UK
Simon J. Teat
CCLRC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD, UK
Amnon Stanger
Department of Chemistry, The Institute of Catalysis Science and Technology, and
The Lise Meitner-MinerVa Center for Computational Quantum Chemistry,
TechnionsIsrael Institute of Technology, Haifa 32000, Israel
kpcV@berkeley.edu
Received April 27, 2004
ABSTRACT
The parent and dipropyl-substituted anti (1a,b) and syn doublebent (2a,b) [5]phenylenes have been assembled by CpCo-catalyzed double
cyclization of regiospecifically constructed appropriate hexaynes. 1H NMR, NICS, and an X-ray structural analysis of 1a reflect the aromatizing
effect of double angular fusion on the central ring of the linear [3]phenylene substructure.
The various topological manifestations of the phenylenes are
of fundamental synthetic1 and theoretical interest.2 In this
context, hydrocarbons 1 and 2 are unusual in their mixed
topology, composed of the respective linear and angular
substructures 33 and 44 (Figure 1). The hitherto only example
of this type is “bent” [4]phenylene 5.5 They also represent
additional isolated6 members of the family of 12 [5]-
phenylenes2d and stand out in the series as the most stable
unbranched isomers, despite the presence of linear sub-
structures.2d To anticipate the properties of 1 and 2, it is
instructive to refer to those of their substructure 5,5 which
(1) For a review, see: (a) Vollhardt, K. P. C.; Mohler, D. L. In AdVances
in Strain in Organic Chemistry; Halton, B., Ed.; JAI: London, 1996; pp
121-160. For recent progress, see: (b) Han, S.; Bond, A. D.; Disch, R. L.;
Holmes, D.; Schulman, J. M.; Teat, S. J.; Vollhardt, K. P. C.; Whitener, G.
D. Angew. Chem., Int. Ed. 2002, 41, 3223. (c) Han, S.; Anderson, D. R.;
Bond, A. D.; Chu, H. V.; Disch, R. L.; Holmes, D.; Schulman, J. M.; Teat,
S. J.; Vollhardt, K. P. C.; Whitener, G. D. Angew. Chem., Int. Ed. 2002,
41, 3227. (d) Bruns, D.; Miura, H.; Vollhardt, K. P. C.; Stanger, A. Org.
Lett. 2003, 5, 549.
† CAS names: Benzo[1′′,2′′:3,4;5′′,4′′:3′,4′]dicyclobuta[1,2a:1′,2′a′]-
bisbiphenylene (syn isomer) and benzo[1′′,2′′:3,4;4′′,5′′:3′,4′]dicyclobuta-
[1,2-a:1′,2′-a′]bisbiphenylene (anti isomer).
‡ Present address: University of Southern Denmark, Department of
Chemistry, Campusvej 55, 5230 Odense M, Denmark.
10.1021/ol049225v CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/27/2004

Scheme 1a
a Reaction conditions: For 1a: (a) 1-ethynyl-2-(dimethylthexy-
lsilylethynyl)benzene, PdCl2(PPh3)2, CuI, NEt3, 72%. (b) TMSA,
PdCl2(PPh3)2, CuI, NEt3, 120 °C, 70%. (c) Bu4N+F-, THF, (95%).
(d) (i) CpCo(C2H4)2, THF, -25 °C; (ii) 1,3-cyclohexadiene, THF,
110 °C, 7% over two steps. For 1b: (a) 1-ethynyl-2-(pent-1-ynyl)-
benzene, PdCl2(PPh3)2, CuI, NEt3, 50 °C, 49%. (b) TMSA,
PdCl2(PPh3)2, CuI, NEt3, 145 °C, 70%. (c) NaOH, THF, CH3OH,
85%. (d) CpCo(CO)2, m-xylene, hν, ∆, 2%.
Figure 1. 1H NMR chemical shifts (δ, ppm; blue) and NICS (1.0)
values (red) for 1-5 (solvent).
reflects the effect of benzocyclobutadiene fusion to 3 and 4,
respectively. Thus, relative to the terminal ring in 3, ring B
exhibits increased bond alternation and lesser aromaticity
(chemical shifts, NICS values; Figure 1). The result of this
effect on B is decreased paratropism in the adjacent four-
membered ring and slightly increased diatropism in ring C,
causing the attached hydrogens to be relatively deshielded.
Conversely, relative to the terminal ring in 4, ring C
undergoes distortion in the sense indicated in the structure
depicted in Figure 1. The consequences of this distortion
are subtly increased bond localization and hence decreased
diatropism in B, relative to the central ring in 4. In 1 and 2,
the seemingly fairly unperturbed “other side” of the linear
substructure in 5 would be altered equally, and the deter-
mination of the consequences on C and of remote effects
was deemed to be important.
The syntheses of 1a,b (Scheme 1) started with tetrahalo-
genated benzene 67 as a C2h symmetric template. Elaboration
by sequential Sonogashira couplings, first with the appropri-
ate alkynyl(ethynyl)benzene and then with trimethylsilyl-
acetylene (TMSA), followed by desilylation provided hexaynes
8a,b, containing all the requisite carbon atoms. Cycloisomer-
ization, while moderately successful toward 1b when em-
ploying the standard protocol with CpCo(CO)2,1 failed for
1a under these conditions, requiring a remarkably improved
two-step protocol developed recently that utilizes CpCo-
(C2H4)2.8 The strategy en route to 2a,b was identical, except
that the starting haloarene was C2V-symmetric 9 (Scheme 2).9
A higher yielding alternative toward 2a is depicted in Scheme
3 and proceeds through tetrabromoarene 12, which could be
subjected to 4-fold Sonogashira coupling to give 13 and then
eventually the target.
(2) For an expose´ of the significance of this class of molecules in graph
theoretical treatments of aromaticity, see: (a) Randic´, M. Chem. ReV. 2003,
103, 3449. For selected other studies, see: (b) Schulman, J. M.; Disch, R.
L. J. Phys. Chem. A. 2003, 107, 5223. (c) Schulman, J. M.; Disch, R. L.;
Jiao, H.; Schleyer, P. v. R. J. Phys. Chem. A 1998, 102, 8051. (d) Schulman,
J. M.; Disch, R. L. J. Phys. Chem. A 1997, 101, 5596. The calculations
reported in this paper were repeated at the B3LYP/6-31G* level of DFT
theory in the present work; NICS (1.0) at GIAO/3-21G. See Supporting
Information.
(3) (a) Schleifenbaum, A.; Feeder, N.; Vollhardt, K. P. C. Tetrahedron
Lett. 2001, 42, 7329. (b) Berris, B. C.; Hovakeemian, G. H.; Lai, Y.-H.;
Mestdagh, H.; Vollhardt, K. P. C. J. Am. Chem. Soc. 1985, 107, 5670.
(4) Diercks, R.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1986,
25, 266.
(5) Bong, D. T.-Y.; Gentric, L.; Holmes, D.; Matzger, A. J.; Scherhag,
F.; Vollhardt, K. P. C. Chem. Commun. 2002, 278.
(6) Known topologies are linear: (a) Blanco, L.; Helson, H. E.;
Hirthammer, M.; Mestdagh, H.; Spyroudis, S.; Vollhardt K. P. C. Angew.
Chem., Int. Ed. Engl. 1987, 26, 1246. Angular: (b) Schmidt-Radde, R. H.;
Vollhardt, K. P. C. J. Am. Chem. Soc. 1992, 114, 9713. Zigzag: (c)
Eickmeier, C.; Holmes, D.; Junga, H.; Matzger, A. J.; Scherhag, F.; Shim,
M.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. 1999, 38, 800. Y-shaped
(C2V) branched: (d) Boese, R.; Matzger, A. J.; Mohler, D. L.; Vollhardt,
K. P. C. Angew. Chem., Int. Ed. Engl. 1995, 34, 1478.
(7) Hart, H.; Katsumasa, K.; Du, C.-J. F. J. Org. Chem. 1985, 50, 3104.
(8) Dosa, P. I.; Whitener, G. D.; Vollhardt, K. P. C.; Bond, A. D.; Teat,
S. J. Org. Lett. 2002, 4, 2075.
(9) Goldfinger, M. B.; Crawford, K. B.; Swager, T. M. J. Am. Chem.
Soc. 1997, 119, 4578.
2250
Org. Lett., Vol. 6, No. 13, 2004

Scheme 2a
Scheme 3a
a Reaction conditions: (a) TMSA, PdCl2(PPh3)2, CuI, NEt3, 96%.
(b) (i) KOH, Et2O/EtOH; (ii) 1-bromo-2-iodobenzene, PdCl2(PPh3)2,
CuI, NEt3, 120 °C, 45% over two steps. (c) TMSA, PdCl2(PPh3)2,
CuI, NEt3, 120 °C, 47%. (d) Bu4N+F-, THF, (95%). (e) (i)
CpCo(C2H4)2, THF, -25 °C; (ii) 1,3-cyclohexadiene, THF, 110
°C, 14% over two steps.
fixation in the terminal rings, in turn subtly increasing
aromaticity in C and attenuating paratropism of cyclobuta-
dienoid nuclei. In contrast, the central protons of the angular
fragment, which are slightly shielded in 5 (δ ) 5.94 and
6.07 ppm, NICS ) -2.9) relative to 4 (δ ) 6.12 ppm, NICS
) -3.3, also vide supra), seem to be unchanged in 2a (δ )
6.06 and 6.12 ppm, NICS ) -2.9). The deshielding effect
of the evolving “bay region” manifests itself in the increased
∆δ of two protons on the C ring: 0.07 ppm in 5, 0.15 ppm
in 2a. Finally, a long-range effect of symmetrization in going
from 5 to 2a seems to be absent, as indicated by the
essentially identical NMR and NICS data for rings A and
B.
a Reaction conditions: For 2a: (a) 1-ethynyl-2-(dimethylthexyl-
silylethynyl)benzene, PdCl2(PPh3)2, CuI, NEt3, 65%. (b) TMSA,
PdCl2(PPh3)2, CuI, NEt3, 120 °C, 70%. (c) Bu4N+F-, THF, 95%.
(d) (i) CpCo(C2H4)2, THF, -25 °C; (ii) 1,3-cyclohexadiene, THF,
110 °C, 14% over two steps. For 2b: (a) 1-ethynyl-2-(pent-1-
ynyl)benzene, PdCl2(PPh3)2, CuI, NEt3, 50 °C, 83%. (b) TMSA,
PdCl2(PPh3)2, CuI, NEt3, 135 °C, 86%. (c) NaOH, THF, CH3OH,
85%. (d) CpCo(CO)2, m-xylene, hν, ∆, 1%.
While it was impossible to obtain solids suitable for
conventional X-ray analysis of all the new [5]phenylenes
reported, 1a eventually yielded single crystals (by slow
The phenylenes 1 and 2 are orange-red solids that
decompose in air, especially in solution. The parent systems
are relatively insoluble (precluding 13C NMR measurements),
1
especially 1a, the H NMR spectrum of which necessitated
the use of hot 1,2-dichlorobenzene. The electronic spectra
exhibit the typical two sets of absorptions at higher (λmax
≈
350-390 nm) and lower energy (highest wavelength λmax
) 505 nm for 1a, 507 nm for 1b), devoid of any significant
indication of the topological differences between the two
isomers, unlike that observed for the series of angular vs
zigzag phenylenes.6b In tune with a trend emerging in the
electronic spectra of the lower phenylenes, i.e., λmax (branched/
angular) < λmax (linear), 1a these bands are at higher energy
than that for the linear [5]phenylene frame (530 nm) but
bathochromically shifted from those in the zigzag- (484 nm),
Y-shaped (C2V) branched (486 nm), and angular isomers (470
1
nm).6 Most revealing are the comparative H NMR spectra
(Figure 1).10 Focusing on 2a, for which data could be
obtained in CDCl3, the effect of additional annelation is
noticeably larger δ values for the hydrogens attached to ring
C, in accord with the changes in NICS values. Thus, the
central protons in the linear fragment experience increasing
deshielding along the series 3 (δ ) 6.24 ppm, NICS ) -5.4)
to 5 (δ ) 6.46, 6.39 ppm, NICS ) -6.4) to 2a (δ ) 6.73,
6.58 ppm, NICS ) -7.5), the result of consecutive bond
Figure 2. Synchrotron radiation crystal structure of 1a: views from
above (top) and the side (bottom). Bond lengths (Å; standard
uncertainties ) 0.003). Thermal ellipsoids are shown at 50%
probability.
Org. Lett., Vol. 6, No. 13, 2004
2251

cooling of a sealed solution of dibutyl ether from 190 °C to
room temperature) that were amenable to synchrotron
diffraction (Figure 2). The crystallographically centrosym-
metric molecule exhibits γ-packing11 and is essentially planar,
the dihedral angles between sets of consecutive four carbons
along the periphery ranging from 0.2 to 3.5°. Ring C adopts
the characteristic bisallylic pattern (average allyl bond length
1.387 Å) present also in 3 (1.392 Å)3a and (a silyl derivative
of) 9,10-(SiMe3)2-5 (1.389 Å).5 Conversely, ring B exhibits
even more bond fixation (66%) than the center of 4 (62%)12
but the same as in B of silylated 5 (67%). The terminal rings
in all systems are almost identically minimally distorted (vide
supra). The calculated structure of 1a (B3LYP/6-31G*)
faithfully reproduces the experimentally determined data,
with deviations ∆avg ) 0.008 Å and ∆max ) 0.016 Å.
Computed 2a is essentially identical, suggesting that the
details in Figure 2 also apply to this isomer.
Finally, heats of formation calculations of the entire family
of [5]phenylenes (see Supporting Information) reveal that
1a and 2a, despite the presence of the linear substructure,
are not destabilized relative to their all-angular isomers 14-
16 (Figure 3). We had traced this phenomenon to the
opposing effects of the σ- (relatively stabilizing) and
π-frames (relatively destabilizing) on the energetics of linear
versus angular fusion.1d Since NICS (1.0) values are reflec-
tive primarily of the properties of the π-system, total NICS
(i.e., the sum of all NICS values)13 should rectify the relative
ordering of these isomers. Indeed (Figure 3), such an effect
is found, the entire series exhibiting a fairly good linear
correlation between ∆Hf and total NICS (R2 ) 0.9816).
In summary, the synthesis of the title hydrocarbons
constitutes a significant step in the understanding of the
influence of topology on the properties of the phenylenes.
Efforts continue to make the entire family of [5]phenylenes
available for scrutiny in this respect.
Figure 3. Relative heats of formation (kcal mol-1) and total NICS
(red) of 1a, 2a, and the all-angular [5]phenylenes 14-16.
Acknowledgment. The NSF (CHE-0071887) funded this
work. The Center for New Directions in Organic Synthesis
is supported by Bristol-Myers Squibb as a Sponsoring
Member and Novartis as a Supporting Member. We are
grateful for postdoctoral fellowships to R.D. (NATO) and
M.M.H. (NSF), graduate fellowship to A.J.M. (Syntex; ACS
Division of Organic Chemistry, sponsored by Rohm and
Haas Co.), and a US-Israel BSF grant (No. 2000136). A.S.
thanks the VPR fund and the fund for promotion of research
at the Technion for financial support.
Supporting Information Available: Computational and
experimental procedures, characterization of all new com-
pounds, CIF for 1a, and XYZ files of calculated phenylenes.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(10) Assignments were made on the basis of signal multiplicity, including
the simplification of the spectra in 1b and 2b, comparison to the NMR
spectra of 3-5, and calculated chemical shifts (see Supporting Information).
(11) Desiraju, G. R. Chem. Commun. 1997, 1475.
(12) As defined in: Beckhaus, H.-D.; Faust, R.; Matzger, A. J.; Mohler,
D. L.; Rogers, D. W.; Ru¨chardt, C.; Sawhney, A. K.; Verevkin, S. P.;
Vollhardt, K. P. C.; Wolff, S. J. Am. Chem. Soc. 2000, 122, 7819.
(13) Moran, D.; Stahl, F.; Bettinger, H. F.; Schaefer, H. F., III; Schleyer,
P. v. R. J. Am. Chem. Soc. 2003, 125, 6746.
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Org. Lett., Vol. 6, No. 13, 2004