Regiocontrolled Synthesis of CpCo-Cyclobutadienyl-Bridged p-Cyclophanes via Annulation of Acyclic Diynes

Full text of DOI:10.1021/jo971022f

6708
J . Org. Chem. 1997, 62, 6708-6709
Sch em e 1
Regiocon tr olled Syn th esis of
Cp Co-Cyclobu ta d ien yl-Br id ged
p-Cyclop h a n es via An n u la tion of Acyclic
Diyn es
Ronald G. Brisbois,*,† Louis E. Fogel,
Olivier J .- C. Nicaise, and Peter J . DeWeerd
Department of Chemistry, Hamline University, 1536 Hewitt
Avenue, St. Paul, Minnesota 55104-1284
Noncovalent interactions between aromatic units are
key facets of host-guest chemistry1 and are thought to
be important in protein folding.2 In the extreme, two
aromatic moieties can orient either π-face to π-face or
π-face to π-edge. In order to examine the degree to which
such interactions can constrain conformational mobility,
we initiated a program of research directed toward the
synthesis of o,p-cyclophanes derived from a structural
core which remains conformationally dynamic (on the
NMR time scale) even at low temperature.3 Along with
classical approaches4 to this series of compounds, we have
also probed Co-mediated [2 + 2 + 2] aromatic annula-
tions5 on bis-alkyne 1 as a potential means of maximizing
synthetic convergence (eq 1). The required closure of the
specific opportunity/challenge of working with acyclic
diynes as a function of the two possible regiochemical
outcomes in the Co-mediated [2 + 2] annulation: 1,2-
tethered (6) and/or 1,3-tethered (7) products. Either
through careful separation of regioisomers or by regio-
control in the Co-mediated [2 + 2] annulation, mixed
cyclophanes with π-face (aryl)/π-edge (CpCo-cyclobuta-
dienyl) or π-face (aryl)/π-face (CpCo-cyclobutadienyl)
geometries could, in principle, be obtained. We report
here our preliminary results.
The first case we investigated (5a ) featured five-atom
tethering chains to ensure a high degree of conforma-
tional freedom and allow for the formation of either
cyclophane 6 or 7. The attempted annulation of 5a was
inconclusive, yet encouraging, because an extremely
unstable product mixture was obtained which we tenta-
tively assigned as an unknown ratio of 6a and 7a . Our
experience in isolating and handling the stable compound
3, along with literature precedent,7b suggested investiga-
tion of acyclic diyne 5b. Reaction of 5b proceeded
smoothly to afford only the 1,2-tethered product 6b in
40% yield. Gleiter and co-workers have observed similar
regiocontrol in the reaction of cyclic silyl-substituted
diynes.8f Our repeated attempts to isolate/characterize
the corresponding 1,3-tethered product 7b have proven
fruitless thus far. Mixed cyclophane 6b is highly crystal-
line and readily yielded crystals suitable for X-ray
analysis. A synopsis of some key structural features of
6b is provided in Figure 1.9
medium/large bridging ring was very inefficient and
unreproducible;6 however, an interesting compound (3),
containing bis-CpCo-cyclobutadienyl moieties, was iso-
lated and characterized.7 We were motivated by this
result to redirect a portion of our efforts to the synthesis
and characterization of mixed aryl/CpCo-cyclobutadienyl
cyclophanes via a highly convergent, Co-mediated [2 +
2] annulation of readily accessible acyclic diyne precur-
sors (Scheme 1).
Gleiter and co-workers have reported elegant work on
the Co-mediated conversion of cyclic diyne precursors to
CpCo-cyclobutadienyl superphanes.8 We viewed the
The next case we investigated provided a gratifying
result. Annulation of acyclic diyne 5c afforded only the
1,3-tethered product 7c in 37% yield. Mixed cyclophane
7c is also highly crystalline, and structural details are
provided in Figure 1.9 Multiple attempts to isolate/
characterize the corresponding 1,2-tethered product 6c
have been unsuccessful. Clearly, the CO2Et group mani-
fests its own unique mode of regiocontrol in the Co-
mediated [2 + 2] annulation.
† NSF-Presidential Faculty Fellow, 1993-97.
(1) (a) Host-Guest Chemistry; Vo¨gtle, F., Weber, E., Eds.; Springer-
Verlag: Berlin, 1985. (b) Cyclophanes; Diederich, F.; CRC Press, Inc.:
Boca Raton, FL, 1991. (c) Calixarenes; Gutsche, C. D.; CRC Press,
Inc.: Boca Raton, FL, 1989.
(2) (a) Burley, S. K.; Petsko, G. A. Adv. Protein Chem. 1988, 39,
125. (b) Serrano, L.; Bycroft, M.; Fersht, A. R. J . Mol. Biol. 1991, 218,
465.
(3) (a) Brisbois, R. G.; Wanke, R. A.; Burns, S. J .; Rappath, D. W.
Unpublished results. (b) Asami, M.; Krieger, C.; Staab, H. A. Tetra-
hedron Lett. 1991, 32, 2117.
Why do the SiMe3 and CO2Et groups exert opposite
modes of regiocontrol in the Co-mediated annulation?
Gleiter8f and Vollhardt5 have discussed the importance
(4) (a) Cyclophanes; Keehn, P. M., Rosenfeld, S. M., Eds.; Academic
Press: New York, 1983; Vols.
Cyclophanes II; Vo¨gtle, F., Ed.; Topics in Current Chemistry 113 and
115; Springer-Verlag: Berlin, 1983.
I and II. (b) Cyclophanes I and
(9) The authors have deposited atomic coordinates for structures
depicted in Figure 1 with the Cambridge Cystallographic Data Centre.
The coordinates can be obtained, upon request, from the Director,
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge,
CB2 1EZ, U.K.
(10) A number of cobaltacyclopentadienes have been isolated and
characterized. (a) McAlister, D. R.; Bercaw, J . E.; Bergman, R. G. J .
Am. Chem. Soc. 1977, 99, 1666. (b) McDonnell Bushnell, L. P.; Evitt,
E. R.; Bergman, R. G. J . Organomet. Chem. 1978, 157, 445. (c)
Yamazaki, H.; Wakatsuki, Y. J . Organomet. Chem. 1977, 139, 157.
(d) Yamazaki, H.; Wakatsuki, Y. J . Am. Chem. Soc. 1980, 102, 4363.
(11) (a) Comparison of the acidities of (i-Pr)2NH (pKa ≈ 40) and
(Me3Si)2NH (pKa ≈ 28) provides an example which can be used to
advantage in enolate generation. See: Brown, C. A. J . Org. Chem.
1974, 39, 3913. Danheiser, R. L.; Miller, R. F.; Brisbois, R. G; Park, S.
Z. J . Org. Chem. 1990, 55, 1959 and references cited therein. (b) Colvin,
E. Silicon in Organic Synthesis; Springer-Verlag: Berlin, 1983.
(5) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539.
(6) For an example of successful closure of a medium/large ring via
Co-mediated [2 + 2 + 2] aromatic annulation, see: Lofthagen, M.;
Chadha, R.; Siegel, J . S. J . Am. Chem. Soc. 1991, 113, 8785.
(7) (a) Rausch, M. D.; Genetti, R. A. J . Org. Chem. 1970, 35, 3888.
(b) Hillard, R. L., III; Vollhardt, K. P. C. J . Am. Chem. Soc. 1977, 99,
4058. (c) Efraty, A. Chem. Rev. 1977, 77, 691.
(8) (a) Gleiter, R. Angew. Chem., Int. Ed. Engl. 1992, 31, 27 and
references cited therein. (b) Gleiter, R.; Merger, R.; Nuber, B. J . Am.
Chem. Soc. 1992, 114, 8921. (c) Gleiter, R.; Merger, R.; Irngartinger,
H.; Nuber, B. J . Org. Chem. 1993, 58, 2025. (d) Gleiter, R.; Langer,
H.; Nuber, B. Angew. Chem., Int. Ed. Engl. 1994, 33, 1272. (e) Gleiter,
R.; Langer, H.; Schehlmann, V.; Nuber, B. Organometallics 1995, 14,
975. (f) Gleiter, R.; Stahr, H.; Nuber, B. Tetrahedron Lett. 1995, 36,
4607.
S0022-3263(97)01022-0 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 20, 1997 6709
Sch em e 2a
a
For clarity, E ) CO2Et and R ) tethering chains to benzene
moiety.
which yielded a zirconacyclopentadiene-based cyclophane
macrocycle.12
Although the CO2Et group is not as bulky as SiMe3, it
is better at stabilizing R-anion character. Therein,
perhaps, is the key to its regiodirecting effect. As
outlined in Scheme 2, the increased ability of the CO2Et
group to polarize intermediates, in a push-pull fashion,
might lead to an oxidative addition process that
featuressin the extremescharge character akin to 1,4-
nucleophilic addition (15a to 16). Alternatively, the
oxidative addition might be proceeding stepwise, wherein
a 1,4-nucleophilic addition effectively does take place
(15a /15b to 17 to 16). We have no direct evidence for
this speculation; however, in work related to that of
Bergman (eq 2), Yamazaki and Wakatsuki observed a
strong preference for 2,4-positioning of CO2CH3 moieties
in cobaltacyclopentadiene formation (eq 3), leading them
to discuss a possible competition between concerted and
stepwise oxidative addition processes which might be
substituent dependent.10c
F igu r e 1. 1,2-Tethered cyclophane 6b (top) and 1,3-tethered
cyclophane 7c (bottom), with key aspects of the cyclobutadienyl
moiety summarized.
F igu r e 2. Regiochemical permutations for the cobaltacyclo-
pentadiene formed upon oxidative addition.
of having the bulky SiMe3 groups positioned R to cobalt
in the cobaltacyclopentadiene formed upon oxidative
addition (Figure 2).10 In this regard, Bergman and co-
workers reported the synthesis and characterization of
13 (eq 2).10b Although diyne 11 lacks the conformational
We have demonstrated that mixed CpCo-cyclobutadi-
enyl-bridged p-cyclophanes can be prepared easily from
acyclic diynes. Most importantly, we have found that,
under the reaction conditions used, judicious choice of
the diyne (terminal) substituent allows for complete
regiocontrol in the key Co-mediated [2 + 2] annulation,
giving either a π-face (aryl)/π-edge (CpCo-cyclobutadi-
enyl) (6b) or π-face (aryl)/π-face (CpCo-cyclobutadienyl)
(7c) geometry in the product. We are currently investi-
gating the regiodirecting effects of other substituents,
different tether lengths, and alternative bridging orienta-
tions on the aryl moiety. Results will be reported in due
course.
flexibility of diyne 5b, its conversion to 13 clearly
demonstrates that the steric size of the SiMe3 group does
not preclude the formation of intermediate 8. Addition-
ally, we believe that the ability of silicon to stabilize
R-anion character11 plays an important role and, in the
conversion of 5b to 6b, works with steric factors in
positioning the SiMe3 groups upon oxidative addition
(Scheme 2), such that reductive elimination provides only
the 1,2-tethered product 6b via intermediate 8. A recent
report by Tilley and Mao supports this conclusion, given
their observation of the same regiodirecting effect in a
Zr-mediated polymerization/cyclization reaction sequence
Ack n ow led gm en t. This work was supported by an
NSF-Presidential Faculty Fellowship (CHE 9350393)
and the Hamline University Lund Fund. We gratefully
acknowledge Dr. Victor G. Young (X-Ray Crystal-
lographic Laboratory, 160 Kolthoff Hall, Chemistry
Department, University of Minnesota) for the X-ray
structural determinations.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the synthesis of compounds 5a -c, 6b, and 7c, as
well as 1H NMR spectra (9 pages).
(12) (a) Mao, S. S. H.; Tilley, T. D. J . Am. Chem. Soc. 1995, 117,
5365. (b) Mao, S. S. H.; Tilley, T. D. J . Am. Chem. Soc. 1995, 117,
7031.
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