Indolophanetetrayne cobalt complexes via Nicholas reactions

Article abstract of DOI:10.1021/ol027564n

(Matrix presented) Indole N-substituted diyne tetracobalt complexes (4) undergo a Lewis acid mediated dimerization - cyclization reaction through the indole 3-position to afford indolophanetetrayne cobalt complexes (7). Substitution of the indole fragment of (4) with a 3-methyl function allows analogous formation of indolophanetetrayne complex (9), linked through the indole 2-position.

Full text of DOI:10.1021/ol027564n

ORGANIC
LETTERS
2003
Vol. 5, No. 7
1003-1005
Indolophanetetrayne Cobalt Complexes
via Nicholas Reactions
Romelo Gibe, James R. Green,* and Greg Davidson
Department of Chemistry and Biochemistry, UniVersity of Windsor,
Windsor, ON, N9B 3P4, Canada
jgreen@uwindsor.ca.
Received December 27, 2002
ABSTRACT
Indole N-substituted diyne tetracobalt complexes (4) undergo a Lewis acid mediated dimerization−cyclization reaction through the indole
3-position to afford indolophanetetrayne cobalt complexes (7). Substitution of the indole fragment of (4) with a 3-methyl function allows
analogous formation of indolophanetetrayne complex (9), linked through the indole 2-position.
Alkyne-containing cyclophane molecules, or cyclophynes,
have been the subject of much recent interest. The ability of
the alkyne unit(s) to give the cyclophanes cavities with shape
persistence1 has often been reflected in an ability to complex
metals or organic molecules,2 or to self-aggregate in some
cases.3 In addition, cyclophynes have often been prepared
as systems with extended π-conjugation4 or as fullerene
precursors.5 On occasion, they have been studied as enediyne
antitumor analogues or Bergman cylization precursors.6 They
have also been subjects for studying the consequences of
angle strain on the alkyne function.7
plexes, which we have employed predominantly for the
tandem formation and nucleophilic substitution of their
propargylic cations (the Nicholas reaction).8,9 The widespread
(4) (a) Orita, A.; An, D. L.; Nakano, T.; Yaruva, J.; Ma, N.; Otera, J.
Chem. Eur. J. 2002, 8, 2005. (b) Hueft, M. A.; Collins, S. K.; Yap, G. P.
A.; Fallis, A. G. Org. Lett. 2001, 3, 2883. (c) Ohkita, M.; Ando, K.; Tsuji,
T. Chem. Commun. 2001, 2570. (d) Boydston, A. J.; Bondarenko, L.; Dix,
I.; Weakley, T. J. R.; Hopf, H.; Haley, M. M. Angew. Chem., Int. Ed. 2001,
40, 2986. (e) Ge, P.-H.; Fu, W.; Herrmann, W. A.; Herdtweck, E.; Campana,
C.; Adams, R. D.; Bunz, U. H. F. Angew. Chem., Int. Ed. 2000, 39, 3607.
(f) Haley, M. M.; Pak, J. J.; Brand, S. C. Top. Curr. Chem. 1999, 201, 81.
(g) Bodwell, G. J.; Satou, T. Angew. Chem., Int. Ed. 2002, 41, 4003. (h)
Tobe, Y.; Nagano, A.; Kawabata, K.; Sonoda, M.; Naemura, K. Org. Lett.
2000, 2, 3265.
(5) (a) Tobe, Y.; Furukawa, R.; Sonoda, M.; Wakabayashi, T. Angew.
Chem., Int. Ed. 2001, 40, 4072. (b) Tobe, Y.; Nakagawa, N.; Kishi, J. Y.;
Sonoda, M.; Naemura, K.; Wakabayashi, T.; Shida, T.; Achiba, Y.
Tetrahedron 2001, 57, 3629. (c) Rubin, Y.; Parker, T. C.; Pastor, S. J.;
Jalisatgi, S.; Boulle, C.; Wilkins, C. L. Angew. Chem., Int. Ed. 1998, 37,
1227. (d) Faust, R. Angew. Chem., Int. Ed. 1998, 37, 2825.
(6) (a) Suffert, J.; Raeppel, S.; Raeppel, F.; Didier, D. Synlett 2000, 874.
(b) Srinivasan, M.; Sankararaman, S.; Dix, I.; Jones, P. G. Org. Lett. 2000,
2, 3849.
Our interest in these systems stems for our work on the
synthetic chemistry of hexacarbonyldicobalt alkyne com-
(1) (a) Godt, A.; Duda, S.; U¨ nsal, O¨ .; Thiel, J.; Ha¨rter, A.; Roos, M.;
Tschierske, C.; Diele, S. Chem. Eur. J. 2002, 5094. (b) Srinivasan, M.;
Sankararaman, S.; Hopf, H.; Dix, I.; Jones, P. G. J. Org. Chem. 2001, 66,
4299. (c) Ohkita, M.; Ando, K.; Suzuki, T.; Tsuji, T. J. Org. Chem. 2000,
65, 4385. (d) Ho¨ger, S. J. Polym. Sci., A, Polym. Chem. 1999, 37, 2685.
(e) Moore, J. S. Acc. Chem. Res. 1997, 30, 402.
(2) (a) Youngs, W. J.; Tessier, C. A.; Bradshaw, J. D. Chem. ReV. 1999,
99, 3153. (b) Yamaguchi, Y.; Kobayashi, S.; Amita, N.; Wakamiya, T.;
Matusbara, Y.; Sugimoto, K.; Yoshida, Z.-i. Tetrahedron Lett. 2002, 43,
3277 and references therein.
(3) (a) Tobe, Y.; Utsumi, N.; Kawabata, K.; Nagano, A.; Adachi, K.;
Araki, S.; Sonoda, M.; Hirose, K.; Naemura, K. J. Am. Chem. Soc. 2002,
124, 5350. (b) Nakamura, K.; Okubo, H.; Yamaguchi, M. Org. Lett. 2001,
3, 1097.
(7) (a) Yamato, Y.; Fujita, K.; Abe, T.; Tsuzuki, H. New J. Chem. 2001,
728 and references therein. (b) Collins, S. K.; Yap, G. P. A.; Fallis, A. G.
Org. Lett. 2002, 4, 11.
(8) (a) Lu, Y.; Green, J. R. Synlett 2001, 243. (b) Guo R.; Green, J. R.
Synlett 2000, 746. (c) Patel, M. M.; Green, J. R. Chem. Commun. 1999,
509. (d) Green, J. R. Chem. Commun. 1998, 1751.
(9) (a) Green, J. R. Synlett 2001, 353. (b) See also: Burlison, J. A.;
Gray, J. M.; Young, D. G. J. Tetrahedron Lett. 2001, 42, 5363.
10.1021/ol027564n CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/07/2003

Scheme 1. Indolophane Precursor Synthesis
Figure 1. Cyclophanetetraynes (2) and precursor complex (1).
applicability of Nicholas reaction chemistry on these com-
plexes,10 the ability of the group to allow nonconventional
alkyne geometries, and their ability to participate in novel
cycloaddition reactions11,12 make them excellent candidates
as intermediates for the preparation and modification of many
types of cyclophynes.13,14 Recently, we have discovered that
derivatives of bis(propargyl alcohol) tetracobalt complexes
are capable of reaction with electron-rich arenes to afford
cyclophanediynes or cyclophanetetraynes in a single synthetic
operation, depending upon the spacer between the two alkyne
units.15,16 In particular, we have reported recently that
p-phenyl-linked bis(propargyl acetate) complex 1 is capable
of assembling cyclophanetetrayne complexes 2.16 We were
interested in applying this chemistry to the synthesis of
indole-containing cyclophanes (indolophanes), due to a recent
increase of interest in these infrequently encountered
systems.17-19
were chosen as starting points for these syntheses. The
propargyl acetate-hexacarbonyldicobalt function for the final
dimerization-cyclization would then be built upon this unit.
Specifically, preparation of the N-functionalized indole
cyclization precursor 4a was initiated by Sonogashira
coupling of N-propargylindole 3a21 with iodoarylpropargyl
acetate 522 to give 6a in 88% yield. Both alkyne units of
diyne 6a could be converted to their Co2(CO)6 complexes
in the presence of excess Co2(CO)8, giving 4a in 84% yield;
no evidence of single alkyne complexation products could
be detected under these conditions. Treatment of a solution
of 4a (0 °C, 10-2 M, CH2Cl2, 5.5 h) with excess BF3-OEt2
(6.5 equiv) gave two chromatographically separable main
products. The initially eluting compound possessed highly
characteristic H+, Na+, and K+ positive ion adducts (m/z
1679, 1701, 1717, respectively) and the Cl- negative ion
adduct (m/z 1713) in its electrospray mass spectra, identifying
it as the dimerized indolophanetetrayne complex 7a (55%
yield). The other major product (28% yield) possessed no
ions of significant abundance in the 1600-1800 m/z region
of its positive ion electrospray mass spectrum. X-ray
crystallographic analysis showed the compound to be 8, the
trimerized indolophanehexayne complex linked through the
indole 3-position, and this was confirmed by the presence
of M + Cl- - nCO (n ) 2, 4-11) ions in the negative ion
electrospray mass spectrum, the most intense of which was
the M + Cl- - 5CO ion (m/z 2412).
Our approach to indolophanetetraynes linked through their
nitrogen atoms required a change from our cyclophanetet-
rayne synthetic pathway, as a consequence of the fact that
the N-atoms of indoles are known to participate only poorly
in Nicholas reactions.20 Therefore, N-propargylindoles (3)
(10) (a) Green, J. R., Curr. Org. Chem. 2001, 5, 809. (b) Mu¨ller, T. J.
J. Eur. J. Org. Chem. 2001, 2021. (c) Teobald, B. J. Tetrahedron 2002, 58,
4133.
(11) (a) Sugihara, T.; Yamaguchi, M.; Nishizawa, M. Chem. Eur. J. 2001,
7, 1589. (b) Brummond, K. M.; Kent, J. I. Tetrahedron 2000, 56, 3263. (c)
Chung, Y. K. Coord. Chem. ReV. 1999, 188, 297. (d) Fletcher, A. J.; Christie,
S. D. R. J. Chem. Soc., Perkin Trans. 1 2000, 1657. (e) Geis, O.; Schmalz,
H.-G. Angew. Chem., Int. Ed. 1998, 37, 911.
(12) (a) Sugihara, T.; Wakabayashi, A.; Takao, H.; Imagawa, H.;
Nishizawa, M. Chem. Commun. 2001, 2456. (b) Son, S. U.; Chung, Y. K.;
Lee, S.-G. J. Org. Chem. 2000, 65, 6142.
(13) For recent reviews on hexacarbonyldicobalt alkyne complexes,
see: (a) Welker, M. E. Curr. Org. Chem. 2001, 5, 785. (b) Went, M. J.
AdV. Organomet. Chem. 1997, 41, 69.
(14) For cyclophyne or dehydrobenzannulene cobalt complexes, see ref
2a and: (a) Dosa, P. I.; Erben, C.; Iyer, V. S.; Vollhardt, K. P. C.; Wasser,
I. M. J. Am. Chem. Soc. 1999, 121, 10430. (b) Zhang, D.; Tessier, C. A.;
Youngs, W. J. Chem. Mater. 1999, 11, 3050. (c) Hamilton, D. G.; Sanders,
J. K. Chem. Commun. 1998, 1749. (d) Haley, M. M.; Langsdorf, B. L.
Chem. Commun. 1997, 1121. (e) Adams, R. D.; Bunz, U. H. F.; Fu, W.;
Nguyen, L. J. Organomet. Chem. 1999, 578, 91.
We wished to determine whether this synthetic route could
be applied to the individual preparations of analogous
indolophanetetraynes linked through the C-2 and C-3 posi-
tions. As a result, we chose C-2 methylated, C-3 linked 7b
and the C-3 methylated, C-2 linked 9 as targets. For access
to 7b, 2-methylindole was propargylated under conventional
conditions (NaH, propargyl bromide + Bu4NI, THF) to give
3b (71%). In a fashion analogous to that for 3a, propar-
gylindole 3b was subjected to Sonogashira coupling with 5
to give 6b (85% yield), and both alkyne functions complexed
(15) Guo, R.; Green, J. R. Chem. Commun. 1999, 2503.
(16) Gibe, R.; Green, J. R. Chem. Commun. 2002, 1550.
(17) (a) Bodwell, G. J.; Li, J.; Miller, D. O. Tetrahedron 1999, 55, 12939.
(b) Ortner, B.; Waibel, R.; Gmeiner, P. Angew. Chem., Int. Ed. 2001, 40,
1283. (c) Bodwell, G. J.; Li, J. Angew. Chem., Int. Ed. 2002, 41, 3261.
(18) (a) Black, D. StC.; Craig, D. C.; Rezaie, R. Chem. Commun. 2002,
810. (b) Black, D. StC.; Kumar, N.; McConnell, D. B. Tetrahedron 2000,
56, 8513. (c) Black, D. StC.; McConnell, D. B. Heteroat. Chem. 1996, 7,
437. (d) Black, D. StC.; Craig, D. C.; Kumar, N. Aust. J. Chem. 1996, 49,
311. (e) Black, D. StC.; Craig, D. C.; Kumar, N. Tetrahedron Lett. 1995,
36, 8075.
(20) (a) Nakagawa, M.; Ma, J.; Hino, T. Heterocycles 1990, 30, 451.
(b) Roth, K.-D. Synlett 1993, 529.
(21) Broggini, G.; Bruche´, L.; Zecchi, G. J. Chem. Soc., Perkin Trans.
1 1990, 533.
(19) For related compounds, see: Raehm, L.; Hamilton, D. G.; Sanders,
J. K. M. Synlett 2002, 1743.
(22) Prepared by Sonogashira coupling of 1,4-diiodobenzene and pro-
pargyl alcohol (80% yield) and subsequent acetylation (95% yield).
1004
Org. Lett., Vol. 5, No. 7, 2003

Figure 3. MM3 minimized structures of indolophanetetrayne
complexes 7b and 9. The carbonyl ligands and nonbenzylic H atoms
are removed for clarity. Key: gray ) C, white ) H, blue ) N,
violet ) Co.
q
decoalesced to two AB patterns at a higher T (∆G298K
)
15.1 kcal/mol). Definitive descriptions of these fluxional
processes await suitable crystals for X-ray diffraction studies
on 7 and 9; however, MM3 calculations and molecular
models suggest 7a and 7b assume a chairlike conformation,24
with approximately coplanar indole units (Figure 3). The
spectral properties are consistent with a chair-chair inter-
conversion, with 7a at the fast exchange limit and exchange
slowed for 7b. Analogous modeling on 9 supports an anti-
parallel orientation of the indole units (Figure 3), with the
p-disubstituted benzenes canted away from a parallel con-
Figure 2. Indolophanetetrayne complexes and the indolophane-
hexayne complex prepared from 4.
with excess Co2(CO)8 to form 4b (90% yield). For access
to 9, 3-methylindole was propargylated under conventional
conditions to give 3c (68%).23 Propargylindole 3c then was
coupled with 5 to form 6c (81% yield) and complexed with
excess Co2(CO)8 to form 4c (92% yield). Subjecting 4b to
treatment with excess BF3-OEt2 under high dilution condi-
tions (-10 °C, 10-4 M, CH2Cl2, 12 h) gave C-3 linked
indolophanetetrayne 7b in 40% yield. Conversely, subjecting
4c to BF3-OEt2 resulted in a noticeably more sluggish
reaction, but at room temperature (10-4 M, CH2Cl2, 4 h),
C-2 linked indolophanetetrayne 9 could be obtained in 25%
yield.
1
formation by differing degrees. Nevertheless, only two H
NMR resonances are observed for these p-phenylene units
in 9, as well as in 7a and 7b, indicating rotation about the
arene-alkyne carbon atoms is rapid over the entire temper-
ature range investigated (-50 to + 40 °C).
Acknowledgment. We are grateful to NSERC Canada
The presence of the methyl groups in 7b and 9 had a
noticeable affect on the fluxionality of the C-2 and C-3 linked
indolophanetetraynes. While the 1H NMR spectra of unsub-
stituted 7a displayed sharp singlets for all methylene groups,
7b gave two very broadened resonances at room temperature,
which decoalesced to four doublets at low T, corresponding
for support of this research.
Supporting Information Available: Experimental pro-
cedures for the preparation of and characterization data for
4a-c, 6a-c, 7a,b, 8, and 9, and crystallographic data for 8.
This material is available free of charge via the Internet at
http://pubs.acs.org.
q
to a ∆G283K of 12.2 kcal/mol. The methylene protons for
9 in the 1H NMR spectrum were similarly broad, and
OL027564N
(23) Black, D. StC.; Craig, D. C.; Deb-Das, R. B.; Kumar, N. Aust. J.
Chem. 1993, 46, 603.
(24) Ho¨gberg, A. G. S. J. Am. Chem. Soc. 1980, 102, 6046.
Org. Lett., Vol. 5, No. 7, 2003
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