π-conjugated conjoined double helicene via a sequence of three oxidative CC- and NN-homocouplings

Article abstract of DOI:10.1021/ja051521v

Dimerization of planarized diamine 2 using benzoyl peroxide gave dihydrazine 1 in about 70% yield; that is, three dehydrogenations (one CC- and two NN-homocouplings) and two ring closures were attained in one synthetic step. Dihydrazine 1 may be viewed as

Full text of DOI:10.1021/ja051521v

Published on Web 06/08/2005
π-Conjugated Conjoined Double Helicene via a Sequence of Three Oxidative
CC- and NN-Homocouplings
Kouichi Shiraishi,† Andrzej Rajca,*,† Maren Pink,‡ and Suchada Rajca†
Department of Chemistry, UniVersity of Nebraska, Lincoln, Nebraska 68588-0304, and IUMSC, Department of
Chemistry, Indiana UniVersity, Bloomington, Indiana 47405
Received March 9, 2005; E-mail: arajca1@unl.edu
Chiral π-conjugated systems with helically annelated aromatic
rings possess extraordinary chiral properties.1 Although significant
advances in the synthesis of helical and doubly helical molecules
have been made in recent years,1-3 typical syntheses of such highly
annelated molecules are tedious and produce relatively low yields.
Novel efficient synthetic approaches to adequately functionalized,
strongly chiral molecules are critical in enabling emerging applica-
tions for chiral π-conjugated materials.4,5
Herein we describe an efficient synthesis of a chiral π-conjugated
dihydrazine 1, in which the two [5]helicene-like fragments are
annelated in their mid-sections to give a conjoined double helicene
structure (Figure 1).
Figure 1. Dihydrazine 1. Each of the two homochiral [5]helicene-like
fragments is shown in stick-and-ball.
The synthesis of 1 was discovered during screening for the
optimum routes to the dinitroxide, derived from diamine 2 (Scheme
1).6 The remarkable aspect of this synthesis is that the chiral
Scheme 1 a
Figure 2. Molecular structure and conformation for dihydrazine 1 and
a (i) 4-tert-Butylaniline (2.2 equiv), t-BuONa (∼3 equiv), Pd(OAc)2 (0.01
diamine 2: (A) top view of 1; (B) side view of 1; (C) top view of 2; and
equiv), t-Bu3P (0.03 equiv), toluene, under N2, 90 °C for 12 h; (ii) H3PO4,
85 wt % in water, under N2, 90 °C for 3-4 h; (iii) (PhCO2)2 (1.75-2.1
equiv), CH2Cl2, under air, 0 °C for 3 h.
(D) side view of 2. Carbon and nitrogen atoms are depicted with thermal
ellipsoids set at the 50% probability level. Only one of the two unique
molecules of 1, in which hydrogen atoms are omitted for clarity, is shown.
For 2, disorder is omitted for clarity.
structure 1 is obtained in high yield in a single, atom-efficient
synthetic step from planarized diamine 2 via three oxidative
homocouplings (one CC and two NN), and two annelating
cyclizations, using a single reagent, such as benzoyl peroxide,
(PhCO2)2.7 Diamine 2 is prepared by annelation of 3 using
electrophilic aromatic substitution.8 3 is obtained from 4,6-
diisopropenyl-1,3-dibromobenzene9 and 4-tert-butylaniline, using
Pd-catalyzed CN bond cross-coupling.10
may possess either a D2 (as in Figure 1) or C2h point group. In
particular, diastereotopic splitting (∆ν ≈ 100 Hz) for the methyl
groups of the dihydropyridine rings is observed, with no line broad-
ening up to at least 70 °C. However, upon addition of chiral shift
reagent, ytterbium[tris(3-heptafluoropropylhydroxymethylene)-(+)-
camphorate], the 1H NMR (400 MHz, benzene-d6) spectrum shows
additional diastereomeric splittings, in particular, the methyl groups
of the t-Bu groups appear as two well-resolved 1:1 singlets (e.g.,
∆δ ≈ 0.01 ppm). This precludes the achiral C2h point group and
indicates that the D2-symmetric double helical structure of 1 is
1
The H and 13C NMR data for 1 in solution are consistent with
a conjoined double helicene structure, in which [5]helicene-like
fragments are either homochiral or heterochiral (meso); that is, 1
1
configurationally stable on the H NMR time scale, providing the
lower limit of 16 kcal mol-1 for the barrier for racemization in 1.
† University of Nebraska.
‡ Indiana University.
9
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J. AM. CHEM. SOC. 2005, 127, 9312-9313
10.1021/ja051521v CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2 a
isotropic may be envisioned. Resolution and syntheses of analogues
of 1 with extended conjoined helical structures are being pursued.18
Acknowledgment. This research was supported by the National
Science Foundation (CHE-0414936) and the Air Force Office of
Scientific Research (FA9550-04-1-0056). We acknowledge CCDC
Software Limited for Mercury software. We thank R. Rainbolt and
S. Janicki for multigram preparation of 4,6-diisopropenyl-1,3-
dibromobenzene.
a (i) AcOH, 110 °C, 1 h, 66-73%; (ii) H2NNH2, AcOH, 110 °C, 10
min, quant.; (iii) (PhCO2)2 (2.0 equiv), CH2Cl2, under air, 0 °C, ∼4 h,
∼75%; (iv) (PhCO2)2 (0.75 equiv), CH2Cl2, under air, 0 °C, 3 h, 59-70%.
Supporting Information Available: Experimental section, includ-
ing X-ray crystallographic files in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
Structures of dihydrazine 1 and diamine 2 are confirmed by
single-crystal X-ray analysis (Figure 2).
References
In diamine 2, the annelated structure of five six-membered rings
is approximately planar.11a Dihydrazine 1, which may be viewed
as a dimer of 2, possesses an approximate D2 point group. In the
structure of 1, each monomeric diamine moiety derived from 2
adopts a chairlike conformation, with the dihedral angles of 40.96-
(3) and 43.90(3)° and dihedral angles of 40.85(3) and 43.64(3)°
for the two independent molecules A and B, respectively. The two
“chairs” are oriented antiparallel to each other, with their fused
seats forming the approximately planar central part of the molecule,
consisting of four six-membered rings.11b Therefore, the overall
structure of 1 is conjoined helical, with two homochiral [5]helicene-
like fragments annelated in their mid-sections (Figures 1 and 2).12,13
Furthermore, the “four-armed” molecular shape of 1 results in
inefficient crystal packing. It is conceivable that a single enantiomer
may not crystallize but rather form an isotropic glassy material.5b
Because of the possible cooperativity in double chair-to-chair
flips and inversion of configuration for both [5]helicene-like
fragments, the barrier for the racemization of 1 is likely to be much
(1) (a) Meurer, P. P.; Vo¨gtle, F. Top. Curr. Chem. 1985, 127, 1-76. (b)
Oxidative coupling: Larsen, J.; Bechgaard, K. J. Org. Chem. 1996, 61,
1151-1152. (c) Katz, T. J. Angew. Chem., Int. Ed. 2000, 39, 1921-1923.
(d) 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, 3223-3227. (e) Urbano, A. Angew. Chem., Int. Ed. 2003, 42,
3986-3989. (f) Schmuck, C. Angew. Chem., Int. Ed. 2003, 42, 2448-
2452. (g) Rajca, A.; Miyasaka, M.; Pink, M.; Wang, H.; Rajca, S. J. Am.
Chem. Soc. 2004, 126, 15211-15222.
(2) π-Conjugated double helices: (a) Rajca, A.; Safronov, A.; Rajca, S.;
Schoemaker, R. Angew. Chem., Int. Ed. 1997, 36, 488-491. (b) Marsella,
M. J. Acc. Chem. Res. 2002, 35, 944-951. (c) An, D. L.; Nakano, T.;
Orita, A.; Otera, J. Angew. Chem., Int. Ed. 2002, 41, 171-173.
(3) Triple and double helicenes: (a) Pen˜a, D.; Cobas, A.; Pe´rez, D.; Guitia´n,
E.; Castedo, L. Org. Lett. 2000, 2, 1629-1632. (b) Pen˜a, D.; Cobas, A.;
Pe´rez, D.; Guitia´n, E.; Castedo, L. Org. Lett. 2003, 5, 1863-1866. (c)
Gomez-Lor, B.; Echavarren, A. M. Org. Lett. 2004, 6, 2993-2996.
(4) Selected examples: (a) Zahn, S.; Swager, T. M. Angew. Chem., Int. Ed.
2002, 41, 4225-4230. (b) Percec, V.; Glodde, M.; Bera, T. K.; Miura,
Y.; Shiyanovskaya, I.; Singer, K. D.; Balagurusamy, V. S. K.; Heiney, P.
A.; Schnell, I.; Rapp, A.; Spiess, H.-W.; Hudson, S. D.; Duan, H. Nature
2002, 419, 384-387. (c) Field, J. E.; Muller, G.; Riehl, J. P.; Venkat-
araman, D. J. Am. Chem. Soc. 2003, 125, 11808-11809.
(5) Chiral optical waveguides using chiral isotropic glasses: (a) Herman, W.
N. J. Opt. Soc. Am. A 2001, 18, 2806-2818. (b) Miyasaka, M.; Rajca,
A.; Pink, M.; Rajca, S. Chem.sEur. J. 2004, 10, 6531-6539.
(6) Oxidation of 2 to the corresponding dinitroxide will be reported elsewhere.
(7) Two NN-homocouplings in cyclodehydrogenation of tetra(benzimidazol-
2-yl)benzenes: Wu, W.; Grimsdale, A. C.; Mu¨llen, K. Chem. Commun.
2003, 1044-1045.
(8) Hellwinkel, D.; Schmidt, W. Chem. Ber. 1980, 113, 358-384.
(9) Rajca, A.; Utamapanya, S. J. Org. Chem. 1992, 57, 1760-1767.
(10) Goodson, F. E.; Hauck, S. I.; Hartwig, J. F. J. Am. Chem. Soc. 1999,
121, 7527-7539.
1
higher than the lower limit estimate by H NMR spectroscopy.
Analogous cooperativity may be demonstrated for the double chair-
to-boat flips, corresponding to the isomerization of the D2-
symmetric 1 to its C2h-symmetric diastereomer (1-C2h). Such
isomerization occurs readily in acetic acid at moderate temperatures
(Scheme 2), indicating that 1-C2h is the thermodynamic product.
However, in the absence of acid, 1 isomerizes to 1-C2h with a half-
life of ∼3 h at 180 °C in naphthalene solution. This corresponds
to a free energy barrier of ∼35 kcal mol-1 for the inversion of one
of the [5]helicene-like fragments in the D2-symmetric structure 1.
This relatively high barrier, compared to the barrier of 24.1 kcal
mol-1 in [5]helicene,14 may be indicative of cooperativity in the
conversion from two chairs in D2 to two boats in the C2h point
group.15
Dihydrazine 1 is reduced to achiral tetraamine 4 (Scheme 2).
Oxidation of 4 with (PhCO2)2 gives exclusively dihydrazine 1; upon
partial oxidation of 4, only 1 and unreacted 4 are detected.
Interestingly, 4 is obtained in good isolated yield via partial
oxidation of diamine 2. These results suggest that 4, that is, CC-
monocoupling product of 2, is an intermediate in the oxidation
pathway from 2 to 1.16
(11) (a) In diamine 2, the mean deviation from a calculated least-squares plane,
including all five six-membered rings (C1-C20, N1, N2) is 0.0834 Å.
(b) In dihydrazine 1, the mean deviations from a calculated least-squares
plane, including the two center benzene rings and the nitrogens (C7, C8,
C9, C10, C11, C18, C19, C20, N1, N2, C7#1, C8#1, C9#1, C10#1, C11#1
,
C18#1, C19#1, C20#1, N1#1, N2#1, with symmetry operation #1: -x, y, 0.5
- z), are 0.0237 and 0.0314 Å for the two independent molecules.
(12) With the middle benzene ring of the [5]helicene-like fragment as a
reference, the inner helix climbs 3.3 Å and turns in-plane by 280°.
(13) Benzo[c]benzo[3,4]cinnolino[1,2]cinnoline: (a) Neugebauer, F. A.; Ku-
hnha¨user, S. Angew. Chem., Int. Ed. 1985, 24, 596-597. (b) Fischer, H.;
Krieger, C.; Neugebauer, F. A. Angew. Chem., Int. Ed. 1986, 25, 374-
375. (c) Dietrich, M.; Heinze, J.; Krieger, C.; Neugebauer, F. A. J. Am.
Chem. Soc. 1996, 118, 5020-5030.
(14) Goedicke, C.; Stegemeyer, H. Tetrahedron Lett. 1970, 937-940.
(15) (a) Double nitrogen inversion in the hydrazine moiety may contribute to
the cooperativity. (b) Racemization of 1 would involve double nitrogen
inversion in both hydrazine moieties. (c) Nelsen, S. F.; Frigo, T. B.; Kim,
Y.; Thompson-Colon, J. A. J. Am. Chem. Soc. 1986, 108, 7926-7934.
(16) Formation of 4 may involve either the CC-homocoupling via radical cation
(or diradical dication) of 2 or the NN-homocoupling followed by benzidine
rearrangement (e.g., [3,3]-sigmatropic shift): Cepanec, I. Synthesis of
Biaryls; Elsevier: Amsterdam, 2004; Chapter 6, pp 209-239.
UV/vis absorption spectra in n-heptane showed the expected red
shift from λmax ) 275 nm (sh 333 nm) for diamine 2 to λmax ) 409
nm (sh 439 nm) for dihydrazine 1.17 A blue fluorescence is found
(17) (a) 1: UV/vis (n-heptane): λmax/nm (ꢀmax/L mol-1 cm-1) ) 289 (7.4 ×
104), 333 (sh, ∼8 × 103), 409 (∼4 × 103), 439 (sh, ∼3 × 103).
Fluorescence (n-heptane): λmaxem/nm (λexc/nm, ΦF/%) ) 472 (289, ∼15),
472 (409, ∼15); the emission spectra for 1 are concentration independent
(6.0 × 10-6 - 1.5 × 10-5 M, λexc/nm ) 409). (b) 2: UV/vis (n-heptane):
em
for 1 in n-heptane, with quantum efficiency, ΦF ≈ 15%, at λmax
) 472 nm (excitation in the λexc ) 289 and 409 nm).17
λ
max/nm (ꢀmax/L mol-1 cm-1) ) 275 (∼3 × 104), 333 (sh, ∼3 × 103); the
In summary, the synthesis of 1 provides a novel, highly efficient
approach to a chiral π-conjugated conjoined double helicene with
remarkable configurational stability. Considering the molecular
shape, the hydrazine moieties of 1, and the possible analogues of
1, organic materials that are strongly chiral, electroactive, and
data for 2 are only qualitative, due to its very low solubility in n-heptane.
(18) Our approach is based upon replacement of 4-tert-butylaniline with 2,4-
disubstituted anilines and angularly connected aromatic amines in the
synthetic route in Scheme 1, for example, using 1-aminonaphthalene to
obtain the conjoined double helicene of [7]helicene-like fragments.
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