Synthesis and Diatropicity of trans-N-Cyclohexyl-2′,5′,10b,10c-tetramethyl-pyrrolo[3,4-e]-10b,10c- dihydropyrene. the First Example of an Iso[17]annulenopyrrole

Full text of DOI:10.1021/jo970430g

6060
J . Org. Chem. 1997, 62, 6060-6063
513 have, however, been reported. The difference in
Syn th esis a n d Dia tr op icity of
chemical shifts between the internal and external protons
of 4 and 5 are <0.35 ppm, indicating that there is hardly
any detectable ring current (aromatic character) in these
systems. The bisdehydroiso[17]annulenofuran 614 and
iso[17]annulenofurans 715 and 816 on the other hand show
experimentally observable diatropicity (aromaticity). It
tr a n s-N-Cycloh exyl-2′,5′,10b,10c-tetr a m eth yl-
p yr r olo[3,4-e]-10b,10c-d ih yd r op yr en e. Th e
F ir st Exa m p le of a n
Iso[17]a n n u len op yr r ole
Yee-Hing Lai* and Pu Chen
Department of Chemistry, National University of Singapore,
Singapore 119260, Republic of Singapore
Received March 10, 1997
Aromaticity is a fundamental concept discussed in
many aspects of chemistry.1-3 The general criteria for
heteroaromaticity are, however, not fully defined, al-
though many qualitative and quantitative approaches
have been reported to describe the aromatic character
in heterocyclic compounds.3-5 Contradictory results are
sometimes observed among different theoretical ap-
proaches. Reports6 based on the discussion of resonance
energy, for example, indicate that the order of decrease
in aromaticity is accepted as thiophene > pyrrole > furan.
More recently, Bird’s heteroaromaticity index7 and Katritz-
ky’s independent “classical” and “magnetic” aromaticity
scales,8 however, strongly suggest that pyrrole is more
aromatic than thiophene.
The fusion of these 5-membered heterocycles at their
3,4-positions to unsaturated carbocycles (i.e, isoannela-
tion)9 is also of special interest. Theoretical estimations
of the topological resonance energy per π-electron have
been reported10 for several linear heteropolycycles to
correlate their “percentage benzene character per π-elec-
tron”. In each series of 1, 2, and 3, nitrogen is shown to
be the most effective heteroatom resulting in the most
aromatic heteropolycycle. Oxygen is always the least
ideal. None of the members of the 18π 3 has been
isolated, and thus, the above order of aromaticity could
not be verified experimentally. The syntheses of
iso[17]annulenofuran11 412 and iso[17]annulenothiophene11
is apparent that an isoannelated heterocycle should be
held geometrically rigid to maximize the extent of π-de-
localization, thus allowing its diatropicity (aromaticity)
to be investigated effectively. Going from 7 to 8 results
in a decrease in diatropicity due to unfavorable steric
interactions and, thus, a deviation from molecular pla-
narity, with the external methyl groups located in the
bay regions in 8. The iso[17]annulenofuran 8 exhibits
only <7% of the ring current observed in the parent
[14]annulene 12.16 Before this work, there was no known
example of an iso[17]annulenopyrrole.11 It would thus
be interesting to determine experimentally whether a
significant increase in diatropicity (aromaticity) is ob-
served going from 8 to 10 (or a derivative) similar to that
predicted theoretically going from 3a to 3c. We wish to
(1) (a) Garratt, P. J . Aromaticity; Wiley: New York, 1986. (b) Badger,
G. M. Aromatic Character and Aromaticity; University Press: Cam-
bridge, 1969.
(2)
(a) Balaban, A. T. Pure Appl. Chem. 1980, 52, 1409. (b) Gorelik, M.
V. Russ. Chem. Rev. 1990, 59, 116.
(3) Balaban, A. T.; Banciu, M.; Ciorba, V. Annulene, Benzo-, Hetero-,
Homo-Derivatives, and Their Valence Isomers; CRC Press Inc.: Boca
Raton, FL, 1987; Vols. 1-3.
(4) (a) Katritzky, A. R.; Lagowski, J . M. The Principles of Heterocyclic
Chemistry; Chapman and Hall Ltd.: London, 1967. (b) Kellogg, R. M.
In Comprehensive Heterocyclic Chemistry; Bird, C. W., Cheeseman, G.
W. H., Eds.; Pergamon Press: Oxford, 1984; Vol. 4, Part 3.
(5) Cook, M. J .; Katritzky, A. R.; Linda, P. Adv. Heterocycl. Chem.
1974, 17, 255.
(6) (a) George, P.; Bock, C. W.; Trachtman, M. Tetrahedron Lett.
1985, 26, 5667. (b) Bedford, A. F.; Beezer, A. E.; Mortimer, C. T. J .
Chem. Soc. 1963, 2039. (c) Guthrie, G. B.; Scott, D. W.; Hubbard, W.
N.; Katz, C.; McCollough, J . P.; Gross, M. E.; Williamson, K. D.;
Waddington, G. J . Am. Chem. Soc. 1952, 74, 4662.
(7) (a) Bird, C. W. Tetrahedron 1992, 48, 335. (b) Bird, C. W.
Tetrahedron 1986, 42, 89; (c) Tetrahedron 1985, 41, 1409.
(8) (a) Katritzky, A. R.; Karelson, M.; Malhotra, N. Heterocycles
1991, 32, 127. (b) Katritzky, A. R.; Barczynski, P.; Musumarra, G.;
Pisano, D.; Szafran, M. J . Am. Chem. Soc. 1989, 111, 7.
(9) (a) Vollhardt, K. P. C.; Bergman, R. G. J . Am. Chem. Soc. 1972,
94, 8950. (b) LeGoff, E.; LaCount, R. B. Tetrahedron Lett. 1965, 2787.
(c) Warrener, R. N. J . Am. Chem. Soc. 1971, 93, 2346. (d) Wege, D.
Tetrahedron Lett. 1971, 2337. (e) Wiersum, U. E.; Mijs, W. J . J . Chem.
Soc., Chem. Commun. 1972, 347.
(12) (a) Beeby, P. J .; Weavers, R. T.; Sondheimer, F. Angew. Chem.,
Int. Ed. Engl. 1974, 13, 138. (b) Cresp, T. M.; Sondheimer, F. J . Am.
Chem. Soc. 1975, 97, 4412.
(13) J ones, R. R.; Brown, J . M.; Sondheimer, F. Tetrahedron Lett.
1975, 4183.
(14) (a) Ebe, H.; Nakagawa, T.; Iyoda, M.; Nagakawa, M. Tetrahe-
dron Lett. 1981, 22, 4441. (b) Iyoda, M.; Nagakawa, T.; Ebe, H.; Oda,
M.; Nakagawa, M.; Yamamoto, K.; Higuchi, H.; Ojima, J . Bull. Chem.
Soc. J pn. 1994, 67, 778.
(15) (a) Mitchell, R. H.; Zhou, P. Tetrahedron Lett. 1991, 32, 6319.
(b) Mitchell, R. H.; Iyer, V. S.; Khalifa, N.; Mahadevan, R.; Venugo-
palan, S.; Weerawarna, S. A.; Zhou, P. J . Am. Chem. Soc. 1995, 117,
1514.
(10) J unic, A.; Sabljic, A.; Trinajstic, N. J . Heterocycl. Chem. 1984,
21, 273.
(11) This term is derived qualitatively from isobenzofuran, isoben-
zothiophene and isobenzopyrrole.
(16) Lai, Y.-H.; Chen, P. J . Org. Chem. 1996, 61, 935.
S0022-3263(97)00430-1 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 17, 1997 6061
describe in this paper the synthesis and diatropicity of
the iso[17]annulenopyrrole 11.
reactions reported for the syntheses of the corresponding
diarylfurans.16 The optimized overall yield of dibromide
26 was about 30%. The existence of anti and syn
conformers in this series of compounds is evident by the
resolution of the corresponding pairs of methyl groups
on the pyrrole and/or benzene rings. A study of the
rotation barriers in these compounds will be discussed
later.
Resu lts a n d Discu ssion
(a ) Syn th esis. 2,5-Diarylfurans are known to undergo
acid-catalyzed hydrolysis to afford the corresponding 1,4-
diketones, which could be cyclized again to form either
2,5-diarylthiophenes or 2,5-diarylpyrroles.17 A potential
route to the pyrrole-annelated thiacyclophane 15, and
perhaps the thiophene-annelated thiacyclophane 14, was
using the furan-annelated thiacyclophane 1316 as a
precursor. In all our attempts, compound 13 was,
however, very resistant to hydrolysis and failed to yield
the 1,4-diketone 17. Treatment of the reported 1,4-
diketone 1816 with either P2S5 or sulfur melt19 surpris-
18
ingly yielded the furan 19 instead of the thiophene 20.
The sulfur-containing reagents served as a dehydrating
agent but failed to achieve deoxygenation.19 Reaction of
18 with ammonium acetate gave a low yield of the pyrrole
21. An attempt to convert the dichloride 21 to a dinitrile
(for subsequent functional transformations, see the later
discussion on 22) by the von Braun reaction20 was,
however, unsuccessful due to thermal decomposition
resulting in noncharacterizable products.
The methyl protons on the pyrrole rings (see later
discussion on assignment) of 26 appear as two singlets
at δ 2.05 and 2.11 in a 1:1 ratio. An intramolecular
coupling reaction of 26 using sodium sulfide under high
dilution conditions21 led to the isolation of only a low yield
(20%) of the anti-thiacyclophane 16 with no detectable
amount of the corresponding syn isomer. The anti
stereochemistry of 16 is supported by a high-field signal
at δ 0.89 for the internal methyl protons shielded by the
opposite benzene rings.
A Wittig rearrangement of 16 in the presence of
n-butyllithium followed by methyl iodide quench gave the
ring-contracted product 27 in high yield (96%). The anti
stereochemistry is again confirmed by a shielded signal
at δ 0.58 for the internal methyl protons. The pseu-
doequatorial stereochemistry of the methylsulfanyl group
is suggested by the absence of deshielding of the adjacent
methyl protons on the benzene ring, thus the unresolved
signal for all six internal methyl protons. Remethylation
of 27 with dimethoxycarbonium fluoroborate provided the
corresponding sulfonium salt, which when treated with
potassium tert-butoxide at room temperature afforded
compound 28. The structure of 28 is supported by a
shielded signal at δ 1.23 and a singlet at δ 6.41 for the
internal methyl and bridge-olefinic protons, respectively.
The first example of an iso[17]annulenopyrrole, namely
compound 11, was then obtained by irradiation of a
solution of 28 in thoroughly degassed benzene with UV
light at 254 nm. A purple solution was obtained after
irradiation for 1 h, and the presence of 11 was clearly
indicated by two new singlets at δ -0.42 (internal methyl
protons) and 2.82 (external methyl protons) in a 1:1 ratio
Protection of the NH function in 21 was thus required.
Treating the diketone 18 in cyclohexylamine, which has
a sufficiently high boiling point, gave the diarylpyrrole
22 in a high yield. Conversion of 22 to 26 was achieved
with minor modifications via a similar sequence of
(18) (a) Allen, G. F. H.; Gates, J . W., J r. J . Am. Chem. Soc. 1943,
65, 1283. (b) Cava, M. P.; Scheel, F. M. J . Org. Chem. 1967, 32, 1304.
(c) Garratt, P. J .; Neoh, S. B. J . Org. Chem. 1975, 40, 970.
(19) (a) Mukaiyama, T.; Hata T. Bull. Chem. Soc. J pn. 1961, 43,
99. (b) Nozaki, N.; Koyama, T.; Mori, T. Tetrahedron 1969, 25, 5357.
(20) New, M. S. Organic Syntheses; Wiley: New York, 1955; Collect.
Vol. III, p 631.
(21) (a) Rossa, L.; Vo¨gtle, F. Top. Curr. Chem. 1983, 113, 1. (b)
Knops, P.; Sendhoff, N.; Mekelburger, H.-B.; Vo¨gtle, F. Ibid. 1991, 161,
1. (c) Ostrowicki, A.; Koepp, E. Vo¨gtle, F. Ibid. 1991, 161, 37.
(17) (a) Whitesides, G. M.; Pawson, B. A.; Cope, A. C. J . Am. Chem.
Soc. 1968, 90, 639. (b) Cram, D. J .; Montgomery, C. S.; Knox, G. R. J .
Am. Chem. Soc. 1966, 88, 515. (c) Haley, J . F., J r.; Resenfeld, S. M.;
Keehn, P. M. J . Org. Chem. 1977, 42, 1379. (d) Lee, A. W.; Keehn, P.
M.; Ramos, S. M.; Rosenfeld, S. M. Heterocycles 1977, 7, 81. (e) Marcel,
S. F.; Lie, J . K.; Fasih, A. J . Chem. Soc., Chem. Commun. 1981, 1110.
(f) Rosenfeld, S. M.; Sanford, E. M. Tetrahedron Lett. 1987, 4775. J .
Am. Chem. Soc. 1968, 90, 639.

6062 J . Org. Chem., Vol. 62, No. 17, 1997
Notes
Ta ble 1. P r oton Ch em ica l Sh ifts of th e In ter n a l a n d
Exter n a l Meth yl P r oton s in Com p ou n d s 22-26 in CDCl3
a n d C6D5NO2
Ta ble 2. Dyn a m ic NMR Da ta for th e Ba r r ier s to
Rota tion in Com p ou n d s 22-26
∆ν at Tc (Hz)a,b ∆Gcq (kJ mol-1
Tc (°C)
Ac Bd
)
in CDCl3
in C6D5NO2
compd
X
Ac
Bd
Ac
Bd
compd
protons Aa
protons Bb
protons Aa
protons Bb
22
23
24
25
26
Cl
CN
CHO
CH2OH
CH2Br
1.5
1.0
1.5
1.5
1.0
4.8
4.1
5.2
3.1
0.3
140
125
163 97.5 ( 1.5 98.8 ( 0.5
145 95.1 ( 2.4 95.2 ( 0.6
22
23
24
25
26
2.02, 2.07
2.11, 2.03
2.12, 2.09
2.03, 1.98
2.11, 2.05
2.17, 2.10
2.31, 2.19
2.46, 2.32
2.10
2.17, 2.15
2.20, 2.18
2.21, 2.19
2.18, 2.12
2.17, 2.15
2.25, 2.19
2.41, 2.34
2.58, 2.51
2.27, 2.22
2.26, 2.24
142.5 165 98.0 ( 1.5 99.0 ( 0.5
143
140
158 98.1 ( 1.6 99.2 ( 0.8
140 98.7 ( 2.2 100.3 ( 2.8
2.13
a
Data obtained from spectra determined using ca. 25 mg of
sample in 0.5 mL of C6D5NO2. b Calculated by linear extrapolation
to Tc of the chemical shift differences observed at 75-105 °C.
a
b
Methyl protons on pyrrole. Methyl protons on benzene.
d
c Methyl protons on pyrrole. Methyl protons on benzene.
1
in the H NMR spectrum of the mixture. A similar spec-
trum was observed when a solution of 28 was warmed
to about 80 °C for several hours. However, no complete
conversion of 28 to 11 could be observed under either
thermal or photochemical conditions. Decomposition of
11 was apparent in attempts involving longer reaction
times.
the key factor resulting in an increase in energy barriers
to rotation.
(b) Rota tion a l Ba r r ier s. The conformational behav-
ior of 1,2-di-o-tolylbenzene and its 3′,3′′-disubstituted
1
derivatives has been investigated by dynamic H NMR
studies.22 The 3,4-diaryl derivatives of five-membered
heteroaromatic rings in principle are expected to involve
lower rotational energy barriers than those in the cor-
responding 1,2-diarylbenzenes. With the presence of the
2,5-dimethyl groups in the pyrrole ring in compounds
22-26 the rotational energy barriers in the this series
are, however, expected to increase significantly. The
methyl signals would serve as good probes for the
dynamic 1H NMR studies of 22-26. Assignments of
these protons are thus required. The methyl protons on
the benzene rings in compounds 22-24, respectively, are
expected to be deshielded by the anisotropic effects of the
adjacent Cl, CN, and CHO functions. On the other hand,
chemical shifts of the methyl protons on the pyrrole ring
would be very similar. The methyl proton signals are
thus assigned accordingly (Table 1).
(c) Isoa n n ela tion a n d Dia tr op icity. The shielded
internal methyl protons (δ -0.42) and the deshielded
external methyl protons (δ 2.82) are both indicative of
an appreciable diamagnetic ring current in the 18π
marcroring in 11. Pyrrole is known to behave as a poor
1,3-diene and only undergoes Diels-Alder reactions with
very reactive dienophiles such as benzyne.24 The isoan-
nelated benzo- and naphthopyrroles 1c and 2c, however,
form Diels-Alder adducts readily with a series of dieno-
philes.25 Treatment of 28 with dimethyl acetylenedicar-
boxylate in refluxing benzene (during which thermal
conversion of 28 to 11 occurred) gave the Diels-Alder
adduct 32 in a good yield. The internal methyl protons
in 32 appear as two singlets at δ -3.45 and -3.81,
indicating a significantly higher diatropicity in the 14π
macroring in 32.
An estimation of the energy barrier for the anti h syn
interconversion process in 22-26 could be obtained from
the coalescence temperature method.22,23 The high-
temperature 1H NMR studies were carried out using
C6D5NO2 in which the two pairs of methyl proton signals
are resolved in each of the compounds 22-26. An
appreciable dependence of the frequency separation (∆ν)
of the two pairs of methyl signals on temperature was,
however, observed. Thus, the chemical shift difference
(∆ν) at the coalescence temperature (Tc) was calculated
by extrapolating a linear plot of the ∆ν values observed
at ca. 75-105 °C where the rate of the site exchange is
expected to be slow within the NMR time scale. Although
the ∆ν values are small in several cases (Table 2),
separate analyses of the two pairs of methyl signals could
be carried out that collectively should give a reasonably
reliable estimation of the transition-state free energy at
q
coalescence, ∆Gc (Table 2). The energy barriers to
rotation in 22-26 of 95-100 kJ mol-1 (Table 2) are 25-
30 kJ mol-1 higher than those observed in the corre-
sponding diarylbenzenes 29.22 The additional steric
effects induced by the 2,5-dimethyl groups on the pyrrole
ring going from the transition state 30 to 31 are clearly
Qualitatively, there is a large decrease in ring current
effect going from 32 or the parent dihydropyrene 12
(δCH3 ) -4.25)26 to the iso[17]annulenopyrrole 11.
Using 12 and the nonaromatic compound 33 (δCH3
)
(22) Mitchell, R. H.; Yan, J . S. H. Can. J . Chem. 1980, 58, 2584.
(23) (a) Lai, Y.-H. J . Chem. Soc., Perkin Trans. 2 1986, 1667. (b)
Oki, M. Applications of Dynamic NMR Spectroscopy to Organic
Chemistry; VCH Publishers: Deerfield Beach, FL, 1985. (c) Calder, I.
C.; Garratt, P. J . J . Chem. Soc. B 1967, 660. (d) Kessler, H. Angew.
Chem., Int. Ed. Engl. 1970, 9, 219. (e) Gygax, R.; Wirz, J .; Sprague, J .
T.; Allinger, N. L. Helv. Chim. Acta 1977, 60, 2522. (f) Hutton, H. H.;
Hiebert, W. E.; Mark, V. Can. J . Chem. 1978, 56, 1261.
(24) See, for example: (a) Barlow, M. G.; Hazeldine, R. N.; Hubbard,
R. J . Chem. Soc., Chem. Commun. 1966, 143. (b) Wittig, G.; Beichel,
B. Chem. Ber. 1963, 96, 2851.
(25) White, J . D.; Mann, M. E. Adv. Heterocycl. Chem. 1969, 10, 113.
(26) Mitchell, R. H.; Boekelheide, V. J . Am. Chem. Soc. 1974, 96,
1547.

Notes
J . Org. Chem., Vol. 62, No. 17, 1997 6063
0.97)27 as reference systems and assuming that proton
shielding is proportional to ring current,16,28 11 exhibits
only about 27% of the ring current of 12. The ring
current of 11 is, however, about 20% stronger than that
of the furano system 8.16 In the calculation of the
topological resonance energy of the heteroaromatic sys-
tems 1a -3a and 1c-3c,10 going from the nitrogen series
to the corresponding members of the oxygen series results
in a decrease of >30% of aromatic character of benzene
per π electron. Using diatropicity (ring current) as a
parameter for aromatic character, our experimental
result has, however, indicated a significantly smaller
difference in the ability of oxygen and nitrogen in
contributing to the aromaticity of an isoannelated het-
eroaromatic system.
N-Cycloh exyl-2,5-d im eth yl-3,4-bis[3-(h yd r oxym eth yl)-2-
m eth ylp h en yl]p yr r ole (25).29 Recrystallization (benzene) af-
forded colorless crystals of 25 (76%): mp 112-114 °C; 1H NMR
δ 6.9-7.1 (m, 6H), 4.11-3.85 (m, 1H), 2.10 (s, 6H), 1.98, 2.03 (s,
ratio 1:1, total 6H), 1.94 (br s, 10H), 1.63 (s, 2H); IR (KBr) 3450
(OH) cm-1; MS m/z 417 (M+, 100), 402 (10), 325 (12); Mr calcd
for C28H35NO2 417.2668, found (MS) 417.2660.
N-Cycloh exyl-2,5-d im et h yl-3,4-b is[3-(b r om om et h yl)-2-
m eth ylp h en yl]p yr r ole (26).29 Recrystallization (benzene/n-
hexane) gave colorless crystals of 26 (72%): mp 158-160 °C;
1H NMR δ 6.8-7.1 (m, 6H), 4.48, 4.46 (s, ratio 1:1, total 4H),
3.95-4.11 (m, 1H), 2.13 (s, 6H), 2.05, 2.11 (s, ratio 1:1, total 6H),
1.94-1.96 (m, 10H); MS m/z 541 (M+, 36), 463 (36), 462 (100),
380 (29), 300 (27), 270 (28), 229 (18). Anal. Calcd for
C28H33Br2N: C, 61.89; H, 6.12; N, 2.58. Found: C, 62.25; H,
6.30; N, 2.66.
a n t i -N -C y c l o h e x y l -8 ,1 6 ,2′,5 ′-t e t r a m e t h y l -1 -t h i a -
[3.2]m etacyclo[9,10-c]pyr r ole (16).30 Chromatography (dichlo-
romethane/n-hexane (1:2)) on silica gel yielded colorless crystals
of 16 (20%): mp 261-263 °C; 1H NMR δ 6.9-7.2 (m, 6H), 3.99-
4.14 (m, 1H), 3.65, 3.81 (AB q, J ) 12.9, 4H), 2.48 (s, 6H), 2.03
(br s, 10H), 0.89 (s, 6H); MS m/z 415 (M+, 100), 300 (12). Anal.
Calcd for C28H33NS: C, 80.91; H, 8.00; N, 3.37. Found: C, 81.18;
H, 8.25; N, 3.48.
Exp er im en ta l Section
Melting points are uncorrected. 1H NMR spectra were
recorded in CDCl3 on a 90 or 300 MHz spectrometer with Me4Si
as internal standard. Coupling constants (J ) are given in Hz.
Mass spectra were obtained using EI ionization at 70 eV. UV
photolysis was carried out in a Rayonet photochemical reactor
(254 nm, 400 W). Microanalyses were performed by the Mi-
croanalytical Laboratory of the Department of Chemistry,
National University of Singapore.
2,5-Dim et h yl-3,4-b is(3-ch lor o-2-m et h ylp h en yl)p yr r ole
(21). Ammonium acetate (107 mg, 1.39 mmol) was added to a
solution of 1816 (250 mg, 0.69 mmol) in 95% ethanol (10 mL).
The reaction mixture was then brought to reflux for 3 h.
Dichloromethane and water were added to the mixture. The
organic layer was separated, washed, dried, and evaporated. The
crude product was chromatographed on silica gel using dichlo-
romethane/hexane (1:2) as eluant to give 21: 105 mg (44%).
Recrystallization from hexane yielded colorless crystals of 21:
mp 156-158 °C; 1H NMR δ 7.72 (br s, 1H, exchanged with D2O),
6.8-7.2 (m, 6H), 2.12 (s, 6H), 2.08 (s, 6H); IR (KBr) 3355 (NH)
cm-1; MS m/z 345 (M+, 60), 344 (40), 343 (100), 328 (33), 293
(11). Anal. Calcd for C20H19Cl2N: C, 69.77; H, 5.56; N, 4.07.
Found: C, 69.70; H, 5.49; N, 4.00.
N-Cycloh exyl-2,5-dim eth yl-3,4-bis(3-ch lor o-2-m eth ylph e-
n yl)p yr r ole (22). The diketone 1816 (100 mg, 0.28 mmol) was
added to cyclohexylamine (5 mL). The reaction mixture was
heated at reflux for 3 h and then cooled, washed with 1 N HCl,
and extracted with dichloromethane. The crude product was
chromatographed on silica gel using dichloromethane as an
eluant to afford 22: 110 mg (94%). Recrystallization from
hexane gave colorless crystals of 22: mp 180-182 °C; 1H NMR
δ 6.6-7.2 (m, 6H), 3.94-4.10 (m, 1H), 2.10, 2.17 (s, ratio 1:1,
total 6H), 2.02, 2.07 (s, ratio 1:1, total 6H), 1.94 (br s, 10H); MS
m/z 425 (M+, 100), 410 (12), 382 (10), 343 (27), 328 (23), 215
(13). Anal. Calcd for C26H29Cl2N: C, 73.23; H, 6.85; N, 3.28.
Found: C, 73.24; H, 6.94; N, 3.51.
N-Cycloh exyl-2,5-d im eth yl-3,4-bis(3-cya n o-2-m eth ylp h e-
n yl)pyr r ole (23).29 Recrystallization (benzene/n-hexane) yielded
colorless crystals of 23 (65%): mp 190-192 °C; 1H NMR δ 7.0-
7.45 (m, 6H), 4.04-4.13 (m, 1H), 2.19, 2.31 (s, ratio 1:1, total
6H), 2.03, 2.11 (s, ratio 1:1, total 6H), 1.95 (br s, 10H); IR (KBr)
2220 (C≡N) cm-1; MS m/z 407 (M+, 100), 325 (75), 310 (27). Anal.
Calcd for C28H29N3: C, 82.52; H, 7.17; N, 10.31. Found: C,
82.50; H, 7.01; N, 9.98.
a n t i-N -C y c lo h e x y l-8,16,2′,5′-t e t r a m e t h y l-1-(m e t h y l-
su lfa n yl)[2.2]m eta cyclo[9,10-c]p yr r ole (27).30 Chromatog-
raphy (dichloromethane/n-hexane (1:2)) on silica gel gave color-
1
less crystals of 27 (96%): mp 121-123 °C; H NMR δ 6.9-7.7
(m, 6H), 3.97-4.13 (m, 1H), 3.81 (t, J ) 2.9, 1H), 3.11 (dd, J )
2.9, 3.2, 1H), 2.58 (dd, J ) 2.9, 3.2, 1H), 2.54 (s, 6H), 2.14 (s,
3H), 2.03 (br s, 10H), 0.58 (s, 6H); MS m/z 429 (m+, 51), 399
(12), 382 (41), 367 (47), 366 (100), 352 (42), 284 (33), 270 (23);
Mr calcd for C29H35NS 429.2490, found (MS) 429.2489.
a n t i -N -C y c l o h e x y l -8 , 1 6 , 2 ′, 5 ′-t e t r a m e t h y l [ 2 . 2 ] -
m eta cyclo[9,10-c]p yr r ole-1-en e (28).30 Chromatography (cy-
clohexane) on silica gel gave gray (due to a minute amount of
11) crystals of 28 (33%): mp 153-155 °C; 1H NMR δ 6.7-7.2
(m, 6H), 6.41 (s, 2H), 3.82-4.15 (m, 1H), 2.51 (s, 6H), 2.01 (br s,
10H), 1.23 (s, 6H); MS m/z 381 (M+, 30), 366 (100), 351 (78),
336 (12), 283 (78), 268 (91), 226 (25). Anal. Calcd for C28H31N:
C, 88.14; H, 8.19; N, 3.67. Found: C, 87.84; H, 8.32; N, 3.38.
P h otoch em ica l Va len ce Isom er iza tion of 28 To Give 11.
A solution of 28 in benzene (5 mL) in a quartz cell was irradiated
with UV light at 254 nm for 1 h. A dark purple solution was
obtained. The solvent was rapidly removed, and the sample
contained a mixture of 11 and 28 in a 1:8 ratio based on the
integration ratios of the two pairs of methyl signals in the 1H
NMR spectrum: δ 6.7-7.2 (m, 6H), 6.41 (s, 2H), 3.82-4.15 (m,
1H), 2.82, 2.51 (s, ratio 1:8, total 6H), 2.01 (br s, 10H), 1.23, -0.42
(s, ratio 8:1, total 6H).
Diels-Ald er Rea ction betw een 11 a n d Dim eth yl Acety-
len ed ica r boxyla te. Dimethyl acetylenedicarboxylate (0.50 g,
3.52 mmol) was added to a solution of 28 in benzene (15 mL).
The reaction mixture was then brought to reflux for 15 h. The
solvent was removed, and the crude product was chromato-
graphed on silica gel using dichloromethane as an eluant to give
1
green crystals of 32: 24 mg (73%); mp 78-79.5 °C; H NMR δ
7.8-8.8 (m, 8H), 3.62 (s, 3H), 3.58 (s, 3H), 1.47 (br s, 10H), -3.45
(s, 3H), -3.81 (s, 3H); IR (KBr) 1720 (CdO) cm-1; MS m/z 523
(M+, 11), 508 (18), 366 (98), 351 (69), 284 (47), 283 (53), 269 (100),
268 (84) 226 (36). Anal. Calcd for C34H37NO4: C, 77.98; H, 7.12;
N, 2.67. Found: C, 77.66; H, 7.10; N, 2.92.
N-Cycloh exyl-2,5-dim eth yl-3,4-bis(3-for m yl-2-m eth ylph e-
n yl)p yr r ole (24).29 Chromatography (dichloromethane/n-hex-
ane (1:1)) on silica gel gave colorless crystals of 24 (89%): mp
1
162-164 °C; H NMR 10.25, 10.21 (s, ratio 1:1, total 2H), 7.0-
Ack n ow led gm en t . This work was supported
(RP910649) by the National University of Singapore
(NUS). P.C. thanks the NUS for the Research Student-
ship. Assistance from the technical staff of the Depart-
ment of Chemistry, NUS, is gratefully acknowledged.
7.7 (m, 6H), 3.87-4.20 (m, 1H), 2.32, 2.46 (s, ratio 1:1, total 6H),
2.09, 2.12 (s, ratio 1:1, total 6H), 2.04 (br s, 10H); IR (KBr) 1685
(CdO) cm-1; MS m/z 413 (M+, 100), 398 (12), 385 (23), 370 (13),
331 (13), 316 (12), 303 (16). Anal. Calcd for C28H31NO2: C,
81.32; H, 7.55; N, 3.39. Found: C, 81.13; H, 7.42; N, 3.48.
J O970430G
(27) Boekelheide, V.; Phillips, J . B. J . Am. Chem. Soc. 1967, 89,
1695.
(28) Mitchell, R. H.; Yan, J . S. H. Can. J . Chem. 1977, 55, 3347.
(29) Reaction conditions for the series of functional group transfor-
mations going from 22 to 26 were similar to those reported for the
furano16 and/or benzo22 series.
(30) The cyclization-Wittig rearrangement-Hofmann elimination
sequence going from 16 f 27 f 28(11) was similar to that reported
for the furano16 series.