Synthesis and Properties of Pyrrole-Substituted Cyclopentadienes

Full text of DOI:10.1021/jo970818b

J . Org. Chem. 1997, 62, 7877-7881
7877
formal dianionic intermediate, 5. This nucleophilic spe-
cies, in turn, was reacted with 2 to give the disubstituted
materials 6a -c. Not surprisingly, as shown in Scheme
2, a mixture of isomers was also obtained in this case.
Fortunately, in this instance, it proved possible to
separate the individual isomers (vide infra). On the other
hand, 6a -c were obtained in lower yields than 4a ,b. This
is the result, presumably, of undefined side-reactions
arising, perhaps, from NH-deprotonation.6
Syn th esis a n d P r op er ties of
P yr r ole-Su bstitu ted Cyclop en ta d ien es
Markus Scherer, J onathan L. Sessler,*
Andreas Gebauer, and Vincent Lynch
Department of Chemistry and Biochemistry, University of
Texas at Austin, Austin, Texas 78705
Received May 7, 1997
Once the assignments were made (see below) it became
clear that in the mixture formed by the reaction of 5 with
2 it was the 5,5-, 1,2-, and 2,3 isomers (6a , 6b, and 6c,
respectively) that were obtained with the first of these
being formed in highest yield over the 1,2- and 2,3-
species. Interestingly, no other isomers appeared to have
been produced. Specifically, no evidence for the forma-
tion of a 1,4-substituted species was obtained.7
Recently, Berlin and Lash independently reported
syntheses of so-called carbaporphyrins (1), an achieve-
ment that marks an important milestone in the develop-
ment of new porphyrin analogues.1 The synthetic route
involved a “3 + 1” condensation between a tripyrrane
fragment and a stabilized cyclopentadiene subunit
(Scheme 1). The success of this strategy has led us to
consider whether it might be possible to generate small,
acyclic cyclopentadiene-pyrrole conjugates. Such frag-
ments could serve as potential precursors to other “carba
macrocycles” as well as possible platforms for the entry
into the hitherto unexplored realm of pyrrole-metal-
locene chemistry. In this report, we describe the syn-
thesis and properties of the mono- and dipyrrole-
functionalized cyclopentadiene systems 4a ,b and 6a -c.
To the best of our knowledge, these constitute the first
acyclic pyrrole-cyclopentadiene conjugates to be de-
scribed in the literature.2
The key step leading to the monopyrrole-functionalized
cyclopentadiene involves the reaction between sodium
cyclopentadienide anion (NaCp) and an activated, benzyl-
like pyrrole (i.e., either an R-acetoxymethylpyrrole3 2 or
an R-chloromethylpyrrole4 3) as shown in Scheme 2.5 In
all cases an inseparable regioisomeric mixture, consisting
of species 4a and 4b in an approximately 1:1 ratio, was
obtained. In both 4a and 4b the Cp moities are substi-
tuted in their vinylic positions (indeed, the presence of
an allylic functionalized analog has never been observed).
Although characterized in the form of a mixture, room
temperature 1H NMR spectra recorded in CDCl3 revealed
well-resolved signals arising from the methylene groups
in the Cp units. On this basis, it is assumed that
sigmatropic shifts, involving migrations of elements
around the Cp perimeter, are not favored. Likewise, no
evidence of a Diels-Alder type dimerization process has
ever been observed, even when 4a and 4b were subject
to prolonged heating in toluene at reflux.
As implied above, it proved easy to separate the
individual species present in the mixture 6a -c. This was
done via a fractional crystallization procedure involving
the use of Et2O at -30 °C. In the case of the tert-butyl
ester the 2,3-substituted cyclopentadiene 6b was found
to be obtained quantitatively after a first recrystalliza-
tion. A second recrystallization under the same condi-
tions then allowed the 1,2-isomer 6c to be isolated from
the more soluble 5,5-compound 6a . Using a similar
procedure, we also succeeded in obtaining the ethyl esters
6a -c in pure form. In this case, interestingly, the 1,2-
isomer 6c was found to exhibit a lower solubility than
the corresponding 2,3-substituted species 6c.8
Providing structural assignments for isomers 6a -c
proved to be straightforward for 6a but more difficult for
isomers 6b and 6c. In the case of 6a , the use of 1H and
13C NMR spectroscopic analyses allowed the structure to
be determined unambiguously. This is because this
isomer contains no methylene protons within the Cp core.
Furthermore, an exact analogy for the substitution
pattern of this isomer, and its Cp-derived 1H NMR
signals, was found in the known material 5,5-bis(tri-
methylgermyl)cyclopentadiene.9
(6) In an attempt to augment the yield of 6a -c, an effort was made
to N-protect the starting materials 4a ,b. However, we were unable to
obtain such N-protected species using a variety of reagents. Separately,
we found that an N-protected (H replaced by Me or t-Boc) form of the
(acetoxymethyl)pyrrole 2 failed to react with cyclopentadienide anion.
This latter result, in accord with literature suggestions (a) Evans, J .
N. S.; Fagerness, P. E.; Mackenzie, N. E.; Scott, A. I. J . Am. Chem.
Soc. 1984, 106, 5738. (b) Falk, H.; Schlederer, T. Monatsh. Chem. 1981,
112, 501), can be rationalized in terms of an inability to form a
presumed-to-be-requisite azafulvene intermediate 7 as shown below.
The dipyrrole-substituted cyclopentadienes 6a -c were
prepared from the cyclopentadienes 4a ,b generated as
described above. These latter systems, used in the form
of a mixture, were activated by deprotonating with 2
equiv of NaH. This resulted in the formation of a single
* Author to whom correspondence should be addressed. Phone:
+512-471-5009, e-mail: sessler@mail.utexas.edu.
(1) (a) Berlin, K. Angew. Chem. 1996, 108, 1955; Angew. Chem., Int.
Ed. Engl. 1996, 35, 1820. (b) Lash, T. D. Angew. Chem., Int. Ed. Engl.
1997, 36, 839. (c) Lash, T. D., Hayes, M. J . Ibid. 1997, 36, 840.
(2) Only a pyrrolylfulvene has been mentioned in the literature:
Treibs, A.; Ha¨berle, N. Liebig’s Ann. Chem. 1970, 739, 220.
(3) J ohnson, A. W.; Kay, I. T.; Markham, E.; Price, P.; Shaw, K. B.
J . Chem. Soc. 1959, 3416.
(7) Unfortunately, this fact has precluded the syntheses of carbap-
orphyrins using these precursors.
(8) Here, it is worth mentioning that a mixture consisting of 6a -c
was already isolated as a side-product during the synthesis of the
cyclopentadienylpyrromethanes 4a ,b. It is likely that the NaCp, which
had to be used in excess, causes the cyclopentadiene units present in
4a ,b to undergo deprotonation. The resulting anions then react with
2 to form 6a -c.
(9) A predilection toward geminal 5,5-substituted cyclopentadienes
was also observed in the syntheses of bis(trimethylsilyl-, germyl-, and
stannyl)cyclopentadienes, systems obtained via metathesis as well:
Ustynyuk, Y. A.; Kisin, A. V.; Zenkin, A. A. J . Organomet. Chem. 1972,
37, 101.
(4) Ballantine, J . A.; J ackson, A. H.; Kenner, G. W.; McGillivray,
G. Tetrahedron 1966, Supplement No. 7, 241.
(5) Such an organometallic-based approach to pyrrole functional-
ization appears to be without precedent in the context of pyrrole-related
chemistry. It does, however, have ample antecedents in the more
general literature. See, for example: Rees, W. S.; Dippel, K. A. Org.
Prep. Proceed. Int. 1992, 24, 527; J utzi, P.; Dahlhaus, J . Synthesis 1993,
684.
S0022-3263(97)00818-9 CCC: $14.00 © 1997 American Chemical Society

7878 J . Org. Chem., Vol. 62, No. 22, 1997
Notes
Sch em e 1
Sch em e 2. Syn th esis of Mon o- (4a ,b) a n d Dip yr r ole (6a -c)-Su bstitu ted Cyclop en ta d ien es
In the case of 6c (R ) Et) the assignment was made
using X-ray diffraction methods. Here suitable single
crystals were obtained from CHCl3 under conditions of
slow solvent evaporation. As seen in Figure 1, the
structure clearly reveals the 1,2-substitution pattern in
the Cp moiety.10 Because of our interest in the location
of the double bonds on the cyclopentadiene ring, the
hydrogen atoms on this moiety were observed from a ∆F
map and refined with isotropic displacement parameters.
Furthermore, the relevant bond lengths in the Cp subunit
are within the expected range typical for carbon-carbon
double bonds (C1-C2: 1.350(7) Å; C3-C4: 1.358(8) Å) and
single bonds (C2-C3: 1.470(9), C4-C5: 1.445(11), C1-C5:
1.501(8)). These values are consistent with those ex-
pected for the assigned configuration.
With the configuration of isomers 6a and 6c assigned,
only the structure of 6b remained undetermined. Proton
and 13C NMR spectral analyses were insufficient to allow
an unambiguous assignment. The spectra in question,
however, were only consistent with a highly symmetric
structure. On the basis of this, isomer 6b was considered
to correspond to either a 2,3- or 1,4-substituted Cp
derivative.
In order to characterize systems 6a -c more fully and
to assign more completely the structure of 6b, investiga-
tions into the possible fluxional properties of these
isomers were made. In the case of 6a no indications of
sigmatropic rearrangement processes were observed.
This was true even under conditions of prolonged heating
in toluene at reflux. Systems 6b and 6c, on the other
(10) X-ray experimental for C27H36N2O4: colorless needles by slow
evaporation from CHCl3, crystal size ) 0.13 × 0.17 × 0.31 mm, triclinic,
P1h, Z ) 2, a ) 10.882(1) Å, b ) 11.218(1) Å, c ) 12.282(1) Å, â ) 111.44-
(1), V ) 1257.1(2) Å3, Fcalc ) 1.20 g/cc, F(000) ) 488. A total of 5657
reflections were measured, 4830 unique (Rint ) 0.062) on a Siemens
P4 diffractometer using graphite monochromatized Mo KR radiation
2
(λ ) 0.71073 Å). The structure was refined on F to a Rw ) 0.209,
with a conventional R ) 0.0784, with a goodness of fit ) 0.999 for 323
refined parameters. The authors have deposited atomic coordinates
for this structure with the Cambridge Crystallographic Data Centre.
The data can be obtained, on request, from The Director, CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK.

Notes
J . Org. Chem., Vol. 62, No. 22, 1997 7879
However, such species are never observed. Using similar
logic, the possibility of concurrent carbon and hydrogen
fluxionality can be ruled out. Such processes would give
rise to the coincident formation of more than two isomers,
something that is not observed.11
In summary, a facile synthetic pathway leading to
cyclopentadiene-substituted pyrrolic entities has been
described. Such systems could constitute important
organometallic precursors and might represent interest-
ing products in their own right. For instance, using the
Cp systems 6c (R ) Et) we recently succeeded in
synthesizing a 1,1′,2,2′-tetrapyrrolic-substituted ferrocene
derivative. This species undergoes a remarkable self-
assembly process both in solution and in the solid state.12a
We have also found out that species 4a ,b (R ) Bn) may
be used as a precursor for the generation of dipyrrolic
bridged ansa-ferrocenes, materials that exhibit interest-
ing anion-binding properties.12b
F igu r e 1. X-ray structure of 6c (ethyl ester); thermal el-
lipsoids are scaled to the 30% probability level.
Exp er im en ta l Section
Gen er a l. Proton and 13C NMR spectra, and low and high
resolution CI mass spectra, were obtained using instrumenta-
tion described previously.12a Tetrahydrofuran (THF) was dried
by distillation under nitrogen from sodium melt. Methanol
was dried by distillation from calcium hydride under a nitrogen
atmosphere. tert-Butyl hypochlorite13 was synthesized accord-
ing to a literature procedure. All other solvents, acids, bases,
and reagents were obtained from commercial sources and used
as received unless indicated otherwise. Pyrrolic starting
compounds of general formula 23 and 34 as well as 2-(tert-
butoxycarbonyl)-4-ethyl-3-methyl-5-methylpyrrole14 are well
known. Some of the specific derivatives used in this study
have not, apparently, been described in the literature. Brief
summaries of their syntheses as well as relevant characteriza-
tion data are, therefore, included here.
2-(ter t-Bu toxyca r bon yl)-4-eth yl-3-m eth yl-5-m eth ylp yr -
r ole. tert-Butyl acetoacetate (159 g, 0.99 mol) was dissolved
in glacial acetic acid (250 mL) and cooled to 0 °C. To this, a
solution of NaNO2 (77.3 g, 1.12 mol) dissolved in water (100
mL) was added dropwise, so as to maintain the temperature
below 40 °C. The resulting mixture was stirred for 1 h and
subsequently added via an addition funnel to a mechanically
stirred solution of 3-ethyl-2,4-pentadione (143.3 g, 1.12 mol)
in acetic acid (250 mL). Zinc (granules, 230 g, 3.52 mol) was
also added concurrently over the course of 2 h. The mixture
was stirred overnight and then poured into 1 L of water. The
precipitate that formed was filtered off, washed with water,
and redissolved in 1 L of dichloromethane. The resulting
aqueous phase was separated off and discarded. The organic
phase was collected, dried over NaSO4, and then taken to
dryness in vacuo to afford the crude product. Recrystallization
from EtOH (500 mL) then gave 117.50 g (53%) of the title
compound. 1H NMR (300 MHz, CDCl3): δ ) 1.06 (t, 3H), 1.52
(s, 9H), 2.16 (s, 3H), 2.22 (s, 3H), 2.33 (q, 2H), 8.52 (bs, 1H);
LRMS (CI+) m/e: 223 (74), 168 (100); HRMS (CI+) m/e calcd
for C13H21NO2: 223.1572, found: 223.1563.
F igu r e 2. 1H NMR spectroscopic study of the ethyl esters 6c
and 6b carried out in in toluene-d8; (500 MHz; room temper-
ature). The region showing the vinylic cyclopentadiene protons
is depicted (the multiplet at 6.05 ppm is ascribed to 6c whereas
the broad singlet at 5.8 ppm is assigned to 6b). A: spectrum
of untreated 6c. B: spectrum obtained after heating a toluene-
d8 solution of 6c at reflux for 40 min and then cooling back to
room temperature.
hand, showed more interesting characteristics. Indeed,
at high temperatures they were found to interconvert.
This chemistry, which establishes the structure of 6b as
being the 2,3-isomer as shown in Scheme 2, is reflected
in Figure 2. Specifically, although no rearrangement
processes are observable at room temperature, when pure
toluene solutions of 6c are heated it can be seen that a
second signal ascribable to the vinylic Cp protons grows
in as a function of increased temperature. Further, at
equilibrium, a ca. 1:1 ratio of these two signals is found
to exist. The new signal that was found to grow in as
solutions of 6c are heated was found to correspond to the
vinylic Cp protons of compound 6b. This same signal,
not surprisingly, was found to decrease in intensity (in
favor of the signal for 6c) when pure solutions of 6b in
toluene are heated. Thus, whether one starts from 6b
or 6c, an identical final spectrum is obtained.
Since the rearrangement products obtained by heating
toluene solutions of either 6b or 6c bear substituents
exclusively in the Cp vinyl positions, the observed rear-
rangement process implicates a hydrogen shift rather
than a carbon shift. Structure 6b can thus be assigned
unambiguously as being the 2,3-substituted Cp deriva-
tive. By contrast, were a carbon migration taking place,
heating 6c would lead to the formation of not only allylic
2,5- but also geminal 5,5-substituted materials (e.g., 6a ).
5-(Acet oxym et h yl)-2-(ter t-b u t oxyca r b on yl)-4-et h yl-3-
m eth ylp yr r ole (2). 2-(tert-Butoxycarbonyl)-4-ethyl-3-methyl-
5-methylpyrrole (47.94 g, 215 mmol) was dissolved in 1 L of
glacial acetic acid under an argon blanket. Lead tetraacetate
(100 g, 225 mmol) was then added all at once while the solution
was stirred vigorously. The reaction mixture was stirred at
room temperature for an additional 2 h and then poured into
2 L of ice-water. The precipitate that formed was filtered off
and washed thoroughly with water before it was taken up in
700 mL of dichloromethane, washed with water (2 × 300 mL),
(12) (a) Scherer, M.; Sessler, J . L.; Moini, M.; Gebauer, A.; Lynch,
V. Chem. Eur. J ., in press. (b) Scherer, M.; Sessler, J . L.; Gebauer ,
A.; Lynch, V. Chem. Commun., submitted.
(11) For a review discussing inter alia the rearrangement behavior
of two-fold substituted Cp systems, see: J utzi, P. Chem. Rev. 1986,
86, 983-996.
(13) Teeter, H. M.; Bell, E. W. Org. Synth. 1952, 32, 20-22.
(14) Bullock, E.; J ohnson, A. W.; Markham, E.; Shaw, K. B. J . Chem.
Soc. 1958, 1438.

7880 J . Org. Chem., Vol. 62, No. 22, 1997
Notes
NaClsat. (1 × 300 mL) and finally dried over NaSO4. The
solvent was removed using a rotary evaporator to give a crude
product that, after recrystallization from EtOH (200 mL)
produced 2 in 91% yield (54.98 g). 1H NMR (300 MHz,
CDCl3): δ ) 1.05 (t, 3H), 1.55 (s, 9H), 2.04 (s, 3H), 2.23 (s,
3H), 2.46 (q, 2H), 4.99 (s, 2H), 8.85 (bs, 1H); LRMS (CI+)
128.8, 130.1, 130.9, 131.8, 132.3, 134.0, 134.7, 143.1, 145.3,
161.8. LRMS (CI+) m/e: 288 (100), 232 (99); HRMS (CI+)
m/e calcd for C18H25NO2: 287.1885, found: 287.1881; CHN
analysis calcd (found): C 75.22 (75.12), H 8.77 (8.64), N 4.87
(4.71).
5-(Cyclop en ta d ien -1-ylm eth yl)-2-(ben zyloxyca r bon yl)-
4-eth yl-3-m eth ylp yr r ole (4a , R ) Bn ) a n d 5-(Cyclop en -
t a d ie n -2-ylm e t h yl)-2-(b e n zyloxyca r b on yl)-4-e t h yl-3-
m eth ylp yr r ole (4b, R ) Bn ). Using the generalized proce-
dure noted above, these isomers were isolated in a combined
yield of 71%. 1H NMR (300 MHz, CDCl3): δ ) 1.02, 1.03 (2 ×
t, 3H), 2.29 (s, 3H), 2.00, 2.17 (2 × q, 2H), 2.83 and 2.97 (2 ×
s, 2H), 3.62, 3.65 (2 × s), 5.26 (s, 2H), 6.05-6.44 (m, 3H), 7.29-
7.41 (m, 5H), 8.50 (bs, 1H); 13C NMR (75.5 MHz, CDCl3): δ )
10.6, 15.4, 15.5, 17.1, 17.2, 26.7, 27.5, 41.5, 43.2, 65.3, 65.4,
116.9, 123.9, 124.1, 127.2, 127.3, 127.9, 128.0, 128.1, 128.4,
128.5, 128.9, 131.3, 131.8, 132.2, 133.9, 134.8, 136.7, 143.0,
145.2, 161.4. LRMS (CI+) m/e: 321 (100), 256 (65); HRMS
(CI+) m/e calcd for C21H23NO2: 321.1729, found: 321.1724;
CHN analysis calcd (found): C 78.47 (78.39), H 7.21 (7.22), N
4.36 (4.38).
m/e: 281 (82), 222 (100); HRMS (CI+) m/e calcd for C15H23
-
NO4: 281.1627, found: 281.1628.
2-(Ch lor om eth yl)-5-(eth oxyca r bon yl)-3-eth yl-4-m eth -
ylp yr r ole (3). Over the course of 10 min, a solution of tert-
butyl hypochlorite (5.54 g, 51.3 mmol) in CCl4 (40 mL) was
added to a vigorously stirred solution of 2-(ethoxycarbonyl)-
4-ethyl-3-methyl-5-methylpyrrole13 (10.00 g, 51.3 mmol) in dry
CCl4 (500 mL) held at 3 °C. After 1 h, the reaction mixture
was concentrated to 100 mL with the aid of a rotary evapora-
tor. In order to precipitate the product, the solution was then
stored for 1.5 h at a temperature of -10 °C. Subsequently,
the crystallized compound was filtered off and washed with
hexanes to afford 3 (8.34 g, 71%). The product, which was
used without further purification, should be stored under
nitrogen well protected from light. 1H NMR (300 MHz,
CDCl3): δ ) 1.09 (t, 3H), 1.33 (t, 3H), 2.28 (s, 3H), 2.41 (q,
2H), 4.28 (q, 2H), 4.65 (s, 2H), 8.98 (bs, 1H); 13C NMR (75.5
MHz, CDCl3): δ ) 10.1, 14.3, 15.3, 17.0, 36.5, 59.9, 125.7,
126.1, 127.4, 127.9, 161.4. LRMS (CI +) m/e: 230 (68), 196
(100); HRMS (CI+) m/e calcd for C11H17ClNO2: 230.0948,
found: 230.0950.
Syn th eses of Mon op yr r ole-Su bstitu ted Cyclop en ta -
d ien es 4a a n d 4b (Gen er a lized P r oced u r e). By using
Schlenk-techniques, 59.3 mmol, respectively, of the ethyl-, tert-
butyl, and benzyl ester forms of 2 was dissolved in dry THF
(300 mL) under an argon blanket. This solution was then
cooled to 0 °C. Subsequently, a 2.0 M solution of NaCp in THF
(0.119 mmol, Aldrich) was added dropwise over the course of
30 min. The resulting mixture was stirred for 4 h while being
allowed to warm to room temperature. At this juncture, the
reaction was quenched by the addition of dry MeOH (150 mL)
and, after 30 more min, by the addition of degassed water (200
mL). After stirring for an additional 45 min, Et2O (350 mL)
was added, and the phases were separated. The aqueous layer
was extracted with Et2O (2 × 100 mL), and the combined
organic phases were washed with water (3 × 150 mL) and
NaClsat. (1 × 150 mL). After drying over MgSO4, the solvent
was removed from the organic phase and the resulting residue
dried in vacuo for 4 h. The resulting crude product was taken
up in a small amount of CH2Cl2 and purified using flash
column chromatography (80 × 5 cm; silica gel; eluant: initially
30% hexanes in CH2Cl2 but then decreasing hexanes). The
two monopyrrole-substituted cyclopentadiene isomers 4a and
4b were eluted together as the first main fraction.
Syn th esis of Dip yr r ole-Su bstitu ted Cyclop en ta d ien es
6a -c (R ) Et). Using Schlenk-techniques, fresh NaH (0.96
g, 40 mmol) was suspended in 120 mL of dry THF. While
maintaining the temperature at 0 °C, a solution consisting of
an isomeric mixture of 4a ,b (R ) Et; 5.17 g, 20 mmol) in THF
(180 mL) was added dropwise over the course of 45 min. The
resulting mixture was then stirred for additional 2 h. At this
juncture, while still maintaining a temperature of 0 °C, a
solution of 2 (R ) Et) (5.08, 20 mmol) in THF (50 mL) was
added over the course of 30 min. The resulting dark-colored
mixture was then stirred for 24 h under an argon atmosphere
before the reaction was quenched by the addition of water (150
mL). The emulsion that resulted was stirred for 30 min before
dichloromethane (200 mL) was added. The phases were
separated with the aqueous layer being further extracted with
dichloromethane (2 × 100 mL). The organic phases were
combined and washed with water (2 × 100 mL) and NaClsat.
(1 × 100 mL) before being dried over MgSO4. The solvent was
then removed using a rotary evaporator. The resulting crude
product was dried in high vacuum for 3 h, taken up in
dichloromethane and then purified by flash column chroma-
tography (50 × 5 cm; silica gel; eluant: CH2Cl2). Unreacted
4a ,b (1.87 g; 7.2 mmol) was isolated as the first main fraction.
The last main fraction contained the desired products 6a -c
as an isomeric mixture. These isomers were separated by
treating the dried residue, obtained after removing the solvent
from the relevant chromatography fractions with 30 mL of
diethyl ether. This caused the 1,2-substituted cyclopentadiene
6c to begin precipitating even at room temperature. Storing
the ether solution at -30 °C for 48 h then resulted in a more
quantitative precipitation of this species (6c). Filtration
afforded 6c (0.524 g, 9.0%). The product obtained in this way
was usually pure. However, as needed, this crystallization
procedure could be repeated until pure 6c was in fact obtained.
Carrying out a second low temperature recrystallization from
diethyl ether but employing the filtrate obtained after solid
6c had been collected off, allowed the precipitation of material
that was enriched in 6b over 6a . Fractional recrystallization
of this mixture yielded 0.158 g (0.3 mmol, 2.7%) of pure 6b
(as the precipitate) and 0.926 g (1.1 mmol, 16.0%) of pure 6a
(from the filtrate).
5-(Cyclop en t a d ien -1-ylm et h yl)-2-(et h oxyca r b on yl)-4-
eth yl-3-m eth ylp yr r ole (4a , R ) Et) a n d 5-(Cyclop en ta -
dien -2-ylm eth yl)-2-(eth oxycar bon yl)-4-eth yl-3-m eth ylpyr -
r ole (4b , R ) E t ). Using the above procedure, these
compounds were obtained in a combined yield of 75%. By
using this same method starting with 3 instead of 2, a 58%
yield was obtained. 1H NMR (300 MHz, CDCl3): δ ) 1.02,
1.03 (2 × t, 3H), 1.31 (t, 3H), 2.27 (s, 3H), 2.38, 2.39 (2 × q,
2H), 2.83 and 2.84 (2 × s, 2H), 3.62, 3.65 (2 × s), 4.25, 4.26 (q,
2H), 6.04-6.44 (m, 3H), 8.50 (bs, 1H); 13C NMR (75.5 MHz,
CDCl3): δ ) 10.5, 14.6, 15.5, 17.2, 26.7, 27.5, 41.5, 43.3, 59.7,
117.6, 123.8, 123.9, 126.5, 128.4, 128.8, 130.8, 131.4, 131.9,
132.3, 134.0, 134.8, 143.1, 145.4, 161.9. LRMS (CI+) m/e: 260
(98), 196 (100); HRMS (CI+) m/e calcd for C16H22NO2: 260.1650,
found: 260.1646; CHN analysis calcd (found): C 74.10 (74.19),
H 8.16 (8.16), N 5.40 (5.31).
5,5-Bis(2-(et h oxyca r b on yl)-4-et h yl-3-m et h ylp yr r ol-5-
ylm et h yl)cyclop en t a d ien e (6a ): 1H NMR (300 MHz,
CDCl3): δ ) 1.01 (t, 6H), 1.31 (t, 6H), 2.22 (s, 6H), 2.34 (q,
4H), 2.89 (s, 4H), 4.22 (q, 4H), 6.35 (m, 4H), 8.41 (bs, 2H); 13
C
NMR (75.5 MHz, CDCl3): δ ) 10.5, 14.6, 15.4, 17.3, 31.1, 59.6,
60.4, 117.2, 124.5, 125.9, 129.2, 132.2, 142.8, 161.6. LRMS
(CI+) m/e: 453 (100); HRMS (CI+) m/ e calcd for C27H37N2O4:
453.2753, found: 453.2749, CHN analysis calcd (found): C
71.65 (71.53), H 8.02 (7.98), N 6.19 (6.21).
5-(Cyclopen tadien -1-ylm eth yl)-2-(ter t-bu toxycar bon yl)-
4-eth yl-3-m eth ylp yr r ole (4a , R ) t-Bu ) a n d 5-(Cyclop en -
t a d ie n -2-ylm e t h yl)-2-(t er t -b u t oxyca r b on yl)-4-e t h yl-3-
m eth ylp yr r ole (4b, R ) t-Bu ). Using the above procedure,
1
these materials were obtained in a combined yield of 57%. H
NMR (300 MHz, CDCl3): δ ) 1.02, 1.03 (2 × t, 3H), 1.52, 1.53
(2 × s, 9H), 2.24 (s, 3H), 2.39, 2.41 (2 × q, 2H), 2.84 and 2.97
(2 × bs, 2H), 3.61, 3.65 (2 × s), 6.06-6.40 (m, 3H), 8.36 (bs,
1H); 13C NMR (75.5 MHz, CDCl3): δ ) 10.5, 15.6, 17.2, 26.6,
27.5, 28.5, 41.5, 43.2, 80.1, 118.3, 124.0, 124.1, 125.9, 128.4,
2,3-Bis(2-(et h oxyca r b on yl)-4-et h yl-3-m et h ylp yr r ol-5-
ylm et h yl)cyclop en t a d ien e (6b ): 1H NMR (300 MHz,
CDCl3): δ ) 1.00 (t, 6H), 1.31 (t, 6H), 2.25 (s, 6H), 2.35 (q,
4H), 2.71 (s, 2H), 3.56 (s, 4H), 4.25 (q, 4H), 6.07 (bs, 2H) 8.41
(bs, 2H); 13C NMR (75.5 MHz, CD2Cl2): δ ) 10.3, 14.5, 16.0,

Notes
J . Org. Chem., Vol. 62, No. 22, 1997 7881
17.8, 28.1, 45.1, 60.0, 117.8, 124.2, 127.1, 128.4, 130.8, 144.3,
161.9. LRMS (CI+) m/e: 453 (65), 407 (100); HRMS (CI+)
m/ e calcd for C27H36N2O4: 452.2675, found: 453.2668, CHN
analysis calcd (found): C 71.65 (71.03), H 8.02 (8.06), N 6.19
(6.15).
1,2-Bis(2-(et h oxyca r b on yl)-4-et h yl-3-m et h ylp yr r ol-5-
ylm et h yl)cyclop en t a d ien e (6c): 1H NMR (300 MHz,
CDCl3): δ ) 1.03 (t, 6H), 1.31 (t, 6H), 2.26 (s, 6H), 2.38 (q,
4H), 2.90 (s, 2H), 3.61 (d, 4H), 4.25 (q, 4H), 6.24 (m, 2H), 8.29
(bs, 2H); 13C NMR (75.5 MHz, CDCl3): δ ) 10.4, 14.5, 15.3,
15.4, 17.2, 24.2, 24.9, 44.3, 59.7, 117.3, 117.4, 123.6, 123.8,
126.8, 130.5, 131.2, 132.0, 134.6, 137.0, 138.1, 161.8. LRMS
(CI +) m/e: 452 (37), 407 (100); HRMS (CI+) m/e calcd for
C27H36N2O4: 452.2675, found: 452.2666, CHN analysis calcd
(found): C 71.65 (71.46), H 8.02 (8.01), N 6.19 (6.14).
Syn th esis of Dip yr r ole-Su bstitu ted Cyclop en ta d ien es
6a -c (R ) t-Bu ). These materials were prepared using a
procedure essentially identical to the one noted above. In this
instance, the first fraction off the flash chromatography column
(60 × 5 cm; silica gel; eluant: CH2Cl2) proved again to be
unreacted 4a ,b (1.95 g; 6.8 mmol). Likewise, the last main
fraction eluted from the column was found to contain products
6a -c as an isomeric mixture. In this case, the separation of
the isomers involved extracting the dried residue from the
chromatography column with 40 mL of diethyl ether. This
resulted in the formation of a slurry due to the insoluble nature
of the 2,3-substituted isomer 6b. A more quantitative pre-
cipitation of this isomer was achieved by storing the ether
slurry at -30 °C overnight. This afforded 1.70 g (3.3 mmol;
15.7%) of 6b. The filtrate, obtained after filtering off 6b, was
reduced to a volume of 30 mL and recrystallized from diethyl
ether at -30 °C as above. This resulted in the precipitation
of the 1,2-substituted Cp compound 6c (0.96 g, 1.9 mmol,
8.9%). After the precipitation of 6c was complete, 2.41 g (4.7
mmol, 21.9%) of 6a could be isolated from the filtrate.
5,5-Bis(2-(ter t-bu toxycar bon yl)-4-eth yl-3-m eth ylpyr r ol-
5-ylm et h yl)cyclop en t a d ien e (6a ): 1H NMR (300 MHz,
CDCl3): δ ) 1.01 (t, 6H), 1.52 (s, 18H), 2.19 (s, 6H), 2.34 (q,
4H), 2.88 (s, 4H), 6.35 (m, 4H), 8.39 (bs, 2H); 13C NMR (75.5
MHz, CDCl3): δ ) 10.5, 15.4, 17.3, 28.6, 31.2, 60.5, 80.0, 118.4,
124.4, 124.9, 128.5, 132.1, 143.0, 161.2. LRMS (CI+) m/ e: 509
(100); HRMS (CI+) m/ e calcd for C31H44N2O4: 508.3301,
found: 508.3294, CHN analysis calcd (found): C 73.19 (73.11),
H 8.72 (8.73), N 5.51 (5.42).
2,3-Bis(2-(ter t-bu toxycar bon yl)-4-eth yl-3-m eth ylpyr r ol-
5-ylm et h yl)cyclop en t a d ien e (6b ): 1H NMR (300 MHz,
CD2Cl2): δ ) 0.96 (t, 6H), 1.52 (s, 18H), 2.22 (s, 6H), 2.33 (q,
4H), 2.95 (s, 2H), 3.48 (s, 4H), 6.07 (bs, 2H) 8.37 (bs, 2H); 13
C
NMR (75.5 MHz, CD2Cl2): δ ) 10.6, 15.6, 17.5, 25.6, 28.7, 39.9,
80.3, 119.1, 124.1, 126.1, 129.8, 130.9, 143.9, 161.5; LRMS
(CI+) m/e: 508 (24), 299 (100); HRMS (CI+) m/e calcd for
C31H44N2O4: 508.3301, found: 508.3290, CHN analysis calcd
(found): C 73.19 (72.64), H 8.72 (8.75), N 5.51 (5.47).
1,2-Bis(2-(ter t-bu toxycar bon yl)-4-eth yl-3-m eth ylpyr r ol-
5-ylm et h yl)cyclop en t a d ien e (6c): 1H NMR (300 MHz,
CDCl3): δ ) 1.02 (t, 6H), 1.53 (s, 18H), 2.20 (s, 6H), 2.35 (q,
4H), 2.91 (s, 2H), 3.63 (d, 4H), 6.24 (m, 2H), 8.30 (bs, 2H); 13
C
NMR (75.5 MHz, CDCl3): δ ) 10.3, 15.4, 15.5, 17.2, 24.1, 24.8,
28.6, 44.1, 80.1, 117.1, 117.5, 123.5, 124.0, 126.3, 130.4, 131.0,
131.8, 134.4, 137.0, 138.0, 161.6. LRMS (CI +) m/ e: 509 (75),
435 (100); HRMS (CI+) m/ e calcd for C31H44N2O4: 508.3301,
found: 508.3302, CHN analysis calcd (found): C 73.19 (73.20),
H 8.72 (8.79), N 5.51 (5.51).
Ack n ow led gm en t. M.S. wishes to thank the Alex-
ander von Humboldt foundation for a postdoctoral
research fellowship (Feodor-Lynen stipend). This work
was further supported by the National Science Founda-
tion (grant CHE 9122161 to J .L.S.).
Su p p or tin g In for m a tion Ava ila ble: X-ray experimental
for 6c and tables of crystallographic data, collection proce-
dures, parameters, complete atomic coordinates, bond dis-
tances and angles, torsion angles, and least square planes (18
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O970818B