A Direct Synthesis of 2-(Trimethylstannyl)pyrroles from Michael Acceptors and Stannylated Tosylmethyl Isocyanide

Article abstract of DOI:10.1021/jo972216y

A series of 2-(trimethylstannyl)pyrroles 3, with substituents at the 3- and 4-positions, is synthesized efficiently by a base-induced reaction of stannylated TosMIC with Michael acceptors. Stille cross-couplings with bromobenzene and double cross-couplings with 1,4-dibromobenzene have been achieved successfully with the N-methyl derivative (5a) and the N-Boc derivative (6a) of 3-benzoyl-2-(trimethylstannyl)-4-phenylpyrrole (3a), despite the bulk of these stannylpyrroles. Homo-coupling reactions of the same stannylpyrroles with the corresponding bromopyrroles (prepared from stannylpyrroles 3 and NBS) were unsuccessful, probably for steric reasons.

Full text of DOI:10.1021/jo972216y

5332
J . Org. Chem. 1998, 63, 5332-5338
A Dir ect Syn th esis of 2-(Tr im eth ylsta n n yl)p yr r oles fr om Mich a el
Accep tor s a n d Sta n n yla ted Tosylm eth yl Isocya n id e1
Harm P. Dijkstra, Ronald ten Have, and Albert M. van Leusen*
Department of Organic and Molecular Inorganic Chemistry, Groningen University,
Nijenborgh 4, 9747 AG Groningen, The Netherlands
Received December 8, 1997
A series of 2-(trimethylstannyl)pyrroles 3, with substituents at the 3- and 4-positions, is synthesized
efficiently by a base-induced reaction of stannylated TosMIC with Michael acceptors. Stille cross-
couplings with bromobenzene and double cross-couplings with 1,4-dibromobenzene have been
achieved successfully with the N-methyl derivative (5a ) and the N-Boc derivative (6a ) of 3-benzoyl-
2-(trimethylstannyl)-4-phenylpyrrole (3a ), despite the bulk of these stannylpyrroles. Homo-coupling
reactions of the same stannylpyrroles with the corresponding bromopyrroles (prepared from
stannylpyrroles 3 and NBS) were unsuccessful, probably for steric reasons.
In tr od u ction
pyrrole derivatives 2 with a Me3Sn substituent in an
apparently unequivocally determined position, according
to eq 1.
In this paper, we report the first applications of a
stannylated derivative of tosylmethyl isocyanide (TosMIC).
The use of this new reagent is demonstrated by the
synthesis of a series of 2-(trimethylstannyl)pyrroles 3.
This synthesis of pyrroles 3 has two novel characteris-
tics: (1) the trimethylstannyl group in compounds 3 is
not the result of a substitution onto a precursor-pyrrole,
instead the stannyl group is introduced as part of the
pyrrole ring-forming process; (2) stannylated pyrroles
with a free N-H function have not been reported previ-
ously. Stannylated pyrroles such as 3 can be used, for
example, in Stille cross-coupling reactions.2
So far, only a few (N-protected) 2-stannylpyrroles have
been reported6 and just one 3-stannylpyrrole: 3-(tri-n-
butylstannyl)-1-(triisopropylsilyl)pyrrole.7 These stann-
ylpyrroles have been used almost exclusively in Stille
coupling reactions.2b There is explicit interest in these
Stille reactions for the synthesis of oligopyrroles, as a
potential entry into conducting polypyrrole-polymers.8
So far, 2- and 3-stannylated pyrroles have been pre-
pared only by reaction of 2- or 3-lithiopyrroles (prepared
by direct lithiation or by halogen-lithium exchange) and
Bu3SnCl or Me3SnCl. This stannylation procedure is
possible only when the pyrrole nitrogen is substituted
(protected).3 N-Unprotected 2-stannylindoles have been
reported recently as intermediates in the synthesis of 2,3-
disubstituted (and 3-monosubstituted) indoles from o-
isocyanostyrenes. In this interesting process, tributyltin
radicals (from Bu3SnH and AIBN) induce a ring closure
in o-isocyanostyrenes to form 2-stannylindoles, which
have been employed in the Stille reaction.4
Resu lts a n d Discu ssion
Our first experiments were carried out with chalcone
(trans-benzylideneacetophenone). The best results were
obtained when TosMIC was reacted in THF at -75 °C
with 2 equiv of n-BuLi (to form dilithio-TosMIC),9 and
then with excess of Me3SnCl (2 equiv). Next, 1 equiv of
chalcone was added at the same temperature. Workup
provided one single (trimethylstannyl)pyrrole in 90%
yield (Table 1, entry 1). Structure 2a (R ) Ph, R′ ) Me3-
Sn, EWG ) PhCO) was assigned to this product initially,
following eq 1. Much to our surprise, however, X-ray
analysis of the N-Boc derivative unambiguously showed
the product to be 3-benzoyl-4-phenyl-2-(trimethyl-
stannyl)pyrrole (3a , eq 2, Table 1), rather than 4-benzoyl-
3-phenyl-2-(trimethylstannyl)pyrrole (2a ). X-ray analy-
sis10 became a necessity when the 1H and 13C NMR
structure determination turned out not to be entirely
unambiguous. The same approach was used to synthe-
size a series of analogous (trimethylstannyl)pyrroles 3
using other Michael acceptors (Table 1). In no case were
indications found for the presence of a second, isomeric
stannylpyrrole (of type 2).
TosMIC (1, R′ ) H), and its substituted derivatives (1,
R′ ) alkyl/aryl), are being used extensively in the
synthesis of 3,4-disubstituted and 2,3,4-trisubstituted
pyrroles, respectively (eq 1). The substituent at position
4 is usually an electron-withdrawing group (EWG),
originating from the Michael acceptor substrate.5 With
these results in mind, we decided to introduce a stannyl
substituent in TosMIC, as in 1 with R′ ) Me3Sn, and to
apply this synthon in the TosMIC-based pyrrole synthe-
sis. This, according to expectations, should lead to
(1) Chemistry of Sulfonylmethyl Isocyanides. 45. For part 44, see:
ten Have, R.; van Leusen, A. M. Tetrahedron 1998, 54, 1913.
(2) (a) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b)
Farina, V.; Krishnamurthy, V.; Scott, W. J . Org. React. 1997, 50,
1-652.
(3) See refs 2b, 6, 7, and 8.
(4) Fukuyama, T.; Chen, X.; Peng, G. J . Am. Chem. Soc. 1994, 116,
3127.
The actual ring-forming species of eq 2 has not been
identified. It is, however, unlikely to be the anticipated
S0022-3263(97)02216-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/18/1998

Direct Synthesis of 2-(Trimethylstannyl)pyrroles
J . Org. Chem., Vol. 63, No. 16, 1998 5333
Ta ble 1. 2-(Tr im eth ylsta n n yl)p yr r oles 3 fr om Mich a el
Accep tor s, TosMIC, a n d Me3Sn Cl in a On e-P ot Op er a tion
The yield of pyrrole 3a was lowered from 90% (Table
1, entry 1) to 80% when the excess of Me3SnCl was
reduced from 2 to 1.2 equiv. A much lower yield of 3a
was obtained when an attempt was made to prepare the
stannylated TosMIC derivative 4 in a different way:
subsequent reaction of TosMIC in THF at -75 °C with 1
equiv of n-Buli, then Me3SnCl (2 equiv), followed by a
second equivalent of n-BuLi and by chalcone gave 3a in
less than 5% yield. Presumably, the reacting species 4
is formed only in an efficient manner from the stronger
nucleophilic dilithio-TosMIC9 and (excess) Me3SnCl. The
corresponding reaction of n-Bu3SnCl with TosMIC and
chalcone did not lead to the tributylstannyl analogue of
3a , possibly due to steric overcrowding.
Scheme 3 shows some applications of the newly formed
(trimethylstannyl)pyrroles 3, of which the Stille reaction2
is the most obvious one. In as much as the Stille reaction
has been applied to pyrroles, only N-substituted (pro-
tected) stannylpyrroles have been used.6-8,12 We have
prepared both the N-Me and the N-Boc derivatives of 3a
by two methods (Scheme 2, Table 2). First of all,
(trimethylstannyl)pyrrole 3a was N-methylated with MeI
under PTC conditions to give 5a in 86% yield; the N-Boc
group was introduced in 3a with the use of Boc2O to give
6a in 79% yield (Method 1; Table 2, entries 1 and 2,
respectively). The same compounds were also prepared
in the “classical” way from 3-benzoyl-1-methyl-3-phe-
nylpyrrole (8) and 3-benzoyl-1-(tert-butoxycarbonyl)-3-
phenylpyrrole (9), via ortho-litiation using lithium 2,2,6,6-
tetramethylpiperidide (LTMP), to give 5a and 6a in 72
and 79% yields, respectively (Method 2; Table 2, entries
1 and 2). Method 2 was also used to prepare the
corresponding (trimethylstannyl)pyrroles 5j and 6j (Table
2, entries 3 and 4, respectively).
entry
R
EWG
product yield (%)
mp (°C)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
COPh
COMe
CO2Me
CO2Et
CO2Ph
CN
3a
3b
3c
3d
3e
3f
3g
3h
3i
90
60a
68
70
70
61
40
64
b
174-175
80-87
169-170
134-135
151-152
182-183
179-181
oil
NO2
CO2Me
CO2Me
PhCHdCH COMe
PhCHdCH COPh
10
3j
b
a
Yield estimated from 1H NMR, purification by column chro-
b
matography and crystallization not successful. Impure product
only, isolation by column chromatography and crystallization not
successful.
Sch em e 1. P r op osed Mech a n ism for F or m a tion
of (Tr im eth ylsta n n yl)p yr r ole 3a
Although the overall yields of 5a and 6a from chalcone
by the two methods may be comparable, Method 2
requires three steps and Method 1 two. Furthermore,
the ortho-lithiation step of Method 2 appears not to be
site-specific in all cases. Whereas Method 2 gave single
pyrroles 5a , 5j, and 6a from 8a , 8j, and 9a , respectively,
in case of R1 ) Ph, the corresponding reaction with R1 )
TosCLi(SnMe3)NdC, since that would imply either an
integral migration of the Me3Sn group in 2a to form 3a ,
or a regioreversal of the usual Michael type addition-
cyclization depicted in eq 1. We tentatively propose that
the reacting species, formed in situ from dilithio-TosMIC
and Me3SnCl, be TosCLidNCSnMe3 T TosCLidN+dC--
SnMe3 (4). A cycloaddition of 4 to chalcone by a Michael
type addition-cyclization as in Scheme 1 (in one step or
two steps)5 would explain the formation of 3a in a
straightforward manner. There is a certain resemblance
with the formation of 3-benzoyl-2,4-diphenylpyrrole from
chalcone and TosCH2NdC(SMe)Ph using NaH. In this
process, the TosMIC-isocyano carbon bears two substit-
uents, of which the SMe is lost in the pyrrole ring
formation.11
(6) The first stannylated pyrrole, 1-(dimethylamino)-2-(trimethyl-
stannyl)pyrrole, was reported in 1981: Martinez, G. R.; Grieco, P. A.;
Srinivasan, C. V. J . Org. Chem. 1981, 46, 3760. The first application
in
a Stille cross-coupling (of 1-methyl-2-(trimethylstannyl)pyrrole)
dates from 1986: Bailey, T. R. Tetrahedron Lett. 1986, 27, 4407.
(7) Alvarez, A.; Guzman, A.; Ruiz, A.; Velarde, E.; Muchowski, J .
M. J . Org. Chem. 1992, 57, 1653.
(8) Leading references: Zerbi, G.; Veronelli, M.; Martina, S.; Schlu¨t-
er, A.-D.; Wegner, G. Adv. Mater. 1994, 6, 315. Groenendaal, L.;
Peerlings, H. W. I.; Havinga, E. E.; Vekemans, J . A. J . M.; Meijer, E.
W. Synth. Metals 1995, 69, 467. Groenendaal, L. Ph.D. Thesis,
Eindhoven (The Netherlands), 1996. Wang, J .; Scott, A. I. Tetrahedron
Lett. 1996, 37, 3247.
(9) van Nispen, S. P. J .; Mensink, C.; van Leusen, A. M. Tetrahedron
Lett. 1980, 21, 3723.
(10) The X-ray structure of the N-Boc derivative of 3a was published
elsewhere: Meetsma, A.; Dijkstra, H. P.; ten Have, R.; van Leusen, A.
M. Acta Crystallogr. 1996, C52, 2747. This paper, which also describes
the nonoptimized synthesis of 3a and its N-Boc derivative, is to be
considered the preliminary of the present paper.
(11) Houwing, H. A.; van Leusen, A. M. J . Heterocycl. Chem. 1981,
18, 1127, and ref 5h. Furthermore, for the use of Pd, Pt, and W
complexes of isocyanides, see: Fehlhammer, W. P.; Bartel, K.; Vo¨lkl,
A.; Achatz, D Z. Naturforsch. 1982, 37b, 1044.
(12) The limitation of the Stille reaction to N-substituted (protected)
pyrroles probably has more to do with the preparation of the stann-
ylpyrroles3 than with the Stille reaction itself. As a matter of fact many
functional groups are compatible with the Stille reaction. In the many
applications of the Stille reaction to indoles, N-substituted (protected)
indoles were used, with one recent exception.2 This one exception4 may
be seen as an indication that the Stille reaction of N-unprotected
pyrroles ought to be possible too.
(5) Some references are as follows: (a) Possel, O.; van Leusen, A.
M. Heterocycles 1977, 7, 77. (b) Moskal, J .; van Leusen, A. M. J . Org.
Chem. 1986, 51, 4131. (c) Magnus, P.; Gallagher, T.; Schultz, J .; Or,
Y.-S.; Ananthanarayan, T. P. J . Am. Chem. Soc. 1987, 109, 2706. (d)
van Leusen, D.; Flentge, E.; van Leusen, A. M. Tetrahedron 1991, 47,
4639. (e) van Leusen, D.; van Echten, E.; van Leusen, A. M. J . Org.
Chem. 1992, 57, 2245. (f) Dell’Erba, C.; Giglio, A.; Mugnoli, A.; Novi,
M.; Petrillo, G.; Stagnaro, P. Tetrahedron 1995, 51, 5181. (g) van
Leusen, A. M.; van Leusen, D. In Encyclopedia of Reagents for Organic
Synthesis; Paquette, L. A., Ed.; Wiley: New York, 1995; Vol. 7, p 4973.
(h) van Leusen, A. M.; van Leusen, D. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.; Wiley: New York, 1995, Vol.
5, p 3605. (i) ten Have, R.; Leusink, F. R.; van Leusen, A. M. Synthesis
1996, 871. For an exhaustive account, see: (j) van Leusen, D.; van
Leusen, A. M. Org. React., in press.

5334 J . Org. Chem., Vol. 63, No. 16, 1998
Sch em e 2. Tw o Ap p r oa ch es to N-P r otected (Tr im eth ylsta n n yl)p yr r oles 5 a n d 6
Dijkstra et al.
Ta ble 2. P yr r oles 7, 8, a n d 9 a n d (Tr im eth ylsta n n yl)p yr r oles 5 a n d 6 Accor d in g to Sch em e 2
entry
R1
compda
yield (%)
70
mp (°C)
compd
R2
yield (%)
mp (°C)
oil
129-131
109-110
130-132
compd
yield (%)
mp (°C)
1
2
3
4
Ph
(E)-PhCHdCH
7a
229-231
8a
9a
8j
9j
Me
Boc
Me
92
78
54
81
5a
6a
5j
6j
86b/72c
79b/79c
74
103-105
122-123
146-148
7j
98
172-175
Boc
60d
For starting material 3a , see Table 1. Yield by using Method 1. c Yield by using Method 2. Mixture of two isomers (see text and
a
b
d
Experimental Section).
Ta ble 3. (Tr im eth ylsta n n yl)p yr r oles 5a a n d 6a Ap p lied
in th e Stille Rea ction a n d in NBS Br om in a tion
Sch em e 3. Som e Ap p lica tion s of Sta n n ylp yr r oles
5a a n d 6a
entry
R
product
yield (%)
mp (°C)
1
2
3
4
5
6
7
8
Me
Boc
Me
Boc
Me
Boc
Me
10
11
12
13
14
15
16
17
65
71
50
21
87
75
b
120-122
92-93
295-296
a
107-108
oil
Boc
b
a
Decomposition at ca. 190 °C. b Reaction unsuccessful (see text).
2-bromopyrroles 14 and 15 were unsuccessful, possibly
as a result of steric overcrowding. The bromopyrroles
14 and 15 were obtained by replacement of the Me3Sn
group in 5a and 6a , in 87 and 75% yields, respectively,
with N-bromosuccinimide (NBS).
Primarily as additional evidence of the structure of
compounds 3, 3-benzoyl-2,4-diphenyl-1-methylpyrrole (10)
was prepared independently by N-methylation of 3-ben-
zoyl-2,4-diphenylpyrrole.11 The two samples were identi-
cal by 1H NMR. 4-Benzoyl-1-methyl-2,3-diphenylpyrrole
(18), isomeric with 10, was prepared by reaction of
chalcone with 1-tosylbenzyl isocyanide17 followed by
N-methylation (see Experimental Section).
(E)-PhCHdCH not only gave 6j but also the isomeric
4-benzoyl-1-(tert-butoxycarbonyl)-3-(2-phenylethenyl)-2-
trimethylstannylpyrrole (6j′) (ratio 1.2:1 or 1:1.2, see
Experimental Section). Unfortunately, we have been
unable to compare the results of entries 3 and 4 by
Method 2 with Method 1, since 3j was not obtained in
pure state.
Scheme 3 and Table 3 show some reactions of stann-
ylpyrroles 5a and 6a . The Stille cross-coupling with
bromobenzene to the 2-phenylpyrroles 10 and 11 took
place in 65 and 71% yields, respectively. The yields of
the double cross-coupling with 1,4-dibromobenzene to 12
and 13 were lower (25 and 21%, respectively). The homo-
coupling reactions of 5a and 6a with the corresponding
Exp er im en ta l Section
All experiments, with the exception of the N-methylation
reactions, were carried out in a dry nitrogen atmosphere. The
Michael acceptors used in the preparation of 3a , 3b, 3c, 3d ,
(13) Fuson, T. C.; Thomas, N. J . Org. Chem. 1953, 18, 1762.
(14) Worall, D. E. Organic Syntheses; Wiley: New York, 1947;
Collect. Vol. I, p 413.
(15) Diehl, L.; Einhorn, A. Ber. Dtsch. Chem. Ges. 1885, 18, 2320.
(16) Thomas, J . F.; Branch, G. J . Am. Chem. Soc. 1953, 75, 4793.
(17) van Leusen, A. M.; Siderius, H.; Hoogenboom, B. E.; van
Leusen, D. Tetrahedron Lett. 1972, 5337.

Direct Synthesis of 2-(Trimethylstannyl)pyrroles
J . Org. Chem., Vol. 63, No. 16, 1998 5335
3f, 3h , trimethylstannyl chloride, bis(triphenylphosphine)-
palladium(II) chloride, and tetrakis(triphenylphosphine)-
palladium(0) are commercial products (Aldrich), which have
been used as received. The Michael acceptors used for the
preparation of 3e,13 3g,14 3i,15 and 3j16 were prepared according
to the literature procedures indicated. Tosylmethyl isocyanide
(TosMIC), purchased from Ofichem (Ter Apel, The Nether-
lands), was chromatographed (Al2O3, CH2Cl2) before use.
Column chromatographies were performed on basic alumina
(Brockmann 90, II/III 0.063-0.200 mm) or on neutral alumina
(aluminum oxide 90, activity I, Merck) using CH2Cl2 as eluent.
CH2Cl2 was distilled over P2O5 before use. THF was distilled
from Na wire. Melting points are uncorrected. 1H NMR
spectra were recorded at 500, 300, or 200 MHz. 1H NMR
chemical shifts were determined relative to the solvent and
were converted to the TMS scale using δ(CHCl3) ) 7.26. 13C
NMR spectra were recorded at 125.7, 75.4, or 50.4 MHz. 13C
NMR chemical shifts were determined relative to the solvent
and were converted to the TMS scale using δ(CDCl3) ) 76.91.
119Sn NMR spectra were recorded at 186.4 or 111.9 MHz.
119Sn NMR chemical shifts were determined relative to Me3-
SnCl and were converted to the TMS scale using δ(Me3SnCl)
) 167.4.
3-Ben zoyl-4-p h en yl-2-(tr im eth ylsta n n yl)p yr r ole (3a ).
Typ ica l P r oced u r e. n-BuLi (1.6 M in n-hexane, 2.6 mL, 4.2
mmol) was added to a solution of TosMIC (0.39 g, 2.0 mmol)
in THF (30 mL) at -75 °C. After 5 min of stirring at -75 °C,
Me3SnCl (0.80 g, 4.0 mmol) in THF (5 mL) was added
dropwise. After another 5 min of stirring at -75 °C, a solution
of chalcone (0.42 g, 2.0 mmol) in THF (5 mL) was added
dropwise. The temperature of the reaction mixture was
allowed to rise to room temperature in 30 min, and stirring
was continued for 2 h. Water (50 mL) was added, and the
mixture was extracted with Et2O (3 × 50 mL). The combined
extracts were washed with water and with brine, dried
(MgSO4), and concentrated. The solid residue was filtered
through a short (1 cm) column of neutral alumina (CH2Cl2) to
give, after removal of the solvent, 0.74 g (90%) of compound
3a as a white solid, which was analytically pure, mp 174-
175 °C: 1H NMR (CDCl3, 200 MHz) δ 0.37 (s, 9H), 6.97-7.26
(m, 9H), 7.50 (d, J ) 1.5 Hz, 1H), 7.52 (d, J ) 4.9 Hz, 1H),
8.69 (br, 1H); 13C NMR (CDCl3, 50.3 MHz) δ -8.7 (q), 121.4
(d), 122.5 (s), 125.5 (d), 127.2 (d), 127.5 (d), 127.9 (s), 128.9
(d), 129.3 (d), 131.0 (d), 135.1 (s), 139.0 (s), 142.7 (s), 194.3 (s);
119Sn NMR (CDCl3, 186.4 MHz) δ -59.2; MS (relative intensity,
%) m/z 28 (29.6), 77 (22.6), 105 (15.4), 170 (22.1), 247 (19.2),
364 (15.0), 396 (100.0), 411 (M+, 0.7); HRMS m/z calcd for
r ole (3d ). Following the procedure described for 3a , ethyl
trans-cinnamate (0.35 g, 2.0 mmol) gave, after being washed
with dry pentane, analytically pure 3d as a white solid (0.53
1
g, 70%): mp 134-135 °C; H NMR (CDCl3, 200 MHz) δ 0.37
(s, 9H), 1.20 (t, 3H), 4.21 (q, 2H), 6.95 (d, J ) 2.2 Hz, 1H),
7.23-7.49 (m, 5H), 8.49 (br, 1H); 13C NMR (CDCl3, 50.3 MHz)
δ -8.6 (q), 14.0 (q), 59.5 (t), 121.4 (s), 122.1 (d), 126.2 (d), 127.3
(d), 127.9 (s), 129.4 (d), 135.4 (s), 141.6 (s), 166.1 (s); 119Sn NMR
(CDCl3, 111.9 MHz) δ -57.7; MS (relative intensity, %) m/z
28 (66.9), 159 (11.0), 170 (11.8), 288 (17.5), 318 (35.4), 334
(12.0), 364 (100.0), 379 (M+, 4.6); HRMS m/z calcd for C16H21
-
NO2Sn 379.059, found 379.059. Anal. Calcd for C16H21NO2-
Sn: C, 50.84; H, 5.60; N, 3.71; Sn, 31.40. Found: C, 50.75;H,
5.61; N, 3.69; Sn, 31.30.
3-P h en oxyca r bon yl-4-p h en yl-2-(tr im eth ylsta n n yl)p yr -
r ole (3e). Following the procedure described for 3a , phenyl
trans-cinnamate13 (0.48 g, 2.0 mmol) gave analytically pure
1
3e as a white solid (0.60 g, 70%): mp 151-152 °C; H NMR
(CDCl3, 200 MHz) δ 0.37 (s, 9H), 7.02-7.55 (m, 11H), 8.55 (br,
1H); 13C NMR (CDCl3, 50.3 MHz) δ -8.6 (q), 120.0 (s), 121.7
(d), 122.2 (d), 125.0 (d), 126.1 (d), 127.3 (d), 128.5 (s), 129.0
(d), 129.1 (d), 134.7 (s), 143.0 (s), 150.3 (s), 163.9 (s); 119Sn NMR
(CDCl3, 111.9 MHz) δ -52.9; MS (relative intensity, %) m/z
28 (56.6), 94 (18.9), 120 (12.9), 170 (31.1), 288 (20.8), 304 (27.1),
318 (25.8), 334 (100.0), 412 (88.9), 427 (M+, 1.3); HRMS m/z
calcd for C20H21NO2Sn 427.059, found 427.059. Anal. Calcd
for C20H21NO2Sn: C, 56.38; H, 4.97; N, 3.29; Sn, 27.86.
Found: C, 56.41; H, 5.05; N, 3.30; Sn, 27.52.
3-Cyan o-4-ph en yl-2-(tr im eth ylstan n yl)pyr r ole (3f). Fol-
lowing the procedure described for 3a , cinnamonitrile (0.26 g,
2.0 mmol) gave, after one crystallization from CH2Cl2, analyti-
cally pure 3f as a white solid (0.40 g, 61%): mp 182-183 °C;
1H NMR (CDCl3, 200 MHz) δ 0.48 (s, 9H), 7.14 (d, J ) 2.4 Hz,
1H), 7.26-7.66 (m, 5H), 8.64 (br, 1H); 13C NMR (CDCl3, 75.4
MHz) δ -8.2 (q), 101.5 (s), 119.5 (s), 120.5 (d), 127.4 (d), 127.7
(d), 129.3 (s), 129.5 (d), 133.7 (s), 143.4 (s); 119Sn NMR (CDCl3,
186.4 MHz) δ -45.8; MS (relative intensity, %) m/z 28 (74.6),
115 (15.7), 120 (15.8), 140 (12.0), 168 (21.6), 287 (36.1), 317
(100.0), 332 (M+, 32.8); HRMS m/z calcd for C14H16N2Sn
332.033, found 332.033. Anal. Calcd for C14H16N2Sn: C,
50.60; H, 4.86; N, 8.43; Sn, 36.11. Found: C, 50.73; H, 4.87;
N, 8.40; Sn, 35.96.
3-Nitr o-4-ph en yl-2-(tr im eth ylstan n yl)pyr r ole (3g). Fol-
lowing the procedure described for 3a , â-nitrostyrene14 (0.30
g, 2.0 mmol) gave, after filtration through a short (4 cm)
column of neutral Al2O3 (CH2Cl2), analytically pure 3g as a
1
yellow solid (0.28 g, 40%): mp 179-181 °C; H NMR (CDCl3,
C
20H21NOSn 411.065, found 411.065. Anal. Calcd for C20H21
-
200 MHz) δ 0.42 (s, 9H), 6.88 (d, J ) 2.4 Hz, 1H), 7.26-7.46
(m, 5H), 8.54 (br, 1H); 13C NMR (CDCl3, 75.4 MHz) δ -8.9
(q), 122.5 (d), 123.0 (s), 127.1 (d), 127.8 (d), 129.2 (d), 132.7
(s), 140.2 (s); 119Sn NMR (CDCl3, 186.4 MHz) δ -48.6; MS
(relative intensity, %) m/z ) 28 (47.6), 32 (12.3), 307 (16.7),
337 (100.0), 352 (M+, 1.1); HRMS m/z calcd for C13H16N2O2Sn
352.023, found 352.023. Anal. Calcd for C13H16N2O2Sn: C,
44.32; H, 4.58; N, 7.96; Sn, 34.06. Found: C, 44.35; H, 4.62;
N, 7.86; Sn, 33.83.
NOSn: C, 58.38; H, 5.15; N, 3.41; Sn, 29.17. Found: C, 58.42;
H, 5.11; N, 3.34; Sn, 28.96.
3-Acetyl-4-ph en yl-2-(tr im eth ylstan n yl)pyr r ole (3b). Fol-
lowing the procedure decribed for 3a , (E)-4-phenyl-3-buten-2-
one (0.29 g, 2.0 mmol) was stirred for 2 h while the temper-
ature of the reaction mixture was kept below -30 °C. After
workup a mixture (0.61 g, mp 80-87 °C) was obtained, which
consisted of 3b (about 60% based on 1H NMR), TosMIC, and
other unidentified compounds. Purification by column chro-
matography and crystallization did not succeed: 1H NMR
(CDCl3, 200 MHz) δ 0.32 (s, 9H), 2.02 (s, 3H), 6.92 (d, J ) 2.4
Hz, 1H), 7.37 (s, 5H), 8.58 (br, 1H).
3-Meth oxyca r bon yl-4-p h en yl-2-(tr im eth ylsta n n yl)p yr -
r ole (3c). Following the procedure described for 3a , methyl
trans-cinnamate (0.32 g, 2.0 mmol) gave analytically pure 3c
as a white solid (0.50 g, 68%): mp 169-170 °C; 1H NMR
(CDCl3, 200 MHz) δ 0.37 (s, 9H), 3.72 (s, 3H), 6.95 (d, J ) 2.4
Hz, 1H), 7.24-7.51 (m, 5H), 8.53 (br, 1H); 13C NMR (CDCl3,
50.3 MHz) δ -8.6 (q), 50.4 (q), 120.8 (s), 122.2 (d), 126.2 (d),
127.5 (d), 128.0 (s), 129.3 (d), 135.2 (s), 142.0 (s), 166.1 (s);
119Sn NMR (CDCl3, 111.9 MHz) δ -57.2; MS (relative intensity,
%) m/z 28 (44.8), 32 (11.5), 170 (12.3), 288 (17.3), 318 (34.1),
350 (100.0), 365 (M+, 4.3); HRMS m/z calcd for C15H19NO2Sn
365.044, found 365.044. Anal. Calcd for C15H19NO2Sn: C,
49.31; H, 5.25; N, 3.84; Sn, 32.85. Found: C, 49.33; H, 5.28;
N, 3.81; Sn, 32.71.
3,4-Dim et h oxyca r b on yl-2-(t r im et h ylst a n n yl)p yr r ole
(3h ). Following the procedure described for 3a , dimethyl
fumarate (0.72 g, 5.0 mmol) gave, after filtration through a
short (4-cm) column of neutral Al2O3 (CH2Cl2), 3h as a brown
oil (1.1 g, 64%), pure according to 1H NMR. 3h : 1H NMR
(CDCl3, 200 MHz) δ 0.33 (s, 9H), 3.81 (s, 3H), 3.82 (s, 3H),
7.49 (s, 1H), 8.63 (br, 1H); 13C NMR (CDCl3, 50.3 MHz) δ -8.7
(q), 51.0 (q), 51.3 (q), 116.7 (s), 122.8 (s), 128.9 (d), 143.0 (s),
164.8 (s), 165.4 (s); 119Sn NMR (CDCl3, 111.9 MHz) δ -53.9;
MS (relative intensity, %) m/z 44 (8.8), 136 (8.4), 149 (13.5),
151 (14.3), 270 (23.9), 300 (100), 332 (M+ - Me, 88.1); HRMS
m/z calcd for C10H14NO4Sn 331.9945, found 331.9920.
At t em p t ed Syn t h esis of (E)-3-Acet yl-4-(2-p h en yl-
eth en yl)-2-(tr im eth ylsta n n yl)p yr r ole (3i). Following the
procedure described for 3a , (E,E)-6-phenyl-3,5-hexadien-2-
one15 (0.34 g, 2.0 mmol) gave a yellow foam (0.75 g), which
according to 1H NMR consisted of mixture of 3i and other
unidentified compounds. Purification by column chromatog-
raphy and crystallization was unsuccessful.
3-E t h oxyca r b on yl-4-p h en yl-2-(t r im et h ylst a n n yl)p yr -

5336 J . Org. Chem., Vol. 63, No. 16, 1998
Dijkstra et al.
At t em p t ed Syn t h esis of (E)-3-Ben zoyl-4-(2-p h en yl-
eth en yl)-2-(tr im eth ylsta n n yl)p yr r ole (3j). Following the
procedure described for 3a , (E,E)-1,5-diphenyl-2,4-pentadien-
1-one16 (0.47 g, 2.0 mmol) gave a pale yellow oil, which
according to 1H NMR consisted of a mixture of 3j, starting
material, and other unidentified compounds. Purification by
column chromatography and crystallization was unsuccessful.
3-Ben zoyl-1-m eth yl-4-p h en yl-2-(tr im eth ylsta n n yl)p yr -
r ole (5a ). Meth od 1. KOH (50% in water, 3 mL) was added
to a solution of 3-benzoyl-4-phenyl-2-(trimethylstannyl)pyrrole
(3a , 0.41 g, 1.0 mmol), CH3I (0.5 mL, 8 mmol), and benzyltri-
ethylammonium chloride (25 mg, 0.15 mmol) in CH2Cl2 (10
mL). The reaction mixture was stirred for 1 h; then water
(20 mL) was added. The organic layer was separated, dried
(MgSO4), and concentrated to give 5a as a white solid (0.37 g,
86%). Crystallization from petroleum ether (bp 40-60 °C)
gave white crystals, mp 103-105 °C: 1H NMR (CDCl3, 300
MHz) δ 0.27 (s, 9H), 3.71 (s, 3H), 6.76 (s, 1H), 6.87-7.16 (m,
8H), 7.42-7.45 (m, 2H); 13C NMR (CDCl3, 75.4 MHz) δ -6.0
(q), 38.7 (q), 125.3 (d), 126.2 (d), 127.2 (d), 127.5 (d), 128.8 (d),
129.5 (d), 131.0 (d), 131.9 (s), 135.0 (s), 139.0 (s), 143.8 (s),
178.4 (s), 194.1 (s); 119Sn NMR (CDCl3, 186.4 MHz) δ -65.8;
MS (relative intensity, %) m/z 57 (12.1), 69 (10.3), 77 (7.8),
105 (6.4), 115 (5.3), 129 (6.3), 184 (47.6), 205 (7.9), 244 (15.2),
261 (43.9), 380 (26.7), 410 (M+, 100); HRMS m/z calcd for
was filtered through a short column of neutral Al2O3 (CH2-
Cl2). The eluent was concentrated, and the product was
crystallized from petroleum ether (bp 40-60 °C) to give 6a as
white crystals (0.81 g, 79%): mp 115-117 °C (lit.10 mp 118-
119 °C). Analytically pure 6a was obtained by crystallization
1
from CH2Cl2: mp 122-123 °C; H NMR (CDCl3, 300 MHz) δ
0.11 (s, 9H), 1.63 (s, 9H), 7.09-7.50 (m, 9H), 7.85-7.89 (m,
2H); 13C NMR (CDCl3, 75.4 MHz) δ -6.1 (q), 27.8 (q), 84.4 (s),
121.2 (d), 126.5 (d), 127.8 (d), 128.0 (d), 128.1 (d), 129.1 (s),
130.1 (d), 132.8 (d), 133.6 (s), 135.9 (s), 138.3 (s), 150.1 (s),
195.2 (s); 119Sn NMR (CDCl3, 186.4 MHz) δ -49.9; MS (relative
intensity, %) m/z 57 (16.6), 77 (4.9), 105 (9.0), 149 (13.0), 167
(7.5), 279 (5.6), 366 (9.5), 440 (100), 496 (M+ - Me, 22.7);
HRMS m/z calcd for C25H29NO3Sn 496.0935, found 496.0935.
Anal. Calcd for C25H29NO3Sn: C, 58.69; H, 5.72; N, 2.74; Sn,
23.46. Found: C, 58.74; H, 5.62;N, 2.79; Sn, 23.35. Meth od
2. n-BuLi (1.6 M in n-hexane, 9.8 mL, 15.7 mmol) was added
dropwise to 2,2,6,6-tetramethylpiperidine (2.0 g, 14.3 mmol)
in THF (100 mL) at -80 °C. The yellow solution was allowed
to warm to 0 °C and was kept at that temperature for 10 min.
The solution was cooled again to -80 °C, and a solution of
3-benzoyl-1-(tert-butoxycarbonyl)-4-phenylpyrrole (9a , 4.5 g,
3.0 mmol, see below) in THF (50 mL) was added dropwise.
After another 30 min of stirring at -80 °C, a solution of Me3-
SnCl (2.84 g, 14.3 mmol) in THF (25 mL) was added. The
mixture was stirred for 30 min at the same temperature and
then another 30 min while the temperature was allowed to
rise to room temperature. The reaction was poured into water
(75 mL) and extracted with Et2O (2 × 75 mL). The combined
organic layers were washed with brine, dried (MgSO4), con-
centrated, and filtered through a short column of neutral Al2O3
(CH2Cl2). The eluent was concentrated to give 6a as a pale
C
C
20H20NOSn 410.0567, found 410.0557. Anal. Calcd for
20H20NOSn: C, 59.47; H, 5.47; N, 3.30; Sn, 27.99. Found:
C, 59.44; H, 5.46; N, 3.36, Sn, 27.94. Meth od 2. n-BuLi (1.6
M in n-hexane, 16.1 mL, 25.7 mmol) was added dropwise to
2,2,6,6-tetramethylpiperidine (3.31 g, 23.4 mmol) in THF (100
mL) at -80 °C. The solution was allowed to warm to 0 °C
and was kept at that temperature for 10 min. The solution
was cooled again to -80 °C, and a solution of 3-benzoyl-1-
methyl-4-phenylpyrrole (8a , 5.57 g, 21.3 mmol, see below) in
THF (50 mL) was added dropwise. After another 15 min of
stirring at -80 °C, a solution of Me3SnCl (4.66 g, 23.4 mmol)
in THF (25 mL) was added dropwise. The mixture was stirred
for 30 min at the same temperature and for another 60 min
while the temperature was allowed to rise to -10 °C. The
reaction mixture was poured into water (75 mL), and the
solution was extracted with Et2O (2 × 75 mL). The combined
organic layers were washed with brine, dried (MgSO4), con-
centrated, and filtered through a short column of neutral Al2O3
(CH2Cl2). The eluent was concentrated, and the pale brown
solid was crystallized from petroleum ether (bp 40-60 °C) to
give 5a as a white solid (6.5 g, 72%), which was identical to
1
yellow solid (5.25 g, 79%), pure according to H NMR. This
material was identical by 1H NMR and 13C NMR with the
compound prepared by Method 1.
(E)-3-Ben zoyl-1-(ter t-bu toxyca r bon yl)-4-(2-p h en yleth -
en yl)-2-(tr im eth ylsta n n yl)-p yr r ole (6j) a n d (E)-4-Ben -
zoyl-1-(ter t-bu toxyca r bon yl)-3-(2-p h en yleth en yl)-2-(tr i-
m eth ylsta n n yl)p yr r ole (6j′). Following the procedure de-
scribed for 6a (Method 2), 3-benzoyl-1-(tert-butoxycarbonyl)-
4-(2-phenylethenyl)pyrrole (9j, 1.87 g, 5.0 mmol, see below),
2,2,6,6-tetramethylpiperidine (0.77 g, 5.5 mmol), n-BuLi (1,6
M in n-hexane, 3.8 mL, 6.05 mmol), and Me3SnCl (1.1 g, 5.5
mmol) gave a red oil (1.6 g, 60%) which contained a mixture
of two stannylated pyrroles 6j and 6j′ in a ratio of 1:1.2 or
1.2:1, as was established by 119Sn NMR of the mixture. 119Sn
NMR (CDCl3, 186.4 MHz) δ -49.8 and -51.3.
1
the above material according to H NMR.
(E)-3-Ben zoyl-1-m et h yl-4-(2-p h en ylet h en yl)-2-(t r im e-
th ylsta n n yl)p yr r ole (5j). Following the procedure described
for 5a (Method 2), (E)-3-benzoyl-1-methyl-4-(2-phenylethenyl)-
pyrrole (8j, 0.86 g, 3.0 mmol, see below), 2,2,6,6-tetramethyl-
piperidine (0.47 g, 3.3 mmol), n-BuLi (1,6 M in n-hexane, 2.3
mL, 3.6 mmol), and Me3SnCl (0.66 g, 3.3 mmol) gave 5j as a
yellow solid (1.0 g, 74%). Crystallization from Et2O gave 5j
as pale yellow crystals: mp 146-148 °C; 1H NMR (CDCl3, 200
MHz) δ 0.36 (s, 9H), 3.79 (s, 3H), 6.40 (d, J ) 16.1 Hz, 1H),
6.58 (d, J ) 16.4 Hz, 1H), 7.00-7.28 (m, 6H), 7.40-7.55 (m,
3H), 7.75-7.80 (m, 2H); 13C NMR (CDCl3, 125.7 MHz) δ -6.0
(q), 38.9 (q), 121.7 (d), 123.8 (s), 124.8 (d), 125.6 (d), 125.9 (d),
126.5 (d), 128.0 (d), 128.3 (d), 129.3 (d), 131.4 (d), 132.3 (s),
137.8 (s), 140.5 (s), 144.1 (s), 193.7 (s); 119Sn NMR (CDCl3,
186.4 MHz) δ -63.1; MS (relative intensity, %) m/z 77 (8.7),
105 (8.0), 167 (5.9), 182 (17.0), 210 (17.0), 287 (50.7), 406 (17.6),
436 (100), 451 (M+, 3.0); HRMS m/z calcd for C23H25NOSn
451.0958, found 451.0996. Anal. Calcd for C23H25NOSn: C,
61.18; H, 5.59; N, 3.16; Sn, 26.58. Found: C, 61.41; H, 5.59;
N, 3.14; Sn, 26.42.
3-Ben zoyl-4-p h en ylp yr r ole17 (7a ). TosMIC (6.0 g, 31
mmol) in THF (40 mL) was added dropwise to a stirred
solution of t-BuOK (3.7 g, 33 mmol) in THF (125 mL) at -80
°C. After 10 min of stirring at -80 °C, a solution of chalcone
(6.3 g, 30 mmol) in THF (40 mL) was added dropwise. The
reaction mixture was stirred for 90 min while the temperature
was allowed to rise to room temperature. The reaction mixture
was poured into ice/water (300 mL), and the solid was collected
by filtration to give 7a as a pale yellow solid (6.4 g, 86%), pure
1
according to H NMR: mp 228-229 °C (lit.17 yield 70%, mp
229-231 °C); 1H NMR (DMSO-d6, 300 MHz) δ 7.07-7.74 (m,
12 H), 11.63 (br, 1H); 13C NMR (DMSO-d6, 75.4 MHz) δ 119.6
(d), 120.6 (s), 125.5 (s), 125.6 (d), 127.7 (d), 128.1 (d), 128.2
(d), 128.4 (d), 128.9 (d), 131.5 (d), 135.2 (s), 140.0 (s), 190.4
(s); MS (relative intensity, %) m/z 77 (7.8), 115 (22.2), 142 (9.6),
170 (96.5), 218 (11.1), 247 (M+, 100); HRMS m/z calcd for
C
17H13NO 247.0997, found 247.0999. Anal. Calcd for C17H13-
NO: C, 82.57; H, 5.30; N, 5.66. Found: C, 82.30; H, 5.33; N,
5.65.
(E)-3-Ben zoyl-4-(2-p h en yleth en yl)p yr r ole (7j). TosMIC
(5.9 g, 30 mmol) in THF (50 mL) was added dropwise to a
stirred solution of t-BuOK (6.8 g, 61 mmol) in THF (100 mL)
at -80 °C. After 10 min of stirring at -80 °C, a solution of
(E,E)-1,5-diphenyl-2,4-pentadien-1-one16 (5.4 g, 28 mmol) in
THF (50 mL) was added dropwise. The reaction mixture was
stirred for 1 h while the temperature was allowed to rise to
room temperature. The reaction mixture was poured into ice/
water (400 mL), and the solid was collected by filtration to
3-Ben zoyl-1-(ter t-bu toxyca r bon yl)-4-p h en yl-2-(tr im e-
th ylsta n n yl)p yr r ole (6a ). Meth od 1. 3-Benzoyl-4-phenyl-
2-(trimethylstannyl)pyrrole (3a , 0.82 g, 2.0 mmol), di-tert-butyl
dicarbonate (0.48 g, 2.2 mmol), and t-BuOK (0.11 g, 1.0 mmol)
in THF (40 mL) were refluxed for 1 h. The reaction mixture
was quenched with water (25 mL) and was extracted with Et2O
(2 × 50 mL). The combined organic layers were washed with
brine, dried (MgSO4), and concentrated. The crude product

Direct Synthesis of 2-(Trimethylstannyl)pyrroles
J . Org. Chem., Vol. 63, No. 16, 1998 5337
give 7j as a pale yellow solid (6.7 g, 98%), pure according to
1H NMR: mp 172-175 °C; 1H NMR (CDCl3, 200 MHz) δ 6.83
(d, J ) 16.5 Hz, 1H), 7.03-7.47 (m, 10H), 7.61 (d, J ) 16.5
Hz, 1H), 7.70-7.73 (m, 2H), 8.65 (br, 1H); 13C NMR (CDCl3,
75.4 MHz) δ 116.6 (d), 121.4 (d), 121.9 (s), 124.4 (s), 126.2 (d),
126.9 (d), 127.4 (d), 127.6 (d), 128.1 (d), 128.4 (d), 129.0 (d),
131.4 (d), 137.9 (s), 140.4 (s), 192.1 (s); MS (relative intensity,
%) m/z 77 (9.4), 105 (8.2), 139 (6.0), 168 (28.7), 196 (33.0), 244
(9.0), 256 (5.7), 273 (M+, 100); HRMS m/z calcd for C19H15NO
273.1154, found 273.1173. Anal. Calcd for C19H15NO: C,
83.49; H, 5.53; N, 5.12. Found: C, 83.11; H, 5.55; N, 5.09.
3-Ben zoyl-1-m eth yl-4-p h en ylp yr r ole (8a ). A solution of
KOH (50% in water, 75 mL) was added to a solution of
3-benzoyl-4-phenylpyrrole (7a , 6.18 g, 25.0 mmol), benzyltri-
ethylammonium chloride (2.0 g, 8.8 mmol), and MeI (6.2 mL,
100 mmol) in CH2Cl2 (100 mL). The suspension was stirred
vigorously for 1 h. Water (75 mL) was added to the clear
reaction mixture, and the organic layer was separated, dried
(MgSO4), and filtered through a short column of basic Al2O3
(CH2Cl2). The eluent was concentrated to give 8a as a pale
yellow oil (6.0 g, 92%), pure according to 1H NMR. 8a : 1H
NMR (CDCl3, 300 MHz) δ 3.70 (s, 3H), 6.74 (d, J ) 2.6 Hz,
1H), 7.05 (d, J ) 2.6 Hz, 1H), 7.20-7.48 (m, 8H), 7.79-7.82
(m, 2H); 13C NMR (CDCl3, 75.4 MHz) δ 36.5 (q), 121.6 (s), 122.4
(d), 126.1 (d), 127.5 (s), 127.8 (d), 128.5 (d), 129.3 (d), 130.4
(d), 131.3 (d), 134.5 (s), 139.9 (s), 190.9 (s); MS (relative
intensity, %) m/z 57 (6.5), 77 (7.5), 115 (8.4), 129 (10.2), 184
(100), 232 (7.3), 244 (7.3), 261 (M+, 75.1); HRMS m/z calcd for
(s), 117.2 (d), 120.2 (d), 124.4 (s), 126.2 (s), 126.3 (d), 127.2
(d), 128.2 (d), 128.4 (d), 129.1 (d), 129.3 (d), 132.0 (d), 137.4
(s), 139.3 (s), 147.9 (s), 191.5 (s); MS (relative intensity, %)
m/z 69 (79.8), 81 (46.2), 95 (14.6), 105 (15.5), 121 (10.1), 137
(18.6), 149 (11.2), 168 (31.5), 196 (33.0), 244 (9.3), 256 (8.9),
273 (100), 317 (46.8), 373 (M+, 7.5); HRMS m/z calcd for C24H23
-
NO3 373.1678, found 373.1678. Anal. Calcd for C24H23NO3:
C, 77.19; H, 6.21; N, 3.75. Found: C, 76.99; H, 6.24; N, 3.78.
3-Ben zoyl-1-m eth yl-2,4-d ip h en ylp yr r ole (10). 3-Ben-
zoyl-1-methyl-4-phenyl-2-(trimethylstannyl)pyrrole (5a , 0.42
g, 1.0 mmol), bromobenzene (0.17 g, 1.1 mmol), and bis-
(triphenylphosphine)palladium(II) chloride (14 mg, 0.02 mmol)
were refluxed in THF (5 mL) for 40 h. The reaction mixture
was concentrated and filtered through a short column of basic
Al2O3 (CH2Cl2). The crude product was purified by crystal-
lization from EtOH (96%) to give 10 as pale yellow crystals
1
(0.22 g, 65%): mp 120-122 °C; H NMR (CDCl3, 200 MHz) δ
3.60 (s, 3H), 6.86 (s, 1H), 7.07-7.31 (m, 13H), 7.64-7.69 (m,
2H); 13C NMR (CDCl3, 125.7 MHz) δ 34.7 (q), 121.0 (s), 121.1
(d), 125.8 (d), 125.9 (s), 127.4 (d), 127.9 (d), 127.9 (d), 128.1
(d), 129.7 (d), 130.5 (d), 130.9 (s), 131.7 (d), 134.6 (s), 137.3
(s), 138.8 (s), 193.7 (s); MS (relative intensity, %) m/z 77 (4.6),
169 (11.1), 217 (5.2), 260 (85.5), 337 (M+, 100); HRMS m/z calcd
for C24H19NO 337.1467, found 337.1460. Anal. Calcd for
C
24H19NO: C, 85.42; H, 5.68; N, 4.15. Found: C, 85.31; H,
5.68; N, 4.13. Alternatively, 3-benzoyl-2,4-diphenylpyrrole11
was methylated according to the procedure described for 8a .
The compound so obtained was identical with compound 10
1
C
18H15NO 261.1154, found 261.1165.
according to H NMR and 13C NMR.
(E)-3-Ben zoyl-1-m eth yl-4-(2-ph en yleth en yl)pyr r ole (8j).
3-B e n z o y l-1-(t er t -b u t o x y c a r b o n y l)-2,4-d ip h e n y l-
p yr r ole (11). 3-Benzoyl-1-(tert-butoxycarbonyl)-4-phenyl-2-
(trimethylstannyl)pyrrole (6a , 0.26 g, 0.5 mmol), bromobenzene
(0.85 g, 0.55 mmol), and bis(triphenylphosphine)palladium-
(II) chloride (7.0 mg, 0.01 mmol) were refluxed in THF (5 mL)
for 70 h. The reaction mixture was concentrated and filtered
through a short column of basic Al2O3 (CH2Cl2). The crude
product was purified by crystallization from 2-propanol to give
11 as a white solid (0.15 g, 71%): mp 92-93 °C; 1H NMR
(CDCl3, 200 MHz) δ 1.31 (s, 9H), 7.13-7.31 (m, 13H), 7.55 (s,
1H), 7.64-7.67 (m, 2H); 13C NMR (CDCl3, 125.7 MHz) δ 27.4
(q), 84.5 (s), 118.9 (d), 125.9 (s), 126.6 (s), 126.7 (d), 127.3 (d),
127.7 (d), 127.8 (d), 127.8 (d), 128.2 (d), 129.5 (d), 130.2 (d),
132.0 (s), 132.5 (d), 133.2 (s), 135.0 (s), 137.8 (s), 148.8 (s), 193.9
(s); MS (relative intensity, %) m/z 57 (44.8), 105 (14.3), 189
(6.6), 217 (7.7), 246 (54.5), 306 (5.2), 323 (100), 367 (42.4), 423
(M+, 20.4); HRMS m/z calcd for C28H25NO3 423.1834, found
423.1834. Anal. Calcd for C28H25NO3: C, 79.41; H, 5.95; N,
3.31. Found: C, 78.74; H, 6.02; N, 3.31.
1,4-D i [3-b e n z o y l-1-m e t h y l-4-p h e n y l-2-p y r r o ly l]-
ben zen e (12). Pyrrole 5a (0.85 g, 2.0 mmol), 1,4-dibromoben-
zene (0.24 g, 1.0 mmol), and bis(triphenylphosphine)palladium-
(II) chloride (28 mg, 0.04 mmol) were refluxed in THF (10 mL)
for 70 h. After cooling, the white precipated solid was collected
and washed with pentane (25 mL) to give 12 (0.30 g, 50%),
pure according to 1H NMR. Crystallization from a mixture of
EtOH (96%)-CH2Cl2 (1:1) gave 12 as white crystals, mp 295-
296 °C: 1H NMR (CDCl3, 500 MHz) δ 3.56 (s, 6H), 6.93 (s,
2H), 7.15-7.20 (m, 8H), 7.24-7.28 (m, 6H), 7.34-7.36 (m, 6H),
7.70 (d, J ) 7.02 Hz, 4H); 13C NMR (CDCl3, 125.7 MHz) δ 34.7
(q), 121.0 (s), 121.4 (d), 125.9 (d), 126.2 (s), 127.4 (d), 128.0
(d), 128.1 (d), 129.7 (d), 130.2 (d), 130.6 (s), 131.5 (d), 134.5
(s), 136.8 (s), 139.0 (s), 193.5 (s); MS (relative intensity, %)
m/z 44 (7.3), 105 (24.4), 221 (5.4), 259 (5.1), 298 (5.4), 519 (8.1),
596 (M+, 100); HRMS m/z calcd for C42H32N2O2 596.2464, found
596.2509. Anal. Calcd for C42H32N2O2: C, 84.53; H, 5.41; N,
4.70. Found: C, 83.78; H, 5.40; N, 4.62.
Following the procedure described for 8a , (E)-3-benzoyl-4-(2-
phenylethenyl)pyrrole (7j, 3.0 g, 11.0 mmol) gave, after
crystallization from Et2O, 8j as yellow crystals (1.7 g, 54%):
mp 109-110 °C; 1H NMR (CDCl3, 500 MHz) δ 3.64 (s, 3H),
6.88-6.97 (m, 3H), 7.19-7.33 (m, 3H), 7.43-7.54 (m, 5H),
7.72-7.80 (m, 3H); 13C NMR (CDCl3, 125.7 MHz) δ 37.0 (q),
120.4 (d), 121.5 (d), 121.5 (q), 124.8 (q), 126.0 (d), 126.7 (d),
127.1 (d), 127.9 (d), 128.3 (d), 128.7 (d), 130.7 (d), 131.1 (d),
137.9 (q), 140.5 (q), 191.4 (q); MS (relative intensity, %) m/z
77 (5.6), 105 (5.0), 167 (11.0), 182 (35.4), 210 (39.7), 258 (11.0),
287 (M+, 100); HRMS m/z calcd for C20H17NO 287.1310, found
287.1332. Anal. Calcd for C20H17NO: C, 83.60; H, 6.09; N,
4.90. Found: C, 83.52, H, 6.03, N, 4.82.
3-Ben zoyl-1-(ter t-bu toxycar bon yl)-4-ph en ylpyr r ole (9a).
3-Benzoyl-4-phenyl-pyrrole (7a , 6.4 g, 26 mmol), di-tert-butyl
dicarbonate (6.2 g, 29 mmol), and t-BuOK (0.56 g, 5.0 mmol)
in THF (200 mL) were refluxed for 1 h. The reaction mixture
was poured into water (50 mL), and the solution was extracted
with Et2O (2 × 75 mL). The combined organic layers were
washed with brine, dried (MgSO4), and concentrated. The
crude product was filtered through a short column of basic
Al2O3 (CH2Cl2). The eluent was concentrated to give 9a as a
pale yellow solid (7.0 g, 78%), pure according to 1H NMR.
Crystallization from EtOH (96%) gave 9a as glassy crystals:
mp 129-131 °C; 1H NMR (CDCl3, 500 MHz) δ 1.63 (s, 9H),
7.23-7.30 (m, 3H), 7.36-7.41 (m, 5H), 7.50-7.53 (m, 1H), 7.66
(d, J ) 2.2 Hz, 1H), 7.84-7.86 (m, 2H); 13C NMR (CDCl3, 125.7
MHz) δ 27.8 (q), 85.2 (s), 119.1 (d), 124.8 (s), 126.6 (d), 126.9
(d), 128.0 (d), 128.1 (d), 128.4 (d), 128.8 (s), 129.5 (d), 132.3
(d), 133.3 (s), 138.6 (s), 148.0 (s), 191.1 (s); MS (relative
intensity, %) m/z 28 (87.74), 32 (18.80), 39 (10.4), 41 (32.4), 44
(15.9), 57 (100), 77 (14.8), 115 (16.1), 170 (60.8), 246 (20.8),
247 (54.5), 291 (36.9), 347 (M+, 7.3); HRMS m/z calcd for
C
22H21NO3 347.1521, found 347.1522. Anal. Calcd for C22H21-
NO3: C, 76.06; H, 6.09; N, 4.03. Found: C, 75.88, H, 6.11, N,
4.06.
3-Ben zoyl-1-(ter t-bu toxycar bon yl)-4-(2-ph en yleth en yl)-
p yr r ole (9j). Following the procedure described for 9a , (E)-
3-benzoyl-4-(2-phenylethenyl)pyrrole (7j, 3.0 g, 11.0 mmol), di-
tert-butyl dicarbonate (2.64 g, 12.1 mmol), and t-BuOK (0.22
g, 2.0 mmol) in THF (75 mL) gave, after crystallization from
EtOH (96%), 9j as off-white crystals (3.32 g, 81%), mp 130-
132 °C: 1H NMR (CDCl3, 200 MHz) δ 1.63 (s, 9H), 6.98 (d, J
) 16.6 Hz, 1H), 7.23-7.37 (m, 3H), 7.45-7.60 (m, 8H), 7.84-
7.88 (m, 2H); 13C NMR (CDCl3, 125.7 MHz) δ 27.8 (q), 85.3
1,4-Di[3-b en zoyl-1-(ter t-b u t oxyca r b on yl)-4-p h en yl-2-
p yr r olyl]ben zen e (13). Pyrrole 6a (0.51 g, 1.0 mmol), 1,4-
dibromobenzene (0.12 g, 0.5 mmol), and tetrakis(triphenylphos-
phine)palladium(0) (23 mg, 0.02 mmol) were refluxed in
toluene (10 mL) and aqueous Na2CO3 (1 M, 10 mL) for 138 h.
After cooling, the reaction mixture was extracted with CH2-
Cl2 (2 × 50 mL). The combined organic layers were washed
with brine, dried (MgSO4), and concentrated. After column
chromatography (basic Al2O3, CH2Cl2), the first fraction gave

5338 J . Org. Chem., Vol. 63, No. 16, 1998
Dijkstra et al.
13 as a pale yellow solid. Crystallization from EtOH (96%)
gave 13 as pale yellow crystals (75 mg, 21%): the compound
decomposed at ca. 190 °C;18 1H NMR (CDCl3, 500 MHz) δ 1.13
(s, 18H), 7.13-7.26 (m, 20H), 7.51 (s, 2H), 7.60-7.62 (m, 4H);
13C NMR (CDCl3, 125.6 MHz) δ 27.2 (q), 84.8 (s), 119.0 (d),
126.3 (s), 126.3 (s), 126.7 (d), 127.5 (d), 127.8 (d), 128.2 (d),
129.3 (d), 129.5 (d), 131.6 (s), 132.6 (d), 133.2 (s), 133.9 (s),
137.8 (s), 148.8 (s), 193.6 (s); MS and HRMS were not
determined due to thermal instability of the compound.
3-Ben zoyl-2-br om o-1-m eth yl-4-p h en ylp yr r ole (14). A
solution of pyrrole 5a (2.54 g, 6.0 mmol) in THF (50 mL) was
cooled to -70 °C. NBS (1.17 g, 6.6 mmol) was added in small
portions; then stirring was continued for 30 min at -70 °C.
Next, the reaction mixture was stirred at 0 °C for 25 h. Water
(25 mL) was added, and the mixture was extracted with CH2-
Cl2 (2 × 50 mL). The combined organic layers were washed
with brine (2 × 50 mL), dried (MgSO4), and filtered through a
short column of basic Al2O3 (CH2Cl2). Concentration of the
eluent gave 14 as a pale yellow oil. Crystallization from
2-propanol gave 14 as white crystals (1.78 g, 87%), pure
according to 1H NMR. 14: mp 107-108 °C; 1H NMR (CDCl3,
300 MHz) δ 3.70 (s, 3H), 6.89 (s, 1H), 7.10-7.38 (m, 8H), 7.73-
7.78 (m, 2H); 13C NMR (CDCl3, 75.4 MHz) δ 35.7 (q), 107.4
(s), 121.2 (d), 121.7 (s), 126.1 (d), 126.9 (s), 127.8 (d), 127.8
(d), 128.0 (d), 129.9 (d), 132.2 (d), 134.0 (s), 138.0 (s), 129.3
(s); MS (relative intensity, %) m/z 77 (14.8), 130 (23.1), 155
(12.4), 183 (29.4), 262 (82.7), 264 (81.6), 339 (M+, 100); HRMS
m/z calcd for C18H14BrNO 339.0259, found 339.0261. Anal.
Calcd for C18H14BrNO: C, 63.55; H, 4.15; N, 4.12; Br, 23.49.
Found: C, 63.08; H, 4.12; N, 4.12; Br, 23.65.
0 °C for 24 h. Na2SO3 (0.81 g, 6.5 mmol) was added, and the
mixture was stirred for 15 min; then the solvent was removed.
CCl4 (20 mL) was added, the mixture was filtered, and the
filtrate concentrated. The crude product was dissolved in CH2-
Cl2, washed with water (2 × 50 mL), dried (MgSO4), and
filtered through a short column of basic Al2O3 (CH2Cl2), and
the eluent was removed to give 15 as a colorless oil (1.28 g,
1
75%), pure according to H NMR. 15: 1H NMR (CDCl3, 200
MHz) δ 1.66 (s, 9H), 7.16-7.56 (m, 9H), 7.84-7.89 (m, 2H);
13C NMR (CDCl3, 75.4 MHz) δ 27.8 (q), 85.9 (s), 102.3 (s), 120.2
(d), 127.1 (d), 127.4 (d), 127.5 (s), 127.6 (s), 128.0 (d), 128.3
(d), 128.3 (d), 130.0 (d), 132.5 (s), 133.2 (d), 137.1 (s), 147.5
(s), 192.5 (s); MS (relative intensity, %) m/z 57 (74.0), 77 (12.9),
105 (11.3), 123 (9.3), 140 (6.7), 169 (15.1), 189 (6.9), 217 (8.8),
248 (40.0), 325 (100), 369 (10.7), 425 (M+, 9.7); HRMS m/z calcd
for C22H20BrNO3 425.0611, found 425.0586.
4-Ben zoyl-1-m eth yl-2,3-d ip h en ylp yr r ole (18). 4-Ben-
zoyl-2,3-diphenylpyrrole17 was methylated according to the
procedure described for 8a . 18: 1H NMR (CDCl3, 300 MHz) δ
3.57 (s, 3H), 7.09 (br s, 5H), 7.19-7.46 (m, 9H), 7.81-7.83 (m,
2H); 13C NMR (CDCl3, 75.4 MHz) δ 35.3 (q), 121.8 (s), 124.6
(s), 125.7 (d), 127.3 (d), 127.7 (d), 128.2 (d), 129.3 (d), 129.9
(d), 130.4 (d), 130.9 (d), 131.1 (s), 131.2 (d), 133.4 (s), 134.5
(s), 139.9 (s), 190.9 (s); MS (relative intensity, %) m/z 69 (5.8),
77 (4.9), 105 (11.7), 169 (8.9), 189 (5.5), 217 (8.5), 245 (5.4),
260 (59.5), 337 (M+, 100); HRMS m/z calcd for C24H19NO
337.1467, found 337.1452. Anal. Calcd for C24H19NO: C,
85.42; H, 5.68; N, 4.15, Found: C, 85.24; H, 5.60; N 4.16.
Su p p or tin g In for m a tion Ava ila ble: 1H and/or 13C NMR
spectra of compounds 3h , 8a , 13, and 15 (7 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.
3-Ben zoyl-2-b r om o-1-(ter t-b u t oxyca r b on yl)-4-p h en -
ylp yr r ole (15). A solution of pyrrole 6a (2.0 g, 4.0 mmol) in
THF (25 mL) was cooled to -70 °C. NBS (0.76 g, 4.3 mmol)
was added in small portions; then stirring was continued for
30 min at -70 °C. Next, the reaction mixture was stirred at
(18) For thermolytic removal of the Boc group, see: Rawal, V. H.;
Cava, M. P. Tetrahedron Lett. 1985, 26, 6141.
J O972216Y