Divergent pathways in the intramolecular reactions between rhodium-stabilized vinylcarbenoids and pyrroles: Construction of fused tropanes and 7-azabicyclo[4.2.0]octadienes

Article abstract of DOI:10.1021/jo952127q

The rhodium(II)-catalyzed intramolecular reaction between vinyldiazomethanes and pyrroles leads to a novel synthesis of fused tropanes. The reaction occurs by a stepwse 3 + 4 annulation mechanism between a rhodium-stabilized vinylcarbenoid intermediate and the pyrrole rather than by the typical tandem cyclopropanation/Cope rearrangement sequence. The outcome of the reaction is very sensitive to the vinylcarbenoid structure. In particular, the presence of a 2-siloxy substituent on the vinylcarbenoid strongly favors the formation of fused tropanes. In the absence of such functionality, the formation of fused 7-azabicyclo[4.2.0]octadienes becomes the dominant reaction pathway.

Full text of DOI:10.1021/jo952127q

J . Org. Chem. 1996, 61, 2305-2313
2305
Diver gen t P a th w a ys in th e In tr a m olecu la r Rea ction s betw een
Rh od iu m -Sta bilized Vin ylca r ben oid s a n d P yr r oles: Con str u ction
of F u sed Tr op a n es a n d 7-Aza bicyclo[4.2.0]octa d ien es
Huw M. L. Davies,* J ulius J . Matasi, and Gulzar Ahmed
Department of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260-3000
Received December 1, 1995X
The rhodium(II)-catalyzed intramolecular reaction between vinyldiazomethanes and pyrroles leads
to a novel synthesis of fused tropanes. The reaction occurs by a stepwise 3 + 4 annulation
mechanism between a rhodium-stabilized vinylcarbenoid intermediate and the pyrrole rather than
by the typical tandem cyclopropanation/Cope rearrangement sequence. The outcome of the reaction
is very sensitive to the vinylcarbenoid structure. In particular, the presence of a 2-siloxy substituent
on the vinylcarbenoid strongly favors the formation of fused tropanes. In the absence of such
functionality, the formation of fused 7-azabicyclo[4.2.0]octadienes becomes the dominant reaction
pathway.
Sch em e 1
The tandem cyclopropanation/Cope rearrangement
between vinylcarbenoids and pyrroles1 is the basis of a
general method for the construction of the tropane
skeleton.2,3 This method has been applied to the syn-
thesis of (()-ferruginine1 and (-)-anhydroecgonine meth-
yl ester,4 as well as a number of novel tropanes with
potent CNS activity.5 As part of a continued program to
generate novel tropanes with selective neurochemical
activity, we required the availability of tropanes contain-
ing conformationally constrained functionality. The in-
tramolecular version of the reaction between vinylcar-
benoids and pyrroles appeared to be a very direct method
to prepare such compounds (eq 1). The development of
such a process is the focus of this paper. These studies
resulted in an efficient approach to the synthesis of
conformationally constrained tropanes. In addition, a
number of unusual transformations were observed that
illustrate some of the subtle factors that govern carbenoid
reactivity.6
Resu lts a n d Discu ssion
A series of vinylcarbenoid precursors were synthesized
according to Schemes 1 and 2. Treatment of Boc-
X Abstract published in Advance ACS Abstracts, March 1, 1996.
(1) Davies, H. M. L.; Saikali, E.; Young, W. B. J . Org. Chem. 1991,
56, 5696.
(2) (a) Lounasmaa, M. Alkaloids 1988, 33, 1. (b) Fodor, G.; Dhara-
nipragada, R. Nat. Prod. Rep. 1990, 7, 540. (c) Fodor, G.; Dharani-
pragada, R. Nat. Prod. Rep. 1986, 3, 181. (d) Fodor, G.; Dharanipraga-
da, R. Nat. Prod. Rep. 1985, 2, 221. (e) Fodor, G.; Dharanipragada, R.
Nat. Prod. Rep. 1984, 1, 231.
(3) For other approaches to the tropane skeleton, see (a) Willsta¨tter,
R. Ber. 1896, 29, 936. (b) Willsta¨tter, R. J ustus Liebigs Ann. Chem.
1903, 326, 23. (c) Robinson, R. J . Chem. Soc. 1917, 111, 762. (d)
Hayakawa, Y.; Baba, Y.; Makino, S.; Noyori, R. J . Am. Chem. Soc.
1978, 100, 1786. (e) Tufariello, J . J .; Trybuiski, E, J . J . Chem. Soc.,
Chem. Commun. 1973, 720. (f) Iida, H.; Watanabe, Y.; Kibayashi, C.
J . Org. Chem. 1985, 50, 1818. (g) Petersen, J . S.; Toteberg-Kaulen, S.;
Rapoport, H. J . Org. Chem. 1984, 49, 2948.
(4) Davies, H. M. L.; Huby, N. J . S. Tetrahedron Lett. 1992, 33, 6935.
(5) (a) Davies, H. M. L.; Saikali, E.; Huby, N. J . S.; Gilliatt, V. J .;
Matasi, J . J .; Sexton, T.; Childers, S. R. J . Med. Chem. 1994, 37, 1262.
(b) Bennett, B. A.; Wichems, C. H.; Hollingsworth, C. K.; Davies, H.
M. L.; Thornley, C.; Sexton, T.; Childers, S. R. J . Pharmacol. Exp. Ther.
1995, 272, 1176.
protected (hydroxymethyl)pyrroles 1a ,b with diketene
and p-acetamidobenzenesulfonyl azide (p-ABSA) resulted
in the formation of the diazoacetoacetates 2a ,b.7 Conver-
sion of 2a ,b to the vinyldiazomethanes 3a ,b was readily
achieved by reduction of the ketone in 2a ,b with sodium
borohydride followed by dehydration of the resulting
alcohol with phosphorus oxychloride in the presence of
triethylamine.8 The silyl-substituted vinylcarbene 4 was
prepared by silylation of 2a with TBDMS triflate in the
presence of triethylamine.9 The phenyl-substituted vi-
nyldiazomethanes 6a ,b were prepared in a two-step
(7) Baum, J . S.; Shook, D. A.; Davies, H. M. L.; Smith, H. D., Synth.
Commun. 1987, 17, 1709.
(8) Davies, H. M. L.; Hougland, P. W.; Cantrell, W. R., J r. Synth.
Commun. 1992, 22, 971.
(6) For a preliminary account of a portion of this work, see: Davies,
H. M. L.; Matasi, J . J . Tetrahedron Lett. 1994, 35, 5209.
(9) Ueda, Y.; Roberge, G.; Vinet, V. Can. J . Chem. 1984, 62, 2936.
0022-3263/96/1961-2305$12.00/0 © 1996 American Chemical Society

2306 J . Org. Chem., Vol. 61, No. 7, 1996
Davies et al.
Sch em e 2
tial side reactions occurring via zwitterionic intermedi-
ates.1 Decomposition of 3a with rhodium(II) octanoate
in refluxing benzene resulted in a very clean transforma-
tion as determined from the 1H NMR of the crude
reaction mixture, but the product was slightly unstable
to chromatography and was isolated in only 49% yield.
The spectral data of the product were inconsistent with
that of the expected tropane structure 19. Instead, the
product was assigned to be the fused 7-azabicyclo[4.2.0]-
1
octadiene 20, based on its distinctive H NMR spectrum
at 95 °C (to avoid broadened signals due to hindered
rotation), which included signals for the two vinyl
protons, the diastereotopic butyrolactone protons, and the
four azetidine protons. The signal for the methine proton
Ha is particularly distinctive because it displays coupling
to all the other azetidine protons as well as homoallylic
coupling to one of the butyrolactone methylene protons.
Further evidence to confirm this structural assignment
was obtained by treatment of 20 with TFA which resulted
in a 2 + 2 cycloreversion and the formation of the
phthalide (21) in 80% yield.
sequence by reaction of 1a ,b with 4-phenyl-3-butenoyl
chloride followed by a diazotransfer reaction on 5a ,b
using p-ABSA and DBU as base.7 The synthesis of the
methyl-substituted vinyldiazomethane 10 was achieved
in a related manner to the formation of 4 except that the
initial reaction was carried out with the propionylated
Meldrum’s acid (7) instead of diketene.10 The Z config-
uration of 10 was determined by NOE difference analysis
which showed a distinctive enhancement of the vinyl
methyl protons on irradiation of the silyl methyl protons.
The synthesis of the vinylcarbenoid precursors 13
and 15 containing a longer tether between the vinylcar-
benoid and pyrrole required a slightly modified procedure
because transfer of the Boc group from nitrogen to the
alcohol occurred using the general procedures described
in Scheme 1. The unprotected pyrrole 11 was first
acylated with 4-phenyl-3-butenoyl chloride to form 12
which was then readily Boc-protected and diazotized to
form 13 (Scheme 2). Similarly, 11 was acylated by
diketene and converted to the diazoacetoacetate 14. At
this stage N-Boc protection followed by silylation pro-
ceeded uneventfully to form the vinyldiazomethane 15.
Two additional vinyldiazomethane systems, 17 and 18,
were prepared, containing a tether at the 3-position of
the pyrrole ring. The synthesis of 17 and 18 required
the 3-(hydroxymethyl)pyrrole 1c as starting material and
followed the procedures described in Scheme 1.
A reasonable mechanism to explain the formation of
20 is shown in eq 3. The reaction is considered to proceed
by initial intramolecular capture of the rhodium carben-
oid 22 by the pyrrole, leading to a zwitterionic structure
23 rather than direct cyclopropanation.11 Presumably,
the steric constraints caused by the tether in 23 disfavor
cyclopropane formation as compared to the analogous
intermolecular system;1 thus, an alternative rearrange-
ment pathway occurs to form the unsaturated imine 24.
This type of rearrangement is known for furanocyclopro-
panes12 and has been observed on flash vacuum pyrolysis
of a pyrrolocyclopropane.13 The resulting double bond
geometry in 24 enables the system to undergo a ther-
mally allowed conrotatory 8π electrocyclization to form
the dihydroazocine 25. This type of electrocyclic ring
closure is well documented for the formation of cyclooc-
tatrienes.14 The resulting dihydroazocine 25 then un-
dergoes a well-precedented disrotatory 6π electrocycliza-
tion15 to form the 7-azabicyclo[4.2.0]octadiene 20.
(11) Many examples are known of intramolecular reactions of
carbenoids with aromatic systems proceeding through dipolar inter-
mediates. See: (a) Doyle, M. P.; Shanklin, M. S.; Pho, H. Q.; Maha-
patro, S. N. J . Org. Chem. 1988, 53, 1017. (b) Davies, H. M. L.; McAfee,
M. J .; Oldenburg, C. E. M. J . Org. Chem. 1989, 54, 930.
(12) Padwa, A.; Wisnieff, T. J .; Walsh, E. J . J . Org. Chem. 1989,
54, 299 and references cited therein.
(13) Tanny, S. R.; Grossman, J .; Fowler, F. W. J . Am. Chem. Soc.
1972, 94, 6495.
(14) (a) Marvell, E. N.; Seubert, J . J . Am. Chem. Soc. 1967, 89, 3377.
(b) Huisgen, R.; Dahmen, A.; Huber, H. Tetrahedron Lett. 1969, 1461.
(c) Huisgen, R.; Dahmen, A.; Huber, H. J . Am. Chem. Soc. 1967, 89,
7130. (d) Huisgen, R.; Dahmen, A.; Huber, H. Tetrahedron Lett. 1969,
1465.
The decomposition studies began with the vinyldiaz-
omethane 3a . On the basis of previous studies,1 rhod-
ium(II) octanoate as the catalyst and either benzene or
hexanes as the solvent were considered to be the opti-
mum reaction conditions. The use of a moderately
electron rich catalyst such as rhodium(II) octanoate and
nonpolar solvents tends to enhance the tandem cyclo-
propanation/Cope rearrangement over numerous poten-
(10) Oikawa, Y.; Sugano, K.; Yonemitsu, O. J . Org. Chem. 1978, 43,
2087.
(15) Paquette, L. A.; Kakihana, T.; Kelly, J . F. J . Org. Chem. 1971,
36, 435.

Reactions of Rh-Stabilized Vinylcarbenoids with Pyrroles
J . Org. Chem., Vol. 61, No. 7, 1996 2307
tropanes would become the favored reaction pathway.
The rhodium(II) octanoate/nonpolar solvent reaction
conditions were already optimized to minimize the oc-
currence of zwitterionic intermediates.1 Consequently,
the emphasis was placed on introduction of functionality
into the carbenoid that would limit stabilization of the
negative charge in the zwitterionic intermediates. On
the basis of these considerations, the decomposition of
the (1-siloxyvinyl)diazomethane 4 was examined. This
resulted in a major change in reaction outcome. Forma-
tion of the 7-azabicyclo[4.2.0]octadiene product was not
observed, and the tropane 30 crystallized from the
reaction mixture and was isolated in 63% yield.
The next series of experiments explored what struc-
tural features of the vinylcarbenoid and pyrrole would
be effective at altering the outcome of this chemistry so
that tropane products would be formed. Rhodium(II)
octanoate catalyzed decomposition of the 5-methylpyrrole
derivative 3b once again resulted in the clean formation
of a fused 7-azabicyclo[4.2.0]octadiene (26) as determined
by the 1H NMR of the crude reaction mixture. This
product, however, was moderately unstable to chromato-
graphic purification and was isolated in only 37% yield.
Confirmation of the structural assignment was achieved
by conversion of 26 to the aromatic system 27. The
observed regiochemistry is consistent with the mecha-
nism proposed in eq 3.
The synthesis of tropanes with control of stereochem-
istry at the 4-position is possible by using more elaborate
siloxy-substituted vinyldiazomethanes as substrates. Rhod-
ium(II) octanoate-catalyzed decomposition of the (Z)-(2-
methyl-1-siloxyvinyl)diazomethane 10 resulted in the
formation of the tropane 31 in 56% yield. The exo stereo-
chemistry for the methyl group in 31 was assigned based
on the characteristic lack of coupling in this system for
the protons at the endo and bridgehead positions.16,17
The effect of vinylcarbenoid substituents was also
explored as shown in eq 5. Rhodium(II) octanoate-
catalyzed decomposition of the styryldiazomethanes 6
still resulted in the exclusive formation of fused 7-
azabicyclo[4.2.0]octadienes. In the case of both 6a and
6b, a 2:1 mixture of isomeric 7-azabicyclo[4.2.0]octadienes,
28 and 29, were formed. These products showed greater
stability to chromatography and were isolable in higher
yields than was the case for 20 and 26. The isomers were
not separable by chromatography but were readily dis-
tinguished and assigned on the basis of coupling con-
stants for the azetidine protons and the shielding effect
of the phenyl ring.
Extension of this reaction to the higher homologue led
to intriguing results. Decomposition of the styryldiaz-
omethane 13 using the rhodium(II) octanoate/hexane
reaction conditions resulted in inefficient capture of the
carbenoid. On the assumption that a more electrophilic
carbenoid would likely lead to enhanced reactivity with
the pyrrole, the reaction was repeated using rhodium-
(II) N-(p-tert-butylphenylsulfonyl)prolinate (32)18 as the
catalyst (eq 8). Under these conditions the major prod-
ucts were two fused 7-azabicyclo[4.2.0]octadienes 33 and
34 (51% combined yield) along with two isomeric tropanes
35 and 36 (24% combined yield). The stereochemistry
for 35 and 36 was readily assigned based on the distinc-
tive coupling constants at the bridgehead.16,17
The formation of the exo isomer 31 and both endo (35)
and exo (36) isomers of the tropanes was unexpected
because the Cope rearrangement of divinylcyclopropanes
proceeds through a well defined boat transition state and
this would have led to the formation of only an endo
product.16,17 The exo product 36 was shown not to be
formed by isomerization of the endo product 35 because
35 was stable when subjected to the reaction conditions
of its formation. Therefore, it was concluded that the
formation of the exo products 31 and 36 in these reactions
must involve an intermediate capable of undergoing
equilibration at the vinyl group. A possible intermediate
(16) Davies, H. M. L.; Clark, T. J .; Smith, H. D. J . Org. Chem. 1991,
56, 3817.
(17) Davies, H. M. L. Tetrahedron 1993, 49, 5203.
(18) Davies, H. M. L.; Hutcheson, D. K. Tetrahedron Lett. 1993, 34,
7243.
As the formation of the fused 7-azabicyclo[4.2.0]-
octadienes was considered to arise from zwitterionic
intermediates, attempts were made to disfavor the oc-
currence of such intermediates so that the formation of

2308 J . Org. Chem., Vol. 61, No. 7, 1996
Davies et al.
The dramatic influence of the 1-siloxy group to enhance
tropane formation was further observed in the reaction
of the (1-siloxyvinyl)diazomethane 18. Rhodium(II) oc-
tanoate-catalyzed decomposition of 18 resulted in the
formation of the tropane 41 which crystallized out of the
reaction mixture on cooling. The formation of this
tropane, which would be expected to have significant ring
strain underscores the synthetic power of the reaction
between vinylcarbenoids and pyrroles to synthesize aza-
polycyclic compounds.
that may be capable of doing this would be the zwitte-
rionic structure 37 (eq 9). Such a conclusion implies that
in these intramolecular reactions, the formation of tro-
panes occurs from zwitterionic intermediates and does
not involve initial formation of cyclopropanes followed by
a Cope rearrangement.
The stereochemical studies demonstrate convincingly
that the tropanes are derived from zwitterionic interme-
diates. The presence of a siloxy group strongly favors
the formation of tropanes over the 7-azabicyclo[4.2.0]-
octadienes. Two possible factors can be proposed for this
controlling influence. First, the siloxy group would be
expected to decrease the ability of the vinyl group to
delocalize the negative charge in the zwitterionic inter-
mediate. However, it is rather surprising that the siloxy
group would have such a dramatic effect, such that
tropanes are the major product formed from (1-siloxyvi-
nyl)diazomethanes while products from zwitterionic in-
termediates dominate from unsubstituted vinyldiaz-
omethanes. Secondly, the presence of the siloxy group
increases the nucleophilicity of the vinyl group, which
may enhance attack at the allyl cation function in the
zwitterion. A third factor that could play a role is that
the presence of the siloxy group alters the conformation
of the vinylcarbenoid such that even if the reaction
proceeds through zwitterionic intermediates, the vinyl
group is still ideally positioned to allow rearrangement
to the tropane product to occur. In earlier studies, we
have shown that the effect of bulky substituents at the
central carbon of vinylcarbenoids causes a major change
in product outcome that can be explained by a change in
the preferred conformation of the rhodium-vinylcar-
benoid complex.19 If a similar effect is occurring here,
then conformation A should be preferred for the unsub-
stituted vinylcarbenoid while conformer B would be
favored for the (1-siloxyvinyl)cabenoid (Figure 1). The
vinyl group in conformer B is appropriately positioned
to enable rearrangement to the tropane to occur directly
from the zwitterionic intermediate that would be formed
without requiring any bond rotation. This is not the case
in conformer A, and so, ring opening to the trienimine
becomes the dominant pathway.
In the case of the higher homologue series, the use of
the siloxy substituent once again leads to the clean
formation of the tropane product. The decomposition of
the (1-siloxyvinyl)diazomethane 15 was not successful
when rhodium(II) octanoate was used as catalyst, but the
reaction proceeded smoothly when the more electrophilic
rhodium(II) N-(p-tert-butylphenylsulfonyl)prolinate (32)18
was employed as catalyst and the tropane 38 was
obtained in 32% yield after chromatography (eq 10).
The final series of experiments explored the effect of
having the vinyldiazomethane tethered to the 3-position
of pyrrole. Rhodium(II) octanoate-catalyzed decomposi-
tion of the unsubstituted vinyldiazomethane 17 resulted
in the formation of the trienimine 39 in moderate yield
(eq 11). This would be the expected product from the
zwitterionic intermediate 40, as ring opening of 40 would
form 39, which is incapable of undergoing an 8π-electro-
cyclization. Related structures have been formed in
intramolecular reactions of carbenoids with furans.12
(19) Davies, H. M. L.; Hu, B.; Saikali, E.; Bruzinski, P. R. J . Org.
Chem. 1994, 59, 4535.

Reactions of Rh-Stabilized Vinylcarbenoids with Pyrroles
J . Org. Chem., Vol. 61, No. 7, 1996 2309
for C9H15NO3: C, 60.90; H, 7.67; N, 7.10. Found: C, 60.79;
H, 7.61; N, 7.00.
1-(1,1-Dim eth yleth oxyca r bon yl)-2-(h yd r oxym eth yl)-5-
m eth ylp yr r ole (1b) was prepared from 5-methylpyrrole-2-
carboxaldehyde (20.00 g, 183.3 mmol) in 97% overall yield by
treatment with di-tert-butyl dicarbonate followed by NaBH4
reduction according to the procedure described for the syn-
thesis of 1a : IR (CDCl3) 3534, 3090, 2926, 1696, 1593 cm-1
;
F igu r e 1.
1H NMR (200 MHz, CDCl3) δ 6.05 (d, J ) 3.2 Hz, 1 H), 5.83
(d, J ) 3.2 Hz, 1 H), 4.57 (d, J ) 7.3 Hz, 2 H), 3.55 (t, J ) 7.3
Hz, 1 H), 2.36 (s, 3 H), 1.61 (s, 9 H); 13C NMR (50 MHz, CDCl3)
δ 151.1, 135.1, 132.3, 112.3 111.0, 84.6, 58.4, 28.0, 16.7. Anal.
Calcd for C11H17NO3: C, 62.54; H, 8.11; N, 6.63. Found: C,
62.42; H, 8.08; N, 6.52.
In summary, we have shown that the rhodium(II)-
catalyzed intramolecular reaction of vinylcarbenoids and
pyrroles leads to a novel synthesis of fused tropanes. The
stereochemical results of these studies are not consistent
with a tandem cyclopropanation/Cope rearrangement
mechanism. Instead the 3 + 4 annulation is considered
to occur in a stepwise mode by means of zwitterionic
intermediates that are capable of undergoing double bond
isomerization prior to ring closure. Also shown is the
delicate effect that a 1-siloxy substituent on the vinyl-
carbenoid system has on the outcome of this chemistry.
Further studies to elaborate these fused tropanes to
specific target molecules with selective interactions at the
central nervous system will be described in due course.
1-(1,1-Dim et h ylet h oxyca r b on yl)-3-(h yd r oxym et h yl)-
p yr r ole (1c) was prepared from pyrrole-3-carboxaldehyde
(4.25 g, 44.7 mmol) in 68% overall yield by treatment with
di-tert-butyl dicarbonate followed by sodium borohydride
reduction according to the procedure described for the syn-
thesis of 1a : IR (CDCl3) 3671, 3162, 2934, 2729, 1746, 1599
1
cm-1; H NMR (200 MHz, CDCl3) δ 7.18 (d, J ) 2.5 Hz, 2 H),
6.22 (t, J ) 2.5 Hz, 1 H), 4.50 (s, 2 H), 1.70 (br. s, 1 H), 1.56
(s, 9 H); 13C NMR (50 MHz, CDCl3) δ 148.7, 127.2, 120.5, 117.5,
111.5, 83.5, 58.0, 27.8; HRMS calcd for C10H15NO3 197.1052,
found 197.1051.
[1-(1,1-Dim et h ylet h oxyca r b on yl)-2-p yr r olyl]m et h yl
2-Dia zo-3-oxobu ta n oa te (2a ). A 50% solution of diketene
in acetone (12.79 g, 152.1 mmol) was added to a refluxing
solution of 1a (10.0 g, 50.7 mmol), p-acetamidobenzenesulfonyl
azide (15.65 g, 65.2 mmol), and sodium acetate (0.42 g, 5.2
mmol) in dry acetonitrile (60 mL) over a 30 min period.24 The
resulting mixture was cooled to rt and stirred for a further 7
h. Water was added, and the mixture was extracted with
ether. The ether extract was quickly washed with 15% KOH
solution, dried (MgSO4) and then the solvent was evaporated
under vacuum. Flash column chromatography on silica gel
using petroleum ether/ether (4:1) as eluting solvent gave 2a
as an oil (7.18 g, 46% yield): IR (CDCl3) 3162, 2933, 2873,
Exp er im en ta l Section
Gen er a l Meth od s. Ether, hexane, and THF were distilled
from sodium benzophenone ketyl. Dichloromethane was
distilled from calcium hydride. Benzene and toluene were
dried over molecular sieves (4 Å). Anhydrous dimethylforma-
mide (DMF) from Aldrich Chemical Co. was used without
further purification. 1H and 13C NMR spectra were recorded
on 200, 300, or 400 MHz NMR spectrometers. Column
chromatography was carried out on silica gel 60 (230-400
mesh). Thin layer chromatography (TLC) was performed on
Whatman (TLC) plates. Pyrrole-2-carboxaldehyde, diketene,
and Meldrum’s acid were bought from Aldrich Chemical Co.
Pyrrole-3-carboxaldehyde,20 5-methylpyrrole-2-carboxalde-
hyde,21 4-phenyl-3-butenoic acid,22 5-propionyl-Meldrum's acid
(7),10 and p-acetamidobenzenesulfonyl azide23 were prepared
by literature methods.
1-(1,1-Dim et h ylet h oxyca r b on yl)-2-(h yd r oxym et h yl)-
p yr r ole (1a ). DMAP (1.96 g, 16.8 mmol) and di-tert-butyl
dicarbonate (43.75 g, 200.1 mmol) were added to a solution of
pyrrole-2-carboxaldehyde (19.06 g, 200.1 mmol) in dry aceto-
nitrile (25 mL) under an argon atmosphere. The resulting
mixture was stirred at 25 °C for 24 h, and then the solvent
was removed at reduced pressure and the residue was purified
by column chromatography on silica gel using petroleum ether:
ether (4:1) as the eluting solvent to give 1-(tert-butoxycarbo-
nyl)pyrrole-2-carboxaldehyde (38.91 g, 99% yield).
2150, 1722, 1644, 1138 cm-1 1H NMR (200 MHz, CDCl3) δ
;
7.28 (dd, J ) 3.2, 1.8 Hz, 1 H), 6.30 (dd, J ) 3.2, 1.8 Hz, 1 H),
6.13 (t, J ) 3.2 Hz, 1 H), 5.42 (s, 2 H), 2.45 (s, 3 H), 1.54 (s, 9
H); 13C NMR (50 MHz, CDCl3) δ 190.2, 161.2, 148.7, 127.9,
123.2, 116.3, 110.2, 87.5, 84.3, 60.0, 28.2, 27.9, (CdN2 not
observed). Anal. Calcd for C14H17N3O5: C, 54.72; H, 5.58; N,
13.67. Found: C, 54.58; H, 5.62; N, 13.59.
[1-(1,1-Dim eth yleth oxyca r bon yl)-5-m eth yl-2-p yr r olyl]-
m eth yl 2-d ia zo-3-oxobu ta n oa te (2b) was prepared from 1b
(10.0 g, 47.4 mmol), in 43% yield by treatment with diketene
and p-acetamidobenzenesulfonyl azide according to the pro-
cedure described for the synthesis of 2a : IR (CDCl3) 3173,
2984, 2147, 1708, 1658, 1596 cm-1; 1H NMR (200 MHz, CDCl3)
δ 6.17 (d, J ) 3.3 Hz, 1 H), 5.87 (d, J ) 3.3 Hz, 1 H), 5.37 (s,
2 H), 2.45 (s, 3 H), 2.39 (s, 3 H), 1.57 (s, 9 H); 13C NMR (50
MHz, CDCl3) δ 190.2, 161.2, 149.6, 134.3, 127.8, 115.1, 110.6,
84.2, 61.0, 28.2, 27.9, 16.5, (CdN2 not observed). Anal. Calcd
for C15H19N3O5: C, 56.07; H, 5.96; N, 13.08. Found: C, 56.17;
H, 6.03; N, 12.99.
[1-(1,1-Dim et h ylet h oxyca r b on yl)-2-p yr r olyl]m et h yl
2-Dia zo-3-bu ten oa te (3a ). NaBH4 (0.80 g, 21.1 mmol) was
added over 30 min to a solution of 2a (2.16 g, 7.0 mmol) in
methanol (50 mL) at 0 °C under argon. The mixture was
stirred for a further 1 h, and then ice cold water was added.
The mixture was then extracted with CH2Cl2 (3 × 50 mL), the
extract was washed with NaHCO3 and brine, dried (MgSO4),
and the solvent was then evaporated to give the alcohol. The
alcohol was used in the next step without purification. To a
solution of the alcohol and triethylamine (2.83 g, 28.0 mmol)
in dry CH2Cl2 (60 mL) at 0 °C under argon was added POCl3
(1.61 g, 10.6 mmol) in dry CH2Cl2 (2 mL) over a period of 30
min. The resulting mixture was left to stir at 0 °C overnight.
The solution was then washed with ice cold water until there
was no color in the aqueous layer, washed with cold brine, and
dried (Na2SO4), and then the solvent was evaporated at a
To a solution of aldehyde from above (38.91 g, 199.4 mmol)
in methanol (250 mL) at 0 °C was added NaBH4 (7.55 g, 199.4
mmol) in portions under argon. The mixture was stirred for
a further 1 h before quenching with cold water. The mixture
was then extracted with ether and the ether extract was
washed with saturated aqueous sodium bicarbonate and then
with saturated aqueous sodium chloride. The organic phase
was then dried (MgSO4), and the solvent was removed under
reduced pressure to give 1a as an oil (35.53 g, 90% yield) and
used without further purification: IR (CDCl3) 3671, 3162,
2934, 2729, 1746, 1599 cm-1 1H NMR (200 MHz, CDCl3) δ
;
7.16 (dd, J ) 3.4, 1.7 Hz, 1 H), 6.17 (dd, J ) 3.4, 1.7 Hz, 1 H),
6.09 (t, J ) 3.4 Hz, 1 H), 4.64 (d, J ) 7.3 Hz, 2 H), 3.58 (t, J
) 7.3 Hz, 1 H), 1.61 (s, 9 H); 13C NMR (50 MHz, CDCl3) δ
149.9, 134.7, 121.6, 113.3, 110.2, 84.3, 57.5, 27.8. Anal. Calcd
(20) Bray, B. L.; Mathias, P. H.; Naef, R.; Solas, D. R.; Tidwell, T.
T.; Artis, D. R.; Muchewski, J . M. J . Org. Chem. 1990, 55, 6317.
(21) Silverstein, R. M.; Ryskiewicz, E. E.; Willard, C. Organic
Syntheses; Wiley: New York, 1963; Coll. Vol. IV, p 831.
(22) Hoye, T. R.; Richardson, W. S. J . Org. Chem. 1989, 54, 688.
(23) Davies, H. M. L.; Cantrell, W. R., J r.; Romines, K. R.; Baum,
J . S. Org. Synth. 1991, 70, 93.
(24) Doyle, M. P.; Bagheri, V.; Wandless, T. J .; Harn, N. K.; Brinker,
D. A.; Eagle, C. T.; Loh, K-L. J . Am. Chem. Soc. 1990, 112, 1906.

2310 J . Org. Chem., Vol. 61, No. 7, 1996
Davies et al.
reduced pressure. The residue was purified by column chro-
matography on silica gel using pentane:ether (19:1) as eluting
solvent to give 3a as an oil (1.60 g, 78% yield): IR (neat) 2981,
2088, 1748, 1743, 1716, 1616 cm-1; 1H NMR (200 MHz, CDCl3)
δ 7.29 (dd, J ) 3.3, 1.9 Hz, 1 H), 6.30 (m, 1 H), 6.12 (m, 1 H),
6.12 (dd, J ) 17.4, 11.0 Hz, 1 H), 5.39 (s, 2 H), 5.09 (d, J )
11.0 Hz, 1 H), 4.83 (d, J ) 17.4 Hz, 1 H), 1.57 (s, 9 H). Due to
lack of stability, elemental analysis was not attempted on 3a .
[1-(1,1-Dim eth yleth oxyca r bon yl)-5-m eth yl-2-p yr r olyl]-
m eth yl 2-d ia zo-3-bu ten oa te (3b) was prepared from 2b
(2.00 g, 6.2mmol) in 43% yield by treatment with NaBH4
followed by POCl3 according to the procedure described for the
synthesis of 3a : IR (neat) 3089, 2982, 2926, 2088, 1744, 1699,
1621, 1542, 1458, 1390, 1378 cm-1; 1H NMR (200 MHz, CDCl3)
δ 6.18 (dd, J ) 17.4, 11.0 Hz, 1 H), 6.16 (m, 1 H), 5.87 (m, 1
H), 5.36 (s, 2 H), 5.11 (d, J ) 11.0 Hz, 1 H), 4.85 (d, J ) 17.4
Hz, 1 H), 2.42 (s, 3 H), 1.59 (s, 9 H). Due to lack of stability,
elemental analysis was not attempted on 3b.
[1-(1,1-Dim et h ylet h oxyca r b on yl)-2-p yr r olyl]m et h yl
2-D i a z o -3-[(1 ,1-d i m e t h y l e t h y l )d i m e t h y l s i l o x y ]-3-
bu ten oa te (4). Triethylamine (2 mL, 14.3 mmol) was added
to a stirring solution of 2a (3.1 g, 10.1 mmol) in CH2Cl2 (26
mL) at 0 °C under argon. tert-Butyldimethylsilyl trifluo-
romethanesulfonate (2.8 mL, 12.2 mmol) was added after 5
min, and the mixture was further stirred for 30 min at 0 °C.
The reaction mixture was diluted with hexanes (100 mL), and
the organic phase was washed with dilute aqueous NaHCO3
(100 mL) and brine (100 mL). The organic layer was dried
(Na2SO4), and the solvent was removed under reduced pres-
sure to yield 4 as a yellow oil which was used without further
purification: IR (neat) 2955, 2928, 2858, 2107, 1748, 1710,
1612, 1476 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.34 (m, 1 H),
6.32 (m, 1 H), 6.17 (t, J ) 3.2 Hz, 1 H), 5.43 (s, 2 H), 5.04 (d,
J ) 2.1 Hz, 1 H), 4.27 (d, J ) 2 Hz, 1 H), 1.62 (s, 9 H), 0.94 (s,
9 H), 0.25 (s, 6 H). Due to lack of stability, elemental analysis
was not attempted on 4.
resulting mixture was washed with saturated aqueous NH4-
Cl and dried (MgSO4). The solvent was removed under
reduced pressure, and the residue was chromatographed on
silica gel using petroleum ether:ether (9:1 to 8:2) as solvent
gradient to give 6a as a red oil (3.35 g, 60% yield): IR (CCl4)
2979, 2081, 1742, 1716, 1699, 1686 cm-1; 1H NMR (200 MHz,
CDCl3) δ 7.12-7.37 (m, 6 H), 6.47 (d, J ) 15.6 Hz, 1 H), 6.31
(brs, 1 H), 6.18 (d, J ) 15.6 Hz, 1 H), 6.15 (brs, 1 H), 5.44 (s,
2 H), 1.58 (s, 9 H). Due to lack of stability, elemental analysis
was not attempted on 6a .
[1-(1,1-Dim eth yleth oxyca r bon yl)-5-m eth yl-2-p yr r olyl]-
m eth yl 2-d ia zo-4-p h en yl-3(E)-bu ten oa te (6b) was prepared
from 5b (4.57 g, 12.9 mmol) in 29% yield by treatment with
DBU and p-acetamidobenzenesulfonyl azide according to the
procedure described for the synthesis of 6a : IR (CCl4) 2961,
2081, 1743, 1701, 1450 cm-1 1H NMR (200 MHz, CDCl3) δ
;
7.10-7.36 (m, 5 H), 6.46 (d, J ) 16.3 Hz, 1 H), 6.17 (d, J ) 3.2
Hz, 1 H), 6.16 (d, J ) 16.3 Hz, 1 H), 5.88 (d, J ) 3.2 Hz, 1 H),
5.38 (s, 2 H), 2.41 (s, 3 H), 1.58 (s, 9 H). Due to lack of stability,
elemental analysis was not attempted on 6b.
[1-(1,1-Dim et h ylet h oxyca r b on yl)-2-p yr r olyl]m et h yl
3-Oxop en ta n oa te (8). A solution of 1a (5.18 g, 26.2 mmol),
7 (5.26 g, 26.2 mmol), and pyridine (2.2 mL, 27.2 mmol) in
benzene (70 mL) was heated at 65 °C for 14 h under argon.
The mixture was then cooled to rt and diluted with ether (50
mL), and the resulting mixture was washed with saturated
aqueous NH4Cl (100 mL) and dried (Na2SO4). The solvent was
removed under pressure, and the residue was purified by
chromatography on silica gel with 1:4 ether:hexanes as
solvents to yield 8 as an oil (6.45 g, 83% yield): Rf ) 0.55 in
1:1 ether:pentane; IR (neat) 2977, 2939, 1743, 1710, 1650, 1623
1
cm-1; H NMR (300 MHz, CDCl3) δ 7.20 (d, J ) 1.8 Hz, 1 H),
6.22 (brs, 1 H), 6.05 (m, 1 H), 5.24 (s, 2 H), 3.36 (s, 3 H), 2.47
(q, J ) 7.2 Hz, 2 H), 1.50 (s, 9 H), 0.95 (t, J ) 7.1 Hz, 3 H); 13
C
NMR (75 MHz, CDCl3) δ 203.1, 167.0, 148.8, 128.8, 122.8,
115.8, 110.1, 83.9, 59.9, 48.6, 35.6, 27.4, 7.0. Anal. Calcd for
C15H21NO5: C, 61.00; H, 7.17; N, 4.74. Found: C, 61.10; H,
7.21; N, 4.81.
[1-(1,1-Dim et h ylet h oxyca r b on yl)-2-p yr r olyl]m et h yl
4-P h en yl-3(E)-bu ten oa te (5a ). A solution of 4-phenyl-3-
butenoyl chloride (4.38 g, 24.3 mmol) in dry CH2Cl2 (50 mL)
was added to stirred solution of 1a (5.00 g, 25.4 mmol) and
pyridine (2.16 g, 27.3 mmol) in CH2Cl2 (30 mL) at 0 °C, under
argon. The ice bath was then removed, and the mixture was
stirred at rt overnight. The mixture was then washed with a
saturated aqueous NH4Cl and dried (MgSO4), and the solvent
was removed at reduced pressure. The residue was purified
by column chromatography on silica gel using petroleum ether/
ether (9:1) as eluting solvent to give 5a as an oil (5.60 g, 68%
yield): IR (neat) 3032, 2972, 2929, 1743, 1504, 1411, 1373,
[1-(1,1-Dim et h ylet h oxyca r b on yl)-2-p yr r olyl]m et h yl
2-Dia zo-3-oxop en ta n oa te (9). Triethylamine (3.3 mL, 23.7
mmol) was added to a stirred solution of p-acetamidobenze-
nesulfonyl azide (5.5 g, 22.9 mmol) and 8 (6.45 g, 21.9 mmol)
in acetonitrile (50 mL) at rt under argon. The reaction mixture
was stirred overnight at room temperature and then diluted
with 1:2 ether:pentane (100 mL). The resulting precipitate
was filtered and rinsed with 1:2 ether:pentane (50 mL). The
filtrate was concentrated under reduced pressure, and the
residue was chromatographed on silica gel with 1:3 ether:
hexanes as solvent to yield 9 as an oil (6.32 g, 90% yield): Rf
) 0.81 in ether:pentane; IR (neat) 2972, 2939, 2123, 1743,
1
1352 cm-1; H NMR (200 MHz, CDCl3) δ 7.25-7.50 (m, 6H),
6.58 (d, J ) 16.0 Hz, 1 H), 6.39 (dt, J ) 16.0, 6.7 Hz, 1 H),
overlapping broad doublet at δ 6.39 (1 H), 6.23 (t, J ) 3.3 Hz,
1
1716, 1650, 1313 cm-1; H NMR (400 MHz, CDCl3) δ 7.26 (d,
1 H), 5.40 (s, 2 H), 3.36 (d, J ) 6.7 Hz, 2 H), 1.65 (s, 9 H); 13
C
J ) 2 Hz, 1 H), 6.29 (brs, 1 H), 6.11 (t, J ) 3.4 Hz, 1 H), 5.31
(s, 2 H), 2.54 (q, J ) 6.8 Hz, 2 H), 1.56 (s, 9 H), 1.03 (t, J ) 6.8
Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 194.2, 161.8, 149.3,
128.5, 127.7, 116.7, 110.7, 84.6, 60.2, 33.9, 28.1, 8.3 (CdN2 not
observed). Anal. Calcd for C15H19N3O5: C, 56.07; H, 5.96; N,
13.08. Found: C, 56.12; H, 6.00; N, 13.01.
NMR (50 MHz, CDCl3) δ 171.1, 148.8, 136.9, 133.6, 128.6,
128.5, 127.5, 126.3, 122.9, 121.7, 115.7, 110.2, 84.1, 59.9, 38.4,
27.9. Anal. Calcd for C20H23NO4: C, 70.36; H, 6.79; N, 4.10.
Found: C, 70.25; H, 6.80; N, 4.09.
[1-(1,1-Dim eth yleth oxyca r bon yl)-5-m eth yl-2-p yr r olyl]-
m eth yl 4-p h en yl-3(E)-bu ten oa te (5b) was prepared from
1b (5.93 g, 28.1 mmol) in 52% yield by treatment with
4-phenyl-3-butenoyl chloride and pyridine according to the
procedure described for the synthesis of 5a : IR (neat) 3065,
3027, 2983, 2834, 1743, 1667, 1602, 1537, 1450 cm-1; 1H NMR
(200 MHz, CDCl3) δ 7.25-7.50 (m, 6 H), 6.57 (d, J ) 15.7 Hz,
1 H), 6.36 (dt, J ) 15.7, 6.6 Hz, 1 H), 6.26 (d, J ) 3.3 Hz, 1 H),
5.96 (d, J ) 3.3 Hz, 1 H), 5.34 (s, 2 H), 3.34 (d, J ) 6.6 Hz, 2
H), 2.50 (s, 2 H), 1.65 (s, 9 H); 13C NMR (50 MHz, CDCl3) δ
171.2, 149.7, 136.8, 134.2, 133.4, 128.5, 128.3, 127.5, 126.3,
121.8, 114.6, 110.6, 84.0, 60.8, 38.5, 27.9, 16.4. Anal. Calcd
for C21H25NO4: C, 70.96; H, 7.09; N, 3.94. Found: C, 70.68;
H, 7.24; N, 3.77.
[1-(1,1-Dim et h ylet h oxyca r b on yl)-2-p yr r olyl]m et h yl
2-Dia zo-4-p h en yl-3(E)-bu ten oa te (6a ). DBU (2.79 g, 18.3
mmol) was added dropwise to a solution of 5a (5.21 g, 15.3
mmol) and p-acetamidobenzenesulfonyl azide (4.39 g, 18.3
mmol) in acetonitrile (100 mL) at 0 °C under argon. The
mixture was stirred overnight, and then ether was added. The
[1-(1,1-Dim eth yleth oxycar bon yl)-2-pyr r olyl]m eth yl 2-di-
a zo-3-[(1,1-d im e t h yle t h yl)d im e t h ylsiloxy]-3-p e n t e n -
oa te (10) was prepared from 9 (1.05 g, 3.27 mmol) by
treatment with tert-butyldimethylsilyl trifluoromethane-
sulfonate and triethylamine according to the procedure de-
scribed for the synthesis of 5: IR (neat) 2960, 2934, 2862, 2091,
1744, 1708, 1662 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.29 (m,
1 H), 6.27 (brs, 1 H), 6.13 (m, 1 H), 5.37 (s, 1 H), 5.27 (q, J )
8.0 Hz, 1 H), 1.65 (d, J ) 8.0 Hz, 3 H), 1.58 (s, 9 H), 0.94 (s, 9
H), 0.13 (s, 6 H). NOE data: irradiation at δ 0.12, enhance-
ments at δ 0.94 (1.4%) and 1.65 (0.5%); irradiation at δ 1.65,
enhancements at δ 0.12 (1.4%), 0.94 (0.8%), and 5.27 (3.6%).
Due to lack of stability, elemental analysis was not attempted
on 10.
2-(2-P yr r olyl)et h yl 4-p h en yl-3(E)-b u t en oa t e (12) was
prepared from 11 (1.95 g, 17.6 mmol) in 46% yield by treatment
with 4-phenyl-3-butenoyl chloride and pyridine according to
the procedure described for the synthesis of 5a : IR (neat) 3386,
3027, 2961, 2912, 1732, 1650, 1580, 1450, 1270, 1168 cm-1
;

Reactions of Rh-Stabilized Vinylcarbenoids with Pyrroles
J . Org. Chem., Vol. 61, No. 7, 1996 2311
1H NMR (200 MHz, CDCl3) δ 8.20 (brs, 1 H), 7.20-7.45 (m, 5
H), 6.53 (d, J ) 17 Hz, 1 H), 6.53 (m, 1 H), 6.30 (dt, J ) 17,
6.4 Hz, 1 H), 6.22 (m, 1 H), 5.98 (m, 1 H), 4.33 (t, J ) 6.4 Hz,
2 H), 3.28 (d, J ) 7.2 Hz, 2 H), 2.95 (t, J ) 6.4 Hz, 2 H); 13C
NMR (50 MHz, CDCl3) δ 171.3, 136.6, 133.8, 128.6, 128.1,
127.7, 126.3, 121.5, 117.1, 108.3, 106.4, 64.6, 38.5, 27.2; MS
(M + 1, 256.2); HRMS calcd for C16H18NO2 256.1338, found
256.1329.
2-[1-(1,1-Dim eth yleth oxycar bon yl)-2-pyr r olyl]eth yl 2-di-
a zo-4-p h en yl-3(E)-bu ten oa te (13) was prepared from 12
(2.00 g, 7.8 mmol) in 36% overall yield by treatment with di-
tert-butyl dicarbonate according to the procedure described for
the synthesis of 1a followed by treatment with DBU and
p-acetamidobenzenesulfonyl azide according to the procedure
described for the synthesis of 6a . The product was purified
by column chromatography on silica gel using petroleum ether:
ether (9:1) as eluting solvent: IR (neat) 3059, 3021, 2989, 2945,
2086, 1743, 1705, 1629, 1602, 1503, 1450 cm-1; 1H NMR (200
MHz, CDCl3) δ 7.15-7.45 (m, 6 H), 6.48 (d, J ) 16.3 Hz, 1 H),
6.19 (d, J ) 16.3 Hz, 1 H), 6.12 (t, J ) 3.3 Hz, 1 H), 6.07 (m,
1 H), 4.51 (t, J ) 6.7 Hz, 2 H), 3.29 (t, J ) 6.7 Hz, 2 H), 1.61
(s, 9 H). Due to lack of stability, elemental analysis was not
attempted on 13.
148.3, 121.2, 120.7, 119.8, 112.2, 84.0, 60.2, 28.1, 27.8, (CdN2
not observed). Anal. Calcd for C14H17NO5: C, 54.72; H, 5.58;
N, 13.67. Found: C, 54.80; H, 5.63; N, 13.59.
[1-(1,1-Dim eth yleth oxycar bon yl)-3-pyr r olyl]m eth yl 2-di-
a zo-3-bu ten oa te (17) was prepared from 16 (1.05 g, 3.42
mmol) in 37% yield by treatment with sodium borohydride
followed by phosphorus oxychloride according to the procedure
described for the synthesis of 3a : IR (neat) 2983, 2933, 2087,
1748, 1710, 1623 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.23 (brs,
1 H), 7.16 (brs, 1 H), 6.21 (d, J ) 1.77 Hz, 1 H), 6.13 (dd, J )
11.1, 17.4 Hz, 1 H), 5.06 (m, 3 H), 4.81 (d, J ) 17.4 Hz, 1 H),
1.55 (s, 9 H). Due to lack of stability, elemental analysis was
not attempted on 17.
[1-(1,1-Dim eth yleth oxycar bon yl)-3-pyr r olyl]m eth yl 2-di-
azo-3-[(1,1-dim eth yleth yl)dim eth ylsiloxy]-3-bu ten oate (18)
was prepared from 16 (1.0 g, 3.25 mmol) by treatment with
tert-butyldimethylsilyl trifluoromethanesulfonate and triethy-
lamine according to the procedure described for the synthesis
of 4: IR (neat) 2955, 2928, 2858, 2102, 1754, 1716, 1612 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.20 (brs, 1 H), 7.13 (brs, 1 H),
6.17 (brs, 1 H), 5.02 (brs, 2 H), 4.95 (brs, 1 H), 4.17 (brs, 1 H),
1.51 (s, 9 H), 0.84 (s, 9 H), 0.15 (s, 6 H); 13C NMR (75 MHz,
CDCl3) δ 164.3, 148.6, 140.8, 122.0, 120.6, 119.5, 112.3, 90.3,
83.6, 59.5, 27.5, 25.3, 17.7, -5.2, (CdN2 not observed). Due
to lack of stability, elemental analysis was not attempted on
18.
2-[1-(1,1-Dim eth yleth oxycar bon yl)-2-pyr r olyl]eth yl 2-Di-
a zo-3-oxobu ta n oa te (14). 2-[2-Hydroxyethyl]pyrrole (11)
(3.0 g, 27 mmol) was dissolved in acetonitrile (50 mL) under
argon. Diketene (3.4 g, 40.4 mmol) in acetonitrile (50 mL) and
pyridine (1 mL) were added, and after stirring for a further
15 min, the mixture was heated under reflux for 4 h. The
solvent was removed under reduced pressure, and the residue
was purified by columnn chromatography on silica gel using
1:2 ether:pentane as solvent to give 2-(2-pyrrolyl)ethyl 3-ox-
obutanoate in 65% yield: Rf ) 0.13 in 1:4 ethyl acetate:
pentane; IR (neat): 3385, 3096, 2962, 2922, 1737, 1712, 1649,
1571 cm-1; 1H NMR (200 MHz, CDCl3) δ 8.71 (brs, 1 H), 6.73
(dd, J ) 2.6, 4.2 Hz, 1 H), 6.12 (dd, J ) 2.8, 5.7 Hz, 1 H), 5.96
(brs, 1 H), 4.35 (t, J ) 6.1 Hz, 2 H), 3.52 (s, 2 H), 2.97 (t, J )
6.1 Hz, 2 H), 2.26 (s, 3 H); 13C NMR (50 MHz, CDCl3) δ 201.4,
166.6, 127.6, 117.0, 107.7, 105.8, 64.9, 49.6, 30.0, 26.7.
Compound 14 was prepared from 2-(2-pyrrolyl)ethyl 3-ox-
obutanoate (1.75 g, 8.97 mmol) in 66% overall yield by
treatment with triethylamine and p-acetamidobenzenesulfonyl
azide according to the procedure described for the synthesis
of 9 followed by treatment with di-tert-butyl dicarbonate
according to the procedure described for the synthesis of 1a :
Rf ) 0.69 in 1:1 ether:pentane; IR (neat) 2978, 2934, 2871,
2140, 1738, 1660, 1493, 1478 cm-1; 1H NMR (200 MHz, CDCl3)
δ 7.19 (dd, J ) 1.8, 3.3 Hz, 1 H), 6.07 (t, J ) 3.3 Hz, 1 H), 6.00
(m, 1 H), 4.46 (t, J ) 6.6 Hz, 2 H), 3.25 (t, J ) 6.6 Hz, 2 H),
2.44 (s, 3 H), 1.58 (s, 9 H); 13C NMR (50 MHz, CDCl3) δ 189.7,
160.9, 149.0, 130.3, 121.3, 112.8, 109.8, 83.5, 63.8, 28.1, 27.9,
27.7, (CdN2 not observed). Anal. Calcd for C15H19N3O5: C,
56.07; H, 5.96; N, 13.08. Found: C, 56.17; H, 6.02; N, 13.10.
2-[1-(1,1-Dim eth yleth oxycar bon yl)-2-pyr r olyl]eth yl 2-di-
azo-3-[(1,1-dim eth yleth yl)dim eth ylsiloxy]-3-bu ten oate (15)
was prepared from 14 (0.50 g, 1.55 mmol) by treatment with
tert-butyldimethylsilyl trifluoromethanesulfonate and triethy-
lamine according to the procedure described for the synthesis
of 3: IR (neat) 2965, 2929, 2851, 2100, 1745, 1710, 1611, 1327
cis-1,1-Dim eth yleth yl 1,5a,7,7a-Tetr ah ydr o-1-oxoisoben -
zofu r o[5,4-b]a zete-6(3H)-ca r boxyla te (20). A solution of
3a (2.00 g, 6.9 mmol) in hexane (100 mL) was added dropwise
to a refluxing solution of rhodium(II) octanoate (0.054 g, 0.07
mmol) in hexane (100 mL) under argon. The resulting solution
was refluxed for a further 1 h, and the solvent was removed
and the residue was purified by column chromatography on
silica gel using ether/petroluem ether (4:1) as solvent followed
by recrystallization from petroleum ether/ether mixture to give
20 as colorless crystals (0.87 g, 49% yield): mp 112-114 °C;
IR (CH2Cl2) 3054, 2979, 1752, 1695, 1599, 1473 cm-1; 1H NMR
(200 MHz, DMSO-d6, 95 °C) δ 6.35 (d, J ) 9.8 Hz, 1 H), 6.26
(dd, J ) 9.8, 4.2 Hz, 1 H), 5.16 (dd, J ) 9.8, 4.3 Hz, 1 H), 4.80-
5.05 (m, 2 H), 4.31 (t, J ) 8.1 Hz, 1 H), 3.85 (dd, J ) 8.1, 4.8
Hz, 1 H), 3.52 (m, 1 H), 1.40 (s, 9 H). Anal. Calcd for C14H17
-
NO4: C, 63.87; H, 6.51; N, 5.32. Found: C, 63.94; H, 6.48; N,
5.27.
P h th a lid e 21. A solution of TFA (0.89 mL, 11.6 mmol) in
CH2Cl2 (2 mL) was added dropwise to a stirred solution of
compound 20 (0.31 g, 1.2 mmol) in CH2Cl2 (20 mL) at room
temperature under argon. The resulting mixture was stirred
for a further 30 min, and then the solvent was evaporated
under reduced pressure. Aqueous NH4Cl was added to the
residue, and the mixture was extracted with CH2Cl2. The
organic phase was dried (Na2SO4), and the solvent was
removed under reduced presure. Purification by recrystalli-
zation from ether:petroleum ether gave 21 as a colorless solid
1
(0.151 g, 80%), mp 73-75 °C, lit25a mp 73 °C. The H and 13C
NMR spectra of 21 matched the literature data.25b
cis-1,1-Dim eth yleth yl 1,5a ,7,7a -tetr a h yd r o-5a -m eth yl-
1-oxoisoben zofu r o[5,4-b]azete-6(3H)-car boxylate (26) was
prepared from 3b (0.82 g, 2.7 mmol) in 37% yield by treatment
with rhodium(II) octanoate in hexane according to the proce-
dure described for the synthesis of 20: mp 106-109 °C; IR
1
cm-1; H NMR (300 MHz, CDCl3) δ 7.17 (dd, J ) 1.8, 3.1 Hz,
1
(CH2Cl2) 3070, 2933, 1753, 1691, 1597, 1474 cm-1; H NMR
1 H), 6.05 (t, J ) 3.3 Hz, 1 H), 5.98 (brs, 1 H), 4.39 (t, J ) 6.6
Hz, 2 H), 4.19 (d, J ) 2.0 Hz, 1 H), 3.20 (t, J ) 6.6 Hz, 2 H),
1.55 (s, 9 H), 0.87 (s, 9 H), 0.17 (s, 6 H); 13C NMR (50 MHz,
CDCl3) δ 164.0, 149.3, 140.7, 130.8, 121.3, 112.8, 110.0, 90.3,
83.6, 63.5, 27.9, 25.5, 18.0, 14.0, -3.0, -4.8, (CdN2 not
observed). Due to lack of stability, elemental analysis was not
attempted on 15.
(200 MHz, DMSO-d6, 95 °C) δ 6.28 (d, J ) 9.9 Hz, 1 H), 6.18
(d, J ) 9.9 Hz, 1 H), 4.79-5.02 (m, 2 H), 4.16 (t, J ) 8.1 Hz,
1 H), 3.72 (dd, J ) 8.1, 5.6 Hz, 1 H), 3.21 (m, 1 H), 1.60 (s, 3
H), 1.40 (s, 9 H). Anal. Calcd for C15H19NO4: C, 64.97; H,
6.91; N, 5.05. Found: C, 65.03; H, 6.95; N, 5.04.
6-Meth ylp h th a lid e 27 was prepared from 26 (0.78 g, 2.8
mmol) in 82% yield by treatment with TFA according to the
procedure described for the synthesis of 21: mp 88-91 °C from
ether; IR (neat) 3043, 2923, 1770, 1596, 1504, 1460, 1167, 1063,
1009 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.60 (s, 1 H), 7.43 (d,
J ) 7.9 Hz, 1 H), 7.32 (d, J ) 7.9 Hz, 1 H), 5.20 (s, 2 H), 2.38
[1-(1,1-Dim eth yleth oxycar bon yl)-3-pyr r olyl]m eth yl 2-di-
a zo-3-oxobu ta n oa te (16) was prepared from 1c (5.0 g, 27.6
mmol) in 58% yield by treatment with diketene and p-
acetamidobenzenesulfonyl azide according to the procedure
described for the synthesis of 2a : IR (CH2Cl2) 3150, 2984,
2937, 2143, 1712, 1654, 1590, 1458 cm-1; 1H NMR (200 MHz,
CDCl3) δ 7.28 (dd, J ) 2.4, 1.7 Hz, 1 H), 7.19 (dd, J ) 3.2, 2.4
Hz, 1 H), 6.22 (dd, J ) 3.2, 1.7 Hz, 1 H), 5.10 (s, 2 H), 2.45 (s,
3 H), 1.57 (s, 9 H); 13C NMR (50 MHz, CDCl3) δ 189.9, 161.2,
(25) (a) Sunko, D. E. Arkiv Kem. 1955, 27, 183 (Chem. Abstr. 50,
11985b). (b) The Aldrich Library of 13C and 1H FT NMR Spectra, 1st
ed.; 1993; Vol. II, p 1306.

2312 J . Org. Chem., Vol. 61, No. 7, 1996
Davies et al.
(s, 3 H); 13C NMR (50 MHz, CDCl3) δ 170.9, 143.7, 139.0, 135.0,
125.6, 125.3, 121.6, 69.4, 21.1. Anal. Calcd for C9H8O2: C,
72.96; H, 5.44. Found: C, 73.02; H, 5.52.
1,1-Dim eth yleth yl 1,3,4,6a r,8,8a r-Hexa h yd r o-1-oxo-8â-
p h en yl-7H-2-ben zop yr a n o[7,8-b]a zete-7-ca r boxyla te (33),
1,1-Dim eth yleth yl 1,3,4,6a r,8,8a r-Hexa h yd r o-1-oxo-8r-
p h en yl-7H-2-ben zop yr a n o[7,8-b]a zete-7-ca r boxyla te (34),
1,1-Dim et h ylet h yl 3,4,7,8-Tet r a h yd r o-1-oxo-8â-p h en yl-
1H-cycloh ep ta [c]p yr a n -4a r,7r-im in e-10-ca r boxyla te (35)
a n d 1,1-Dim eth yleth yl 3,4,7,8-Tetr a h yd r o-1-oxo-8r-p h en -
yl-1H -cycloh ep t a [c]p yr a n -4a r,7r-im in e-10-ca r b oxyla t e
(36). 13 (0.57 g, 1.5 mmol) was decomposed by treatment with
32 in hexane according to the procedure described for the
synthesis of 20. The solvent was removed and purification
achieved by column chromatography on silica gel using ether/
petroleum ether (3.5:1.5 to 4:1) to give the following compounds
in order of elution from the column. Com p ou n d 35: 0.09 g
(16% yield), mp 158-159 °C; IR (CH2Cl2) 3029, 2980, 1805,
1715, 1620, 1603, 1584, 1496 cm-1; 1H NMR (200 MHz, CDCl3)
δ 7.24-7.36 (m, 3 H), 7.03-7.10 (m, 2 H), 7.02 (dd, J ) 2.8,
1.2 Hz, 1 H), 6.42 (d, J ) 6.1 Hz, 1 H), 5.51 (dd, J ) 6.1, 2.8
Hz, 1 H), 4.92 (ddd, J ) 5.3, 2.8, 1.2 Hz, 1 H), 4.60 (m, 1 H),
4.32 (ddd, J ) 14.6, 9.6, 2.9 Hz, 1 H), 4.22 (dd, J ) 5.3, 2.8
Hz, 1 H), 3.25 (ddd, J ) 16.5, 9.6, 3.8 Hz, 1 H), 2.08 (ddd, J )
16.5, 5.8, 2.9 Hz, 1 H), 1.45 (s, 9 H); 13C NMR (50 MHz, CDCl3)
δ 164.1, 153.5, 142.7, 141.9, 135.5, 134.5, 128.8, 128.0, 127.6,
96.3, 81.0, 65.9, 65.1, 63.1, 43.4, 28.4, 28.0. Anal. Calcd for
C21H23NO4: C, 71.37; H, 6.56; N, 3.96. Found: C, 71.12; H,
6.67; N, 3.85. Com p ou n d 36: 0.04 g (8% yield); IR (CDCl3)
3086, 2981, 1826, 1803, 1689, 1602, 1493, 1342, 1250, 1082
1,1-Dim et h ylet h yl 1,5a r,7,7a r-t et r a h yd r o-1-oxo-7â-
p h en ylisoben zofu r o[5,4-b]a zete-6(3H)-ca r boxyla te (28a )
a n d 1,1-d im eth yleth yl 1,5a r,7,7a r-tetr a h yd r o-1-oxo-7r-
p h en ylisoben zofu r o[5,4-b]a zete-6(3H)-ca r boxyla te (29a )
were prepared as an inseparable mixture (2:1) ratio from 6a
(0.21 g, 0.6 mmol) in 60% yield by treatment with rhodium-
(II) octanoate in benzene according to the procedure described
for the synthesis of 20: IR (neat) 2976, 2924, 1757, 1698, 1450,
1
1391, 1365, 1254, 1137 cm-1; H NMR (200 MHz, DMSO-d6,
95 °C) 28a , δ 7.25-7.45 (m, 5 H), 6.50 (dd, J ) 9.9, 3,9 Hz, 1
H), 6.41 (d, J ) 9.9 Hz, 1 H), 5.40 (dd, J ) 9.8, 3.9 Hz, 1 H),
5.23 (d, J ) 5.0 Hz, 1 H), 5.05 (brd, J ) 17.9 Hz, 1 H), 4.90
(dd, J ) 17.9, 2.4 Hz, 1 H), 3.40 (ddd, J ) 9.8, 5.0, 2.4 Hz, 1
H), 1.27 (s, 9 H); 29a , δ 7.25-7.45 (m, 5 H), 6.32 (m, 2 H),
5.70 (d, J ) 8.6 Hz, 1 H), 5.20 (m, 1 H), 4.70 (dd, J ) 17.8, 2.6
Hz, 1 H), 4.55 (brd, J ) 17.8 Hz, 1 H), 4.05 (ddd, J ) 8.6, 8.6,
2.6 Hz, 1 H), 1.27 (s, 9 H). Anal. Calcd for C20H21NO4: C,
70.78; H, 6.24; N, 4.13. Found: C, 70.62; H, 6.26; N, 4.10.
1,1-Dim et h ylet h yl 1,5a r,7,7a r-t et r a h yd r o-5a -m et h yl-
1-oxo-7â-p h en ylisoben zofu r o[5,4-b]a zete-6(3H)-ca r boxy-
la te (28b) a n d 1,1-d im eth yleth yl 1,5a r,7,7a r-tetr a h yd r o-
5a-m eth yl-1-oxo-7r-ph en ylisoben zofu r o[5,4-b]azete-6(3H)-
ca r boxyla te (29b) were prepared as an inseparable mixture
(3:1) from 6b (0.83 g, 2.2 mmol) in 79% yield by treatment
with rhodium(II) octanoate in toluene (maintained at 80-90
°C) according to the procedure described for the synthesis of
1
cm-1; H NMR (200 MHz, CDCl3) δ 7.10-7.34 (m, 5 H), 6.88
(dd, J ) 3.4, 1.8 Hz, 1 H), 6.36 (d, J ) 6.0 Hz, 1 H), 6.24 (dd,
J ) 6.0, 2.8 Hz, 1 H), 4.73 (dd, J ) 2.8, 1.8 Hz, 1 H), 4.66
(ddd, J ) 14.0, 6.7, 3.5 Hz, 1 H), 4.36 (ddd, J ) 14.0, 8.4, 2.9
Hz, 1 H), 3.33 (d, J ) 3.4 Hz, 1 H), 3.30 (ddd, J ) 14.8, 8.4,
3.5 Hz, 1 H), 2.16 (ddd, J ) 14.8, 6.7, 2.9 Hz, 1 H), 0.99 (s, 9
H); 13C NMR (50 MHz, CDCl3) δ 164.1, 150.9, 142.1, 140.2,
140.0, 134.2, 129.5, 128.8, 128.5, 127.1, 79.9, 66.3, 64.9, 63.2,
45.1, 27.8, 27.7. Anal. Calcd for C21H23NO4: C, 71.37; H, 6.56;
N, 3.96. Found: C, 71.14; H, 6.70; N, 3.93. Com p ou n d 33:
0.21 g (40% yield); IR (neat) 3059, 3032, 2978, 2929, 2902,
1700, 1596, 1460, 1422, 1389 cm-1; 1H NMR (200 MHz, DMSO-
d6, 95 °C) δ 7.20-7.45 (m, 5 H), 6.38 (dd, J ) 9.6, 4.2 Hz, 1
H), 6.16 (d, J ) 9.6 Hz, 1 H), 5.30 (dd, J ) 10.2, 4.2 Hz, 1 H),
5.11 (d, J ) 5.5 Hz, 1 H), 4.25-4.48 (m, 2 H), 3.45 (brdd, J )
10.2, 5.5 Hz, 1 H), 2.30-2.45 (m, 2 H), 1.25 (s, 9 H). Anal.
Calcd for C21H23NO4: C, 71.37; H, 6.56; N, 3.96. Found: C,
71.42; H, 6.60; N, 4.04. Com p ou n d 34: 0.06 g (11% yield);
IR (neat) 3059, 2978, 2923, 1700, 1450, 1390, 1368, 1259, 1140
20: IR (CH2Cl2) 3074, 2982, 2932, 1754, 1693, 1594, 1446 cm-1
;
1H NMR (200 MHz, DMSO-d6, 95 °C) 28b, δ 7.11-7.43 (m, 5
H), 6.45 (d, J ) 9.9 Hz, 1 H), 6.28 (d, J ) 9.9 Hz, 1 H), 5.08 (d,
J ) 6.1 Hz, 1 H), 4.80-5.07 (m, 2 H), 3.09 (d, J ) 6.1 Hz, 1
H), 1.66 (s, 3 H), 1.34 (s, 9 H); 29b, δ 7.11-7.43 (m, 5 H), 6.23
(s, 2 H), 5.67 (d, J ) 8.7 Hz, 1 H), 4.56-4.80 (m, 2 H), 3.68
(brd, J ) 8.7 Hz, 1 H), 1.73 (s, 3 H), 1.34 (s, 9 H). Anal. Calcd
for C21H23NO4: C, 71.37; H, 6.56; N, 3.96. Found: C, 71.30;
H, 6.57; N, 3.98.
1,1-Dim eth yleth yl 6,7-d ih yd r o-8-[(1,1-d im eth yleth yl)-
d im eth ylsiloxy]-1-oxo-1H-cycloh ep ta [c]fu r a n -3H-3a r,6r-
im in e-9-ca r boxyla te (30) was prepared from 4 (4.25 g, 10.1
mmol) by treatment with rhodium(II) octanoate in hexane
according to the procedure described for the synthesis of 20.
After completion of the reaction, the mixture was cooled to
room temperature and stirred for 16 h at room temperature.
The solvent was then removed under reduced pressure, and
the residue was washed with pentane (3 × 20 mL) on a fritted
funnel which yielded the white solid 30 (2.5 g, 63% yield): mp
(petroleum ether:ether) 136-38 °C; IR (neat) 2955, 2950, 2858,
1
cm-1; H NMR (200 MHz, CDCl3) δ 7.12-7.36 (m, 5H), 6.30
(dd, J ) 9.7, 4.3 Hz, 1 H), 5.94 (d, J ) 9.7 Hz, 1 H), 5.72 (d, J
) 8.8 Hz, 1 H), 5.16 (dd, J ) 10.8, 4.3 Hz, 1 H), 4.25 (ddd, J
) 10.8, 8.8, 2.8 Hz, 2 H), 4.04 (ddd, J ) 11.5, 5.5, 3.2 Hz, 1 H),
3.26 (ddd, J ) 11.5, 11.5, 3.2 Hz, 1 H), 2.46 (dddd, J ) 17.7,
11.5, 5.5, 2.8 Hz, 1 H), 1.99 (ddd, J ) 17.7, 3.2, 3.2 Hz, 1 H),
1.37 (s, 9 H); HRMS calcd for C21H24NO4 354.1705, found
354.1689.
1754, 1702, 1639, 1476 cm-1
;
1H NMR (200 MHz, CDCl3) δ
6.34 (d, J ) 5.7 Hz, 1 H), 6.00 (dd, J ) 5.8, 2.7 Hz, 1 H), 5.16
(m, 1 H), 4.75 (dd, J ) 5.2, 2.6 Hz, 1 H), 4.49 (d, J ) 9.9 Hz,
1 H), 2.78 (dd, J ) 18.3, 5.6 Hz, 1 H), 1.84 (d, J ) 18.3 Hz, 1
H), 1.41 (s, 9 H), 0.91 (s, 9 H), 0.20 (s, 6 H); 13C NMR (75 MHz,
CDCl3) δ 165.8, 155.1, 141.1, 128.7, 110.8, 110.5, 81.5, 68.8,
66.7, 59.5, 31.4, 27.9, 25.2, 18.0, -4.3, -4.6. Anal. Calcd for
C20H31NO5Si: C, 61.04; H, 7.94; N, 3.56. Found: C, 60.85; H,
8.02; N, 3.58.
1,1-Dim eth yleth yl 3,4,7,8-tetr a h yd r o-9-[(1,1-d im eth yl-
e t h yl)d im e t h ylsiloxy]-1-oxo-1H -cycloh e p t a [c]p yr a n -
4a r,7r-im in e-10-ca r boxyla te (38) was prepared from 15
(0.67 g, 1.55 mmol) by treatment with 32 in hexane according
to the procedure described for the synthesis of 20. Purification
by silica gel chromatography using 1:4 diethyl ether:pentane
as eluting solvent gave 38 as a white solid (0.2 g, 32% yield):
Rf ) 0.28 in 1:1 diethyl ether:hexanes, mp (pentane:diethyl
1,1-Dim eth yleth yl 6,7-d ih yd r o-8-[(1,1-d im eth yleth yl)-
d im eth ylsiloxy]-7r-m eth yl-1-oxo-1H-cycloh ep ta [c]fu r a n -
3H-3a r,6r-im in e-9-ca r boxyla te (31) was prepared from 10
(1.42 g, 3.26 mmol) by treatment with rhodium(II) octanoate
in hexane according to the procedure described for the
synthesis of 20. After completion of the reaction, the mixture
was cooled to rt and stirred for 16 h at rt. The solvent was
removed under reduced pressure, and the residue was washed
with pentane (3 × 20 mL) on a fritted funnel to yield 31 as a
white solid (0.573 g, 44% yield): mp (hexane:ether) 170-71
°C; IR (neat) 2974, 2928, 2852, 1757, 1704, 1646 cm-1; 1H NMR
(400 MHz, CDCl3) δ 6.63 (d, J ) 4.8 Hz, 1 H), 5.98 (d, J ) 2.8
Hz, 1 H), 5.01 (brs, 1 H), 4.66 (brs, 2 H), 1.97 (q, J ) 6.8 Hz,
1 H), 1.42 (d, J ) 7.8 Hz, 12 H), 0.92 (s, 9 H), 0.29 (s, 3 H),
0.10 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 165.8, 162.1, 156.0,
142.7, 129.4, 110.8, 81.3, 68.8, 67.4, 66.2, 38.0, 27.9, 25.3, 18.2,
17.2, -4.2, -5.0. Anal. Calcd for C21H33NO5Si: C, 61.88; H,
8.16; N, 3.44. Found: C, 61.86; H, 8.12; N, 3.50.
ether) 139-41 °C; IR (neat) 2927, 2856, 1707, 1700, 1653 cm-1
;
1H NMR (200 MHz, CDCl3) δ 6.19 (d, J ) 5.9 Hz, 1 H), 5.92
(dd, J ) 2.6, 5.9 Hz, 1 H), 4.61 (m, 2 H), 4.22 (m, 1 H), 2.91
(m, 2 H), 2.09 (m, 1 H), 1.92 (d, J ) 18.3 Hz, 1 H), 1.43 (s, 9
H), 0.91 (s, 9 H), 0.20 (s, 3 H), 0.15 (s, 3 H); 13C NMR (50 MHz,
CDCl3) δ 162.9, 152.9, 141.9, 126.1, 112.6, 80.4, 64.9, 62.6, 58.3,
34.1, 29.6, 29.2, 28.2, 25.6, 18.4, -4.1, -4.3. Anal. Calcd for
C21H33NO5Si: C, 61.88; H, 8.16; N, 3.44. Found: C, 61.86; H,
8.16; N, 3.44.
(Z)-6H-5-[2-[N-(1,1-Dim eth yleth oxyca r bon yl)im in o]et-
h ylid en e]-3-vin ylp yr a n -2(5H)-on e) (39) was prepared from
17 (0.36 g, 1.2 mmol) by treatment with rhodium(II) octanoate
in hexane according to the procedure described for the
synthesis of 20. Purification by silica gel chromatography

Reactions of Rh-Stabilized Vinylcarbenoids with Pyrroles
J . Org. Chem., Vol. 61, No. 7, 1996 2313
using 1:3 diethyl ether:pentane as eluting solvent gave 39 as
a white solid (0.242 g, 77% yield): Rf ) 0.24 in 1:1 ether:
hexanes, mp (hexane:ether) 117-20 °C; IR (neat) 2979, 2930,
2900, 1771, 1710, 1583, 1414 cm-1; 1H NMR (400 MHz, CDCl3)
δ 6.74 (d, J ) 2.8 Hz, 1 H), 5.65 (d, J ) 17.6 Hz, 1 H), 5.43 (d,
J ) 12 Hz, 1 H), 5.25 (m, 1 H), 5.19 (dd, J ) 10.0, 17.6 Hz, 1
H), 4.51 (d, J ) 8.8 Hz, 1 H), 4.42 (d, J ) 9.6 Hz, 1 H), 4.16 (s,
1 H), 1.49 (s, 9 H). Anal. Calcd for C14H17NO4: C, 63.87; H,
6.51; N, 5.32. Found: C, 63.99; H, 6.55; N, 5.24.
156-57 °C; IR (neat) 2957, 2928, 2852, 1739, 1710, 1594, 1256
1
cm-1; H NMR (300 MHz, CDCl3) δ 5.29 (brs, 1 H), 5.00 (d, J
) 12.3 Hz, 1 H), 4.93 (brs, 1 H), 4.83 (d, J ) 12.2 Hz, 1 H),
4.67 (brs, 1 H), 2.94 (brd, J ) 18 Hz, 1 H), 1.70 (d, J ) 18 Hz,
1 H), 1.40 (s, 9 H), 0.85 (s, 9 H), 0.17 (s, 3 H), 0.12 (s, 3 H); 13
C
NMR (75 MHz, CDCl3) δ 164.0, 153.0, 151.0, 146.7, 118.2,
115.9, 80.7, 66.1, 57.5, 57.3, 32.3, 28.0, 25.3, 18.0, -4.3, -5.1.
Anal. Calcd for C20H31NO5Si: C, 61.04; H, 7.94; N, 3.56.
Found: C, 60.96; H, 7.92; N, 3.50.
11-(1,1-Dim eth yleth oxyca r bon yl)-4r,10r-im in o-2-[(1,1-
d im eth yleth yl)d im eth ylsiloxy]-8-oxa -9-oxobicyclo[4.3.1]-
d eca -1,5-d ien e (41) was prepared from 18 (1.36 g, 3.25 mmol)
by treatment with rhodium(II) octanoate in hexane according
to the procedure described for the synthesis of 20. The residue
was washed with pentane (3 × 20 mL) on a fritted funnel to
yield 41 as a colorless solid (0.68 g, 53% yield): mp (pentane)
Ack n ow led gm en t. Financial support of this work
by the National Institutes of Health (DA-06302) and R.
J . Reynolds Tobacco Co. is gratefully acknowledged.
J O952127Q