Rhodium(II)-catalyzed cyclization of amido diazo carbonyl compounds

Article abstract of DOI:10.1021/jo0009144

A series of acyclic diazo ketoamides were prepared from N-benzoyl-N-alkylaminopropanoic acids and were treated with a catalytic amount of rhodium(II) acetate. The resultant carbenoids underwent facile cyclization onto the neighboring amide carbonyl oxygen atom to generate seven-membered carbonyl ylide dipoles. Subsequent collapse of the dipoles with charge dissipation produce bicyclic epoxides which undergo further reorganization to give substituted 5-hydroxydihydropyridones in good yield. Depending on the nature of the substituent groups, it was possible to trap some of the initially formed carbonyl ylide dipoles with a reactive dipolarophile such as DMAD. In other cases, cyclization of the dipole to the epoxide is much faster than bimolecular trapping. A related cyclization/rearrangement sequence occurred when diazo ketoamides derived from the cyclic pyrrolidone and piperidone ring systems were subjected to catalytic quantities of Rh(II) acetate. With these systems, exclusive O-cyclization of the amido group onto the carbenoid center occurs to generate a seven-ring carbonyl ylide dipole. Starting materials are easily prepared, and the cascade sequence proceeds in good yield and does not require special precautions. The overall procedure represents an efficient one-pot approach toward the synthesis of various indolizidine and quinolizidine ring systems.

Full text of DOI:10.1021/jo0009144

7124
J . Org. Chem. 2000, 65, 7124-7133
Rh od iu m (II)-Ca ta lyzed Cycliza tion of Am id o Dia zo Ca r bon yl
Com p ou n d s
Albert Padwa,* Tadashi Hasegawa, Bing Liu, and Zhijia Zhang
Department of Chemistry, Emory University, Atlanta, Georgia 30322
chemap@emory.edu
Received J une 16, 2000
A series of acyclic diazo ketoamides were prepared from N-benzoyl-N-alkylaminopropanoic acids
and were treated with a catalytic amount of rhodium(II) acetate. The resultant carbenoids
underwent facile cyclization onto the neighboring amide carbonyl oxygen atom to generate seven-
membered carbonyl ylide dipoles. Subsequent collapse of the dipoles with charge dissipation produce
bicyclic epoxides which undergo further reorganization to give substituted 5-hydroxydihydropyri-
dones in good yield. Depending on the nature of the substituent groups, it was possible to trap
some of the initially formed carbonyl ylide dipoles with a reactive dipolarophile such as DMAD. In
other cases, cyclization of the dipole to the epoxide is much faster than bimolecular trapping. A
related cyclization/rearrangement sequence occurred when diazo ketoamides derived from the cyclic
pyrrolidone and piperidone ring systems were subjected to catalytic quantities of Rh(II) acetate.
With these systems, exclusive O-cyclization of the amido group onto the carbenoid center occurs to
generate a seven-ring carbonyl ylide dipole. Starting materials are easily prepared, and the cascade
sequence proceeds in good yield and does not require special precautions. The overall procedure
represents an efficient one-pot approach toward the synthesis of various indolizidine and
quinolizidine ring systems.
The cyclization of cationic species containing internal
functional group containing other nucleophilic atoms, as
in the case of amides. For example, in the halocyclization
reaction of olefinic compounds possessing a tethered
amido group, O-cyclized products are generally obtained
in preference to N-cyclized products11 (Scheme 1). The
O-selective cyclization in these reactions is understand-
able on the basis of HSAB theory;12 that is, an oxygen
atom, more electronegative than a nitrogen atom, should
preferentially attack the iodine-olefin π-complex char-
acterized as a hard electrophile. To obtain N-cyclized
products, it was necessary to carry out the reaction in
the presence of a basic metallic reagent such as n-BuLi.
This crossover in selectivity was attributed to the forma-
tion of a metal imidate intermediate which enhances the
reactivity at the nitrogen atom.13
For the past several years, our group has been inter-
ested in a related cyclization process involving the
interaction of an amido group onto an electrophilic
metallocarbene complex generated from the reaction of
R-diazo carbonyls with Rh(II) carboxylates.14 In our early
studies dealing with the tandem cyclization-cycloaddi-
tion reaction of diazo ketoamides of type 4, the carbonyl
ylide dipole 5 was generated by cyclization of the amido
oxygen atom onto the electrophilic rhodium carbenoid
center.15 The resulting dipole underwent intramolecular
nitrogen nucleophiles represents a very useful method
for obtaining a wide range of substituted aza hetero-
cycles.1,2 A variety of alkenylamine derivatives, such as
amides,3 carbamates,4 hydroxamic acids,5 imidates,6
imines,7 isoureas,8 oximes,9 and ureas10 have been em-
ployed to effect ring closure by treatment with different
electrophilic reagents. Competitive reactions are often
observed when the nitrogen atom is incorporated in a
* Corresponding author.
(1) Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321.
(2) Nicolaou, K. C.; Petasis, N. A.; Claremon, D. A. In Organosele-
nium Chemistry; Liotta, D., Ed.; Wiley and Sons: New York, 1987;
Chapter 2, pp 127-162.
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Menchen, S. M. J . Org. Chem. 1980, 45, 2120. Takahara, H.; Takehara,
O.; Ohkubo, N.; Momose, T. Tetrahedron: Asymmetry 1990, 1, 561.
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A.; Ward, A. D. Tetrahedron Lett. 1994, 35, 5065.
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Trans. 1 1986, 1837. Toshimitsu, A.; Terao, K.; Uemura, S. J . Org.
Chem. 1987, 52, 2018. Knapp, S.; Levorse, A. T. J . Org. Chem. 1988,
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A. J . Org. Chem. 1997, 62, 2001.
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10.1021/jo0009144 CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/21/2000

Amido Diazo Carbonyl Compounds
J . Org. Chem., Vol. 65, No. 21, 2000 7125
Sch em e 1
Sch em e 3
Sch em e 2
permits both the interconversion of uncomplexed ylides
10 and 11 and their subsequent isolation or capture as
cycloadducts. More recently (see Experimental Section),
we noted that the cyclization reaction can be influenced
by the nature of the substituent group on the nitrogen
atom as well as by the experimental conditions employed.
Thus, the Rh(II)-catalyzed reaction of N-benzyl-N-tert-
butyl diazo amide 8 afforded only products derived from
a carbonyl ylide dipole (i.e., 14; R ) t-Bu). There was no
indication of any rearranged lactam (i.e., 12b; R ) t-Bu)
in the crude reaction mixture, even in the absence of a
trapping dipolarophile. Indeed, no characterizable prod-
ucts could be obtained when DMAD was absent from the
reaction mixture. With both diazo amides 7 and 8, the
bimolecular trapping of carbonyl ylide 11 is faster than
the rearrangement of ammonium ylide 10. The presence
of the bulky tert-butyl group on the nitrogen atom,
however, seems to significantly retard the 1,2-benzylic
shift; perhaps the consequence of a steric effect.
R-Diazo carbonyls which possess an interacting γ-
amido group were found to afford products derived from
a six-ring carbonyl ylide intermediate.20,21 A particularly
interesting example involves the Rh(II)-catalyzed reac-
tion of N-acetyl-2-(1-diazoacetyl)pyrrolidine (15)20 (Scheme
4) which gave the novel rearranged cycloadduct 19 when
treated with DMAD in the presence of a Rh(II) catalyst.
The mechanism proposed to rationalize the formation of
this unusual product involves generation of the expected
carbonyl ylide dipole 16 by intramolecular cyclization of
the keto carbenoid onto the oxygen atom of the amide
group.20 Isomerization of 16 to the thermodynamically
cycloaddition across the tethered π-bond to give cycload-
duct 6 in near-quantitative yield (Scheme 2). In this case,
geometric factors prevent the amido nitrogen atom from
attacking the carbenoid center.
In contrast to this result, treatment of acyclic diazo-
amides such as 7 with Rh2(OAc)4 afforded five-membered
ammonium (10) and carbonyl ylides (11) depending on
the reaction conditions.16 Thus, when the reaction was
carried out in the presence of a typical dipolarophile such
as DMAD, cycloadduct 13 derived from a cyclic carbonyl
ylide was formed as the major product (57%) together
with lesser quantities of the rearranged lactam 12 (23%).
When the reaction of 7 was carried out in the absence of
DMAD, lactam 12 could be isolated in very high yield.
The formation of 12 can be attributed to the initial
formation of ammonium ylide 10 followed by a 1,2-benzyl
shift17 (Scheme 3). It would appear as though the highly
electrophilic carbenoid center15 present in 9 can be
attacked by the lone pair of electrons on the amide
nitrogen18 (ammonium ylide formation) or by the lone
pair of electrons on the carbonyl oxygen (carbonyl ylide
formation). The experimental observations reflect a
catalyst-promoted system of equilibria with a clear-cut
thermodynamic bias in favor of the more stable am-
monium ylide 10.19 The ambident properties of the
rhodium carbenoid 9 flanked by reversible equilibria
(19) Density functional theory (DFT) calculations show that am-
monium ylide 10 is ca. 7 kcal/mol lower in energy than carbonyl ylide
11: Padwa, A.; Snyder, J . P.; Curtis, E. A.; Sheehan, S. M.; Worsen-
croft, K. J .; Kappe, C. O. J . Am. Chem. Soc. 2000, 122, 8155.
(20) Padwa, A.; Dean, D. C.; Zhi, L. J . Am. Chem. Soc. 1992, 114,
593. Padwa, A.; Dean, D. C.; Zhi, L. J . Am. Chem. Soc. 1989, 111, 6451.
Padwa, A.; Price, A. T.; Zhi, L. J . Org. Chem. 1996, 61, 2283.
(21) Rodgers, J . D.; Caldwell, G. W.; Gauthier, A. D. Tetrahedron
Lett. 1992, 33, 3273.
(16) Curtis, E. A.; Worsencroft, K. J .; Padwa, A. Tetrahedron Lett.
1997, 38, 3319.
(17) West, F. G.; Naidu, B. N. J . Org. Chem. 1994, 59, 6051. West,
F. G.; Naidu, B. N.; Tester, R. W. J . Org. Chem. 1994, 59, 6892.
(18) For a related example, see: Kappe, C. O. Tetrahedron Lett.
1997, 38, 3323.

7126 J . Org. Chem., Vol. 65, No. 21, 2000
Padwa et al.
Sch em e 4
Sch em e 6
occurred with charge dissipation to give the observed
cycloadduct 25.
Because of the vast array of pathways available to keto
carbenoids possessing tethered amido groups and the
demonstrated susceptibility of the transient dipoles to
undergo unexpected rearrangement, we felt that a sys-
tematic study of the related 4-(N-acyl)amino-1-diazo-
butan-2-one (26) system was warranted. In this case,
O-cyclization of the amido group on the carbenoid center
would lead to a seven-ring carbonyl ylide dipole (27)
whereas N-cyclization should ultimately afford products
derived from a transient five-ring ammonium ylide of
type 28 (Scheme 6). We therefore initiated a study to
probe the above competition and now wish to report
results emanating from this investigation.
Sch em e 5
Resu lts a n d Discu ssion
The tandem ammonium ylide generation/rearrange-
ment sequence represents a very effective method for the
preparation of nitrogen-containing heterocycles.23 A typi-
cal example involves the ring expansion reaction of a
spirocyclic ammonium ylide such as 31, which has been
nicely exploited for the synthesis of a number of alkaloids.
Thus, the key step in West and Naidu’s enantioselective
synthesis of (-)-epilupinine24 involved the ammonium
ylide-Stevens [1,2]-rearrangement of the (L)-proline de-
rivative 29 which furnished the advanced intermediate
32 in 84% yield and with 76% ee (Scheme 7). In this case,
the starting diazo carbonyl compound has the dialkyl-
amino center six atoms away from the carbenoid site.
Starting from a related (L)-proline derivative 30 (R )
vinyl), Clark and Hodgson synthesized the CE ring
system 33 in their approach to the Mazamine A ring
skeleton via an ammonium ylide-[2,3]-sigmatropic rear-
rangement (Scheme 7).25,26
more stable azomethine ylide 17 occurs via a proton
exchange with a small amount of water that was present
in the reaction mixture. 1,3-Dipolar cycloaddition with
DMAD provided cycloadduct 18 which underwent a
subsequent 1,3-alkoxy shift to afford the tricyclic dihy-
dropyrrolizine 19. Ammonium ylide formation requires
a more highly strained four-membered ring, and conse-
quently, this reactive intermediate is not produced.
Experiments with this particular diazoamide were
followed soon thereafter by a study of systems derived
from acyclic precursors.20 In the case of R-diazo ketoamide
20, the Rh(II)-catalyzed reaction in the presence of
DMAD furnished the novel epoxy-cycloadduct 25. Once
again, the initial cyclization involved generation of a six-
ring carbonyl ylide 21 by intramolecular cyclization of
the keto carbenoid onto the oxygen atom of the amide
group (Scheme 5). This highly stabilized dipole does not
readily undergo 1,3-dipolar cycloaddition but rather
isomerizes to the cyclic ketene N,O-acetal 22 by proton
exchange.22 Structure 22 reacts further with the activated
π-bond of DMAD to produce zwitterion 23. The anionic
portion of 23 then undergoes addition to the adjacent
carbonyl group, affording a new zwitterionic intermediate
24. Under the anhydrous conditions, epoxide formation
To further document the scope and generality of five-
ring ammonium ylide formation of diazo carbonyl com-
pounds bearing a nitrogen substituent in the â-position,
we first opted to study the Rh(II)-catalyzed behavior of
4-(1-pyrrolidino)-1-diazo-2-butanone (34). A Stevens [1,2]-
shift of one of the methylene groups of the anticipated
(23) Padwa, A.; Beall, L. S. Advances in Nitrogen Heterocycles; J AI
Press: Stamford, CT, 1998; Vol. 3, pp 117-158.
(24) West, F. G.; Naidu, B. N. J . Am. Chem. Soc. 1993, 115, 1177.
West, F. G.; Glaeske, K. W.; Naidu, B. N. Synthesis 1993, 977. Naidu,
B. N.; West, F. G. Tetrahedron 1997, 53, 16565.
(25) Clark, J . S.; Hodgson, P. B. J . Chem. Soc., Chem. Commun.
1994, 2701. Clark, J . S.; Hodgson, P. B. Tetrahedron Lett. 1995, 36,
2519.
(26) Wright, D. L.; Weekly, R. M.; Groff, R.; McMills, M. C.
Tetrahedron Lett. 1996, 37, 2165.
(22) For a related proton exchange of a carbonyl ylide derived from
the Rh(II)-catalyzed reaction of an amide with diazoacetic ester, see:
Busch-Petersen, J .; Corey, E. J . Org. Lett. 2000, 2, 1641.

Amido Diazo Carbonyl Compounds
J . Org. Chem., Vol. 65, No. 21, 2000 7127
Sch em e 7
Sch em e 9
Sch em e 10
Sch em e 8
strate. A similar transformation also occurred with
N-benzyl-N-methyl-4-amino-1-diazobutanone (40), which
furnished a 1:1-mixture of butanones 42 and 43 by a
similar mechanism (Scheme 9).
In contrast to these results, the Rh(II)-catalyzed reac-
tion of N-benzoyl-N-phenyl-4-amino-1-diazobutan-2-one
(44) proceeded by way of a seven-ring dipole derived from
O-cyclization of the amido group onto the carbenoid
center. Thus, treatment of 44 with Rh2(OAc)4 afforded
5-hydroxydihydropyridone 49 as the exclusive product in
71% isolated yield. This same compound was isolated in
essentially identical yield when the reaction was carried
out in the presence of a trapping agent such as DMAD.
No signs of any product derived from a five-ring am-
monium ylide could be detected in the crude reaction
mixture. A similar reaction using diazo ketoamides 45
and 46 afforded the related rearranged products 50 and
51 in 75% and 82% yield, respectively. The formation of
these compounds can best be rationalized in terms of an
initially formed carbonyl ylide dipole (i.e., 47) which
collapses to produce epoxide 48 as a transient intermedi-
ate (Scheme 10). A subsequent isomerization of 48 affords
the thermodynamically more stable dihydropyridone
tautomer 49. It would appear as though cyclization of
carbonyl ylide 47 to epoxide 48 is much faster than
bimolecular trapping with DMAD. The overall pathway
is somewhat related to that encountered by Danishefsky
and co-workers in the diazo thioamide coupling reaction
used in the synthesis of the angiotensin converting
enzyme inhibitor A58365A.27
ammonium ylide 35 was expected to give rise to indolizi-
done 36 (Scheme 8). A competing C-H insertion of the
initially formed rhodium carbenoid might also produce
the isomeric indolizidone 37. In the event, diazo keto-
amide furnished a 3:1-mixture of the unexpected pyrrol-
idino butanones 38 and 39 in 58% yield. No detectable
quantities of either indolizidones 36 or 37 were found in
the crude reaction mixture. Both of these products can
be rationalized in terms of the initial formation of
ammonium ylide 35a which seemingly undergoes proton
exchange with an adjacent R-hydrogen to give 35b. A
subsequent C-N bond cleavage then occurs so as to
dissipate the charges. This process would have to occur
at a faster rate than either insertion into a C-H bond or
the Stevens 1,2-shift in order to account for the exclusive
formation of 38 and 39. We assume that 39 is derived
from the Michael reaction of enone 38 with either
pyrrolidine or perhaps the starting diazo carbonyl sub-

7128 J . Org. Chem., Vol. 65, No. 21, 2000
Padwa et al.
Sch em e 11
The facility with which diazo ketoamides 44-46 un-
derwent cyclization led us to study the related cyclic diazo
pyrrolidone and piperidone ring systems (i.e., 52 and 56).
A Rh(II)-catalyzed reorganization similar to that de-
scribed in Scheme 10 would result in the ready formation
of the indolizidine and quinolizidine skeletons.28 Alkaloids
containing these 5,6- and 6,6-ring systems have been
popular targets for total synthesis due to their interesting
biological activity.29 Annulation of cyclic lactams with
closure of the ring at the lactam carbonyl group repre-
sents an attractive method to construct these izidine
skeletons due to the easy availability of the lactam unit.
This annulation strategy has been realized by using such
processes as cyclodehydration,30 metal-induced zipper
reaction,31 titanium-mediated cyclization of ω-vinyl
imides,32 and intramolecular nucleophilic addition of allyl
silane to imides,33 as well as intramolecular 1,4-dipolar
cycloaddition.34 Annulation of thiolactams has also been
carried out by a Rh(II)-mediated diazo thioamide cou-
pling35 and thioisomu¨nchnone cycloaddition.36 Our in-
vestigations along these lines began with a study of the
Rh(II)-catalyzed behavior of diazo pyrrolidone 52 which
is an appropriate starting material for the construction
of the indolizidine skeleton. We found that the treatment
of 52 with a catalytic quantity of Rh2(OAc)4 in chloroform
at 25 °C gave 8-hydroxyhexahydroindolizinone 53 in 86%
yield. Interestingly, when the reaction was carried out
in the presence of 1.2 equiv of DMAD, hexahydropyrrolo-
[1,2-a]azocinone 55 (40%) was obtained in addition to
indolizinone 53 (32%) (Scheme 11). We assume that 55
is derived by a rapid rearrangement of a transient dipolar
cycloadduct (i.e. 54). Apparently, the rate of ring closure
of the carbonyl ylide dipole to a bicyclic epoxide is
sufficiently slow to allow a competitive dipolar cycload-
dition to occur. More than likely, the slower rate of ring
closure is probably a consequence of the more highly
strained nature of the epoxide intermediate (i.e., 48). In
a like manner, the Rh(II)-catalyzed reaction of the related
diazo piperidone system 56 afforded hydroxy quinoliz-
inone 57 in 65% yield. Capture of the transient carbonyl
ylide dipole with DMAD proceeded uneventfully to
produce azocinone 58 in 67% yield.
For comparison purposes, we have also carried out a
study of the Rh(II)-catalyzed reaction of the closely
related amido diazo ketoesters 60 and 61. Incorporation
of a carbomethoxy substituent on a diazo carbonyl group
generally facilitates carbonyl ylide formation since the
initially formed rhodium carbenoid is highly electrophilic
and prone to interact with a neighboring Lewis base.37
In the case of diazo amidoester 60 (or 61), the initially
formed dipole was expected to cyclize in a manner
analogous to that encountered earlier (i.e., 47 f 48)
thereby generating amino epoxide 62 as a transient
species. Since this epoxide does not possess an R-hydro-
gen, deprotonation cannot take place. Although several
possible pathways are available, we found that the
reaction of 60 with Rh2(OAc)4 cleanly afforded the rear-
ranged indolizidone 64 in 80% yield.38 A similar trans-
formation occurred with the homologous piperidinyl
system 61 producing pyrroloazepine 65 in 72% yield
(Scheme 12). When the Rh(II)-catalyzed reaction of 61
was carried out in the presence of 1 equiv of DMAD, the
expected dipolar cycloadduct 66 was obtained in 38%
yield together with lesser quantities of 65 (22%).
(27) Fang, F. G.; Prato, M.; Kim, G.; Danishefsky, S. J . Tetrahedron
Lett. 1989, 30, 3625.
(28) For some representative examples of previous work, see:
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of these alkaloids, see: Michael, J . P. Nat. Prod. Rep. 1999, 16, 675.
Daly, J . W. J . Nat. Prod. 1998, 61, 162.
The most plausible mechanism for the conversion of
60 to 64 involves the intermediacy of aminoepoxide 62.
(37) Padwa, A.; Hornbuckle, S. F. Chem. Rev. 1991, 91, 263. Ye, T.;
McKervey, A. M. Chem. Rev. 1994, 94, 1901.
(38) The two alternative rearranged products i and ii were also
entertained as possible structures. However, structure 64 shows a
characteristic absorption band at 1773 cm-1 in the infrared signifying
the presence of a five-membered ring. A natural abundance double
quantum transfer experiment (Inadequate) rules out structure ii since
no C-C coupling from the carbonyl groups was observed in the 13C-
Inadequate spectrum.39
(30) Miyano, S.; Fujii, S.; Yamashita, O.; Toraishi, N.; Sumoto, K.
J . Org. Chem. 1981, 46, 1737.
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112, 2003.
(36) Padwa, A.; Beall, L. S.; Heidelbaugh, T. M.; Liu, B.; Sheehan,
S. M. J . Org. Chem. 2000, 65, 2684.

Amido Diazo Carbonyl Compounds
J . Org. Chem., Vol. 65, No. 21, 2000 7129
Sch em e 12
Sch em e 13
In summary, we have demonstrated that the overall
sequence of rhodium(II)-catalyzed carbenoid generation/
carbonyl ylide formation/rearrangement utilizing a series
of cyclic diazo ketoamides can be utilized for the synthesis
of the indolizidine and quinolizidine ring skeletons.
Starting materials are easily prepared and the cascade
sequence proceeds in good yield and does not require
special precautions. With these systems, exclusive O-
cyclization of the amido group onto the carbenoid center
occurs to generate a seven-ring carbonyl ylide dipole. The
use of this tandem sequence for the synthesis of alkaloid
targets is currently being investigated, and further
details will be reported in due course.
R-Amino epoxides have been invoked as intermediates
in the oxidation of enamines40-44 and in the rearrange-
ment of R-halo ketones and amines to R-amino ketones.45
These highly reactive three-ring heterocycles undergo
facile rearrangement and the specific product isolated has
been found to be dependent on the nature of the substit-
uents on both the epoxide and nitrogen atom.46 The
isolation of diketo indolizidone 64 strongly suggests that
the reorganization of epoxide 62 to 64 may involve the
intermediacy of aziridinium ion 63 (Scheme 12).
Seven-ring carbonyl ylides derived from the cyclization
of an imido group on the carbenoid center can also
participate in these tandem cyclization-cycloaddition
reactions. Thus, the Rh2(OAc)4 catalyzed reaction of
1-diazo-4-phthalimidobutanone (67) proceeded quite
smoothly with DMAD and N-phenylmaleimide. With
DMAD, cycloadduct 68 was formed in 63% yield. When
N-phenylmaleimide was used as the trapping agent,
cycloadduct 69 (45%) together with dihydropyridone 70
(26%) were isolated as the two major products. Compound
70 is derived by a cyclization-rearrangement reaction
of the initially formed carbonyl ylide followed by attack
of the hydroxyl group of the dihydropyridone on to one
of the carbonyl groups of N-phenylmaleimide (Scheme
13).
Exp er im en ta l Section
Melting points are uncorrected. Mass spectra were deter-
mined at an ionizing voltage of 70 eV. Unless otherwise noted,
all reactions were performed in flame-dried glassware under
an atmosphere of dry argon. Solutions were evaporated under
reduced pressure with a rotary evaporator, and the residue
was chromatographed on a silica gel column using an ethyl
acetate/hexane mixture as the eluent unless specified other-
wise. All solids were recrystallized from ethyl acetate/hexane
for analytical data.
1-(Ben zyl-ter t-b u t ylca r b a m oyl)cyclop r op a n eca r b ox-
ylic Acid . To a solution containing 10.0 g (63 mmol) of 1,1-
cyclopropanecarboxylic acid monoethyl ester in 50 mL of
CH2Cl2 was slowly added 12.6 mL (146 mmol) of oxalyl chloride
and two drops of DMF. After the solution was stirred for 6 h,
the solvent was removed under reduced pressure, and the
crude acid chloride was dissolved in 5 mL of CH2Cl2. The
mixture was added to a solution of 29 mL (158 mmol) of tert-
butylbenzylamine in 50 mL of dry CH2Cl2 and was stirred for
12 h at room temperature. The solvent was removed under
reduced pressure, and the residue was dissolved in a 10% HCl
solution, extracted with ether, dried over anhydrous MgSO4,
filtered, and concentrated to give 18.1 g (95%) of 1-(benzyl-
tert-butylcarbamoyl)cyclopropane carboxylic acid ethyl ester
(39) Freibolin, H. Basic One and Two-Dimensional NMR Spectros-
copy; Wiley VCH: New York, 1998; p 279.
(40) Back, T. G.; Edwards, O. E.; MacAlpine, G. A. Tetrahedron Lett.
1977, 2651.
(41) Fritsch, W.; Schmidt-Thome, J .; Ruschig, H.; Haede, W. Chem.
Ber. 1963, 96, 68.
(42) Nuti, W.; Saettone, M. F. Tetrahedron 1970, 26, 3875.
(43) Bernhard, H. O.; Reed, J . N.; Snieckus, V. J . Org. Chem. 1977,
42, 1093.
(44) Davis, F. A.; Sheppard, A. C. Tetrahedron Lett. 1988, 29, 4365.
(45) Stevens, C. L.; Pillai, P. M. J . Am. Chem. Soc. 1967, 89, 3084.
Stevens, C. L.; Blumbergs, P.; Munk, M. J . Org. Chem. 1963, 28, 331.
(46) Adam, W.; Ahrweiler, M.; Paulini, K.; Reissig, H. U.; Voerckel,
V. Chem. Ber. 1992, 125, 2719.
as a clear oil: IR (neat) 3062, 1723, 1651, 1605, and 1075 cm-1
;
1H NMR (300 MHz, CDCl3) δ 1.25-1.34 (m, 7H), 1.41 (s, 9H),
4.10 (q, 2H, J ) 7.2 Hz), 4.68 (s, 2H), and 7.16-7.38 (m, 5H);
13C NMR (75 MHz, CDCl3) δ 14.0, 15.7, 28.0, 28.4, 31.6, 49.9,
58.4, 61.4, 125.8, 126.8, 126.9, 128.3, 128.5, 139.6, 169.5, and
171.9.
To a stirred solution of 18.0 g (59 mmol) of the above ester
in 200 mL of a 2:1 ethanol-water mixture was added 7.1 g

7130 J . Org. Chem., Vol. 65, No. 21, 2000
Padwa et al.
(126 mmol) of KOH dissolved in 20 mL of water, and the
mixture was stirred at room temperature for 24 h. The solution
was washed with ether, and the aqueous layer was acidified
with a 50% HCl solution to a pH of 2, extracted with ether,
dried over anhydrous MgSO4, and concentrated under reduced
pressure to give 11.5 g (71%) of the title compound as a white
solid: mp 164-165 °C; IR (CHCl3) 3403, 1709, 1595, and 1388
literature procedure47 and was obtained as a yellow liquid: IR
(neat) 2107, 1638 and 1380 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 2.90 (t, 2H, J ) 6.6 Hz), 3.60 (t, 2H, J ) 6.6 Hz), and 5.37 (s,
1H). To a 0.18 g (1 mmol) sample of this diazoketone in 10
mL of ether was added dropwise a solution of 0.14 g (2 mmol)
of pyrrolidine in 5 mL of ether under an argon atmosphere.
After being stirred for 4 h at room temperature, the mixture
was passed through a short silica gel column. Elution with
ethyl acetate gave 0.098 g (59%) of pyrrolidinodiazobutanone
34 as a yellow oil which was immediately used in the next
step: IR (neat) 2102, 1638, and 1361 cm-1; 1H NMR (300 MHz,
CDCl3) δ 1.65-1.77 (m, 4H), 2.39-2.48 (m, 2H), 2.47 (t, 2H, J
) 7.2 Hz), 2.70 (t, 2H, J ) 7.2 Hz), 3.50 (s, 2H), and 5.37 (s,
1H).
1
cm-1; H NMR (360 MHz, CDCl3) δ 1.30-1.51 (m, 4H), 1.45
(s, 9H), 4.75 (s, 2H), 7.20-7.41 (m, 5H) and 11.30 (brs, 1H);
13C NMR (75 MHz, CDCl3) δ 17.0, 29.0, 29.5, 32.6, 50.2, 59.9,
126.3, 127.0, 129.5, 140.0, 169.7, and 178.4. Anal.Calcd for
C16H21NO3: C, 69.78; H, 7.69; N, 5.09. Found: C, 69.65; H,
7.52; N, 4.97.
3-[1-(Ben zyl-ter t-bu tylca r ba m oyl)cyclop r op yl]-3-oxo-
p r op ion ic Acid Eth yl Ester . To a solution containing 1.1 g
(8.0 mmol) of 2-(carboethoxy)acetic acid in 50 mL of CH2Cl2
at 0 °C was slowly added 8.0 mL (16 mmol) of isopropylmag-
nesium chloride. The mixture was stirred at 0 °C for 30 min,
heated to 40 °C, and stirred for an additional 30 min. In a
separate flask, 1.0 mL (11 mmol) of oxalyl chloride and two
drops of DMF were slowly added to a solution of 2.0 g (7.3
mmol) of 1-(benzyl-tert-butylcarbamoyl)cyclopropanecarboxylic
acid in 50 mL of CH2Cl2. The solution was allowed to stir for
2 h at room temperature and was concentrated under reduced
pressure. The residue was dissolved in 5 mL of CH2Cl2, and
this solution was added to the above magnesium dianion
solution. The reaction mixture was stirred at 0 °C for 1 h and
quenched with 50 mL of a 50% HCl solution. The mixture was
extracted with CH2Cl2 and dried over anhydrous MgSO4, and
the solvent was removed under reduced pressure. Purification
of the crude oil by flash chromatography on silica gel gave 1.2
g (48%) of the title compound as a clear oil: IR (neat) 1737,
1694, 1637, and 1388 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.25
(t, 3H, J ) 7.1 Hz), 1.30-1.51 (m, 4H), 1.43 (s, 9H), 3.60 (s,
2H), 4.20 (q, 2H, J ) 7.1 Hz), 4.78 (s, 2H), and 7.20-7.41 (m,
5H); 13C NMR (75 MHz, CDCl3) δ 14.3, 14.4, 17.2, 28.6, 40.8,
46.2, 50.3, 59.1, 61.7, 126.5, 127.4, 128.8, 139.3, 167.1, 170.2,
and 199.2. Anal.Calcd for C20H27NO4: C, 69.53; H, 7.88; N,
4.06. Found: C, 69.41; H, 7.62; N, 3.97.
3-[1-(Ben zyl-ter t-bu tylcar bam oyl)cyclopr opyl]-2-diazo-
3-oxop r op ion ic Acid Eth yl Ester (8). To a stirred solution
of 1.2 g (3.5 mmol) of the above compound in 10 mL of
acetonitrile at 0 °C was added 1.2 g (8.4 mmol) of triethyl-
amine. The mixture was stirred at 0 °C for 30 min, and 0.8 g
(4.2 mmol) of tosyl azide was added in one portion. The
reaction mixture was stirred for 24 h at room temperature,
the solvent was removed under reduced pressure, and the
crude oil was purified by silica gel chromatography to give 1.0
g (80%) of 8 as a yellow oil which was used in the next step
without further purification: IR (neat) 2128, 1723, 1687, 1645,
and 1367 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.28 (t, 3H, J )
7.1 Hz), 1.20-1.31 (m, 4H), 1.36 (s, 9H), 4.25 (q, 2H, J ) 7.1
Hz), 4.71 (s, 2H), and 7.10-7.22 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 14.3, 14.5, 28.1, 38.1, 49.1, 58.5, 61.6, 125.8, 126.7,
128.0, 139.3, 160.5, 169.7, and 186.1.
Dim eth yl 5-Ca r boeth oxy-5,8-ep oxy-8-(ben zyl-ter t-bu -
t ylca r b a m oyl)-4-oxo-6-sp ir o[2.5]oct en e-6,7-d ica r b oxy-
la te (14). To a solution containing 0.17 mL (1.4 mmol) of
dimethyl acetylenedicarboxylate and 2 mg of rhodium(II)
acetate in 5 mL of refluxing benzene was added dropwise 0.06
g (0.17 mmol) of diazo amide 8. The reaction mixture was
heated at reflux for 30 min, and the solution was concentrated
under reduced pressure. The residue was purified by silica gel
chromatography to give 0.06 g (69%) of 14 as a clear oil: IR
(neat) 1737, 1694, and 1388 cm-1; 1H NMR (300 MHz, CDCl3)
δ 1.26 (t, 3H, J ) 7.1 Hz), 1.30-1.41 (m, 4H), 1.42 (s, 9H),
3.74 (s, 3H), 3.77 (s, 3H), 4.01-4.22 (m, 4H), and 7.10-7.22
(m, 5H); 13C NMR (75 MHz, CDCl3) δ 12.6, 13.9, 15.6, 29.5,
32.4, 51.5, 51.7, 52.5, 60.4, 62.3, 76.9, 77.2, 117.4, 117.5, 127.4,
128.1, 128.9, 129.3, 129.6, 158.6, 161.5, 164.7, 165.7, and 170.9.
Anal.Calcd for C26H31NO8: C, 64.30; H, 6.44; N, 2.89. Found:
C, 64.18; H, 6.22; N, 2.71.
1,4-Bis(1-p yr r olid in o)-2-bu ta n on e (39). To a solution
containing 0.099 g (0.6 mmol) diazopyrrolidinone 34 in 10 mL
of dry CH2Cl2 was added 2 mg of rhodium(II) acetate under
an argon atmosphere. After the solution was stirred overnight
at room temperature, the solvent was removed under reduced
pressure and the residue was chromatographed on a short
silica gel column. Elution with ethyl acetate gave 0.026 g (43%)
of 39 as a labile yellow oil which gradually decomposed on
standing: IR (neat) 2963, 2791, 1716, 1459, 1352 and 1142
cm-1; 1H NMR (300 MHz, CDCl3) δ 1.70-1.86 (m, 8H), 2.46-
2.61 (m, 4H), 2.61-2.72 (m, 4H), 2.64-2.80 (m, 4H), and 3.38
(s, 2H). In addition to compound 39, 1-(1-pyrrolidino)-3-buten-
2-one (38) (16%) was also formed but its high lability prevented
isolation of a pure sample. Its structure was determined by
its characteristic NMR spectrum: 1H NMR (300 MHz, CDCl3)
δ 1.60-1.78 (m, 4H), 2.38-2.56 (m, 4H), 3.47 (s, 2H), 5.72 (dd,
1H, J ) 10.4 and 1.7 Hz), 6.29 (dd, 1H, J ) 17.4 and 1.7 Hz),
and 6.45 (dd, 1H, J ) 17.4 and 10.4 Hz).
4-(Ben zylm eth yla m in o)-1-d ia zo-2-bu ta n on e (40). To a
1.59 g (9 mmol) sample of 4-bromo-1-diazo-2-butanone in 50
mL of ethyl acetate was added dropwise 2.2 g (18 mmol) of
N-benzyl-N-methylamine under an argon atmoshere. The
mixture was heated at 65 °C for 12 h, and the solid that formed
was filtered and the filtrate was concentrated under reduced
pressure. The resulting residue was purified by flash silica gel
chromatography to give 1.72 g (88%) of diazobutanone 40 as
a reddish yellow oil which was immediately used in the next
step: IR (neat) 2103, 1639, 1453, and 1360 cm-1; 1H NMR (300
MHz, CDCl3) δ 2.21 (s, 3H), 2.51 (t, 2H, J ) 6.9 Hz), 2.73 (t,
2H, J ) 6.9 Hz), 3.50 (s, 2H), 5.33 (s, 1H) and 7.25-7.35 (m,
5H).
1,4-Bis(ben zylm eth yla m in o)-2-bu ta n on e (43). To a solu-
tion containing 0.6 g (2.8 mmol) of diazobutanone 40 in 10 mL
of dry CH2Cl2 was added 2 mg of rhodium(II) acetate under
an argon atmosphere. After the solution was stirred overnight
at room temperature, the solvent was removed under reduced
pressure and the residue was chromatographed on silica gel
to give 0.22 g (51%) of 43 as a labile yellow oil which
decomposed on standing: IR (neat) 3027, 2944, 2789, 1717,
and 1453 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.16 (s, 3H), 2.27
(s, 3H), 2.61-2.72 (m, 4H), 3.16 (s, 2H), 3.46 (s, 2H), 3.55 (s,
2H), and 7.18-7.39 (m, 10 H). In addition to compound 43,
1-(benzylmethylamino)-3-buten-2-one (42) was also formed
(50% yield) but its high lability prevented isolation of a pure
sample. Its structure was determined by its characteristic
NMR spectrum: 1H NMR (300 MHz, CDCl3) δ 2.30 (s, 3H),
3.32 (s, 2H), 3.59 (s, 2H), 5.76 (dd, 1H, J ) 10.7 and 1.4 Hz),
6.30 (dd, 1H, J ) 17.6 and 1.4 Hz), 6.60 (dd, 1H, J ) 17.6 and
10.7 Hz), and 7.18-7.39 (m, 5 H).
4-(Ben zoylp h en yla m in o)-1-d ia zo-bu ta n -2-on e (44). N-
benzoyl-N-phenylaminopropanoic acid was prepared according
to literature procedures48 and was obtained as a yellow solid;
mp 74-75 °C. Treatment of 5.4 g (19 mmol) of the acid with
1.6 mL (20 mmol) of methyl chloroformate, 2.8 mL (20 mmol)
of triethylamine, and 45 mmol of ethereal diazomethane
afforded diazo ketoamide 44 in 82% yield as a yellow solid:
mp 74-75 °C; IR (neat) 2110, 1640, 1497, 1380, and 708 cm-1
;
(47) Rosenguist, N. R.; Chapman, D. L. J . Org. Chem. 1976, 41,
3326.
(48) Braunholtz, J . T.; Mann, G. F. J . Chem. Soc. 1957, 4166.
4-(1-P yr r olid in o)-1-d ia zo-2-bu ta n on e (34). A sample of
4-bromo-1-diazo-2-butanone was prepared according to a

Amido Diazo Carbonyl Compounds
J . Org. Chem., Vol. 65, No. 21, 2000 7131
1H NMR (300 MHz, CDCl3) δ 2.74 (t, 2H, J ) 7.5 Hz), 4.21 (t,
2H, J ) 7.5 Hz), 5.36 (s, 1H), and 6.98-7.34 (m, 10H); 13C
NMR (75 MHz, CDCl3) δ 37.9, 46.3, 54.5, 126.2, 127.1, 128.1,
128.6, 129.2, 135.0, 142.6, 170.0, and 191.9. Anal. Calcd for
reduced pressure, and the crude residue was chromatographed
on silica gel to give 3.2 g (52%) of diazo ketoamide 46 as a
yellow solid which was immediately used in the next step: mp
40-41 °C; IR (neat) 2110, 1660, 1390, 1105, and 710 cm-1; 1H
NMR (300 MHz, CDCl3) δ 0.71 (brs, 3H), 1.43 (brs, 2H), 2.75
(brs, 2H), 3.19 (brs, 2H), 3.73 (brs, 2H), 5.38 (s, 1H), and 7.23-
7.40 (m, 5H).
C
17H15N3O2: C, 69.61; H, 5.15; N, 14.33. Found: C, 69.65; H,
5.19; N, 14.28.
2,3-Dih yd r o-1,6-d ip h e n yl-5-h yd r oxy-4(1H )-p yr id in -
on e (49). Treatment of 0.85 g (2.9 mmol) of diazo ketoamide
44 in 10 mL of chloroform with 2 mg of rhodium(II) acetate
gave dihydropyridinone 49 in 71% yield as a pale yellow solid
after silica gel chromatography: mp 174-175 °C; IR (neat)
2,3-Dih yd r o-5-h yd r oxy-1-p r op yl-6-p h en yl-4-(1H)-p yr i-
d in on e (51). To a solution containing 0.35 g (1.36 mmol) of
R-diazo ketoamide 46 in 10 mL of dichloromethane was added
2 mg of rhodium(II) acetate, and the mixture was stirred for
2 h at room temperature. The solvent was removed under
reduced pressure, and the crude residue was purified by silica
gel chromatography to give dihydropyridinone 51 as a yellow
solid in 82% yield: mp 97-98 °C; IR (neat) 3380, 1660, 1550,
1
3380, 1640, 1587, 1283, and 1200 cm-1; H NMR (300 MHz,
CDCl3) δ 2.68 (t, 2H, J ) 6.9 Hz), 4.16 (t, 2H, J ) 6.9 Hz),
5.83 (s, 1H), and 6.88-7.54 (m, 10H); 13C NMR (75 MHz,
CDCl3) δ 32.8, 51.9, 122.9, 123.7, 127.4, 128.3, 128.5, 129.6,
1
132.0, 134.6, 140.2, 145.5, and 188.2. Anal. Calcd for C17H15
-
1290, 770, and 720 cm-1; H NMR (300 MHz, CDCl3) δ 0.73
NO2: C, 76.96; H, 5.70; N, 5.28. Found: C, 77.14; H, 5.75; N,
5.20.
(t, 3H, J ) 7.2 Hz), 1.50 (m, 2H), 2.60 (t, 2H, J ) 7.5 Hz), 2.94
(t, 2H, J ) 7.2 Hz), 3.54 (t, 2H, J ) 7.5 Hz), 5.24 (s, 1H), and
7.25-7.45 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 11.0, 22.3,
33.5, 47.1, 53.5, 128.3, 128.7, 129.1, 130.4, 132.0, 148.6, and
184.5. Anal. Calcd for C14H17NO2: C, 72.70; H, 7.41; N, 6.06.
Found: C, 72.43; H, 7.55; N, 5.87.
4-(Ben zoylm eth yla m in o)-1-d ia zo-bu ta n -2-on e (45). A
sample of diazo ketoamide 45 was prepared from 3.0 g (22
mmol) of N-methylbenzamide and 2 mL (22 mmol) of methyl
acrylate using a procedure similar to that described above: IR
(neat) 2110, 1630, 1385, and 1353 cm-1. The high-field NMR
showed that diazo ketoamide 45 exists as a 3:1 mixture of
nitrogen rotamers: 1H NMR (300 MHz, CDCl3; major) δ 2.72
(brs, 2H), 2.97 (s, 3H), 3.78 (brs, 2H), 5.49 (s, 1H) and 7.83 (s,
5H); 13C NMR (75 MHz, CDCl3) δ 37.7, 38.4, 43.3, 54.4, 126.2,
127.7, 128.9, 135.6, 170.8, and 192.3; 1H NMR (300 MHz,
CDCl3; minor) δ 2.49 (brs, 2H), 3.03 (s, 3H), 3.57 (brs, 2H),
5.31 (s, 1H), and 7.83 (s, 5H); 13C NMR (75 MHz, CDCl3) δ
32.2, 38.4, 46.3, 54.7, 125.8, 127.7, 128.9, 135.6, 170.9, and
192.2. This compound was used in the next step without
further purification
1-(4-Dia zo-3-oxobu tyl)-2-p yr r olid on e (52). To a solution
containing 4.1 g (26 mmol) of 3-(2-oxopyrrolidin-1-yl)propionic
acid49 and 3.9 mL (26 mL) of hexachloroacetone in 40 mL of
dry THF at -78 °C was added dropwise a solution of 6.7 g (26
mmol) of triphenylphosphine in 20 mL of dry THF. After the
addition was complete, the mixture was stirred at -78 °C for
1 h and was allowed to warm to room temperature for 30 min.
The crude acid chloride solution was cannulated into 100 mmol
of a diazomethane ethereal solution, and the resulting mixture
was stirred at room temperature overnight. The mixture was
concentrated under reduced pressure, and the residue was
purified by silica gel chromatography to give 2.3 g (41%) of
diazopyrrolidone 52 as a yellow solid: mp 60-62 °C; IR (neat)
2,3-Dih yd r o-5-h yd r oxy-1-m eth yl-6-p h en yl-4(1H)-p yr i-
d on e (50). Treatment of a 0.26 g (1.1 mmol) sample of diazo
ketoamide 45 in 5 mL of CHCl3 with 2 mg of rhodium(II)
acetate afforded dihydropyridone 50 in 75% yield: mp 136-
1
2105, 1680, 1645, 1380, and 1355 cm-1; H NMR (300 MHz,
CDCl3) δ 1.98 (q, 2H, J ) 7.5 Hz), 2.33 (t, 2H, J ) 7.5 Hz),
2.58 (brs, 2H), 3.40 (t, 2H, J ) 6.6 Hz), 3.54 (t, 2H, J ) 6.6
Hz), and 5.34 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 17.4, 30.2,
37.8, 38.0, 47.3, 54.3, 174.5, and 191.9. Anal. Calcd for
C8H11N3O2: C, 53.03; H, 6.12; N, 23.19. Found: C, 53.13; H,
6.16; N, 23.23.
137 °C; IR (neat) 3385, 1643, 1275, 1203, and 780 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 2.64 (t, 2H, J ) 7.7 Hz), 2.70 (s,
3H), 3.47 (t, 2H, J ) 7.7 Hz), 5.22 (brs, 1H), and 7.35-7.52
(m, 5H); 13C NMR (75 MHz, CDCl3) δ 32.8, 40.2, 49.9, 127.9,
128.1, 128.6, 130.5, 131.7, 148.3, and 184.6. Anal. Calcd for
8-Hyd r oxy-2,3,5,6-tetr a h yd r o-1H-in d olizin -7-on e (53).
Treatment of 0.2 g of diazopyrrolidone 52 in 5 mL of chloroform
with 2 mg of rhodium(II) acetate at room temperature for 12
h afforded hydroxyindolizinone 53 in 86% yield: mp 154-155
°C; IR (neat) 3320, 1670, 1547, 1500, 1270, and 1205 cm-1; 1H
NMR (300 MHz, CDCl3) δ 2.07 (tt, 2H, J ) 7.6 and 7.0 Hz),
2.56 (t, 2H, J ) 7.8 Hz), 2.82 (t, 2H, J ) 7.6 Hz), 3.26 (t, 2H,
J ) 7.0 Hz), 3.29 (t, 2H, J ) 7.8 Hz), and 5.24 (brs, 1H); 13C
NMR (75 MHz, CDCl3) δ 21.3, 27.7, 33.6, 45.9, 53.4, 126.9,
154.4, and 182.1. Anal. Calcd for C8H11NO2: C, 62.71; H, 7.24;
N, 9.15. Found: C, 62.68; H, 7.18; N, 9.06.
9,10-Dica r bom eth oxy-1,2,3,5,6,7-h exa h yd r o-8-h yd r oxy-
p yr r olo[1,2a ]-a zocin -7-on e (55).Treatment of a 0.2 g sample
of diazo ketoamide 52 in 5 mL of chloroform with 2 mg of
rhodium(II) acetate at 25 °C for 12 h in the presence of 1.2
equiv of dimethyl acetylenedicarboxylate afforded a mixture
of two major products. The minor fraction isolated (32%) from
the silica gel column corresponded to hydroxyindolizinone 53.
The major fraction (40%) isolated from the column was
assigned as pyrrolo[1,2-a]azocinone 55 on the basis of its
spectral data: mp 159-160 °C; IR (neat) 1730, 1655, 1540,
1445, 1405, 1270, and 1210 cm-1; 1H NMR (300 MHz, CDCl3)
δ 2.00-2.14 (m, 2H), 2.21-2.52 (m, 4H), 3.80 (s, 3H), 3.98 (s,
3H), 3.98-4.17 (m, 2H), 4.21 (ddd, 1H, J ) 10.7, 10.2, and 7.6
Hz), 4.52 (dd, 1H, J ) 10.2 and 7.6 Hz), and 6.83 (s, 1H); 13C
NMR (75 MHz, CDCl3) δ 17.9, 31.1, 32.2, 52.4, 53.8, 62.0, 63.2,
113.6, 124.9, 141.7, 161.3, 162.3, 178.7, and 181.2. Anal. Calcd
for C14H17NO6: C, 56.95; H, 5.80; N, 4.74. Found: C, 56.85;
H, 5.79; N, 4.74.
C
12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 71.08; H,
6.48; N, 6.80.
4-(Ben zoylp r op yla m in o)-1-d ia zobu ta n -2-on e (46). A so-
lution containing 3.1 g (36 mmol) of methyl acrylate and 3.4 g
(57 mmol) of propylamine in 25 mL of chloroform was stirred
at 40 °C for 12 h. The solvent was removed under reduced
pressure to give 5.0 g (95%) of methyl 3-(propylamino)-
propanoate as a colorless liquid: IR (neat) 3430, 2970, 1750,
1460, 1200, and 755 cm-1; H NMR (300 MHz, CDCl3) δ 0.87
(t, 3H, J ) 7.2 Hz), 1.35-1.60 (m, 3H), 2.48 (t, 2H, J ) 6.6
Hz), 2.54 (d, 2H, J ) 7.2 Hz), 2.84 (t, 2H, J ) 6.6 Hz), and
3.60 (s, 3H).
1
The above compound was dissolved in 15 mL of chloroform,
and then 5.8 mL (50 mmol) of benzoyl chloride was added. The
resulting mixture was stirred at room temperature for 2 h.
The solvent was removed under reduced pressure, and the
crude product was chromatographed on silica gel to give 8.9 g
(90%) of methyl 3-(benzoylpropylamino)pentanoate as a color-
less oil: IR (neat) 2957, 1734, 1631, 1419, 1254, 1146, 784,
and 700 cm-1 1H NMR (300 MHz, CDCl3) δ 0.77 (brs, 3H),
;
1.61 (brs, 2H), 2.78 (brs, 2H), 3.23 (brs, 2H), 3.72 (brs, 5H),
and 7.35-7.50 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 10.9, 21.9,
32.3, 41.3, 51.5, 51.6, 126.4, 128.3, 129.2, 136.6, 167.6, and
171.9; HRMS (m/e) calcd for C14H19NO3 249.1365, found
249.1363.
A mixture containing 5.0 g (20 mmol) of the above compound
and 5.1 g (40 mmol) of potassium trimethylsilanolate in 150
mL of tetrahydrofuran was heated at reflux for 5 h, and then
3.1 mL (40 mmol) of methyl chloroformate was added. The
mixture was allowed to stir for 3 h at room temperature, and
the solid that formed was filtered. To the filtrate was added
80 mmol of ethereal diazomethane at 0 °C, and the resulting
solution was stirred overnight. The solvent was removed under
1-(4-Dia zo-3-oxo-bu tyl)p ip er id in -2-on e (56). To a solu-
tion containing 1.0 g (5.8 mmol) of 3-(2-oxopiperidin-1-yl)-
(49) Morosawa, S.; Yokoo, A. Bull. Soc. Chem. J pn. 1963, 36, 179.

7132 J . Org. Chem., Vol. 65, No. 21, 2000
Padwa et al.
propionic acid50 and 1.6 g (5.8 mmol) of hexachloroacetone in
20 mL of dry THF was added dropwise a solution of 1.5 g (5.8
mmol) of triphenylphosphine in 10 mL of THF at -78 °C. The
resulting mixture was stirred at -78 °C for 1 h and allowed
to warm to room temperature. The resulting acid chloride
solution was cannulated into 25 mmol of a diazomethane
ethereal solution. The resultant solution was stirred at room
temperature overnight, and the mixture was then concentrated
under reduced pressure. The residue was purified by silica gel
chromatography to give 0.46 g (41%) of 56 as a pale yellow
solid: mp 54-56 °C; IR (neat) 2945, 2100, 1726, 1624, and
18.3, 31.1, 37.6, 41.1, 48.4, 49.3, 61.7, 167.2, 175.6, and 201.6.
Anal. Calcd for C11H17NO4: C, 58.14; H, 7.54; N, 6.16. Found:
C, 58.39; H, 7.78; N, 6.09.
2-Dia zo-3-oxo-5-(2-oxop yr r olid in -1-yl)p en ta n oic Acid
Eth yl Ester (60). A mixture containing 2.0 g (8.8 mmol) of
the above keto ester, 2.4 g (11 mmol) of p-nitrobenzenesulfonyl
azide, and 3.7 mL (26 mmol) of triethylamine in 50 mL of CH2-
Cl2 was stirred at room temperature for 20 h. The mixture
was concentrated under reduced pressure, and the residue was
purified by silica gel chromatography to give 1.8 g (83%) of
diazo amido ester 60 as a yellow oil: IR (neat) 2981, 2138,
1714, 1690, and 1297 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.30
(t, 3H, J ) 7.2 Hz), 1.98 (p, 2H, J ) 7.2 Hz), 2.33 (t, 2H, J )
7.2 Hz), 3.08 (t, 2H, J ) 7.2 Hz), 3.41 (t, 2H, J ) 7.2 Hz), 3.59
(t, 2H, J ) 7.2 Hz), and 4.27 (q, 2H, J ) 7.2 Hz); 13C NMR (75
MHz, CDCl3) δ 14.5, 18.2, 31.1, 38.2, 38.4, 47.8, 61.8, 161.4,
175.3, and 190.9. Anal. Calcd for C11H15N3O4: C, 52.17; H,
5.97; N, 16.59. Found: C, 52.33; H, 6.04; N, 16.39.
1
1358 cm-1; H NMR (400 MHz, CDCl3) δ 1.72-1.79 (m, 4H),
2.32 (t, 2H, J ) 5.6 Hz), 2.60 (m, 2H), 3.31 (t, 2H, J ) 5.6
Hz,), 3.57 (t, 2H, J ) 7.2 Hz), and 5.36 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 21.4, 23.5, 32.5, 38.8, 44.0, 49.2, 55.3, 170.4,
and 193.4. Anal. Calcd for C9H13N3O2: C, 55.37; H, 6.71; N,
21.52. Found: C, 55.25; H, 6.69; N, 21.42.
1-Hyd r oxy-3,4,6,7,8,9-h exa h yd r oqu in olizin -2-on e (57).
To a suspension containing 10 mg of Rh2(OAc)4 in 50 mL of
CH2Cl2 was added dropwise a solution of 0.9 g (4.6 mmol) of
diazo ketone 56 in 50 mL of CH2Cl2 at room temperature under
an argon atmosphere. After the addition was complete, the
mixture was allowed to stir at room temperature for 3 h and
was concentrated under reduced pressure. The residue was
purified by silica gel chromatography to give 0.5 g (65%) of 57
as a yellow solid: mp 115-117 °C; IR (neat) 3342, 2941, 1622,
1563, and 1288 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.63-1.71
(m, 2H), 1.78-1.85 (m, 2H), 2.48 (t, 2H, J ) 7.8 Hz), 2.64 (t,
2H, J ) 6.6 Hz), 3.10 (t, 2H, J ) 6.6 Hz), 3.23 (t, 2H, J ) 7.8
Hz), and 5.28 (brs, 1H); 13C NMR (75 MHz, CDCl3) δ 19.8, 23.4,
23.5, 33.6, 50.4, 51.3, 129.6, 149.2, and 182.0. Anal. Calcd for
C9H13NO2: C, 64.65; H, 7.84; N, 8.38. Found: C, 64.63; H, 7.84;
N, 8.37.
1,8-Dioxoh exah ydr oin dolizin e-8a -car boxylic Acid Eth -
yl Ester (64). To a solution containing 0.76 g (3.0 mmol) of
diazo amido ester 60 in 100 mL of CH2Cl2 was added 10 mg of
Rh2(OAc)4 under an argon atmosphere. After the solution was
stirred at room temperature for 2 h, the mixture was concen-
trated under reduced pressure and the residue was purified
by flash silica gel chromatography to give 0.54 g (80%) of 64
as a pale yellow oil: IR (neat) 2940, 1773, 1744, 1720, and
1
1248 cm-1; H NMR (400 MHz, CDCl3) δ 1.30 (t, 3H, J ) 7.2
Hz), 2.03-2.09 (m, 1H), 2.41-2.63 (m, 5H), 3.02-3.07 (m, 1H),
3.16-3.22 (m, 1H), 3.30-3.35 (m, 1H), 3.38-3.45 (m, 1H), and
4.31 (dq, 2H, J ) 7.2 and 2.0 Hz); 13C NMR (75 MHz, CDCl3)
δ 14.3, 25.6, 36.2, 39.4, 45.4, 45.5, 62.9, 81.3, 165.6, 201.3, and
202.6; HRMS (m/e) calcd for C11H15NO4 225.1001, found
225.1004.
3-Oxo-5-(2-oxop ip er id in -1-yl)p en ta n oic Acid Eth yl Es-
ter . A mixture containing 5.0 g (29 mmol) of 3-(2-oxopiperidin-
1-yl)propionic acid and 4.7 g (29 mmol) of carbonyldiimidazole
in 80 mL of dry THF was stirred at room temperature for 6 h.
The resulting acylimidazole solution was used directly in the
next step. To a solution of 3.8 g (29 mmol) of ethyl hydrogen
malonate in 30 mL of dry THF was added dropwise 29 mL
(58 mmol) of 2 M isopropylmagnesium chloride/THF solution
at 0 °C. The mixture was stirred at room temperature for 2 h,
and the above acyl imidazole solution was cannulated into this
suspension. The resulting mixture was maintained at room
temperature for 16 h, quenched with 2 M HCl solution, and
extracted with CH2Cl2. The combined organic layers were
washed with brine, dried over Na2SO4, and concentrated under
reduced pressure, and the residue was purified by silica gel
chromatography to give 4.1 g (59%) of the titled compound as
a white solid: mp 50-52 °C; IR (neat) 3442, 2934, 1742, 1711,
9-Hyd r oxy-8-oxo-1,3,4,6,7,8-h exa h yd r o-2H-p yr id o[1,2a ]-
a zocin e-10, 11-d ica r boxylic Acid Dim eth yl Ester (58). To
a suspension containing 5 mg of Rh2(OAc)4 and 0.078 g (0.55
mmol) of DMAD in 4 mL of CH2Cl2 was added dropwise a
solution of 0.07 g (0.36 mmol) of diazo ketone 56 in 6 mL of
CH2Cl2 at room temperature under an argon atmosphere. The
mixture was allowed to stir at room temperature for 4 h and
was concentrated under reduced pressure. The residue was
purified by silica gel chromatography to give 0.074 g (67%) of
cycloadduct 58 as a yellow solid: mp 141-143 °C: IR (neat)
1
3483, 2954, 1738, 1437, and 1264 cm-1; H NMR (300 MHz,
CDCl3) δ 1.54-1.78 (m, 5H), 2.11-2.41 (m, 3H), 2.71 (dt, 1H,
J ) 10.5 and 2.7 Hz), 2.83-2.94 (m, 3H), 3.28 (s, 1H), 3.84 (s,
3H), and 3.92 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 20.7, 24.7,
28.3, 38.6, 49.2, 52.1, 52.9, 53.2, 76.2, 90.3, 130.8, 160.9, 165.3,
173.6, and 200.9. Anal. Calcd for C15H19NO6: C, 58.25; H, 6.19;
N, 4.53. Found: C, 58.47; H, 6.15; N, 4.52.
1630, and 1332 cm-1 1H NMR (400 MHz, CDCl3) δ 1.27 (t,
;
3-Oxo-5-(2-oxop yr r olid in -1-yl)p en t a n oic Acid E t h yl
Ester . A mixture containing 5.0 g (32 mmol) of 3-(2-oxopyr-
rolidin-1-yl)propionic acid and 5.2 g (32 mmol) of carbonyldi-
imidazole (CDI) in 80 mL of dry THF was stirred at room
temperature for 6 h. The resulting acylimidazole solution was
used directly in the next step reaction. To a solution of 4.2 g
(32 mmol) of ethyl hydrogen malonate in 35 mL of dry THF
was added dropwise 32 mL (64 mmol) of a 2 M isopropylmag-
nesium chloride/THF solution at 0 °C. The mixture was stirred
at room temperature for 2 h, and the above acyl imidazole
solution was cannulated into this suspension. The resulting
mixture was maintained at room temperature for 16 h,
quenched with a 2 M HCl solution, and extracted with CH2-
Cl2. The combined organic layers were washed with brine,
dried over Na2SO4, and concentrated under reduced pressure,
and the residue was purified by silica gel chromatography to
give 4.1 g (56%) of the titled compound as a colorless oil: IR
(neat) 3457, 2980, 1737, 1710, 1680, and 1291 cm-1; 1H NMR
(400 MHz, CDCl3) δ 1.27 (t, 3H, J ) 7.2 Hz), 1.99 (p, 2H, J )
7.2 Hz), 2.34 (t, 2H, J ) 7.2 Hz), 2.85 (t, 2H, J ) 6.8 Hz), 3.42
(t, 2H, J ) 7.2 Hz), 3.46 (s, 2H), 3.54 (t, 2H, J ) 6.8 Hz), and
4.18 (q, 2H, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 14.3,
3H, J ) 7.2 Hz), 1.75-1.78 (m, 4H), 2.34 (t, 2H, J ) 7.2 Hz),
2.89 (t, 2H, J ) 6.8 Hz), 3.34 (t, 2H, J ) 7.2 Hz), 3.47 (s. 2H),
3.57 (t, 2H, J ) 6.8 Hz), and 4.18 (q, 2H, J ) 7.2 Hz); 13C NMR
(75 MHz, CDCl3) δ 14.3, 21.4, 23.5, 32.5, 41.1, 43.0, 49.3, 49.5,
61.6, 167.3, 170.4, and 202.1. Anal. Calcd for C12H19NO4: C,
59.73; H, 7.94; N, 5.80. Found: C, 59.49; H, 7.93; N, 5.65.
2-Dia zo-3-oxo-5-(2-oxop ip er id in -1-yl)p en t a n oic Acid
Eth yl Ester (61). A mixture containing 2.9 g (12 mmol) of
the above keto ester, 3.2 g (14 mmol) of p-nitrobenzenesulfonyl
azide, and 4.8 mL (35 mmol) of triethylamine in 80 mL of CH2-
Cl2 was stirred at room temperature for 20 h. The mixture
was concentrated under reduced pressure, and the residue was
purified by silica gel chromatography to give 2.5 g (80%) of 61
as a yellow oil: IR (neat) 2947, 2135, 1717, 1643, and 1299
1
cm-1; H NMR (400 MHz, CDCl3) δ 1.31 (t, 3H, J ) 7.2 Hz),
1.76-1.77 (m, 4H), 2.32 (t, 2H, J ) 6.8 Hz), 3.12 (t, 2H, J )
6.8 Hz), 3.32 (t, 2H, J ) 6.8 Hz), 3.64 (t, 2H, J ) 7.2 Hz), and
4.28 (q, 2H, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 14.5,
21.5, 23.4, 32.5, 38.3, 43.2, 48.7, 61.6, 161.4, 170.0, and 191.3.
Anal. Calcd for C12H17N3O4: C, 53.92; H, 6.41; N, 15.72.
Found: C, 53.76; H, 6.65; N, 15.72.
1,9-Dioxoh exa h yd r op yr r olo[1,2-a ]a zep in e-9a -ca r box-
ylic Acid Eth yl Ester (65). A mixture containing 8 mg of
Rh2(OAc)4 and 0.5 g (1.9 mmol) of diazo amido ester 61 in 80
(50) Adams, R.; J ones, V. V. J . Am. Chem. Soc. 1949, 71, 3826.

Amido Diazo Carbonyl Compounds
J . Org. Chem., Vol. 65, No. 21, 2000 7133
mL of CH2Cl2 was stirred at room temperature for 2 h under
an argon atmosphere. The mixture was concentrated under
reduced pressure, and the residue was purified by flash silica
gel chromatography to give 0.31 g (72%) of 65 as a pale yellow
oil: IR (neat) 2940, 1768, 1727, 1706, and 1230 cm-1; 1H NMR
(400 MHz, CDCl3) δ 1.30 (t, 3H, J ) 7.2 Hz), 1.59-1.65 (m,
1H), 1.76-1.90 (m, 3H), 2.54-2.61 (m, 3H), 2.73-2.81 (m, 1H),
3.02-3.20 (m, 3H), 3.32-3.37 (m, 1H), and 4.27 (dq, 2H, J )
7.2 and 2.0 Hz); 13C NMR (75 MHz, CDCl3) δ 14.5, 22.3, 28.5,
36.8, 42.2, 48.5, 50.7, 62.1, 82.6, 166.1, 202.6, and 203.2. Anal.
Calcd for C12H17NO4: C, 60.24; H, 7.16; N, 5.85. Found: C,
60.05; H, 7.25; N, 5.84.
The resulting solution was stirred at room temperature for 1
h. The solvent was removed under reduced pressure, and the
crude product was subjected to flash chromatography on silica
gel to give 0.45 g (63%) of cycloadduct 68 as a white solid: mp
142-143 °C; IR (KBr) 1727, 1717, 1395, 1328, and 1283 cm-1
;
1H NMR (300 MHz, CDCl3) δ 2.62-2.71 (m, 1H), 2.97-3.14
(m, 2H), 3.55 (s, 3H), 3.90 (s, 3H), 4.52-4.60 (m, 1H), 5.42 (s,
1H), 7.55-7.68 (m, 3H), 7.89 (dd, 1H, J ) 6.3 and 1.5 Hz); 13
C
NMR (75 MHz, CDCl3) δ 32.8, 42.8, 52.7, 53.1, 87.8, 102.9,
123.2, 123.7, 131.0, 132.1, 132.7, 135.4, 139.6, 139.8, 160.5,
160.7, 164.8, and 205.2. Anal. Calcd for C18H15NO7: C, 60.51;
H, 4.23; N, 3.92. Found: C, 60.41; H, 4.27; N, 3.85.
9-Oxo-13-oxa -6-a za t r icyclo[8.2.1.01,6]t r id e c-11-e n e -
10,11,12-t r ica r b oxylic Acid 10-E t h yl E st er 11,12-Di-
m eth yl Ester (66). A mixture containing 10 mg of Rh2(OAc)4,
0.27 g (1.0 mmol) of diazo amido ester 61, and 0.14 g (1.0 mmol)
of DMAD in 10 mL of CH2Cl2 was stirred at room temperature
for 4 h under an argon atmosphere. The mixture was concen-
trated under reduced pressure, and the residue was purified
by flash silica gel chromatography to give 0.053 g (22%) of 65
and 0.14 g (38%) of cycloadduct 66 as a pale yellow solid: mp
Rh odiu m (II)-Catalyzed Cycloaddition Reaction of 1-Di-
a zo-4-p h th a lim id o-2-bu ta n on e (67) w ith N-P h en ylm a le-
im id e. A mixture containing 0.5 g (2 mmol) of diazoimide 67,
2 mg of rhodium(II) octanoate, and 0.35 g (2.0 mmol) of
N-phenyl-maleimide in 15 mL of dichloromethane was allowed
to stir for 10 h at 25 °C. Standard workup followed by silica
gel chromatography afforded cycloadduct 69 in 45% yield: mp
230-232 °C; IR (CHCl3) 1723, 1396, 1182, and 1054 cm-1; 1H
NMR (360 MHz, CDCl3) δ 2.73 (dd, 1H, J ) 13.3 and 5.0 Hz),
3.00-3.20 (m, 2H), 3.70 (d, 1H, J ) 8.0 Hz), 3.91 (d, 1H, J )
8.0 Hz), 4.70-4.85 (m, 1H), 5.22 (s, 1H), and 7.20-7.90 (m,
9H); 13C NMR (75 MHz, DMSO) δ 32.3, 43.2, 51.5, 52.0, 85.7,
100.1, 123.0, 124.1, 127.0, 128.9, 129.2, 130.8, 131.1, 131.9,
132.3, 139.8, 163.7, 172.8, 175.1, and 210.3. Anal. Calcd for
105-106 °C; IR (neat) 2950, 1721, 1649, 1434, and 1250 cm-1
;
1H NMR (400 MHz, CDCl3) δ 1.30 (t, 3H, J ) 7.2 Hz), 1.59-
1.70 (m, 1H), 1.75-1.96 (m, 2H), 2.05-2.14 (m, 1H), 2.59-
2.71 (m, 2H), 2.75-2.81 (m, 1H), 2.99-3.02 (m, 2H), 3.12-
3.20 (m, 1H), 3.72 (s, 3H), 3.76-3.80 (m, 1H), 3.82 (s, 3H), 4.24
(q, 2H, J ) 7.2 Hz), and 4.37 (brs, 1H); 13C NMR (75 MHz,
CDCl3) δ 14.5, 20.0, 20.4, 38.2, 43.2, 47.7, 51.1, 52.2, 52.3, 62.3,
71.7, 80.9, 139.5, 150.8, 161.7, 162.2, 168.7, and 204.0. Anal.
Calcd for C18H23NO8: C, 56.69; H, 6.08; N, 3.67. Found: C,
56.58; H, 6.12; N, 3.54.
C
22H16N2O5: C, 68.04; H, 4.15; N, 7.21. Found: C, 68.04; H,
4.06; N, 7.06.
The second product isolated from the silica gel column in
26% yield was assigned as the rearrangement product 70: mp
163-164 °C; IR (neat) 1773, 1717, 1397, 1187, 1073, and 720
1-Dia zo-4-p h th a lim id o-2-bu ta n on e (67). A solution con-
taining 4.5 g (19 mmol) of N-phthalyl-â-alanine in 20 mL of
thionyl chloride was allowed to stir at room temperature for 4
h. Removal of the excess thionyl chloride under reduced
pressure afforded the acid chloride as a white solid which was
immediately used in the next step. To a freshly prepared
diazomethane (45 mmol) ether solution at 0 °C was slowly
added a tetrahydrofuran solution containing the above acid
chloride. The reaction mixture was stirred for several hours
at 25 °C, and the resulting solid was filtered and washed with
ether to give 4.8 g (98%) of diazoimide 67 as a yellow solid:
mp 129-130 °C; IR (CHCl3) 2108, 1769, 1641, 1364, 1317,
1
cm-1; H NMR (300 MHz, CDCl3) δ 2.47 (t, 2H, J ) 6.7 Hz),
3.59 (dt, 1H, J ) 14.1 and 6.7 Hz), 3.82 (dt, 1H, J ) 14.1 and
6.7 Hz), 6.14 (s, 1H), 6.27 (d, 1H, J ) 6.0 Hz), 6.57 (d, 1H, J
) 6.0 Hz), 7.20-7.36 (m, 5H), and 7.71-7.87 (m, 4H); 13C NMR
(75 MHz, CDCl3) δ 23.4, 34.8, 119.8, 123.2, 123.9, 127.5, 127.7,
128.0, 128.8, 131.7, 133.4, 134.0, 137.4, 140.8, 167.6, and 167.8.
Anal. Calcd for C22H16N2O5 C, 68.04; H, 4.15; N, 7.21. Found:
C, 68.00; H, 4.17; N, 7.16.
Ack n ow led gm en t. We gratefully acknowledge the
National Institutes of Health (Grant GM59384) for their
generous support of this work. We also wish to thank
Lin Zhi and Kimberly J . Worsencroft for some experi-
mental assistance.
1
1143, and 995 cm-1; H NMR (90 MHz, CDCI3) δ 2.77 (t, 2H,
J ) 7.5 Hz), 4.01 (t, 2H, J ) 7.5 Hz), 5.32 (s, 1H), and 7.66-
7.93 (m, 4H). Anal. Calcd for C12H9N3O4: C, 59.26; H, 3.73;
N, 17.28. Found: C, 59.00; H, 3.69; N, 17.12.
1 1 ,1 2 -D i c a r b o m e t h o x y -5 ,9 -d i o x o -1 0 ,1 2a -e p o x y -
5,7,8,9,10,12a -h exa h yd r oa z ocin o[2,1a ]isoin d ole (68). To
a solution containing 0.5 g (2.0 mmol) of diazoimide 67 and
0.4 g (2.8 mmol) of dimethyl acetylenedicarboxylate in 15 mL
of dichloromethane was added 2 mg of rhodium(II) acetate.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectrum
for compound 64. This material is available free of charge via
the Internet at http://pubs.acs.org.
J O0009144