Rhodium generated carbonyl ylides with p-quinones: Synthesis of oxa-bridged polycyclic systems

Article abstract of DOI:10.1016/S0040-4020(01)00657-3

A series of α-diazo carbonyl compounds tethered to substituted cyclopentanone and cyclohexanone units with different tether lengths have been synthesized using diazomethane solution or methanesulphonyl azide. The above synthesized α-diazo carbonyl compounds with rhodium(II) acetate dimer furnish cyclic five- or six-membered-ring carbonyl ylide dipoles, which undergo facile 1,3-dipolar cycloaddition with p-quinones to furnish various novel oxa-bridged polycyclic systems 10, 13 and 11, 14 as C=C and C=O addition products of p-quinones. Very interesting unusual cyclization product, tri-oxapolycyclic compounds 12 and 15 were also obtained. Single-crystal X-ray analyses of 11a, 12d and 14a are reported to firmly establish the structure and stereochemistry of the oxa-bridged polycyclic systems. The molecules 11a and 14a exhibit novel C-H···O hydrogen bonding motif in the crystal structure. On the other hand, the molecule 12d revealed both O-H···O and C-H···O motifs in the solid-state architecture.

Full text of DOI:10.1016/S0040-4020(01)00657-3

TETRAHEDRON
Pergamon
Tetrahedron 57 12001) 7009±7019
Rhodium generated carbonyl ylides with p-quinones:
synthesis of oxa-bridged polycyclic systems
Sengodagounder Muthusamy,p Srinivasarao Arulananda Babu, Chidambaram Gunanathan,
Eringathodi Suresh, Parthasarathi Dastidar and Raksh Vir Jasra
Silicates and Catalysis Discipline, Central Salt and Marine Chemicals Research Institute, Bhavnagar 364 002, India
Received 5 March 2001; revised 30 May 2001; accepted 14 June 2001
AbstractÐA series of a-diazo carbonyl compounds tethered to substituted cyclopentanone and cyclohexanone units with different tether
lengths have been synthesized using diazomethane solution or methanesulphonyl azide. The above synthesized a-diazo carbonyl compounds
with rhodium1II) acetate dimer furnish cyclic ®ve- or six-membered-ring carbonyl ylide dipoles, which undergo facile 1,3-dipolar cyclo-
addition with p-quinones to furnish various novel oxa-bridged polycyclic systems 10, 13 and 11, 14 as CvC and CvO addition products of
p-quinones. Very interesting unusual cyclization product, tri-oxapolycyclic compounds 12 and 15 were also obtained. Single-crystal X-ray
analyses of 11a, 12d and 14a are reported to ®rmly establish the structure and stereochemistry of the oxa-bridged polycyclic systems. The
molecules 11a and 14a exhibit novel C±H´´´O hydrogen bonding motif in the crystal structure. On the other hand, the molecule 12d revealed
both O±H´´´O and C±H´´´O motifs in the solid-state architecture. q 2001 Elsevier Science Ltd. All rights reserved.
9
1. Introduction
zaragozicaicd A
and oxygenated sesquiterpenes like
sambucinol10 2. The angularly condensed tetracyclic
skeleton 13 are important intermediates and can be utilized
in the synthesis of angucycline11 antibiotics which obtained
recently much attention due to their wide range of biological
activity and their interesting chemical structures especially
aquayamycin 3a and elmycin A 3b.
The tandem cyclization±cycloaddition chemistry of
rhodium carbenoids has been developed as a general
approach1 to oxa-bridged ring systems. 1,3-Dipolar
cycloaddition offers a versatile route2 for the construction
of a variety of complex ®ve-membered heterocycles that are
synthetically useful compounds. The carbonyl ylide 1,3-
dipolar cycloaddition reactions have been applied to the
synthesis of variety of natural products such as illudin3
1sesquiterpene), phorbol esters4 1diterpene), vindoline5
1alkaloid) and brevicomin6 1pheromone).
Moreover, the oxa-tetracyclic compounds having benzo-
quinone skeleton 10 are potential intermediates and can be
applied in the synthesis of diterpenoids like abietane
quinones7 such as 1. Dioxa-bridged ring systems are present
in the natural molecules like brevicomin,6 amberketal,8
As a consequence of our interest in the synthesis of new
oxa-polycyclic systems,12 we became aware that the only
one recent report13 available on the dipolar cycloaddition of
carbonyl ylides with p-quinones. As an approach to oxy-
genated sesquiterpenoids and angucycline antibiotics,
starting from cycloalkanoic acids 5, we herein report our
Keywords: benzoquinone; carbonyl ylides; dipolar cycloaddition; diazo
compounds; naphthoquinones; rhodium acetate catalyst.
Corresponding author. Tel.: 191-278-567760; fax: 191-278-567562;
e-mail: salt@csir.res.in
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020101)00657-3

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S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
2. Results and discussion
It was envisaged that the reaction of diazo ketones such as 7
with rhodium1II) acetate dimer, can generate metallo-
carbenoid 8 based on our earlier12 work. The highly electro-
philic carbenoid center1 present in 8 can be attacked by the
lone pair of electrons on the ring carbonyl oxygen to form
®ve- or six-membered-ring carbonyl ylides 9. For investi-
gating the intramolecular formation and intermolecular
cycloaddition of the carbonyl ylides 9 in tandem fashion
with p-quinones as dipolarophile, the requisite starting
materials 7 were prepared from commercially available
materials.
Mild hydrolysis of 2-carbethoxy-2-methyl cyclohexanone
14a) was carried out to afford 1-methyl-2-oxocyclohexane-
carboxylic acid 5a. Treatment of 5a with oxalyl chloride at
room temperature afforded the corresponding acid chloride
6a, which on reaction with freshly prepared ethereal diazo-
methane containing triethylamine at 08C furnished the
a-diazo ketone 7a in 92% yield as a thick yellow oil
1Scheme 1). The same sequence of reactions on
2-carbethoxy-2-methyl cyclopentanone 14b) furnished
a-diazo ketone 7b in good yield. Treatment of 2-12-oxo-
cyclohexane)acetic acid 15c) with ethyl chloroformate and
triethylamine resulted in a white suspension at room
temperature and the formed mixed anhydride 6c was then
treated with freshly prepared ethereal diazomethane at
0±108C furnished a-diazo ketone 7c. The reaction of
1-methyl-2-oxocyclohexanecarboxylic acid 15a) with
oxalyl chloride furnished the corresponding acid chloride,
which on reaction14 with excess Mg-complex of dianion of
monoethyl malonate in a mixture of DCM±THF 11:5)
afforded the active methylene compound 6d. The diazo
Scheme 1. Reagents for substrates a±c: 1i) 5% aq. KOH, rt; 1iii) 1COCl)2,
Ether or ClCOOEt, NEt3, Ether; 1v) CH2N2, Ether; reagents for
substrate d,e: 1ii) 5% aq. KOH, rt; 1iv) 1a) 1COCl)2, Ether; 1b) i-PrMgBr,
EtOOCCH2COOH, DCM±THF 11:5); 1vi) MsN3, NEt3, DCM.
detailed studies on the reaction of various carbonyl ylides
with p-quinones as bifunctional dipolarophiles towards the
synthesis of complex and valuable oxa-bridged polycyclic
systems in a tandem manner.
Scheme 2. Reagents for substrates a±c: 1i) Rh21OAc)4, p-benzoquinone, DCM or C6H6, rt; reagents for substrate d: 1ii) Rh21OAc)4, p-benzoquinone, C6H6,
re¯ux.

S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
7011
The FT-IR spectrum of compound 10a exhibited charac-
teristicpeaks at 1763 and 1677 cm
21
indicating carbonyl
group in oxa-bridged and benzoquinone ring systems,
respectively. The 1H NMR spectrum of product 10a
exhibited a characteristic singlet resonance at d 1.17, 4.80
for the methyl and bridgehead 1H8) proton, two doublets at
d 3.10 and 3.18 due to adjacent H9 and H14 protons, two
doublets at d 6.78 and 6.84 for quinone ring protons 1H11,
H12) and a multiplet around d 1.20±1.85 due to four
methylene groups. 13C NMR and dept-135 spectra of
product 10a showed peaks for one sp3 carbon, four sp2
carbons, four sp carbons and ®ve quaternary carbons that
con®rmed the proposed structure 10a. In the structure 10a,
sp2 carbons C11 and C12 of benzoquinone ring appeared as
a single peak in 13C spectrum. Typically, on the basis of the
lack of coupling between the bridgehead 1H8) proton and
H9 proton clearly indicates the exo-stereochemistry for the
product 10a.
Figure 1. ORTEP view of spiro dioxa-tricyclic compound 11a.
transfer reaction15 of the above substrate 6d was carried out
using mesyl azide±triethylamine to give the corresponding
diazo compound 7d. Similar to compound 7d, the reactions
were carried out to obtain diazo compound 7e from ethyl 3-
methyl-2-oxocyclohexanoneacetate 14e) 1Scheme 1). The
characteristic absorption in FT-IR spectra around
The FT-IR spectrum of compound 11a exhibited charac-
teristicpeaks at 1762 and 1673 cm
1
2100 cm21 and a singlet resonance in H NMR spectra
21
indicating carbonyl
around d 5.3 in compounds 7a±e con®rm the presence
of diazo functionality. All these diazo compounds were
stable for chromatographic puri®cation and spectroscopic
characterization purposes.
group in dioxa-bridged and benzoquinone ring system,
respectively. The 1H NMR spectrum of product 11a
exhibited a characteristic singlet resonance at d 1.24, 4.50
for the methyl and bridgehead 1H8) proton, a multiplet
around d 1.30±2.08 for four methylene groups and four
double doublets at d 6.25, 6.32, 6.50, 6.87 due to quinone
ring protons. The 13C NMR and dept-135 spectra of product
11a showed peaks for one sp3 carbon, four sp2 carbons, ®ve
sp carbons and ®ve quaternary carbons that con®rmed the
proposed structure 11a.
Initially, we investigated the Rh1II) catalyzed behavior of
above synthesized a-diazo ketones 7 with p-benzoquinone
as a dipolarophile. The reaction of a-diazo ketone 7a and an
excess amount of p-benzoquinone with 1 mol% Rh21OAc)4
catalyst in dry benzene was carried out under an argon
atmosphere at room temperature for 8 h followed by neutral
alumina column chromatographic puri®cation of the crude
reaction mixture afforded three products 10a, 11a and 12a
1Scheme 2). These products were characterized from their
interrelated spectral data including single-crystal X-ray
analysis as novel oxa-bridged polycyclic compounds in
59% overall yield.
The FT-IR spectrum of compound 12a exhibited charac-
teristicpeaks at 3326 and 1662 cm 21 indicating the presence
of hydroxy group and carbonyl group of benzoquinone ring
system, respectively. The 1H NMR spectrum of product 12a
exhibited a characteristic singlet resonance at d 1.04, 2.93,
4.70 for the methyl, hydroxy and bridgehead 1H16) proton,
doublets at d 6.06, 6.56 for ole®n protons. Three double
doublets for H9 1labeled as HX) and two H10 protons
1labeled as HA and HB) of compound 12a 1Scheme 2)
indicate ABX pattern of a conformationally locked six-
membered ring with three different coupling constants 1J)
of 16.1, 11.5 and 6.8 Hz. Based on an axial and an equatorial
coupling constant analysis, these double doublets were
characterized for the proton HA at d 2.53, HB at d 3.10
and HX at d 4.42. The presence of hydroxy group at d
2.93 was further con®rmed by deuterium exchange studies.
The 13C NMR spectrum of product 12a showed peaks for
one sp3 carbon, ®ve sp2 carbons, four sp carbons and ®ve
quaternary carbons that con®rmed the proposed structure
12a.
The stereochemical assignments of the methyl group at the
ring juncture, spiro dioxa-tricyclic and trioxa-pentacyclic
ring system of the products were unambiguously established
by single-crystal X-ray analyses of product 11a 1Fig. 1) and
12d 1Fig. 3). In compound 11a, the observed angle of oxa-
bridge 1C1±O11±C8) is 96.038. The presence of methyl
group at the ring juncture 1C6) in compound 11a, endo
with respect to oxido bridge 1C1±O11±C8) and the
same stereochemistry is tentatively assigned for other
products based on their similarity in spectral data. Packing
Figure 2. Network of C±H´´´O interactions in the ab-plane of 11a.

7012
S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
Table 1. Hydrogen-bonding geometry in 11a, 12d and 14a
Ê Ê
H´´´A 1A) D´´´A 1A) D±H´´´A 1deg)
Substrate
D±H´´´A
11a
11a
12d
12d
14a
C15±H15´´´O17
2.557
3.207
3.519
2.872
3.552
3.269
133.6
164.9
152.5
157.6
150.0
C19±H193´´´O18 2.547
O19±H19´´´O22 2.036
C24±H242´´´O20 2.574
C8±H8´´´O22 2.240
arrangement of compound 11a 1Fig. 2) clearly shows that
molecules are self-assembled by novel C±H´´´O type16
hydrogen bonding 1Table 1). Each molecule has got two
donors 1namely C15 and C19) and two acceptors 1namely
O17 and O18). Molecules are assembled by C±H´´´O
hydrogen bonding as zigzag polymericchain propagating
along a-axis and such polymeric chains are packed along b-
axis.
Figure 4. Network of O±H´´´O and C±H´´´O interactions in the ab-plane of
12d.
The formation of trioxa-pentacyclic system was explicitly
con®rmed by single-crystal X-ray analysis of compound
12d. In compound 12d, the observed angle of oxa-bridge
1C1±O17±C16) is 96.68 1Fig. 3). The angles of oxygen
atoms O8 and O15 which were located in ®ve-membered
rings in the angle of 110.4 and 106.48. Similar to compound
11a, the methyl group at the ring juncture 1C6) in compound
12d, endo with respect to oxido bridge 1C1±O17±C16).
Interestingly, the solid-state structure of compound 12d
1Fig. 4) is mainly governed by two types of hydrogen
bonding interactions 1Table 1), namely O±H´´´O and
C±H´´´O. In this compound, the hydroxy group 1O19) and
the ester methylene group 1C24) act as donor and the ester
carbonyl oxygen 1O22) and the benzoquinone ring carbonyl
oxygen 1O20) act as acceptor. Such interactions held
molecules as a linear polymeric chain along a-axis and
such polymeric chains are packed along b-axis.
After obtaining various new oxa-bridged compounds using
p-benzoquinone, we extended the investigation of Rh1II)
catalyzed behavior of the tandem cyclization±cycloaddition
sequence of a-diazo carbonyl compounds 7 with various
1,4-naphthoquinones as dipolarophiles. The reaction of
a-diazo ketone 7a and an excess amount of 1,4-naphtho-
quinone with 1 mol% of Rh21OAc)4 catalyst in dry benzene
was carried out under an argon atmosphere at room
temperature for 9 h followed by neutral alumina column
chromatographic puri®cation of the crude reaction mixture
afforded three products 13a, 14a and 15a 1Scheme 3). These
products were characterized based on their interrelated
spectral data, which showed similar trend exhibited by
p-benzoquinone reactions. The reaction of a-diazo com-
pounds 7b, 7d and 7e with naphthoquinone as well as
2,3-dichloro-1,4-naphthoquinone was carried out under
similar experimental conditions afforded the corresponding
cycloadducts as described above. The product 13 forms an
important skeleton of angucycline antibiotics 3a and 3b,
which we constructed by 1,3-dipolar cycloaddition method-
ology instead of usual Diels±Alder reaction17 approach.
In contrast to the previous observation,13 the reaction of
carbonyl ylide with 1,4-naphthoquinone which provided
only CvC cycloadduct; we could also observe a con-
siderable amount of interesting CvO cycloadducts 14
which were well characterized including single-crystal
X-ray analysis 1Fig. 5). Moreover, we could get major
amount of novel CvO cycloadducts 114b and 14e) in
comparison with CvC cycloadducts when we used 2,3-
dichloro-1,4-naphthoquinone as a dipolarophile. We could
not observe the interesting tri-oxa hexacyclic compound
type 15 when chloro substituent is present over the double
bond of naphthoquinone.
In order to generalize, the Rh1II) catalyzed behavior of
various diazo compounds 7b,d and 7c were also studied
1Scheme 2) to form respective ®ve- and six-membered-
ring carbonyl ylides which further undergoes 1,3-dipolar
cycloaddition in the presence of an excess p-benzoquinone
to furnish the oxa-tetracyclic systems 10, spiro dioxa-
tricyclic systems 11 and trioxa-pentacyclic systems 12
as CvC, CvO and CvO bond addition followed by
cyclization product, respectively.
The formation of CvO addition product of 1,4-naphtho-
quinone was unequivocally established by single-crystal
X-ray analysis of product 14a 1Fig. 5). In compound 14a,
the observed angle of oxa-bridge 1C1±O11±C8) is 96.328
1Fig. 5). Similar to benzoquinone cycloadducts; the methyl
group at the ring juncture 1C6) in compound 14a, endo with
respect to oxido bridge 1C1±O11±C8). The solid-state
structure of compound 14a viewed down c-axis 1Fig. 6)
and is mainly governed by only C±H´´´O type hydrogen
Figure 3. ORTEP view of trioxa-pentacyclic compound 12d.

S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
7013
Scheme 3.
bonding interaction 1Table 1). In this compound, the bridge-
head sp carbon 1C8) act as donor and the carbonyl oxygen
1O22) present in the dioxa-bridged ring system act as an
acceptor. The molecules are arranged in layers along
b-axis, with strong C±H´´´O interactions between the
adjacent layers to create two-dimensional sheet like archi-
tecture in ab-plane.
carbonyl ylides from the a-diazo carbonyl compounds.
The products 10, 11 and 12 were obtained in the range of
1:3:6 ratio in almost all reactions, clearly indicates the
preference for CvO than CvC cycloadduct in the case of
1
p-benzoquinone as a dipolarophile. The H NMR spectra
showed ABX pattern for H8 and two H9 protons of
compound 12b but the same could not be observed in
compounds 12c and 12d. The exo-stereochemistry was
assigned to compounds 10 and 13 on the basis of a lack of
coupling between the bridgehead hydrogens.
Typically the quantity of the catalyst was maintained at
1 mol% for performing all our experiments. Identical results
were obtained with all diazo carbonyl compounds 7a±d in
the cycloaddition of p-benzoquinone, irrespective of the
substituent, the formation of ®ve- or six-membered-ring
The formation of products 10 and 11 can conveniently be
explained as CvC and CvO addition products of p-benzo-
quinone with the carbonyl ylide dipole 9. The formation of
the product 12 and 15 may be explained from the further
reaction of a water molecule with already formed CvO
addition product 11 and 14 under the experimental con-
ditions. Moreover, we have not isolated any C±H insertion
product18 during the course of this reaction. Padwa19 has
studied the reactions of carbonyl ylides with benzaldehydes
and other aldehydes as dipolarophiles, which afforded the
corresponding dioxa-bicyclic systems. The dipolar cyclo-
addition of the six-membered carbonyl ylide to the
o-quinone system was reported20 to afford the product via
cycloaddition of carbonyl ylide with CvO group of
o-quinone. Also it is very interesting to note that the
reactions of carbonyl ylides with a,b-unsaturated ketones
like arylidenetetralones,12b chemoselectively lead to spiro
dioxa-ring systems as the only CvO addition product.
Figure 5. ORTEP view of spirodioxa-pentacyclic compound 14a.

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S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
six-membered-ring carbonyl ylides, lead to various oxa-
polycyclic systems.
In conclusion, we have demonstrated the formation of ®ve-
and six-membered-ring carbonyl ylides and the subsequent
[312]-cycloaddition with p-quinones furnished the CvC,
CvO addition products and followed by very interesting
cyclization of CvO addition product in tandem fashion
which were characterized as novel oxa-polycyclic systems.
Single-crystal X-ray analyses described the interesting
network involving both C±H´´´O and O±H´´´O hydrogen
bonding interactions observed in the solid-state structure
of oxa-bridged polycyclic systems. This tandem cycli-
zation±cycloaddition method provides ready access to
complex functionalized oxa-bridged carbon networks as
intermediates for the synthesis of naturally existing
molecules in a single step operation.
3. Experimental
Melting points are uncorrected. IR spectra were recorded on
a Perkin±Elmer Spectrum GX FT-IR spectrophotometer. 1H
and 13C NMR spectra were recorded on a Bruker Avance
DPX 200 1200 and 50.3 MHz, respectively) spectrometer
and referenced to TMS. Carbon types were determined
from DEPT 13C NMR experiments. Mass analyses were
performed on Finnigan MAT 8230 1with an ionizing voltage
of 70 eV) and Jeol M Station 700 1FD1 method in absolute
dichloromethane) mass spectrometer. Elemental analyses
were performed on a Perkin±Elmer Model 2400 analyzer.
X-ray crystallographic analyses were carried out in an Enraf
Nonius CAD-4 diffractometer with Mo´Ka radiation. All
solvents were puri®ed by distillation. Thin layer chroma-
tography was performed on silica/alumina plates and
components were visualized by observation under iodine
or by sulphuric acid charring. Column chromatography
was performed on neutral alumina. Care has been taken to
avoid light during the course of reaction in the synthesis of
diazo compounds and its further conversion.
Figure 6. Network of C±H´´´O interaction in the ab-plane of 14a.
3.1. General procedure12a for the synthesis of diazo
ketones 7
But cyclic a,b-unsaturated ketones, a route to pterosin
family of sesquiterpenes afforded2 only cycloadduct with
electron de®cient CvC not CvO bond. It is well
known21 that Diels±Alder cycloaddition reactions lead to
speci®cally CvC cycloadditions of p-quinones. 1,3-Dipolar
cycloaddition reactions of isomunchnone dipoles to 1,4-
naphthoquinone resulted22 only CvC addition products.
The dipolar cycloaddition of ®ve-membered carbonyl ylides
with p-benzoquinones appeared13 very recently where ®ve-
membered carbonyl ylides produced both CvC and CvO
addition products of p-benzoquinone and the product ratio is
mainly the solvent and catalyst dependent. We have made
an interesting observation in this work; the dipolar cyclo-
addition of various carbonyl ylides 9 to p-benzoquinone and
2,3-dichloro-1,4-naphthoquinone produced more of CvO
cycloadduct than the electron de®cient CvC cycloadduct;
in the case of 1,4-naphthoquinone major amount of CvC
cycloadduct obtained in addition to CvO cycloadduct. It is
worth noting, both the CvC and CvO bonds of p-quinones
show dipolarophilicatcivity towards ®ve- as well as
3.1.1. For substrates 7a,b. Cycloalkanone ester
4
112 mmol) was carefully hydrolyzed using 5% aqueous
potassium hydroxide solution 120 mL) with stirring at
room temperature. The reaction was monitored by TLC
and continued until the disappearance of the starting
material. The reaction mixture was extracted with ether
13£10 mL), acidi®ed the aqueous layer 1pHˆ5) and
extracted with ether 13£15 mL). The organicphase was
concentrated under reduced pressure at room temperature
to obtain the corresponding keto acids 5. Freshly distilled
oxalyl chloride 120 mmol) was added dropwise to a stirring
solution of the appropriate acid 110 mmol, 5a,b) in dry ether
125 mL) at 258C, and the stirring was continued for 2 h. The
solution was evaporated under reduced pressure, the crude
residual acid chloride was dissolved in freshly prepared dry
ether 1100 mL) and used for next step without further
puri®cation. The crude acid chloride solution was added
dropwise over 0.5 h period to a stirring solution of freshly
prepared diazomethane 113 mmol) and freshly distilled

S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
7015
triethylamine 110 mmol) in dry ether 150 mL) at 08C, and
the stirring was continued for 2 h. The mixture was ®ltered
and the ®ltrate evaporated. Chromatography of the residue
through a short silica gel column 1prewashed by ethyl
acetate) led to the corresponding diazo ketone 7a,b with
10% ethyl acetate±hexane elution.
tion mixture was allowed to stir and followed by TLC until
the disappearance of the starting material. The solvent was
removed under reduced pressure and the crude residue was
puri®ed by neutral alumina column afforded three products
10/13, 11/14 and 12/15 with ethyl acetate±hexane elution in
the range of 1:16/1:25, 1:8 and 1:1/1:3, respectively.
3.1.2. For substrate 7c. To a solution containing 1 equiv.
110 mmol) of keto acid 5c in freshly prepared dry ether
1100 mL) was added 1.2 equiv. of freshly distilled ethyl
chloroformate followed by the slow addition of 1.5 equiv.
of dry triethylamine. The resulting mixture was stirred at
room temperature for 45 min and the solid that formed was
®ltered under inert atmosphere. The ®ltrate was added to
freshly prepared ethereal diazomethane solution 120 mmol)
and then the mixture stirred for 12 h at 08C, after this
duration allowed to warm to 108C for a period of 2 h
under an argon atmosphere. The solvent was removed
under reduced pressure and the residue puri®ed as described
above to obtain 7c.
Method B: The procedure was followed as in method A
using dry benzene as solvent and the reaction mixture was
allowed to re¯ux under an argon atmosphere. The re¯uxing
was continued till the disappearance of the starting material
and puri®ed by alumina column as described above.
3.2.1. Reaction of a-diazo ketone 7a with p-benzo-
quinone. A mixture of p-benzoquinone 1300 mg, 2.8
mmol) and diazo ketone 7a 1250 mg, 1.4 mmol) was
allowed to react with rhodium acetate dimer 16.1 mg) in
benzene solution 110 mL) at room temperature under an
argon atmosphere for 8 h according to the general method
A to afford three products 10a, 11a and 12a in 59% overall
yield. 10a: 22 mg 16%), thick oil; [Found: C, 69.25; H, 6.16.
C15H16O4 requires C, 69.22; H, 6.20%]; nmax 1neat) 2928,
3.1.3. For substrate 7d and 7e. To a solution of freshly
distilled monoethyl malonate 135 mmol) in dry dichloro-
methane 18 mL) was added dropwise a solution of iso-
propylmagnesium bromide 170 mmol) in tetrahydrofuran
150 mL) until propane has been evolved. The temperature
rises to 40±508C. The green-colored solution was then
cooled in an ice/salt bath and crude appropriate acid
chloride obtained from the corresponding acid 5a and 5e
114 mmol) in dichloromethane 12 mL) was added dropwise
with ef®cient stirring. The stirring continued for 1 h, the
cooling bath was removed and the resultant mixture poured
into cold 10% hydrochloric acid 120 mL). After cessation of
the carbon dioxide evolution the clear solution was
extracted with ethyl acetate 13£20 mL), washed with satu-
rated sodium bicarbonate 130 mL) and brine solution. The
2859, 1763, 1677, 1611, 1459, 1378, 1279, 1252, 996 cm21
;
dH 1200 MHz, CDCl3) 6.84 11H, d, Jˆ10.4 Hz), 6.78 11H, d,
Jˆ10.4 Hz), 4.80 11H, s, H8), 3.18 11H, d, Jˆ8.4 Hz), 3.10
11H, d, Jˆ8.4 Hz), 1.85±1.20 18H, m), 1.17 13H, s, CH3); dC
150.3 MHz, CDCl3) 214.0 1CvO), 191.5 1CvO), 191.3
1CvO), 142.9 1vCH), 92.6 1quat-C), 85.7 1OCH), 57.6
1quat-C), 52.0 1CH), 51.2 1CH) 30.9 1CH2), 27.4 1CH2),
22.6 1CH2), 20.1 1CH2), 16.5 1CH3); m/z 260 1M1, 39),
232 134), 204 132), 162 186), 149 164), 123 149), 95 146),
82 158), 41 1100%). 11a: 65 mg 118%), colorless solid, mp
147±1498C 1chloroform±hexane); [Found: C, 69.18; H,
6.23. C15H16O4 requires C, 69.22; H, 6.20%]; nmax 1KBr)
2945, 2866, 1762, 1673, 1633, 1377, 1095, 1048, 978 cm21
;
dH 1200 MHz, CDCl3) 6.87 11H, dd, Jˆ10.2, 3.0 Hz), 6.50
11H, dd, Jˆ10.2, 3.0 Hz), 6.32 11H, dd, Jˆ10.2, 1.9 Hz),
6.25 11H, dd, Jˆ10.2, 1.9 Hz), 4.50 11H, s, H8), 2.08±1.30
18H, m), 1.24 13H, s, CH3); dC 150.3 MHz, CDCl3) 211.5
1CvO), 184.5 1CvO), 147.2 1vCH), 143.0 1vCH), 132.7
1vCH), 129.5 1vCH), 115.8 1quat-C), 87.5 1OCH), 76.3
1quat-C), 54.8 1quat-C), 31.8 1CH2), 27.5 1CH2), 23.5 1CH2),
20.2 1CH2), 15.1 1CH3); m/z 260 1M1, 3), 167 13), 149 128),
123 1100), 95 141), 81 146), 55 158%). 12a: 135 mg 135%),
colorless solid, mp 172±1748C 1chloroform±hexane);
[Found: C, 64.74; H, 6.52. C15H18O5 requires C, 64.70; H,
6.49%]; nmax 1KBr) 3326, 2962, 2935, 1662, 1510, 1380,
1259, 1064, 1037, 987 cm21; dH 1200 MHz, CDCl3) 6.56
11H, d, Jˆ10.2 Hz), 6.06 11H, d, Jˆ10.2 Hz), 4.70 11H, s,
H16), 4.42 11H, dd, Jˆ11.5, 6.8 Hz), 3.10 11H, dd, Jˆ16.1,
6.8 Hz), 2.93 11H, s, OH), 2.53 11H, dd, Jˆ16.1, 11.5 Hz),
2.04±1.15 18H, m), 1.04 13H, s, CH3); dC 150.3 MHz,
CDCl3) 196.3 1CvO), 146.5 1vCH), 130.9 1vCH), 113.6
1quat-C), 112.5 1quat-C), 87.7 1OCH), 84.4 1quat-C), 77.4
1OCH), 52.4 1quat-C), 45.7 1CH2), 31.5 1CH2), 26.8 1CH2),
23.6 1CH2), 21.6 1CH2), 13.8 1CH3); m/z 278 1M1, 29), 151
113), 123 123), 112 1100), 111 129), 95 123), 83 134%).
organicphase was dried over anhydrous MgSO
and
4
concentrated under reduced pressure. The residue was
subjected to column chromatography on silica gel to afford
the corresponding active methylene compound 6d and 6e.
To a solution containing 1 equiv. of active methylene
compound 6d,e and 1.2 equiv. of freshly distilled methane-
sulphonyl azide in dry dichloromethane 15 mL) was added
2 equiv. of freshly distilled triethylamine under an argon
atmosphere at room temperature. The reaction was
monitored by TLC until the disappearance of starting
material. The solvent was removed under reduced pressure
at room temperature and the residue subjected to short
neutral alumina column chromatography to get pure diazo
ketone 7d,e with 15% ethyl acetate±hexane elution.
3.2. General procedure for the rhodium/II) catalyzed
cycloaddition reaction of a-diazo ketones 7 with
p-quinones
Method A: In an oven-dried ¯ask, a solution containing
1 equiv. of the appropriate diazo carbonyl compound
11.5 mmol) and 2 equiv. of p-quinone was taken in dry
benzene 1dried over sodium) or dichloromethane 1dried
over phosphorous pentoxide, 25 mL). To this reaction
mixture was added 1 mol% of rhodium acetate dimer
under an argon atmosphere at room temperature. The reac-
3.2.2. Reaction of a-diazo ketone 7b with p-benzo-
quinone.
A
mixture of p-benzoquinone 1195 mg,
1.8 mmol) and diazo ketone 7b 1150 mg, 0.9 mmol) was
allowed to react with rhodium acetate dimer 14.0 mg) at
room temperature under an argon atmosphere in dry

7016
S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
dichloromethane 110 mL) for 4.5 h according to the general
method A to afford three products 10b, 11b and 12b in 49%
overall yield. 10b: 11 mg 15%), thick oil; [Found: C, 68.36;
H, 5.77. C14H14O4 requires C, 68.28; H, 5.73%]; nmax 1neat)
2930, 2860, 1766, 1680, 1561, 1457, 1346, 1143, 1044,
997 cm21; dH 1200 MHz, CDCl3) 6.90 11H, d, Jˆ
10.4 Hz), 6.85 11H, d, Jˆ10.4 Hz), 4.76 11H, s, H7), 3.17
11H, d, Jˆ8.4 Hz), 3.09 11H, d, Jˆ8.4 Hz), 2.34±2.00 14H,
m), 1.64±1.26 12H, m), 1.19 13H, s, CH3); dC 150.3 MHz,
CDCl3) 211.8 1CvO), 189.1 1CvO), 189.0 1CvO), 143.3
1vCH), 143.2 1vCH), 102.2 1quat-C), 82.8 1OCH), 58.3
1quat-C), 51.8 1CH), 49.9 1CH), 33.7 1CH2), 27.9 1CH2),
23.0 1CH2), 18.0 1CH3); m/z 246 1M1, 34), 218 132), 148
182), 95 147), 55 163), 41 1100%). 11b: 33 mg 115%), color-
less solid, mp 141±1438C 1chloroform±hexane); [Found: C,
68.21; H, 5.69. C14H14O4 requires C, 68.28; H, 5.73%]; nmax
1KBr) 2947, 2858, 1758, 1677, 1634, 1398, 1123, 1099,
1041, 996 cm21; dH 1200 MHz, CDCl3) 6.83 11H, dd, Jˆ
10.2, 3.0 Hz), 6.53 11H, dd, Jˆ10.2, 3.0 Hz), 6.34 11H, dd,
Jˆ10.2, 1.9 Hz), 6.26 11H, dd, Jˆ10.2, 1.9 Hz), 4.51 11H, s,
H7), 2.34±1.85 14H, m), 1.65±1.25 12H, m) 1.13 13H,
s, CH3); dC 150.3 MHz, CDCl3) 211.7 1CvO), 184.6
1CvO), 147.0 1vCH), 143.0 1vCH), 132.8 1vCH),
129.9 1vCH), 115.6 1quat-C), 87.0 1OCH), 76.0 1quat-C),
58.3 1quat-C), 33.9 1CH2), 27.8 1CH2), 23.6 1CH2), 18.9
1CH3); m/z 246 1M1). 12b: 69 mg 129%), colorless solid,
mp 180±1828C 1chloroform±hexane); [Found: C, 63.62; H,
6.08. C14H16O5 requires C, 63.63; H, 6.11%]; nmax 1KBr)
3434, 2961, 1685, 1561, 1458, 1340, 1142, 1061, 1001,
977 cm21; dH 1200 MHz, CDCl3) 6.50 11H, d, Jˆ
10.2 Hz), 6.04 11H, d, Jˆ10.2 Hz), 4.71 11H, s, H15),
4.44 11H, dd, Jˆ11.6, 6.7 Hz), 3.20 11H, s, OH), 3.12
11H, dd, Jˆ16.3, 6.7 Hz), 2.58 11H, dd, Jˆ16.3, 11.6 Hz),
2.40±1.78 14H, m), 1.67±1.25 12H, m), 1.07 13H, s, CH3);
dC 150.3 MHz, CDCl3) 197.0 1CvO), 146.7 1vCH), 131.1
1vCH), 113.3 1quat-C), 112.5 1quat-C), 87.6 1OCH), 84.9
1quat-C), 78.0 1OCH), 57.9 1quat-C), 46.0 1CH2), 33.6
1CH2), 27.0 1CH2), 23.6 1CH2), 18.6 1CH3); m/z 264 1M1,
26), 137 113), 109 127), 98 1100), 83 133%).
11H, dd, Jˆ10.2, 3.0 Hz), 6.36 11H, dd, Jˆ10.2, 1.9 Hz),
6.24 11H, dd, Jˆ10.2, 1.9 Hz), 4.18 11H, s, H9), 2.76±2.55
11H, m), 2.20±1.14 110 H, m); dC 150.3 MHz, CDCl3) 201.2
1CvO), 184.5 1CvO), 147.7 1vCH), 141.1 1vCH), 133.3
1vCH), 128.6 1vCH), 111.6 1quat-C), 87.5 1quat-C), 86.9
1OCH), 43.2 1CH), 41.5 1CH2), 35.7 1CH2), 31.1 1CH2), 24.9
1CH2), 23.8 1CH2); m/z 260 1M1, 16), 243 14), 162 13), 152
112), 151 174), 139 17), 133 18), 95 1100%). 12c: 70 mg
125%), colorless solid, mp 187±1898C 1ethyl acetate-
hexane); [Found: C, 64.74; H, 6.48. C15H18O5 requires C,
64.74; H, 6.52 %]; nmax 1KBr) 3431, 2940, 2860, 1676,
1511, 1469, 1221, 919 cm21; dH 1200 MHz, CDCl3/
DMSO-d6) 8.75 11H, s, OH), 6.62 11H, d, Jˆ10.2 Hz),
6.12 11H, d, Jˆ10.2 Hz), 4.87 11H, s, H17), 4.78 11H, t,
Jˆ8.0 Hz), 3.17±2.96 12H, m), 2.76±1.24 111H, m); dC
150.3 MHz, CDCl3/DMSO-d6) 200.7 1CvO), 149.3
1vCH), 133.5 1vCH), 112.3 1quat-C), 108.7 1quat-C),
87.9 1OCH), 86.4 1quat-C), 80.8 1OCH), 51.5 1CH), 47.3
1CH2), 39.1 1CH2), 35.1 1CH2), 28.6 1CH2), 27.1 1CH2),
27.0 1CH2); m/z 278 1M1).
3.2.4. Reaction of a-diazo ketone 7d with p-benzo-
quinone. A mixture of p-benzoquinone 1170 mg, 1.6
mmol) and diazo ketone 7d 1200 mg, 0.8 mmol) was
allowed to react with rhodium acetate dimer 13.5 mg) in
dry benzene 110 mL) for 3 h at re¯ux under an argon atmos-
phere according to the general method B to afford three
products 10d, 11d and 12d in 48% overall yield. 10d:
11 mg 14%), colorless solid, mp 142±1448C 1chloroform±
hexane); [Found: C, 64.98; H, 6.03. C18H20O6 requires C,
65.05; H, 6.07%]; nmax 1KBr) 2930, 2857, 1763, 1751, 1676,
1612, 1459, 1378, 1279, 1105, 1035 cm21; dH 1200 MHz,
CDCl3) 6.83 11H, d, Jˆ10.4 Hz), 6.78 11H, d, Jˆ10.4 Hz),
4.24 12H, q, Jˆ7.2 Hz, OCH2), 3.15 11H, d, Jˆ8.4 Hz), 3.07
11H, d, Jˆ8.4 Hz), 2.20±1.22 18H, m), 1.17 13H, t, Jˆ
7.2 Hz, CH2CH3), 1.13 13H, s, CH3); dC 150.3 MHz,
CDCl3) 206.0 1CvO), 194.8 1CvO), 194.6 1CvO), 172.5
1COO), 142.8 1vCH), 142.6 1vCH), 93.0 1quat-C), 89.9
1quat-C), 62.9 1OCH2), 55.3 1quat-C), 52.3 1CH), 52.0 1CH),
31.9 1CH2), 27.4 1CH2), 23.2 1CH2), 20.1 1CH2), 15.8 1CH3),
14.3 1CH3); m/z 332 1M1, 16), 304 134), 190 187), 177 166),
149 146), 41 1100%). 11d: 45 mg 117%), colorless solid, mp
153±1558C 1chloroform±hexane); [Found: C, 65.11; H,
6.09. C18H20O6 requires C, 65.05; H, 6.07%]; nmax 1KBr)
2393, 2870, 1775, 1751, 1674, 1635, 1382, 1303, 1141,
1099, 1107, 990 cm21; dH 1200 MHz, CDCl3) 6.78 11H,
dd, Jˆ10.2, 3.0 Hz), 6.53 11H, dd, Jˆ10.2, 3.0 Hz), 6.36
11H, dd, Jˆ10.2, 1.9 Hz), 6.27 11H, dd, Jˆ10.2, 1.9 Hz),
4.23 12H, q, Jˆ7.2 Hz, OCH2), 2.14±1.24 18H, m), 1.30
13H, s, CH3), 1.18 13H, t, Jˆ7.2 Hz, CH2CH3); dC
150.3 MHz, CDCl3) 205.8 1CvO), 184.5 1CvO), 175.0
1COO), 144.4 1vCH), 142.5 1vCH), 132.7 1vCH), 131.0
1vCH), 114.0 1quat-C), 93.9 1quat-C), 82.5 1quat-C), 63.0
1OCH2) 55.2 1quat-C), 32.0 1CH2), 27.4 1CH2), 23.2 1CH2),
20.1 1CH2), 15.3 1CH3), 14.3 1CH3); m/z 332 1M1, 3), 224
143), 206 159), 178 18), 123 1100), 95 116%). 12d: 75 mg
127%), colorless solid, mp 174±176 8C 1chloroform±
hexane); [Found: C, 61.69; H, 6.28. C18H22O7 requires C,
61.71; H, 6.33%]; nmax 1KBr) 3438, 2970, 1704, 1685, 1373,
1339, 1253, 1152, 1108, 1056, 1029 cm21; dH 1200 MHz,
CDCl3) 6.47 11H, d, Jˆ10.2 Hz), 6.08 11H, d, Jˆ10.2 Hz),
4.51 11H, dd, Jˆ10.2, 8.2 Hz), 4.35 12H, q, Jˆ7.2 Hz,
OCH2), 3.70 11H, s, OH), 3.25±2.90 12H, m), 2.20±1.35
3.2.3. Reaction of a-diazo ketone 7c with p-benzo-
quinone. A mixture of p-benzoquinone 1220 mg, 2.0
mmol) and diazo ketone 7c 1180 mg, 1.0 mmol) was
allowed to react with rhodium acetate dimer 14.4 mg) in
dry dichloromethane 110 mL) at room temperature under
an argon atmosphere for 2.5 h according to the general
method A to afford three products 10c, 11c and 12c in
45% overall yield. 10c: 13 mg 15%), thick oil; [Found: C,
69.31; H, 6.26. C15H16O4 requires C, 69.22; H, 6.20%]; nmax
1neat) 2930, 2910, 1731, 1675, 1611, 1460, 1270, 1253,
1035, 913 cm21; dH 1200 MHz, CDCl3) 6.90 11H, d, Jˆ
10.4 Hz), 6.85 11H, d, Jˆ10.4 Hz), 4.68 11H, s, H9), 3.27
11H, d, Jˆ8.4 Hz), 3.20 11H, d, Jˆ8.4 Hz), 2.80±1.24 111H,
m); dC 150.3 MHz, CDCl3) 202.7 1CvO), 193.0 1CvO),
192.9 1CvO), 143.0 1vCH), 142.8 1vCH), 92.7 1quat-C),
86.2 1OCH), 52.3 1CH), 51.3 1CH), 43.4 1CH), 41.6 1CH2),
36.2 1CH2), 31.1 1CH2), 24.9 1CH2), 23.8 1CH2); m/z 260
1M1, 29), 204 131), 149 161), 123 147), 95 143), 55 162), 41
1100%). 11c: 39 mg 115%), colorless solid, mp 145±1478C
1chloroform±hexane); [Found: C, 69.30; H, 6.16. C15H16O4
requires C, 69.22; H, 6.20%]; nmax 1KBr) 2938, 2861, 1730,
1675, 1634, 1396, 1174, 1083, 1051, 915 cm21; dH
1200 MHz, CDCl3) 6.89 11H, dd, Jˆ10.2, 3.0 Hz), 6.52

S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
7017
18H, m), 1.3113H, t, Jˆ7.2 Hz, CH2CH3), 1.09 13H, s, CH3);
dC 150.3 MHz, CDCl3) 196.3 1CvO), 166.4 1COO), 142.9
1vCH), 132.5 1vCH), 112.4 1quat-C), 112.1 1quat-C), 92.3
1quat-C), 85.8 1quat-C), 77.0 1OCH), 63.1 1OCH2), 52.6
1quat-C), 43.3 1CH2), 31.4 1CH2), 26.6 1CH2), 23.4 1CH2),
21.3 1CH2), 14.6 1CH3), 13.8 1CH3); m/z 350 1M1, 9), 295
13), 249 15), 195 17), 157 115), 139 125), 121 1100), 83 112),
65 116%).
1180 mg, 1.0 mmol) was allowed to react with rhodium ace-
tate dimer 14.4 mg) in dry benzene 110 mL) for 12 h at room
temperature under an argon atmosphere according to the
general method A to afford two products 13b and 14b in
34% overall yield. 13b: 15 mg 14%), pale yellow solid, mp
192±1948C 1ethyl acetate-hexane); [Found: C, 60.10; H,
4.19, C19H16Cl2O4 requires C, 60.18; H, 4.25%]; nmax
1KBr) 2940, 2869, 1676, 1677, 1596, 1561, 1297, 1258,
1144, 1035, 1008, 978 cm21; dH 1200 MHz, CDCl3) 8.12±
7.99 12H, m, Arom-H), 7.83±7.62 12H, m, Arom-H), 4.58
11H, s, OCH), 2.20±1.32 18H, m), 1.29 13H, s, CH3); dC
150.3 MHz, CDCl3) 210.4 1CvO), 194.2 1CvO), 193.2
1CvO), 136.7 1quat-C), 136.2 1quat-C), 135.2 1vCH),
134.9 1vCH), 127.5 1vCH), 127.1 1vCH), 94.2 1OCH),
92.9 1quat-C), 92.3 1quat-C), 84.5 1quat-C), 54.5 1quat-C),
33.0 1CH2), 25.5 1CH2), 22.9 1CH2), 19.9 1CH2), 14.6 1CH3);
m/z 379 1M1, 1), 343 17), 228 163), 226 176), 191 1100), 87
126%). 14b: 114 mg 130%), pale yellow solid, mp 214±
2168C 1ethyl acetate±hexane); [Found: C, 60.28; H, 4.29,
C19H16Cl2O4 requires C, 60.18; H, 4.25%]; nmax 1KBr) 2939,
2868, 1762, 1678, 1596, 1561, 1458, 1297, 1258, 1035,
1109 cm21; dH 1200 MHz, CDCl3) 8.16 11H, d, Jˆ7.6 Hz,
Arom-H), 7.78 11H, d, Jˆ7.8 Hz, Arom-H), 7.59±7.49 12H,
m, Arom-H), 4.18 11H, s, OCH), 2.23±1.30 18H, m), 1.30
13H, s, CH3); dC 150.3 MHz, CDCl3) 209.1 1CvO), 176.4
1CvO), 148.8 1quat-C), 142.3 1quat-C), 132.4 1vCH),
129.5 1quat-C), 129.3 1vCH), 128.7 1quat-C), 127.9
1vCH), 127.5 1vCH), 117.4 1quat-C), 90.5 1OCH), 83.6
1quat-C), 54.6 1quat-C), 32.7 1CH2), 26.1 1CH2), 23.1 1CH2),
19.6 1CH2), 14.8 1CH3); m/z 379 1M1, 1), 226 179), 191
1100), 163 162), 135 138), 123 162), 95 128), 87 128%).
3.2.5. Reaction of a-diazo ketone 7a with 1,4-naphtho-
quinone. A mixture of 1,4-naphthoquinone 1320 mg,
2.0 mmol) and diazo ketone 7a 1180 mg, 1.0 mmol) was
allowed to react with rhodium acetate dimer 14.4 mg) in
dry benzene 110 mL) for 9 h at room temperature under an
argon atmosphere according to the general method A to
afford three products 13a, 14a and 15a in 54% overall
yield. 13a: 102 mg 133%), colorless solid, mp 141±1438C
1chloroform±hexane); [Found: C, 73.51; H, 5.89, C19H18O4
requires C, 73.53; H, 5.85%]; nmax 1KBr) 2936, 2864, 1755,
1682, 1591, 1457, 1301, 1269, 1246, 1170, 996 cm21; dH
1200 MHz, CDCl3) 8.06±8.00 12H, m, Arom-H), 7.79±7.75
12H, m, Arom-H), 4.87 11H, s, OCH), 3.32 11H, d, Jˆ
8.4 Hz), 3.24 11H, d, Jˆ8.4 Hz), 2.00±1.30 18H, m), 1.23
13H, s, CH3); dC 150.3 MHz, CDCl3) 214.4 1CvO), 195.0
1CvO), 194.1 1CvO), 136.7 1quat-C), 136.2 1quat-C),
135.2 1vCH), 134.9 1vCH), 127.5 1vCH), 127.1
1vCH), 92.9 1quat-C), 86.4 1OCH), 53.0 1CH), 52.3 1CH),
52.2 1quat-C), 30.9 1CH2), 27.2 1CH2), 22.6 1CH2), 20.1
1CH2), 16.7 1CH3); m/z 310 1M1, 84), 281 1100), 263 187),
253 170), 212 128), 199 126), 172 137), 148 127), 134 178),
133 197%). 14a: 43 mg 114%), colorless solid, mp 190±
1928C 1ethyl acetate±hexane); [Found: C, 73.50; H, 5.82,
C19H18O4 requires C, 73.53; H, 5.85%]; nmax 1neat) 2945,
2876, 1759, 1670, 1630, 1369, 1085, 1047, 978 cm21; dH
1200 MHz, CDCl3) 8.06±8.02 11H, m, Arom-H), 7.77±7.73
11H, m, Arom-H), 7.59±7.43 12H, m, Arom-H), 6.65 11H, d,
Jˆ10.5 Hz), 6.42 11H, d, Jˆ10.5 Hz), 4.23 11H, s, OCH),
2.28±1.32 18H, m), 1.27 13H, s, CH3); dC 150.3 MHz,
CDCl3) 211.0 1CvO), 183.3 1CvO), 145.4 1vCH),142.5
1quat-C), 135.5 1quat-C), 132.7 1vCH), 131.5 1vCH),
128.9 1vCH), 127.8 1vCH), 126.7 1vCH), 115.3 1quat-C),
89.4 1OCH), 82.5 1quat-C), 53.1 1quat-C), 31.8 1CH2), 26.5
1CH2), 23.1 1CH2), 19.9 1CH2), 15.0 1CH3); m/z 310 1M1, 4),
308 14), 247 13), 184 116), 152 142), 123 1100), 122 195), 95
123%). 15a: 23 mg 17%), colorless solid, mp 174±1768C
1chloroform±hexane); [Found: C, 69.49; H, 6.13,
C19H20O5 requires C, 69.50; H, 6.14%]; nmax 1KBr) 3420,
2941, 2807, 1695, 1596, 1452, 1339, 1300, 1253, 1138,
1071, 961 cm21; dH 1200 MHz, CDCl3) 7.96 11H, d, Jˆ
7.6 Hz, Arom-H), 7.75±7.60 12H, m, Arom-H), 7.46 11H,
d, Jˆ7.5 Hz, Arom-H), 4.71 11H, s, OCH), 4.67 11H, dd,
Jˆ8.0, 10.5 Hz), 3.53 11H, s, OH), 3.29 11H, dd, Jˆ16.3
10.5 Hz), 2.70 11H, dd, Jˆ16.3, 8.0 Hz), 2.20±1.30 18H, m),
1.07 13H, s, CH3); dC 150.3 MHz, CDCl3) 196.0 1CvO),
137.7 1quat-C), 134.8 1vCH), 132.0 1quat-C), 129.8
1vCH), 129.0 1vCH), 126.5 1vCH), 113.0 1quat-C),
111.9 1quat-C), 87.9 1OCH), 84.5 1quat-C), 77.2 1OCH),
52.9 1quat-C), 44.0 1CH2), 31.4 1CH2), 26.6 1CH2), 23.5
1CH2), 21.4 1CH2), 13.9 1CH3); m/z 328 1M1).
3.2.7. Reaction of a-diazo ketone 7b with 1,4-naphtho-
quinone. A mixture of 1,4-naphthoquinone 1315 mg,
2.0 mmol) and diazo ketone 7b 1165 mg, 1.0 mmol) was
allowed to react with rhodium acetate dimer 14.4 mg) in
dry benzene 110 mL) for 9 h at room temperature under an
argon atmosphere according to the general method A to
afford three products 13c, 14c and 15c in 37% overall
yield. 13c: 71 mg 124%), colorless solid, mp 164±1678C
1chloroform±hexane); [Found: C, 72.99; H, 5.49,
C18H16O4 requires C, 72.96; H, 5.44%]; nmax 1KBr) 2969,
2930, 1761, 1683, 1590, 1458, 1319, 1300, 1266, 1093, 992,
962 cm21; dH 1200 MHz, CDCl3) 8.08±8.04 12H, m,
Arom-H), 7.81±7.74 12H, m, Arom-H), 4.61 11H, s,
OCH), 3.47 11H, d, Jˆ8.4 Hz), 3.40 11H, d, Jˆ8.4 Hz),
2.34±1.26 11H, m), 1.99±1.82 13H, m), 1.65±1.58 11H,
m), 1.34±1.25 11H, m), 1.17 13H, s, CH3); dC 150.3 MHz,
CDCl3) 211.5 1CvO), 194.3 1CvO), 193.6 1CvO), 135.9
1quat-C), 135.7 1quat-C), 134.7 1vCH), 134.4 1vCH),
127.2 1vCH), 126.9 1vCH), 104.0 1quat-C), 84.7 1OCH),
58.9 1quat-C), 52.6 1CH), 49.1 1CH), 33.9 1CH2), 28.2
1CH2), 22.7 1CH2), 19.3 1CH3); m/z 296 1M1, 8), 268
1100), 267 168), 250 177), 239 145), 221 123), 197 119),
159 134), 119 121), 104 164), 93 135%). 14c: 24 mg 18%),
colorless solid, mp 194±1968C 1ethyl acetate±hexane);
[Found: C, 72.90; H, 5.49, C18H16O4 requires C, 72.96; H,
5.44%]; nmax 1neat) 2933, 2869, 1760, 1668, 1629, 1341,
1081, 1049 cm21; dH 1200 MHz, CDCl3) 8.06±8.01 11H, m,
Arom-H), 7.79±7.29 11H, m, Arom-H), 7.60±7.40 12H, m,
Arom-H), 6.66 11H, d, Jˆ10.5 Hz), 6.41 11H, d, Jˆ
10.5 Hz), 4.20 11H, s, OCH), 2.35±1.83 14H, m), 1.65±
1.26 12H, m), 1.19 13H, s, CH3); dC 150.3 MHz, CDCl3)
3.2.6. Reaction of a-diazo ketone 7a with 2,3-dichloro-
1,4-naphthoquinone. A mixture of 2,3-dichloro-1,4-
naphthoquinone 1455 mg, 2.0 mmol) and diazo ketone 7a

7018
S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
211.2 1CvO), 183.2 1CvO), 145.3 1vCH), 142.5 1quat-C),
135.7 1quat-C), 132.6 1vCH), 131.6 1vCH), 128.9 1vCH),
127.9 1vCH), 126.7 1vCH), 115.0 1quat-C), 89.3 1OCH),
82.2 1quat-C), 58.6 1quat-C), 33.8 1CH2), 28.1 1CH2), 22.7
1CH2), 19.6 1CH3); m/z 296 1M1). 15c: 15 mg 15%), color-
less solid, mp 167±1698C 1chloroform±hexane); [Found: C,
68.87; H, 5.80, C18H18O5 requires C, 68.78; H, 5.77%]; nmax
1KBr) 3390, 2931, 1705, 1599, 1453, 1341, 1320, 1251,
1136, 1071, cm21; dH 1200 MHz, CDCl3) 7.97 11H, d,
Jˆ7.5 Hz, Arom-H), 7.73±7.62 12H, m, Arom-H), 7.49
11H, d, Jˆ7.5 Hz, Arom-H), 4.73 11H, s, OCH), 4.65 11H,
dd, Jˆ8.0, 10.5 Hz), 3.42 11H, s, OH), 3.25 11H, dd,
Jˆ16.3, 10.5 Hz), 2.72 11H, dd, Jˆ16.3, 8.0 Hz), 2.20±
1.30 16H, m), 1.09 13H, s, CH3); dC 150.3 MHz, CDCl3)
196.6 1CvO), 137.0 1quat-C), 134.2 1vCH), 132.6 1quat-
C), 129.2 1vCH), 129.2 1vCH), 126.4 1vCH), 113.1
1quat-C), 111.6 1quat-C), 87.0 1OCH), 84.9 1quat-C), 77.6
1OCH), 52.0 1quat-C), 44.4 1CH2), 32.5 1CH2), 27.6 1CH2),
22.2 1CH2), 13.9 1CH3); m/z 314 1M1).
7.3 Hz, Arom-H), 7.74±7.61 12H, m, Arom-H), 7.46 11H,
d, Jˆ7.3 Hz, Arom-H), 4.68 11H, dd, Jˆ8.0, 10.5 Hz), 4.15
12H, q, Jˆ7.2 Hz, OCH2), 3.63 11H, s, OH), 3.47±3.21 12H,
m), 2.36±1.20 18H, m), 1.15 13H, s, CH3) 0.80 13H, t, Jˆ
7.2 Hz, CH2CH3); dC 150.3 MHz, CDCl3) 195.0 1CvO),
166.5 1COO), 137.6 1quat-C), 134.7 1vCH), 132.2
1quat-C), 129.7 1vCH), 129.3 1vCH), 126.5 1vCH),
111.9 1quat-C), 111.7 1quat-C), 93.2 1quat-C), 86.5
1quat-C), 77.1 1OCH), 62.6 1OCH2), 52.6 1quat-C), 44.2
1CH2), 31.4 1CH2), 26.5 1CH2), 23.5 1CH2), 21.4 1CH2),
14.0 1CH3), 13.9 1CH3); m/z 400 1M1, 16), 299 112), 244
114), 171 1100), 143 111), 123 112), 112 126), 83 112%).
3.2.9. Reaction of a-diazo ketone 7e with 2,3-dichloro-
1,4-naphthoquinone.
A mixture of 2,3-dichloro-1,4-
naphthoquinone 1136 mg, 0.6 mmol) and diazo ketone 7e
180 mg, 0.3 mmol) was allowed to react with rhodium
acetate dimer 11.3 mg) in dry benzene 110 mL) for 5 h at
re¯ux under an argon atmosphere according to the general
method B to afford two products 13e and 14e in 45% overall
yield. 13e: 14 mg 15%), yellow solid, mp 206±2088C 1ethyl
acetate±hexane); [Found: C, 59.41; H, 4.85, C23H22Cl2O6
requires C, 59.37; H, 4.77%]; nmax 1KBr) 2930, 2856,
1760, 1734, 1686, 1596, 1570, 1457, 1372, 1308, 1286,
1109 cm21; dH 1200 MHz, CDCl3) 8.10±8.01 12H, m,
Arom-H), 7.67±7.52 12H, m, Arom-H), 4.13 12H, q, Jˆ
7.2 Hz, OCH2), 2.85±2.62 13H, m), 2.43±1.29 17H, m),
1.39 13H, d, Jˆ7.6 Hz), 1.09 13H, t, Jˆ7.2 Hz, CH2CH3);
dC 150.3 MHz, CDCl3) 204.0 1CvO), 189.0 1CvO), 188.5
1CvO), 172.0 1COO), 141.3 1quat-C), 134.0 1vCH), 131.0
1quat-C), 130.1 1vCH), 127.7 1vCH), 127.5 1vCH), 95.2
1quat-C), 86.9 1quat-C), 74.1 1quat-C), 73.1 1quat-C), 63.1
1OCH2), 42.6 1CH2), 37.9 1CH), 37.0 1CH), 26.0 1CH2), 24.7
1CH2), 16.4 1CH2), 15.8 1CH3), 14.1 1CH3); m/z 465 1M1).
14e: 111 mg 140%), pale yellow solid, mp 210±2138C
1ethyl acetate±hexane); [Found: C, 59.31; H, 4.71,
C23H22Cl2O6 requires C, 59.37; H, 4.77%]; nmax 1KBr)
2927, 2854, 1754, 1734, 1683, 1597, 1574, 1457, 1301,
1280, 1104, 906 cm21; dH 1200 MHz, CDCl3) 8.13 11H, d,
Jˆ7.8 Hz, Arom-H), 7.82 11H, d, Jˆ7.8 Hz, Arom-H),
7.66±7.51 12H, m, Arom-H), 3.84 12H, q, Jˆ7.2 Hz,
OCH2), 2.89±2.65 13H, m), 2.40±1.33 17H, m), 1.47 13H,
d, Jˆ7.6 Hz), 0.89 13H, t, Jˆ7.2 Hz, CH2CH3); dC
150.3 MHz, CDCl3) 200.7 1CvO), 175.6 1CvO), 169.0
1COO), 141.3 1quat-C), 133.7 1vCH), 130.8 1quat-C),
130.1 1vCH), 127.7 1vCH), 127.5 1vCH), 116.3
1quat-C), 115.3 1quat-C), 95.2 1quat-C), 86.9 1quat-C),
79.1 1quat-C), 63.1 1OCH2), 42.6 1CH2), 37.8 1CH), 37.0
1CH), 26.2 1CH2), 24.7 1CH2), 16.4 1CH2), 15.8 1CH3),
13.9 1CH3); m/z 465 1M1, 1), 332 14), 261 15), 238 131),
191 121), 149 174), 95 114), 41 1100%).
3.2.8. Reaction of a-diazo ketone 7d with 1,4-naphtho-
quinone. A mixture of 1,4-naphthoquinone 1155 mg,
1.0 mmol) and diazo ketone 7d 1125 mg, 0.5 mmol) was
allowed to react with rhodium acetate dimer 12.2 mg) in
dry benzene 110 mL) for 6.5 h at re¯ux under an argon
atmosphere according to the general method B to afford
three products 13d, 14d and 15d in 38% overall yield.
13d: 48 mg 125%), colorless solid, mp 168±1708C 1chloro-
form±hexane); [Found: C, 69.19; H, 5.74, C22H22O6
requires C, 69.10; H, 5.80%]; nmax 1KBr) 3023, 2938,
2863, 1775, 1745, 1682, 1595, 1458, 1376, 1320, 1264,
1241, 1073 cm21; dH 1200 MHz, CDCl3) 8.09±7.99 12H,
m, Arom-H), 7.80±7.75 12H, m, Arom-H), 4.43 12H, q,
Jˆ7.2 Hz, OCH2), 3.62 11H, d, Jˆ8.2 Hz), 3.46 11H, d,
Jˆ8.2 Hz), 1.96±1.25 18H, m), 1.41 13H, t, Jˆ7.2 Hz,
CH2CH3) 1.28 13H, s, CH3); dC 150.3 MHz, CDCl3) 207.8
1CvO), 194.1 1CvO), 192.0 1CvO), 163.8 1COO), 144.4
1quat-C), 144.2 1quat-C), 135.1 1vCH), 135.0 1vCH),
127.5 1vCH), 126.8 1vCH), 93.8 1quat-C), 90.6 1quat-C),
62.7 1OCH2), 55.0 1CH), 53.9 1CH), 52.6 1quat-C), 31.0
1CH2), 26.7 1CH2), 22.3 1CH2), 20.0 1CH2), 14.6 1CH3),
14.0 1CH3); m/z 382 1M1, 12), 354 123), 336 163), 281
169), 263 132), 253 151), 211 145), 123 1100), 104 163), 76
148%). 14d: 10 mg 15%), colorless solid, mp 149±1538C
1chloroform±hexane); [Found: C, 69.13; H, 5.84,
C22H22O6 requires C, 69.10; H, 5.80%]; nmax 1neat) 2940,
2879, 1756, 1731, 1669, 1631, 1369, 1089, 1041, 999 cm21
;
dH 1200 MHz, CDCl3) 8.06±7.85 12H, m, Arom-H), 7.65±
7.50 12H, m, Arom-H), 6.72 11H, d, Jˆ10.5 Hz), 6.55 11H,
d, Jˆ10.5 Hz), 4.03 12H, q, Jˆ7.2 Hz, OCH2), 2.41±1.34
18H, m), 1.42 13H, s, CH3), 0.91 13H, t, Jˆ7.2 Hz, CH2CH3);
dC 150.3 MHz, CDCl3) 211.3 1CvO), 184.4 1CvO), 163.8
1COO), 145.4 1vCH), 142.5 1quat-C), 135.5 1quat-C),
132.7 1vCH), 131.5 1vCH), 128.9 1vCH), 127.8
1vCH), 126.7 1vCH), 115.0 1quat-C), 90.9 1quat-C), 81.9
1quat-C), 62.5 1OCH2), 52.9 1quat-C), 31.8 1CH2), 26.5
1CH2), 23.1 1CH2), 19.8 1CH2), 14.9 1CH3), 14.0 1CH3);
m/z 382 1M1, 1), 224 127), 158 16), 123 1100), 95 123%).
15d: 32 mg 18%), colorless solid, mp 178±1808C 1chloro-
form±hexane); [Found: C, 65.97; H, 6.10, C22H24O7
requires C, 65.99; H, 6.04%]; nmax 1KBr) 3411, 2941,
2868, 1710, 1694, 1596, 1381, 1337, 1300, 1253, 1071,
1012, 961 cm21; dH 1200 MHz, CDCl3) 7.94 11H, d, Jˆ
3.3. X-Ray crystal structure analysis
Crystal data for the compound 11a: C15H16O4, Mˆ260.28,
0.15£0.09£0.24 mm3, colorless plates, Monoclinic, P21/a,
Ê
aˆ8.70314), bˆ11.678115), cˆ12.74214) A, bˆ91.7513)8,
Ê 3
Vˆ1294.4118) A , Tˆ29312) K, R1ˆ0.0610, wR2ˆ0.1854
on observed data, zˆ4, Dcalcˆ1.336 Mg m23, F1000)ˆ552,
Absorption coef®cientˆ0.097 mm21, lˆ0.7107 A, 2279
Ê
re¯ections were collected on a CAD-4 diffractometer,
1653 observed re¯ections 1I$2s 1I)). The largest difference
Ê 23
peak and holeˆ0.308 and 20.444e A , respectively.

S. Muthusamy et al. / Tetrahedron 57 '2001) 7009±7019
7019
3. 1a) Padwa, A.; Curtis, E. A.; Sandanayaka, V. P. J. Org. Chem.
1997, 62, 1317±1325. 1b) McMorris, T. C.; Hu, Y.; Yu, J.;
Kelner, M. J. J. Chem. Soc., Chem. Commun. 1997, 315±316.
1c) Kinder, Jr., F. R.; Bair, K. W. J. Org. Chem. 1994, 59,
6965±6967.
Crystal data for the compound 12d: C18H22O7, Mˆ350.36,
0.20£0.18£0.12 mm3, colorless plates, Triclinic, P21, aˆ
Ê
9.29913), bˆ9.93012), cˆ10.21416) A, aˆ98.2113), bˆ
Ê 3
111.9814), gˆ99.4812)8, Vˆ840.816) A , Tˆ29312) K, R1ˆ
0.0562, wR2ˆ0.1357 on observed data, zˆ2, Dcalc
ˆ
1.384 Mg m23
,
F1000)ˆ372, Absorption coef®cientˆ
Ê
4. 1a) McMills, M. C.; Zhuang, L.; Wright, D. L.; Watt, W.
Tetrahedron Lett. 1994, 35, 8311±8314. 1b) Dauben, W. G.;
Dinges, J.; Smith, T. C. J. Org. Chem. 1993, 58, 7635±7637.
5. Padwa, A.; Price, A. T. J. Org. Chem. 1995, 60, 6258±6259.
6. Padwa, A.; Chinn, R. L.; Zhi, L. Tetrahedron Lett. 1989, 30,
1491±1494.
0.107 mm21, lˆ0.7107 A, 2936 re¯ections were collected
on a CAD-4 diffractometer, 1706 observed re¯ections
1I$2s 1I)). The largest difference peak and holeˆ0.252
Ê 23
and 20.382e A , respectively.
7. Yunlong, X.; Dan, W.; Xiaojie, L.; Jian, F. Phytochemistry
1989, 28, 189±191.
Crystal data for the compound 14a: C19H18O4, Mˆ310.33,
0.20£0.16£0.12 mm3, colorless plates, Monoclinic, P21/n,
Ê
8. Conner, A. H.; Nagasampagi, B. A.; Rowe, J. W. Phyto-
chemistry 1980, 19, 1121±1131.
aˆ9.16213), bˆ16.18119), cˆ11.08613) A, bˆ110.3512)8,
Ê 3
Vˆ1540.9111) A , Tˆ29312) K, R1ˆ0.0454, wR2ˆ0.1138
on observed data, zˆ4, Dcalcˆ1.338 Mg m23, F1000)ˆ656,
9. 1a) Hodgson, D. M.; Bailey, J. M.; Villalonga-Barber, C.;
Drew, M. G. B.; Harrison, T. J. Chem. Soc., Perkin Trans. 1
2000, 3432±3443. 1b) Wilson, K. E.; Burk, R. B.; Biftn, T.;
Ball, R. G.; Hoogsteen, K. J. Org. Chem. 1992, 57, 7151±
7158.
Absorption coef®cientˆ0.093 mm21, lˆ0.7107 A, 2696
Ê
re¯ections were collected on a CAD-4 diffractometer,
1783 observed re¯ections 1I$2s 1I)). The largest difference
Ê 23
peak and holeˆ0.156 and 20.182e A respectively. The
10. Zamir, L. O.; Devor, K. A.; Morin, N.; Sauriol, F. J. Chem.
Soc., Chem. Commun. 1991, 1033±1034.
structure was solved by direct methods and re®ned by full-
matrix least squares on F2 using SHELX 97.23 All non-
hydrogen atoms were re®ned anisotropically. Some
hydrogens were located on a difference Fourier map and
some were stereochemically ®xed. Atomic coordinates,
thermal parameters, bond lengths and angles have been
deposited at the Cambridge CrystallographicData Center,
12 Union Road, Cambridge CB2 1EZ, UK. The corre-
sponding CCDC numbers are 160621, 160622, 160623 for
compounds 11a, 12d and 14a, respectively.
11. Krohn, K.; Rohr, J. Top. Curr. Chem. 1997, 188, 128±195.
12. 1a) Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Suresh, E.;
Dastidar, P.; Jasra, R. V. Tetrahedron 2000, 56, 6307±6318.
1b) Muthusamy, S.; Babu, S. A.; Gunanathan, C. Tetrahedron
Lett. 2000, 41, 8839±8842. 1c) Muthusamy, S.; Gunanathan,
C.; Babu, S. A. Tetrahedron Lett. 2001, 42, 523±526.
13. Pirrung, M. C.; Kaliappan, K. P. Org. Lett. 2000, 2, 353±355.
14. Pollet, P.; Gelin, S. Synthesis 1978, 142±143.
15. 1a) Regitz, M.; Hecker, J.; Leidhergener, K. Organic Synthesis
Collected Volume V; Wiley: New York, 1973; pp 179±183.
1b) Taber, D. F.; Ruckle Jr., R. E.; Hennessy, M. J. J. Org.
Chem. 1986, 51, 4077±4078.
Acknowledgements
16. Desiraju, G. R. Acc. Chem. Res. 1991, 24, 290±296.
17. 1a) Krohn, K.; Khanbabaee, K. Angew. Chem., Int. Ed. Engl.
1994, 33, 99±100. 1b) Kim, K.; Sulikowski, G. A. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2396±2398.
This research was supported by CSIR 1Young Scientist
Scheme) and Department of Science and Technology,
New Delhi. We are grateful to Professor W. Sander, Ruhr
University, Germany for performing mass spectral analysis.
We thank Dr P. K. Ghosh, Director for his encouragement of
this work. S. A. B. and C. G thank CSIR, New Delhi for a
fellowship.
18. 1a) Doyle, M. P.; Shanklin, M. S.; Oon, S. M.; Pho, H. Q.; van
der Heide, F. R.; Veal, W. R. J. Org. Chem. 1988, 53, 3384±
3386. 1b) Doyle, M. P.; Tauton, J.; Pho, H. Q. Tetrahedron
Lett. 1989, 30, 5397±5400.
19. Padwa, A.; Fryxell, G. E.; Zhi, L. J. Am. Chem. Soc. 1990,
112, 3100±3109.
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