Tandem cyclization-cycloaddition behavior of rhodium carbenoids with carbonyl compounds: stereoselective studies on the construction of novel epoxy-bridged tetrahydropyranone frameworks.

Ta n d em Cycliza tion -Cycloa d d ition Beh a vior of Rh od iu m

Ca r ben oid s w ith Ca r bon yl Com p ou n d s: Ster eoselective Stu d ies on

th e Con str u ction of Novel Ep oxy-Br id ged Tetr a h yd r op yr a n on e

F r a m ew or k s

Sengodagounder Muthusamy,* Srinivasarao Arulananda Babu, Chidambaram Gunanathan,

Bishwajit Ganguly, Eringathodi Suresh, and Parthasarathi Dastidar

Central Salt and Marine Chemicals Research Institute, Bhavnagar 364 002, India

salt@csir.res.in

Received February 16, 2002

Investigations and stereoselective studies on the tandem reactions of carbonyl ylides generated

from R-diazo ketones in the presence of carbonyl compounds are presented in this paper.

Intramolecular cyclization of rhodium carbenoids generated the transient five- or six-membered-

ring carbonyl ylide dipoles, which efficiently underwent 1,3-dipolar cycloaddition reactions with

various dipolarophiles such as aromatic aldehydes 15, R,â-unsaturated aldehydes 18/24, R,â-

unsaturated ketones 27/28/31, and dienone 34. The transient carbonyl ylides underwent cycload-

ditions with various aromatic aldehydes to furnish diverse epoxy-bridged tetrahydropyranone ring

systems in a diastereoselective manner. The cycloaddition of carbonyl ylides with R,â-unsaturated

aldehydes 18/24 or dienone 34 afforded CdO addition products in a chemoselective manner despite

the presence of CdC bonds in the above dipolarophiles. Alternatively, the cycloaddition of carbonyl

ylides with R,â-unsaturated ketones 27/28 provided both the CdO and CdC cycloaddition products.

The cycloaddition of carbonyl ylides with carbonyl compounds occurred in good yields and was

found to be highly regio- and stereoselective. Single-crystal X-ray analyses were performed to

unambiguously establish the structure and stereochemistry of the novel epoxy-bridged tetrahy-

dropyranone ring systems 35a /38. Compound 35a exhibited both intermolecular C-H‚‚‚O and

intramolecular C-H‚‚‚π interaction motifs in the solid-state architecture. The regio-, chemo-, and

stereoselectivity observed in these reactions have been investigated by semiempirical AM1 MO

calculations. FMO analyses and transition state calculations have been performed for the

cycloaddition of carbonyl ylides with R,â-unsaturated carbonyl compounds such as tetracyclone

(34) and cyclopentenone (27a ). Both FMO and transition state calculations correctly predicted the

regio- and stereochemistry of the cycloadducts. The calculations further revealed that a severe

steric interaction caused by the phenyl rings present in dipolarophile 34 with dipole 14a increases

the activation barrier of the transition state during the cycloaddition process.

In tr od u ction

cloaddition reactions offer a versatile route for the

construction of a variety of complex molecules.³The

tandem cyclization-1,3-dipolar cycloaddition methodolo-

gies involving carbonyl ylides have been shown⁴as an

important tool to construct many bonds with a high

degree of regio- and stereocontrol. As a result, this

technique continues to be a subject of considerable

interest and intensive investigation in synthetic organic

chemistry. Padwa and co-workers have well exploited this

technique to synthesize a variety of complex molecules.

Natural products such as illudins,^5-7phorbol ester de-

Tandem-cyclization processes are superior methods for

the stereocontrolled construction of numerous carbon-

carbon bonds and/or ring systems in a single mode of

operation.¹Cycloaddition reactions are among the most

powerful tools for the efficient assembly of complex

molecular structures.²In particular, the 1,3-dipolar cy-

* Author to whom correspondence should be addressed. Phone: +91-

278-567760. Fax: +91-278-567562 and 566970. E-mail: smuthus@

yahoo.com.

(1) (a) Frontiers in Organic Synthesis. Chem. Rev. 1996, 96, 1-600.

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1993, 32, 131-312.

(2) (a) Padwa, A.; Straub, C. S Advances in cycloaddition; Harmata,

M., Ed.; J AI Press: Greenwich, CT, 1999; Vol. 6. (b) Dell, C. P. J . Chem.

Soc., Perkin Trans. 1 1998, 3873-3905. (c) Comprehensive Organic

Synthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.; Pergamon:

Oxford, UK, 1991; Vol. 5, Chapters 1-9. (d) Cycloaddition Reactions

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Wiley & Sons: New York, 1984; Vols. 1 and 2. (b) Gothelf, K. V.;

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Published on Web 10/16/2002

J . Org. Chem. 2002, 67, 8019-8033

8019

Muthusamy et al.

rivatives,^8,9and various alkaloids^4a,b,10have been synthe-

sized using the tandem cyclization-cycloaddition method

via an inter- or intramolecular manner. Intramolecular

carbenoid-carbonyl group cyclizations have been repre-

sented as one of the most effective methods for generating

carbonyl ylides from R-diazo ketones; their successive

cycloaddition reactions with CdC bonds were well docu-

mented.⁴The stereoselective synthetic methods to ox-

acyclic compounds, mainly molecules comprising complex

tetrahydrofuran and tetrahydropyran skeletons, have

gained substantial interest.^4,11The highly substituted

epoxy-bridged polycyclic moieties are recognized as com-

mon structural units in naturally existing bioactive

compounds, e.g. amberketal,¹²austalide B,¹³frontalin,¹⁴

levoglucosenone,¹⁵and zaragozic acid A.¹⁶The epoxy-

bridged tetrahydropyran skeleton is present in a wide

range of natural products and exists as a part of poly-

cyclic frameworks, e.g. loukacinols 1,¹⁷xanthane epoxide

2¹⁸(Scheme 1), sporol,¹⁹and isogosterones.²⁰

SCHEME 1

SCHEME 2

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269. (b) Padwa, A. Top. Curr. Chem. 1997, 189, 121-158. (c) Calter,

M. A. Curr. Org. Chem. 1997, 1, 37-70. (d) Padwa, A.; Krumpe, K. E.

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(g) Modern Catalytic Methods for Organic Synthesis with Diazo

Compounds. From Cyclopropanes to Ylides; Doyle, M. P., McKervey,

M. A., Ye, T., Eds.; J ohn Wiley & Sons: New York, 1998. (h) Padwa,

A.; Straub, C. S. Org. Lett. 2000, 2, 2093-2095. (i) Baldwin, J . K.;

Mayweg, A. V. W.; Newmann, K.; Pritchard, G. Org. Lett. 1999, 1,

1933-1935.

The 1,3-dipolar cycloaddition chemistry involving vari-

ous dipoles has been well documented³in the literature

but not much studied in the presence of heterodipolaro-

philes. A survey of literature revealed that only a few

reports are available on the reactions of carbonyl ylides

with carbonyl groups as heterodipolarophiles. However,

the chemistry and selectivity observed in these reactions

have not been investigated well. It is worth mentioning

that brevicomins²¹3 and 4 (Scheme 2) and zaragozic acid

A¹⁶have been inventively approached via the tandem

cyclization-cycloaddition methodology in the presence of

carbonyl compounds such as propionaldehyde and methyl

glyoxalate, respectively. In the case of brevicomin, only

the exo isomer is known to be a key component of the

aggregation pheromone. Therefore, control of the stereo-

selectivity in cycloaddition of carbonyl ylides presents a

challenge with the prospect of applications in the syn-

thesis of natural products.

Reactions of carbonyl ylides derived from aliphatic

R-diazo ketones with o-quinones,²²benzaldehyde,^21,23and

isatins²⁴in the presence of rhodium(II) carboxylates have

been reported to afford the cycloaddition products with

regioselectivity. Similarly, reactions of cyclic carbonyl

ylides derived from alicyclic R-diazo carbonyl compounds

with R,â-unsaturated ketones such as arylidenetetralones

led to epoxy-bridged tetrahydropyranone ring systems in

a regio- and chemoselective manner.²⁵Reactions of five-

(5) (a) Padwa, A.; Curtis, E. A.; Sandanayaka, V. P. J . Org. Chem.

1997, 62, 1317-1325. (b) Curtis, E. A.; Sandanayaka, V. P.; Padwa,

A. Tetrahedron Lett. 1995, 36, 1989-1992.

(6) McMorris, T. C.; Hu, Y.; Yu, J .; Kelner, M. J . J . Chem. Soc.,

Chem. Commun. 1997, 315-316.

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6967.

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(9) Dauben, W. G.; Dinges, J .; Smith, T. C. J . Org. Chem. 1993, 58,

7635-7637.

(10) (a) Padwa, A.; Precedo, L.; Semones, M. A. J . Org. Chem. 1999,

64, 4079-4088. (b) Padwa, A.; Harring, S. R.; Semones, M. A. J . Org.

Chem. 1998, 63, 44-54. (c) Padwa, A.; Price, A. T. J . Org. Chem. 1995,

60, 6258-6259. (d) Padwa, A.; Brodney, M. A.; Marino, J . P., J r.;

Sheehan, S. M. J . Org. Chem. 1997, 62, 78-87. (e) Marino, J . P.;

Osterhout, M. H.; Padwa, A. J . Org. Chem. 1995, 60, 2704-2713. (f)

Padwa, A.; Price, A. T. J . Org. Chem. 1998, 63, 556-565. (g) Kissel,

W. S.; Padwa, A. Tetrahedron Lett. 1999, 40, 4003-4006. (h) Padwa,

A.; Hertzog, D. L.; Nadler, W. R. J . Org. Chem. 1994, 59, 7072-7084.

(11) (a) Padwa, A.; Carter, S. P.; Nimmesgern, H.; Stull, P. D. J .

Am. Chem. Soc. 1988, 110, 2894-2900. (b) Lipshutz, B. H. Chem. Rev.

1986, 86, 795-819. (c) Molander, G. A. Acc. Chem. Res. 1998, 31, 603-

609. (d) Molander, G. A.; Alonso-Alija, C. J . Org. Chem. 1998, 63,

4366-4373. (e) Elliott, M. C. J . Chem. Soc., Perkin Trans. 1 1998,

4175-4200. (f) Paquette, L. A.; Moradei, M. O.; Bernardelli, P.; Lange,

T. Org. Lett. 2000, 2, 1875-1878. (g) Doyle, M. P.; Forbes, D. C.;

Protopopova, M. N.; Stanely, S. A.; Vasbinder, M. M.; Xavier, K. R. J .

Org. Chem. 1997, 62, 7210-7215. (h) Classics in Total Synthesis;

Nicolaou, K. C., Sorensen, E. J ., Eds.; VCH: Weinheim, Germany,

1996.

(12) Kongkathip, B.; Kongkathip, N.; J anthorn, S.; Virarangsiya-

korn, D. Chem. Lett. 1999, 51-52.

(13) Paquette, L. A.; Wang, T. Z.; Sivik, M. R. J . Am. Chem. Soc.

1994, 116, 2665-2666.

(19) Corley, D. G.; Rottinghaus, G. E.; Tempesta, M. S. Tetrahedron

Lett. 1986, 27, 427-430.

(14) Whitesell, J . K.; Buchanan, C. M. J . Org. Chem. 1986, 51,

5443-5445.

(20) Tomono, Y.; Hirota, H.; Fusetani, N. J . Org. Chem. 1999, 64,

2272-2275.

(15) Shafizaden, F.; Furneaux, R. H.; Stevenson, T. T. Carbohydr.

Res. 1979, 71, 169-191.

(21) Padwa, A.; Fryxell, G. E.; Zhi, L. J . Am. Chem. Soc. 1990, 112,

3100-3109.

(16) (a) Hodgson, D. M.; Bailley, J . M.; Villalonga-Barber, C.; Drew,

M. G. B.; Harrison, T. J . Chem. Soc., Perkin Trans. 1 2000, 3432-

3443. (b) Kataoka, O.; Kitagaki, S.; Watanabe, N.; Kobayashi, J .;

Nakumura, S.; Shiro, M.; Hashimoto, S. Tetrahedron Lett. 1998, 39,

2371-2374. (c) Koyoma, H.; Ball, R. G.; Berger, G. D. Tetrahedron Lett.

1994, 35, 9185-9188.

(22) Nair, V.; Sheela, K. C.; Radhakrishnan, K. V.; Rath, N. P.

Tetrahedron Lett. 1998, 39, 5627-5630.

(23) Padwa, A.; Chinn, A. L.; Hornbuckle, S. F.; Zhang, Z. J . Org.

Chem. 1991, 56, 3271-3278.

(24) Nair, V.; Sheela, K. C.; Sethumadhavan, D.; Bindu, S.; Rath

N. P.; Eigendorf, G. K. Synlett 2001, 272-274.

(25) Muthusamy, S.; Babu, S. A.; Gunanathan, C. Tetrahedron Lett.

2000, 41, 8839-8842.

(17) Loukaci, A.; Kayser, O.; Bindseil, K.-U.; Siems, K.; Frevert, J .;

Abreu, P. M. J . Nat. Prod. 2000, 63, 52-56.

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8020 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxy-Bridged Tetrahydropyranone Frameworks

SCHEME 3

when the lone pair of electrons on the ring carbonyl

oxygen attack the highly electrophilic carbenoid center

present in 13 (Scheme 4). For investigating the tandem

intramolecular formation and intermolecular cycloaddi-

tion reactions of cyclic carbonyl ylides 14 with carbonyl

groups as dipolarophiles, the required starting materials

12a -d were prepared according to the literature work.^29a

To explore the reaction of cyclic carbonyl ylides 14 with

various carbonyl compounds, initially we planned to

study the reaction of alicyclic diazo carbonyl compounds

12 with aromatic aldehydes. A catalytic amount of Rh₂-

(OAc)₄was added to a dichloromethane solution contain-

ing diazo ketone 12a and p-methyl benzaldehyde 15a

under an inert atmosphere. The reaction was monitored

by TLC and concentrated under reduced pressure, and

column chromatographic purification of the crude reac-

tion mixture afforded the cycloadduct 16a in 79% yield

(Scheme 5). The cycloadduct 16a was characterized as

an epoxy-bridged tetrahydropyranone ring system based

on its interrelated spectral data. The exo and endo

stereochemistry of the cycloadduct 16a can easily be

distinguished by the coupling constant of H^a(H-8) and

or six-membered-ring cyclic carbonyl ylides with p-benzo-

quinones^26a,27and other carbonyl compounds^26bhave also

been studied to afford 1:1 or 1:2 cycloadducts without any

selectivity. In general, the reaction of carbonyl ylide 6

with an R,â-unsaturated ketone 7 may be represented

as shown in Scheme 3 and the expected products are 8a /

8b and 8c via CdC or CdO cycloadditions, respectively.

The presence of two potential dipolarophilic functional-

ities (i.e. CdC or CdO) in 7 makes them interesting from

the vantage point of 1,3-dipolar cycloadditions.

In continuation of our interest to explore the synthetic

utility of R-diazo carbonyl compounds for the synthesis

of highly substituted epoxy-bridged poly- or spirocyclic

frameworks,^27-29herein we report our results on the

reactivity profile of carbonyl ylides with carbonyl com-

pounds. The major objective of this work involves the

stereoselective studies on the tandem cyclization-cyclo-

addition reactions of rhodium(II)-carbenoids with vari-

ous carbonyl compounds, e.g. R,â-unsaturated aldehydes,

aromatic/aliphatic aldehydes, and R,â-unsaturated ke-

tones. The detailed results of these reactions including

theoretical investigations are presented in this paper.

1

H^b(H-9) in the H NMR spectrum as the dihedral angle

between H^aand H^bin the exo cycloadduct 16a is close to

90°, meaning that the coupling constant would be very

small (J ≈ 0-2 Hz). Therefore, the formation of exo

cycloadduct 16a was confirmed based on a characteristic

singlet resonance signal for the bridgehead H^aproton in

1

the H NMR spectrum. This reaction revealed that the

carbonyl ylide 14a generated from diazo ketone 12a

cycloadds diastereoselectively with p-methyl benzalde-

hyde and this observation is in line with the literature.²³

Similarly, reaction of other diazo ketones 12a -c with

aromatic aldehydes gave the respective cycloadducts

16b-d in good yield (Scheme 5, Table 2). The other

expected regioisomeric products 17a -d were not ob-

served and this can be conveniently explained on the

basis of the chemical shift value for the bridgehead H^c

proton, which would be much more downfield than the

observed value for H^ain regioisomers 16a -d .

These results encouraged us for the further study of

the 1,3-dipolar cycloaddition reactions of cyclic carbonyl

ylides with R,â-unsaturated aldehydes in a tandem

manner. To the best of our knowledge, there is no report⁴

available on the reaction of carbonyl ylides with R,â-

unsaturated aldehydes. Treatment of diazo ketone 12a

with trans-cinnamaldehyde (18a ) in the presence of Rh₂-

(OAc)₄provided the cycloadduct 19a in 86% yield in a

chemoselective manner. We have not observed any of the

regioisomeric CdC addition products 20a /21a (Scheme

6).

Resu lts a n d Discu ssion

It was envisaged that the reaction of R-diazo ketones

such as 12 with Rh₂(OAc)₄could generate metallocar-

benoid 13 based on our earlier work.^29aThe transient five-

or six-membered-ring carbonyl ylides 14 could be formed

(26) (a) Pirrung, M. C.; Kaliappan, K. P. Org. Lett. 2000, 2, 353-

355. (b) Ibata, T.; Toyada, J . Bull. Chem. Soc. J pn. 1986, 59, 2489-

2493.

The FT-IR spectrum of compound 19a exhibited a

characteristic band at 1760 cm^-1indicating the presence

(27) Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Suresh, E.;

Dastidar, P.; J asra, R. V. Tetrahedron 2001, 57, 7009-7019.

(28) (a) Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Suresh, E.;

Dastidar, P. Bull. Chem. Soc. J pn. 2002, 75, 801-811. (b) Muthusamy,

S.; Babu, S. A.; Gunanathan, C.; J asra, R. V. Tetrahedron Lett. 2001,

42, 5113-5116. (c) Muthusamy, S.; Babu, S. A.; Gunanathan, C.

Tetrahedron Lett. 2002, 43, 3931-3934. (d) Muthusamy, S.; Babu, S.

A.; Gunanathan, C. Tetrahedron Lett. 2002, 43, 3133-3136.

(29) (a) Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Suresh, E.;

Dastidar, P.; J asra, R. V. Tetrahedron 2000, 56, 6307-6318. (b)

Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Suresh, E.; Dastidar,

P. Synlett 2001, 1407-1410. (c) Muthusamy, S.; Gunanathan, C.; Babu,

S. A. Tetrahedron Lett. 2001, 42, 523-526. (d) Muthusamy, S.;

Gunanathan, C.; Babu, S. A. Synthesis 2002, 471-474. (e) Muthusamy,

S.; Babu, S. A.; Gunanathan, C. Tetrahedron Lett. 2002, 43, 5981-

5984.

1

of a carbonyl group. The H NMR spectrum of product

19a exhibited a characteristic singlet resonance at δ 4.46

for the bridgehead (H-8) proton, a doublet at δ 6.58 due

to the presence of olefin proton H-13 with a coupling

constant of J ) 15.8 Hz, a doubled doublet at δ 6.07 with

coupling constants of J ₁) 15.8 Hz and J ₂) 7.1 Hz for

H-12, and a doublet at δ 4.37 for H-9 with a coupling

constant of J ) 7.1 Hz. ¹³C NMR and dept-135 spectral

analyses of product 19a showed peaks for one CH₃

carbon, four CH₂carbons, seven CH carbons, and four

quaternary carbons, including a carbonyl group at δ

J . Org. Chem, Vol. 67, No. 23, 2002 8021

Muthusamy et al.

SCHEME 4^a

a

Reaction conditions: Reagents for substrates a -c: (i) 8% aq KOH, rt; (iii) oxalyl chloride, ether or ClCO₂Et, NEt₃, ether; (v) CH₂N₂,

ether. Reagents for substrate d : (ii) 8% aq KOH, rt; (iv) (a) oxalyl chloride, ether; (b) i-PrMgBr, EtO₂CCH₂CO₂H, DCM/THF (1:5); (vi)

MsN₃, NEt₃, DCM.

SCHEME 5

SCHEME 6

SCHEME 7

TABLE 1. Dia zo Keton es 12a -d P r od u ced via Sch em e 4

substrate

n

m

R¹

R²

a

b

c

d

2

1

2

0

1

0

CH₃

H

CH₃

COOEt

TABLE 2. Com p ou n d s 16a -d P r od u ced via Sch em e 5

We generalized these results by further performing a

similar experiment using aliphatic R-diazo ketone 22. The

reaction of diazo ketone 22 with trans-cinnamaldehyde

(18a ) or trans-crotonaldehyde (18b) in the presence of

Rh₂(OAc)₄catalyst was carried out. The column chro-

matographic purification of the resulting crude reaction

mixtures gave the CdO cycloaddition products 23a (73%)

and 23b (64%), respectively (Scheme 7), in a chemose-

lective manner.

product

n

m

R¹

R²

reaction time, h

yield,^a

%

a

b

c

d

2

1

2

0

1

CH₃Me

CH₃OMe

3.0

3.5

4.0

3.0

79

73

67

63^b

CH₃

H

a

Yields (unoptimized) refer to isolated and chromatographically

b

pure compounds. Isolated as a mixture of diastereomers in the

ratio of 1:2.

Optimistic from the above results, we extended the

carbonyl ylide reactions with heterocyclic aldehydes to

obtain the highly substituted oxacyclic ring systems. For

this purpose, reactions of diazo ketones 12a /22 with

2-furancarboxaldehyde (24) in the presence of Rh₂(OAc)₄

were carried out to obtain the respective products 25

(68%) and 26 (66%) in a chemoselective manner (Scheme

8). The structure of cycloaddition products 25,26 was

evidently confirmed from their interrelated spectral data.

We have confirmed the formation of exo-cycloadducts 25/

26 based on the singlet resonance signal for the bridge-

213.3. These characteristic spectral data obviously con-

firmed the proposed structure of compound 19a as the

fused epoxy-bridged tetrahydropyranone ring system

(Scheme 6). The stereochemical assignment of exo isomer

19a was made based on the singlet resonance signal for

1

H-8 proton in the H NMR spectrum (as explained for

the cycloadduct 16a ). Subsequently, the reaction of diazo

ketone 12a with trans-crotonaldehyde (18b) in the pres-

ence of Rh₂(OAc)₄afforded the CdO cycloaddition product

19b (Scheme 6).

8022 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxy-Bridged Tetrahydropyranone Frameworks

TABLE 3. P r od u cts 29a -c a n d 30a -c P r od u ced via

Sch em e 9

SCHEME 8

yield,^a

%

product

m

R

reaction time, h

29

30^b

a

2

1

H

3.5

8.0

2.5

64

12

44

23

67

6

b^c

c

COOEt

H

a

Yields (unoptimized) refer to isolated and chromatographically

b

pure compounds 29 and 30. Isolated as a mixture of diastereo-

mers in the ratio of 1:3. ^cReaction was carried out in dry benzene

at reflux.

and four quaternary carbons including two carbonyl

groups at δ 217.2 and 212.2; these spectral data undoubt-

edly confirmed the proposed structure as an oxa-bridged

tetracyclic system. Typically, the presence of a singlet

resonance signal for the bridgehead proton (H-8) and the

lack of coupling with the H-9 proton (which demands the

dihedral angle near 90°) clearly indicated the exo ster-

eochemistry for product 29a .

SCHEME 9

The FT-IR spectrum of compound 30a exhibited bands

at 1764 and 1650 cm^-1, indicating the presence of

carbonyl and CdC groups, respectively. The ¹H NMR

spectrum of product 30a exhibited a characteristic singlet

resonance at δ 4.24 for the bridgehead (H-8) proton. ¹³C

NMR and dept-135 spectral analyses of product 30a

showed peaks for one CH₃carbon, seven CH₂carbons,

three CH carbons, and four quaternary carbons, including

a carbonyl group at δ 214, which clearly confirmed the

proposed structure as a spiro-dioxa ring system.

Further the Rh(II)-catalyzed reaction of diazo com-

pound 12d with cycloalkenone 28 was studied to furnish

an exo isomer of an oxa-bridged tetracyclic system 29b

and a spiro epoxy-bridged tetrahydropyranone ring sys-

tem 30b. Similarly, the reaction of diazo compound 12a

with 2-cyclopenten-1-one (27) afforded the cycloadducts

29c and 30c (Scheme 9). The formation of cycloadducts

29 and 30 can be explained in that the carbonyl ylides

14 underwent CdC and CdO cycloadditions to cycloalk-

enones, respectively. This observation was in line with

the recent reports^26,27in which reactions of carbonyl

ylides with electron-deficient p-quinones furnished both

CdC and CdO addition products. Compounds 30a -c

were isolated as a mixture of diastereomers in the ratio

of 1:3 (Table 3). It is known that the rhodium(II)-induced

carbonyl ylide formation process is highly dependent on

the electronic nature^31aof the substituent attached to the

diazo carbon atom. The yield of cycloaddition products

29b/30b reversed when the electrophilicity of the inter-

mediate rhodium carbenoid was increased (when R )

COOEt). The methyl substituent in all diazo compounds

was required because the apparently highly stabilized

dipole 14 may transfer the proton at a faster rate than

bimolecular 1,3-dipolar cycloaddition.^31bMoreover, we

have not isolated any competitive C-H insertion product

during the course of these reactions.³²It has been

head protons H-8 and H-4, respectively (as explained for

the cycloadduct 16a ). It is interesting to note that in all

the reactions, carbonyl ylides underwent cycloaddition

only to the CdO group of R,â-unsaturated aldehydes to

furnish various epoxy-bridged tetrahydropyranone ring

systems with high regio- and stereoselectivity. Even

though the furan ring is known to undergo cycloaddition

with isomu¨nchnone dipoles,³⁰no other cycloadducts were

observed in our experiments.

After obtaining various epoxy-bridged tetrahydropy-

ranone ring systems using aldehydes, we were further

interested to illustrate the scope and synthetic utility of

the tandem cyclization-cycloaddition sequence using R,â-

unsaturated cyclic ketones. Thus, we investigated the

reaction of R-diazo carbonyl compounds with cycloalk-

enones 27/28. Cycloalkenone derivatives were used as

dipolarophiles in the synthesis of the pterosin family of

sesquiterpenoids via the tandem cyclization-cycloaddi-

tion methodology.^5-7R-Diazo ketone 12a and 2-cyclo-

hexen-1-one (28) were allowed to react in the presence

of Rh₂(OAc)₄catalyst to furnish the cycloadducts 29a

(64%) and 30a (23%) (Scheme 9).

The FT-IR spectrum of compound 29a exhibited strong

bands at 1758 and 1700 cm^-1, indicating the existence

of two carbonyl groups. The ¹H NMR spectrum of product

29a exhibited a characteristic singlet resonance at δ 4.33

for the bridgehead (H-8) proton. ¹³C NMR and dept-135

spectral analyses of product 29a showed the signals for

one CH₃carbon, seven CH₂carbons, three CH carbons,

(31) (a) Dean, D. C.; Krumpe, K. E.; Padwa, A. J . Chem. Soc., Chem.

Commun. 1989, 921-922. (b) Lottes, A.; Landgreb, J . A.; Larsen, K.

Tetrahedron Lett. 1989, 30, 4089-4092.

(32) (a) 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. (b)

Doyle, M. P.; Tauton, J .; Pho, H. Q. Tetrahedron Lett. 1989, 30, 5397-

5400.

(30) Padwa, A.; Hertzog, D. L.; Nadler, W. R. J . Org. Chem. 1994,

59, 7072-7084.

J . Org. Chem, Vol. 67, No. 23, 2002 8023

Muthusamy et al.

SCHEME 10

reported^5-7,33that the reaction of 1-acetyl-1-(diazoacetyl)-

cyclopropane with cycloalkenone in the presence of

rhodium(II) carboxylate catalyst gave exclusively CdC

but not CdO cycloaddition product during the synthesis

of the pterosin family of sesquiterpenoids.

F IGURE 1. ORTEP view of compound 35a .

SCHEME 11

Cosequently, we performed the reaction of diazo ketone

12a with acyclic R,â-unsaturated ketone to understand

the reactivity of a carbonyl ylide. To this end, the reaction

of diazo ketone 12a and benzylideneacetophenone (31,

trans-chalcone) in the presence of Rh₂(OAc)₄was carried

out. Concentration followed by purification afforded

products 32 and 33 as an inseparable mixture. On the

basis of ¹H, ¹³C NMR, and dept-135 spectral data, epoxy-

bridged compounds 32,33 were characterized as regioi-

somers in the ratio of 1:2 (Scheme 10). Surprisingly, this

reaction revealed that the intermediate carbonyl ylide

14a underwent cycloaddition only to the CdC but not

the CdO group of trans-chalcone.

Furthermore, we became involved in widening the

synthetic utility of diazo ketone to obtain distinctive spiro

epoxy-bridged tetrahydropyranone molecules and inter-

ested in probing the stereoselective aspects of the tandem

cyclization-cycloaddition sequence. To this end, we de-

cided to use tetracyclone (34) as a dipolarophile that has

been widely used in Diels-Alder reactions as a 4π^34-36

or 2π³⁷component to synthesize many complex molecules.

The reaction of diazo ketone 12b and dienone 34 in the

presence of Rh₂(OAc)₄catalyst was carried out. Purifica-

tion of the crude reaction mixture on silica gel column

chromatography provided the cycloadduct 35a in 60%

yield (Scheme 11). This reaction divulged that the car-

bonyl ylide underwent cycloaddition to the CdO group

of dienone 34, resulting in an interesting novel spiro

epoxy-bridged tetrahydropyranone ring system in a

chemoselective manner.

other similar compounds) value of around 1 ppm. ¹³C

NMR and dept-135 spectral analyses of the cycloadduct

35a showed peaks for one CH₃carbon, three CH₂carbons,

eleven CH carbons, and twelve quaternary carbons,

including one carbonyl group at 208.6 ppm. The mode of

cycloaddition of carbonyl ylide to tetracyclone and the

regio- and stereochemistry of the interesting cycloadduct

35a (Figure 1) were unambiguously established by the

single-crystal X-ray analysis. The single-crystal X-ray

structure revealed that the presence of the methyl group

at the ring juncture is endo with respect to the oxido-

bridge and the observed angle of oxa-bridge (C1-O10-

C7) is 97.1° in compound 35a . All these spectral data

clearly revealed that the carbonyl ylide underwent cy-

cloaddition to the carbonyl group despite the presence of

the CdC bond in 34.

To generalize, the rhodium(II)-catalyzed behavior of

other diazo carbonyl compounds 12a and 12c in the

presence of 34 was studied to furnish the respective spiro-

dioxa ring systems 35b and 35c (Scheme 11, Table 4).

Similar to compound 35a , methyl group protons of 35b

were also shifted upfield (0.25 ppm). The reaction of diazo

ketone 12c in the presence of rhodium(II) acetate pro-

The FT-IR spectrum of compound 35a exhibited a

characteristic strong band at 1762 cm^-1, indicating the

1

presence of a carbonyl group. The H NMR spectrum of

the cycloadduct 35a exhibited a characteristic singlet

resonance at δ 0.13, 4.72 for a methyl group and

bridgehead (H-7) protons (Scheme 11, n ) 1; m ) 0),

respectively. It is interesting to note that methyl group

protons were shielded from the expected (or reported for

(33) (a) Padwa, A.; Sandanayaka, V. P.; Curtis, E. A. J . Am. Chem.

Soc. 1994, 116, 2667-2668. (b) Padwa, A.; Curtis, E. A.; Sandanayaka,

V. P. J . Org. Chem. 1996, 61, 73-81.

8024 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxy-Bridged Tetrahydropyranone Frameworks

TABLE 4. P r od u cts 35a -c Obta in ed via Sch em e 11

was shifted upfield due to its close proximity with the

phenyl group in the conformation as it was observed for

compounds 35a ,b. The single-crystal analysis of product

35a revealed that the presence of the methyl group at

the ring juncture is endo with respect to the oxido-bridge

and the same is tentatively assigned for all other cyclo-

adducts based on their similarity in spectral data.

Sin gle-Cr ysta l a n d Solid -Sta te Str u ctu r e An a ly-

ses. The cell parameters and intensity were measured

on an Enraf-Nonius CAD-4 diffractometer using graphite

monochromatized Mo KR radiation (0.7107) in the θ

range 2-22.5° and 2-25° for compounds 35a and 38,

respectively, at room temperature. Twenty-five reflec-

tions with θ ) 8-11° were used to obtain the accurate

cell dimensions. Three standard reflections were moni-

tored every 1 h, which showed no significant crystal decay

for the entire period of data collection for both com-

pounds. The crystal orientation, cell refinement, and

intensity measurements were carried out using the

program CAD-4PC.^38aThe raw intensity data were cor-

rected for Lorentz Polarization effects. The Lorentz

Polarization correction and data reduction were carried

out using the NRCVAX program.^38bThe structure was

solved using direct method. The full-matrix least-squares

refinement of all non-hydrogen atoms with isotropic

temperature factor was carried out using SHELXL-97.^38c

After the complete convergence of the isotropic refine-

ment for molecule 35a , six peaks appeared in the

difference Fourier map with electron density ranging

from 3 to 1.4 Å^-3that were accounted for by the highly

disordered solvent molecule. These peaks were incorpo-

rated as carbon atoms of the disordered solvent moiety

with the occupancy factor assigned according to their

peak heights. The isotropic refinement of the disordered

solvent molecule incorporating these peaks improved the

R-value and GOF, but we could not model the solvent

molecule because of its high dynamic disorderliness.

Since the number of reflections-to-parameter ratio was

low, the phenyl rings in the molecule were put in four

different blocks and the rest of the atoms in the fifth

block, using the SHELXL-97 program for anisotropic

refinement. Refinement with anisotropic thermal param-

eters except for the disordered solvent moiety (which was

refined only isotropically) was done in a blocked fashion

and yielded the R value of 11.76% (wR₂) 22.882%) for

compound 35a in the final cycles of least-squares refine-

ment. All the H-atoms were included stereochemically

in the calculated positions and treated as riding atoms.

After the complete anisotropic refinement of all the non-

hydrogen atoms for the cycloadduct 38, eight peaks with

electron density ranging from 3.3 to 1.5 Å^-3appeared in

the difference Fourier map, which were accounted for by

carbon atoms of the disordered solvent molecule and

refined isotropically with temperature factor depending

products

n

m

R

reaction time, h

yield,^a

%

a

b

c

1

2

0

1

CH₃

H

3.0

2.5

2.0

60

65

59^b

a

Yields (unoptimized) refer to isolated and chromatographically

b

pure compounds. Isolated as a mixture of diastereomers in the

ratio of 1:3.

F IGURE 2. ORTEP view of compound 38.

SCHEME 12

vided the cycloadducts as separable diastereomers 35c₁/

35c₂in the ratio of 1:3. We did not observe any CdC

addition products 36/37 in the presence of dienone 34 as

a dipolarophile (Scheme 11).

Finally, we performed an analogous experiment using

aliphatic diazo carbonyl compound 22 with tetracyclone

(34) in the presence of rhodium(II) acetate. This reaction

also afforded the cycloadduct 38 in 53% yield (Scheme

12) as a result of the cycloaddition of carbonyl ylide to

the CdO group of 34. The structure and regio- and

stereochemistry of product 38 were established based on

its interrelated spectral data, including single-crystal

X-ray analysis (Figure 2). The observed angle of the oxa-

bridge (C1-O7-C4) is 96.5° in compound 38. It may be

(34) Nair, V.; Mathew, B.; Radhakrishnan, K. V.; Rath N. P.

Tetrahedron 1999, 55, 11017-11026.

(35) Fieser, L. F.; Haddadin, M. J . Organic Syntheses; Wiley, New

York, 1973; Collect. Vol. V, pp 1037-1042.

(36) Allen, C. H. F. Chem. Rev. 1962, 62, 653-664.

(37) Nair, V.; Nair, A. G.; Radhakrishnan, K. V.; Nandakumar, M.

V.; Rath N. P. Synlett 1997, 767-768.

(38) (a) Enraf-Nonius CAD-4 Software, Version 5.0; Enraf-Nonius:

Delft, The Netherlands, 1989. (b) Gabe, E. J .; Le Page, Y.; Lee, F. L.;

White, P. S. J . Appl. Crystallogr. 1989, 22, 384-387. (c) Sheldrick, M.

SHELX97, Program for the solution of crystal structures; University

of Gottingen: Gottingen, Germany, 1997.

1

noted that in the H NMR spectrum of compound 38, one

of the singlet resonance signals of methyl group protons

J . Org. Chem, Vol. 67, No. 23, 2002 8025

Muthusamy et al.

phenyl rings (C23 to C27). The centroid‚‚‚centroid and

the nearest C-C distances between the offset stacked

phenyl rings are 3.990 and 3.334 Å, respectively. In

addition to an intermolecular H-bonding, the methyl

group hydrogen is involved in C-H‚‚‚π interaction with

the phenyl ring (C15-H15C‚‚‚C1g; H15C‚‚‚C1g ) 2.80

Å, C15‚‚‚C1g ) 3.62 Å and C15-H15C‚‚‚C1g ) 144°,

where C1g is the centroid of the phenyl ring (C17 to C22).

The C-H‚‚‚π interaction is evident from an unusual

upfield shift of the methyl group hydrogens to 0.13 ppm

1

from the expected value of around 1 ppm in the H NMR

spectrum of compound 35a .

F r on tier Molecu la r Or bita l (F MO) An a lysis. The

above experimental results show that diazo ketones 12/

22 were converted into the epoxy-bridged tetrahydropy-

ranone systems via the rapid cyclization of the transient

rhodium carbenoids 13a -d onto the neighboring ring

carbonyl group resulting in carbonyl ylides 14a -d , which

further underwent 1,3-dipolar cycloaddition with carbo-

nyl groups. In all the above reactions, the cycloaddition

of carbonyl ylides to dipolarophiles was highly regio-,

chemo-, and stereoselective. The carbonyl group of tetra-

cyclone (34) underwent 1,3-dipolar cycloaddition with

carbonyl ylides and no CdC cycloadduct has been de-

tected. To understand the factors that influence these

stereoselective cycloadditions, we decided to perform a

detailed computational study. Application of theoretical

aspects of FMO analysis to cycloaddition chemistry has

been used to envisage the relative rate and regiochemical

outcome of many cycloaddition reactions.^40-42In pertur-

bation theory, a few occupied and virtual molecular

orbitals of appropriate symmetry surrounding the fron-

tier MO gap of reactants have been considered. The

calculated energy differences and orbital coefficients are

used to model the transition state. Such a qualitative

approach is ideally suited to predict and understand the

stereochemical products of cycloaddition reactions.

Initially, we performed frontier molecular orbital analy-

sis (FMO) for the reaction of diazo ketone 12a and

dienone 34. The exclusive formation of [3+2] cycloadducts

from carbonyl ylide 14a and dienone 34 can be examined

in terms of the energies and orbital coefficients of the

frontier orbitals of reacting centers. The calculated

energy levels and orbital coefficients of HOMO and

LUMO for 34 and 14a are shown in Figure 4.

F IGURE 3. (a) Network of C-H‚‚‚O interactions in the ab-

plane of 35a . (b) A close view showing the dimeric C-H‚‚‚O

interactions and π‚‚‚π stacking in molecule 35a .

upon their peak height. We could not model the disor-

dered solvent molecule because of its highly dynamic

disorderliness (as in the case of 35a ). The H-atoms were

either fixed or obtained from the difference Fourier map

and the final cycles of refinement yielded an R -value of

8.52% (wR₂) 11.29%) for compound 38.

Next, we analyzed the solid-state architecture arrange-

ments of the interesting molecule 35a . The crystal

packing pattern (Figure 3a) of compound 35a divulged a

large number of close intermolecular links between the

molecules, which are associated as dimers via an inter-

molecular C-H‚‚‚O hydrogen bonding interaction³⁹be-

tween the carbonyl oxygen and the hydrogen from the

C7 carbon atom (H-bonding parameters are C7-H7‚‚‚

O16, C7-H7 ) 1.00 Å, H7‚‚‚O16 ) 2.53 Å, C7‚‚‚O16 )

3.35 Å, C7-H7‚‚‚O16 ) 140°, symmetry code ) 1 - x,

-y, 1 - z). The dimers (Figure 3b) are extended to form

a linear chain through stacking interaction between the

From the correlation diagram, it is evident that the

energy gap between HOMO of 14a and LUMO of 34 is

favored over HOMO of 34 and LUMO of 14a (Figure 4).

Examining the orbital coefficients calculated at the AM1

level of theory showed that these are largely comparable

at both CdC and CdO centers of dipolarophile 34. Hence,

the 1,3-cycloaddition between dipolarophile 34 and dipole

14a should lead to the formation of both CdC and CdO

addition products. Contrary to this, only CdO addition

(40) (a) Houk, K. N. Acc. Chem. Res. 1975, 8, 361-369. (b) Houk,

K. N.; Sims, J .; Watts, C. R.; Luskus, L. J . J . Am. Chem. Soc. 1973,

95, 7301-7315. (c) Sustmann, R. Tetrahedron Lett. 1971, 2717-2720.

(d) Bastide, J .; Henri-Rousseau, O. Bull. Soc. Chim. Fr. 1973, 2294-

2296. (e) Bastide, J .; Elghandour, N.; Henri-Rousseau, O. Tetrahedron

Lett. 1972, 4225-4228.

(41) Fukui, K.; Yonezawa, T.; Nagata, C.; Shingu, H. J . Chem. Phys.

1954, 22, 1433-1442.

(39) (a) Desiraju, G. R. Acc. Chem. Res. 1991, 24, 290-296. (b)

Mazik, M.; Blaser, D.; Boese, R. Tetrahedron 2001, 57, 5791-5797.

(c) Schmuck, C.; Lex, J . Eur. J . Org. Chem. 2001, 1519-1523. (d)

Mehta, G.; Vidya, R. J . Org. Chem. 2000, 65, 3497-3502.

(42) (a) Sustmann, R.; Trill, H. Angew. Chem., Int. Ed. Engl. 1972,

11, 838-840. (b) Sustmann, R. Pure Appl. Chem. 1974, 40, 569-593.

(c) Sustmann, R.; Gleittner, J .; Huisgen, R. Tetrahedron Lett. 1977,

887-880.

8026 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxy-Bridged Tetrahydropyranone Frameworks

F IGURE 6.

14a based on the AM1 level of theory. The calculated

transition state energies predicted that the “syn CdO

attack” (Figure 7) is preferred compared to other modes

of cycloaddition. This calculated result is in accord with

the experimentally observed products (Schemes 11 and

12 and Figure 7). Transition state energies calculated for

the 1,3-dipolar cycloaddition between the CdC unit of

dipolarophile 34 and dipole 14a are much higher (∼12.0

kcal/mol) compared to the corresponding transition states

of the CdO unit addition of dipolarophile (34). Such

energy differences should exclusively lead to the forma-

tion of the CdO cycloadduct and this is evident from our

experimental observation.

F IGURE 4.

An analysis of AM1 transition state geometries sug-

gested that the computed transition states for CdO

addition of dipolarophile 34 to dipole 14a were concerted

and slightly asynchronous in nature (Figure 7). The

transition state structures obtained for the CdC cyclo-

addition of dipolarophile 34 with dipole 14a were highly

unsymmetrical in nature. One of the newly forming bonds

was much smaller (2.0 Å) than the other bond (3.50 Å).

Such a high asynchronicity observed in the transition

states might be due to severe steric interactions between

phenyl rings present in the CdC unit of dipolarophile

34 and dipole 14a . Considering the nature of the 1,3-

dipolar transition states, it is worth mentioning that the

mechanism of 1,3-dipolar cycloaddition has been a topic

of lively debate.^43-45The results of different molecular

orbital calculations for the cycloaddition reactions have

provided support for both the concerted and two-step

diradical mechanisms.^44,46Padwa and co-workers have

demonstrated that a ground-state biradical carbonyl ylide

begins the bond-making process at the cycloaddition

transition state.⁴⁷

Representatively, we extended our theoretical studies

to the reaction of diazo ketone 12a with unsubstituted

cyclopentenone (27). Other groups have reported the

formation of only one cycloadduct between a dipolarophile

such as 27 and a dipole derived from an aliphatic diazo

carbonyl compound in the presence of rhodium(II) acetate

dimer. Presently, we have observed a detectable amount

of another cycloadduct (CdO cycloaddition product 30)

in the 1,3-dipolar cycloaddition reactions of carbonyl

F IGURE 5. Energy-minimized cyclic carbonyl ylide 14a .

products have been observed. Therefore, it appears that

the chemo- and regioselectivity observed in the above

reactions are not associated with the electronic factors

of the FMO model of the dipolar transition state. At this

stage, we decided to perform transition state calculations

for the formation of different cycloadducts between

dipolarophile 34 and dipole 14a . The transition state

energies calculated for cycloadducts and their relative

energy differences will indicate the formation of most

stable cycloadducts. Considering the relatively large size

of the dipolarophile and the dipole, the AM1 semiem-

pirical model has been employed to locate the transition

state for this 1,3-dipolar cycloaddition reaction.

The AM1 calculated cyclohexane fused five-membered-

ring cyclic carbonyl ylide dipole 14a is shown in Figure

5. The calculated results showed that the reactive center

(CdO⁺-C^-) of dipole 14a is completely planar and the

fused cyclohexane ring adopts a chairlike conformation.

A dipolarophile approach can be either syn or anti to the

methyl group of dipole 14a (Figure 5). The presence of a

fused cyclohexane ring and a methyl group in dipole 14a

makes it facially dissymmetric for the approach of a

dipolarophile. In this study, we have considered both syn

and anti approaches of dipolarophile 34 toward dipole

14a . It is important to note that the CdC unit of

dipolarophile 34 can approach the dipole 14a in two

different orientations, having the carbonyl group of

dipolarophile 34 close (in) or away (out) from the cyclo-

hexane ring of dipole 14a (Figure 6).

(43) (a) Huisgen, R. J . Org. Chem. 1968, 33, 2291-2297. (b) Huisgen,

R. J . Org. Chem. 1976, 41, 403-419.

(44) (a) Poppinger, D. J . Am. Chem. Soc. 1975, 97, 7486-7488. (b)

Poppinger, D. Aust. J . Chem. 1976, 29, 465-478. (c) Komornicki, A.;

Goddard, J .; Schaefer, H. F., III J . Am. Chem. Soc. 1980, 102, 1763-

1769. (d) Hiberty, P. C.; Ohanessian, G.; Schlegel, H. B. J . Am. Chem.

Soc. 1983, 105, 719-723.

(45) Dewar, M. J . S.; Olivella, S.; Rzepa, H. S. J . Am. Chem. Soc.

1978, 100, 5650-5659.

(46) (a) Liuch, J . M.; Bertran, J . Tetrahedron 1982, 38, 1847-1852.

(b) Liuch, J . M.; Bertran, J . J . Chem. Soc., Perkin Trans. 2 1982, 1419-

1423. (c) Harcourt, R. D.; Little, R. D. J . Am. Chem. Soc. 1984, 106,

41-46 and references therein.

Six transition states have been calculated for the 1,3-

dipolar cycloaddition between dipolarophile 34 and dipole

(47) Weingarten, M. D.; Prein, M.; Price, T.; Snyder, J . P.; Padwa,

A. J . Org. Chem. 1997, 62, 2001-2010.

J . Org. Chem, Vol. 67, No. 23, 2002 8027

Muthusamy et al.

F IGURE 7. The AM1-calculated TS structures for dipolarophile 34 and dipole 14a and their relative energies (in kcal/mol).

regioselection in these reactions. However, the approach

of the dipolarophile 27 toward the π-face of dipole 14a

(syn vs anti) remains to be answered. Therefore, we

considered possible modes of approach (syn vs anti) of

dipolarophile 27 toward the dipole 14a π-face and

calculated the transition states for such modes of cyclo-

addition. The two possible orientations of the CdC unit

of dipolarophile 27 cycloaddition have also been taken

into account (Figure 6). AM1 calculated transition states

and their relative energies are summarized in Figure 9.

The overall calculated results predicted that the “syn in

CdC attack” (Figure 9) is energetically favored compared

to other transition states. Generally, transition states

appear to be concerted and slightly asynchronous in

F IGURE 8.

nature. Overall, FMO and transition state calculations

ylides. ¹H, ¹³C, and dept-135 NMR studies confirmed that

the formation of CdC cycloaddition products 29a ,c was

predominant. To examine the regioselectivity observed

in these 1,3-dipolar cycloaddition reactions, FMO and

transition state analyses have been performed at the

AM1 level.

The orbital correlation diagram (Figure 8) predicted

the formation of predominant CdC cycloaddition for 1,3-

dipolar cycloaddition between dipolarophile 27 and dipole

14a . The calculated energy levels suggested that the

energy gap between HOMO of 14a and LUMO of 27 is

considerably lower than that of HOMO of 27 and LUMO

of 14a and hence the former interaction is energetically

favored for cycloaddition. It was also evident from the

size of the orbital coefficients calculated at the AM1 level

that the CdC unit of dipolarophile 27 has a larger

coefficient and will have better interaction than the

corresponding CdO coefficient with dipole 14a (Figure

8). From such analyses, it can be concluded that the

HOMO of 14a and LUMO of 27 controls the chemo- and

have predicted correctly the chemo- and regioselectivity

as observed in our experiments.

Finally, it is interesting to note that no anti cycload-

ducts have been observed in the 1,3-dipolar cycloaddition

reactions studied herein. Examination of the AM1 cal-

culated ground-state structure of dipole 14a revealed that

the anti face is sterically more hindered compared to the

corresponding syn face (Figure 5). The 1,3-diaxial hydro-

gens of the cyclohexane ring sterically hinder one of the

reactive centers (CdO⁺-C^-) in the anti face and hence

the dipolarophile prefers to approach from the syn face

of dipole 14a .

The above studies show that the mechanism by which

R-diazo carbonyl compounds were converted into highly

substituted epoxy-bridged tetrahydropyranone ring sys-

tems involved rapid cyclization of the rhodium carbenoid

onto the neighboring ring carbonyl group to afford the

corresponding five- or six-membered-ring cyclic carbonyl

ylides as intermediates, followed by subsequent [3+2]

cycloaddition with various carbonyl groups such as

8028 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxy-Bridged Tetrahydropyranone Frameworks

F IGURE 9. The AM1-calculated TS structures for dipolarophile 27 and dipole 14a and their relative energies (in kcal/mol).

heterodipolarophiles. It is evident that all the above

reactions furnished functionalized oxapoly- and spirocy-

clic frameworks with a high degree of regio-, chemo-, and

stereocontrol. Theoretical calculations for tandem cy-

clization-cycloaddition reactions afforded supporting

evidence in addition to spectral data to assign the regio-

and stereochemistry of the products. It is important to

note that starting from relatively simple precursors and

dipolarophiles, these tandem cyclization-cycloaddition

reactions resulted in the formation of new C-C and C-O

bonds in a stereoselective manner.

methodology in the synthesis of complex epoxy-bridged

natural products.

Exp er im en ta l Section

Gen er a l. The melting points are uncorrected. The FT-IR

spectra were recorded using KBr or neat method unless

otherwise stated. ¹H NMR and ¹³C NMR spectra were (200

and 50.3 MHz, respectively) referenced to TMS. Carbon types

were determined from DEPT ¹³C NMR experiments. Mass

analyses were performed with an ionizing voltage of 70 eV or

FD⁺method in absolute dichloromethane. Single-crystal X-ray

crystallographic analyses were carried out in an Enraf Nonius

CAD-4 diffractometer with Mo KR radiation. All AM1 semiem-

pirical calculations have been performed using MOPAC version

6.0.⁴⁸Complete vibrational analyses have been performed at

the same level of theory to characterize the transition states

and ground-state geometries. All reactions were carried out

under an argon atmosphere and solutions dried with anhy-

drous magnesium sulfate. Analytical thin-layer chromatogra-

phy (TLC) was performed on silica/alumina plates and com-

ponents were visualized by observation under iodine or by

sulfuric acid charring. Column chromatography was performed

on neutral alumina/silica gel (100-200 mesh). Care was taken

to avoid light during the course of reaction in the synthesis of

diazo compounds and their further conversion. Solvents were

purified by distillation under dry argon. Diethyl ether/THF

was distilled from sodium benzophenone ketyl immediately

before use. Benzene was dried over sodium. DCM was dried

using P₂O₅.

Con clu sion

In summary, we have established the scope of the

stereoselective 1,3-dipolar cycloaddition of carbonyl ylides

with carbonyl compounds, e.g. aromatic aldehydes, trans-

cinnamaldehyde, trans-crotonaldehyde, 2-furancarbox-

aldehyde, chalcone, cycloalkenones, and 2,3,4,5-tetraphe-

nylcyclopenta-2,4-dienone. The construction of poly- and

spirocyclic frameworks incorporating the epoxy-bridged

tetrahydropyranone moiety has been well demonstrated

in the case of cyclic or alicyclic R,â-unsaturated ketones

and aldehydes. Although three or more possible cycload-

ducts could be expected to form in each cycloaddition

reaction, only CdO addition products were obtained in

the case of R,â-unsaturated aldehydes 18/24 and 2,3,4,5-

tetraphenylcyclopenta-2,4-dienone (34). These cycload-

dition reactions were found to be highly chemo-, regio-,

and stereoselective, giving the exo cycloadducts in good

yields. FMO analyses and transition state calculations

have been performed for the better understanding of the

reaction of carbonyl ylides with carbonyl compounds.

Currently, we are investigating the application of this

Gen er a l P r oced u r e for t h e Syn t h esis of Dia zo

Keton es.^29a(a ) F or Su bstr a tes 12a ,b. Cycloalkanone ester

9 (12 mmol) was carefully hydrolyzed using 8% aqueous

potassium hydroxide solution (20 mL) with stirring at room

temperature. The reaction was monitored by TLC and con-

(48) Dewar, M. J . S.; Zoebish, E. G.; Healy, E. F.; Stewart, J . J . P J .

Am. Chem. Soc. 1985, 107, 3902-3909.

J . Org. Chem, Vol. 67, No. 23, 2002 8029

Muthusamy et al.

tinued until the disappearance of the starting material. The

reaction mixture was extracted with ether (3 × 10 mL),

acidified the aqueous layer (pH 5), and extracted with ether

(3 × 15 mL). The organic phase was concentrated under

reduced pressure at room temperature to obtain the corre-

sponding keto acids 10. Freshly distilled oxalyl chloride (20

mmol) was added dropwise to a stirring solution of the

appropriate acid (10 mmol, 10a ,b) in dry ether (25 mL) at 25

°C, 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 (100 mL)

and used for the next step without further purification. The

crude acid chloride solution was added dropwise over a 0.5-h

period to a stirring solution of freshly prepared diazomethane

(13 mmol) and freshly distilled triethylamine (10 mmol) in dry

ether (50 mL) at 0 °C, and the stirring was continued for 2 h.

The mixture was filtered and concentrated. Chromatography

of the residue through a short silica gel column (prewashed

by ethyl acetate) led to the corresponding diazo ketone 12a ,b

with 10% ethyl acetate-hexane elution. The diazo ketone 22²⁶

was synthesized in a similar manner.

(EtOAc-hexane mixture as eluent) to afford the respective

cycloadducts.

Meth od B: The procedure was followed as in method A

using dry benzene as solvent and the reaction mixture was

allowed to reflux under an argon atmosphere. The refluxing

was continued until the disappearance of the starting diazo

ketone and purified through a neutral alumina column as

described above.

Rea ction of r-Dia zo Keton e 12a w ith 15a , P r ep a r a tion

of 6-Meth yl-9-p-tolyl-10,11-dioxatr icyclo[6.2.1.0^1,6]u n decan -

7-on e (16a ). A mixture of 4-methylbenzaldehyde (120 mg, 1.0

mmol) and diazo ketone 12a (90 mg, 0.5 mmol) was allowed

to react with rhodium(II) acetate dimer (2.2 mg) in dry DCM

(10 mL) for 3 h at room temperature under an argon atmo-

sphere according to the general method A to afford the

cycloadduct 16a (108 mg) in 79% yield as a colorless solid: mp

113-115 °C (CHCl₃/hexane); IR (KBr) 2947, 2863, 1763, 1460,

1444, 1034, 973 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 7.24 (2H,

d, J ) 7.6 Hz, arom-H), 7.29 (2H, d, J ) 7.6 Hz, arom-H), 4.78

(1H, s, OCH), 4.47 (1H, s, OCH), 2.33 (3H, s, CH₃), 2.30-1.35

(8H, m), 1.20 (3H, s, CH₃); ¹³C NMR (50.3 MHz, CDCl₃) δ 213.7

(CdO), 138.8 (quat-C), 136.5 (quat-C), 129.6 (dCH), 126.7 (d

CH), 110.3 (quat-C), 86.8 (OCH), 77.5 (OCH), 52.4 (quat-C),

31.4 (CH₂), 27.2 (CH₂), 23.6 (CH₂), 21.5 (CH₃), 20.6 (CH₂), 16.2

(CH₃); MS (FD⁺) m/z 272 (M⁺). Anal. Calcd for C₁₇H₂₀O₃: C,

74.97; H, 7.40. Found: C, 74.97; H, 7.41.

(b) F or Su bstr a te 12c. To a solution containing 10 mmol

of keto acid 10c (1 equiv) in freshly prepared dry ether (100

mL) was added freshly distilled ethyl chloroformate (1.2 equiv)

followed by the slow addition of dry triethylamine (1.5 equiv).

The resulting mixture was stirred at room temperature for

45 min and the solid that formed was filtered under an inert

atmosphere. The filtrate was added to freshly prepared

ethereal diazomethane solution (20 mmol) and then the

mixture was stirred for 12 h at 0 °C after which it was allowed

Rea ction of r-Dia zo Keton e 12a w ith 15b, P r ep a r a tion

of 9-(4-Met h oxyp h en yl)-6-m et h yl-10,11-d ioxa t r icyclo-

[6.2.1.0^1,6]u n d eca n -7-on e (16b). A mixture of 4-methoxyben-

zaldehyde (136 mg, 1.0 mmol) and diazo ketone 12a (90 mg,

0.5 mmol) was allowed to react with rhodium(II) acetate dimer

(2.2 mg) in dry DCM (10 mL) for 3.5 h at room temperature

under an argon atmosphere according to the general method

A to afford the cycloadduct 16b (105 mg) in 73% yield as a

to warm to 10 °C for

a period of 2 h under an argon

atmosphere. The solvent was removed under reduced pressure

and the residue purified as described above to obtain 12c.

(c) F or Su bstr a te 12d . To a solution of freshly distilled

monoethyl malonate (35 mmol) in dry DCM (8 mL) was added

dropwise a solution of isopropylmagnesium bromide (70 mmol)

in THF (50 mL) until propane was evolved. The temperature

rises to 40-50 °C. The green solution was then cooled in an

ice/salt bath and crude appropriate acid chloride obtained from

the corresponding acid 10a (14 mmol) in DCM (2 mL) was

added dropwise with efficient stirring. The stirring was

continued for 1 h, the cooling bath was removed, and the

resultant mixture was poured into cold 10% hydrochloric acid

(20 mL). After cessation of the carbon dioxide evolution, the

clear solution was extracted with EtOAc (3 × 20 mL) and

washed with saturated sodium bicarbonate (30 mL) and brine

solution. The organic phase was dried over anhydrous MgSO₄

and concentrated under reduced pressure. The residue was

subjected to column chromatography on silica gel to afford the

corresponding active methylene compound 11d .

colorless oil: IR (neat, NaCl) 2946, 1762, 1461, 1443, 973 cm^-1

;

¹H NMR (200 MHz, CDCl₃) δ 7.30 (2H, d, J ) 7.6 Hz, arom-

H), 6.84 (2H, d, J ) 7.6 Hz, arom-H), 4.76 (1H, s, OCH), 4.45

(1H, s, OCH), 3.78 (3H, s, CH₃), 2.24-2.10 (1H, m), 1.99-1.85

(2H, m), 1.76-1.25 (5H, m), 1.19 (3H, s, CH₃); ¹³C NMR (50.3

MHz, CDCl₃) δ 213.3 (CdO), 159.7 (quat-C), 138.9 (quat-C),

127.6 (dCH), 113.9 (dCH), 113.0 (quat-C), 86.3 (OCH), 77.7

(OCH), 55.2 (OCH₃), 51.9 (quat-C), 30.9 (CH₂), 26.7 (CH₂), 23.2

(CH₂), 20.1 (CH₂), 15.7 (CH₃); MS (EI, 70 eV) m/z 288 (M⁺).

Anal. Calcd for C₁₇H₂₀O₄: C, 70.81; H, 6.99. Found: C, 70.97;

H, 6.87.

Rea ction of r-Dia zo Keton e 12b w ith 15c, P r ep a r a tion

of 5-Meth yl-8-p h en yl-9,10-d ioxa tr icyclo[5.2.1.0^1,5]d eca n -

6-on e (16c). A mixture of benzaldehyde (108 mg, 1.0 mmol)

and diazo ketone 12b (85 mg, 0.5 mmol) was allowed to react

with rhodium(II) acetate dimer (2.2 mg) in dry DCM (10 mL)

for 4 h at room temperature under an argon atmosphere

according to the general method A to afford the cycloadduct

16c (82 mg) in 67% yield as a colorless oil: IR (neat, NaCl)

To a solution containing active methylene compound 11d

(1 equiv) and freshly distilled methanesulfonyl azide (1.2

equiv) in dry dichloromethane (5 mL) was added freshly

distilled triethylamine (2 equiv) under an argon atmosphere

at room temperature. The reaction was continued until TLC

analysis indicated complete 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 afford pure diazo ketone

12d with 15% ethyl acetate-hexane elution.

Gen er a l P r oced u r e for th e Rh od iu m (II)-Ca ta lyzed

Cycloa d d ition Rea ction of r-Dia zo Keton es w ith Ca r -

bon yl Com p ou n d s. Meth od A: To an oven-dried flask

containing a dichloromethane solution of the appropriate

R-diazo carbonyl compound (1.0 mmol) and appropriate dipo-

larophile (2.0 mmol) was added 1 mol % of rhodium(II) acetate

dimer catalyst under an argon atmosphere at room tempera-

ture. The reaction mixture was stirred and monitored by TLC

until the disappearance of the starting diazo ketones. The

solvent was removed under reduced pressure and the crude

residue was purified using a silica gel/neutral alumina column

1

2965, 2927, 1763, 1452, 1036, 985 cm^-1; H NMR (200 MHz,

CDCl₃) δ 7.39-7.33 (5H, m, arom-H), 4.90 (1H, s, OCH), 4.43

(1H, s, OCH), 2.32-2.25 (2H, m), 2.06-1.92 (2H, m), 1.63-

1.56 (2H, m), 1.21 (3H, s, CH₃); ¹³C NMR (50.3 MHz, CDCl₃)

δ 211.7 (CdO), 139.2 (quat-C), 129.2 (dCH), 127.0 (dCH),

123.7 (quat-C), 87.1 (OCH), 79.0 (OCH), 58.1 (quat-C), 32.4

(CH₂), 26.4 (CH₂), 21.4 (CH₂), 18.6 (CH₃); MS (EI, 70 eV) m/z

244 (M⁺). Anal. Calcd for C₁₅H₁₆O₃: C, 73.75; H, 6.60. Found:

C, 74.00; H, 6.61.

Rea ction of r-Dia zo Keton e 12c w ith 15c, P r ep a r a tion

of 10-P h en yl-11,12-d ioxa tr icyclo[7.2.1.0^1,6]d od eca n -8-on e

(16d ). A mixture of benzaldehyde (106 mg, 1.0 mmol) and

diazo ketone 12c (90 mg, 0.5 mmol) was allowed to react with

rhodium(II) acetate dimer (2.2 mg) in dry DCM (10 mL) for 3

h at room temperature under an argon atmosphere according

to the general method A to afford the cycloadduct 16d (81 mg)

as a colorless oil in 63% yield as a mixture of diastereomers

in the ratio of 1:2: IR (neat, NaCl) 3065, 3032, 2936, 2859,

1733, 1448, 1272, 1014 cm^-^{1 1}H NMR (200 MHz, CDCl₃) δ

;

8030 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxy-Bridged Tetrahydropyranone Frameworks

7.29-7.17 (5H, m, arom-H), 4.99 (1H, s, OCH), 4.25 (1H, s,

OCH), 2.86 (1H, dd, J ₁)17.3, J ₂) 8.2 Hz), 2.45-1.66 (10H,

m); ¹³C NMR (50.3 MHz, CDCl₃) δ 203.9 (CdO), 140.8 (quat-

C), 128.9 (dCH), 128.6 (dCH), 126.3 (dCH), 110.1 (quat-C),

87.2 (OCH), 80.2 (OCH), 45.4 (CH), 40.2 (CH₂), 34.3 (CH₂),

31.3 (CH₂), 25.2 (CH₂), 24.1 (CH₂); MS (FD⁺) m/z 258 (M⁺).

Anal. Calcd for C₁₆H₁₈O₃: C, 74.40; H, 7.02. Found: C, 74.43;

H, 7.08.

Rea ction of r-Dia zo Keton e 12a w ith 18a , P r ep a r a tion

of 6-Meth yl-9-styr yl-10,11-dioxatr icyclo[6.2.1.0^1,6]u n decan -

7-on e (19a ). A mixture of 3-phenylpropenal (270 mg, 2.0

mmol) and diazo ketone 12a (180 mg, 1.0 mmol) was allowed

to react with rhodium(II) acetate dimer (4.4 mg) in dry DCM

(10 mL) for 3 h at room temperature under an argon atmo-

sphere according to the general method A to afford the

cycloadduct 19a (245 mg) in 86% yield as a colorless solid: mp

77-79 °C (CHCl₃/hexane); IR (KBr) 2952, 1760, 1450, 1371,

1274, 981, 939 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 7.34-7.19

(5H, m, arom-H), 6.58 (1H, d, J ) 15.8 Hz, dCH), 6.07 (1H,

dd, J ₁) 15.8 Hz, J ₂) 7.1 Hz, dCH), 4.46 (1H, s, OCH), 4.37

(1H, d, J ) 7.1 Hz, OCH), 2.20-1.19 (8H, m), 1.13 (3H, s, CH₃);

¹³C NMR (50.3 MHz, CDCl₃) δ 213.3 (CdO), 136.5 (quat-C),

133.7 (dCH), 129.0 (dCH), 128.5 (dCH), 127.2 (dCH), 126.4

(dCH), 113.4 (quat-C), 85.1 (OCH), 77.3 (OCH), 52.8 (quat-

C), 31.3 (CH₂), 27.4 (CH₂), 23.6 (CH₂), 20.6 (CH₂), 16.0 (CH₃);

MS (FD⁺) m/z 284 (M⁺). Anal. Calcd for C₁₈H₂₀O₃: C, 76.03;

H, 7.09. Found: C, 76.06; H, 7.06.

(CHCl₃/hexane); IR (KBr) 2990, 2973, 2941, 1765, 1468, 1306,

1

1097 cm^-1; H NMR (200 MHz, CDCl₃) δ 5.90-5.60 (1H, m,

dCH), 5.44 (1H, dd, J ₁) 15.2 Hz, J ₂) 7.4 Hz, dCH), 4.33

(1H, s, OCH), 4.16 (1H, d, J ) 7.4 Hz, OCH), 1.72 (3H, d, J )

6.4 Hz, CH₃), 1.56 (3H, s, CH₃), 1.06 (6H, s, CH₃); ¹³C NMR

(50.3 MHz, CDCl₃) δ 214.0 (CdO), 130.5 (dCH), 128.4 (dCH),

114.0 (quat-C), 84.7 (OCH), 77.1 (OCH), 53.1 (quat-C), 20.8

(CH₃), 19.1 (CH₃), 18.0 (CH₃), 15.2 (CH₃); MS (FD⁺) m/z 196

(M⁺). Anal. Calcd for C₁₁H₁₆O₃: C, 67.32; H, 8.22. Found: C,

67.32; H, 8.26.

Rea ction of r-Dia zo Keton e 12a w ith 24, P r ep a r a tion

of 9-F u r a n -2-yl-6-m et h yl-10,11-d ioxa t r icyclo[6.2.1.0^1,6]-

u n d eca n -7-on e (25). A mixture of 2-furancarboxaldehyde

(100 mg, 1.0 mmol) and diazo ketone 12a (90 mg, 0.5 mmol)

was allowed to react with rhodium(II) acetate dimer (2.2 mg)

in dry DCM (5 mL) for 3 h at room temperature under an

argon atmosphere according to the general method A to afford

the cycloadduct 25 (84 mg) in 68% yield as a colorless oil: IR

(neat, NaCl) 2940, 2866, 1767, 1503, 1450, 1378, 1229, 1039

1

cm^-1; H NMR (200 MHz, CDCl₃) δ 7.38 (1H, t, J ) 1.3 Hz,

dCH), 6.33 (2H, d, J ) 1.3 Hz, dCH), 4.83 (1H, s, OCH), 4.69

(1H, s, OCH), 2.10-1.35 (8H, m), 1.17 (3H, s, CH₃); ¹³C NMR

(50.3 MHz, CDCl₃) δ 212.8 (CdO), 151.7 (quat-C), 143.2 (d

CH), 113.6 (quat-C), 110.9 (dCH), 108.8 (dCH), 84.3 (OCH),

71.7 (OCH), 52.5 (quat-C), 31.3 (CH₂), 27.1 (CH₂), 23.5 (CH₂),

20.4 (CH₂), 16.0 (CH₃); MS (FD⁺) m/z 248 (M⁺). Anal. Calcd

for C₁₄H₁₆O₄: C, 67.73; H, 6.50. Found: C, 67.71; H, 6.51.

Rea ction of r-Dia zo Keton e 12a w ith 18b, P r ep a r a tion

of 6-Meth yl-9-p r op en yl-10,11-d ioxa tr icyclo[6.2.1.0^1,6]u n -

d eca n -7-on e (19b). A mixture of but-2-enal (70 mg, 1.0 mmol)

and diazo ketone 12a (90 mg, 0.5 mmol) was allowed to react

with rhodium(II) acetate dimer (2.2 mg) in dry DCM (5 mL)

for 3 h at room temperature under an argon atmosphere

according to the general method A to afford the cycloadduct

19b (74 mg) in 67% yield as a colorless oil: IR (neat, NaCl)

Rea ction of r-Dia zo Keton e 22 w ith 24, P r ep a r a tion

of 3-F u r a n -2-yl-1,6,6-t r im et h yl-2,7-d ioxa b icyclo[2.2.1]-

h ep ta n -5-on e (26). A mixture of 2-furancarboxaldehyde (100

mg, 1.0 mmol) and diazo ketone 22 (75 mg, 0.5 mmol) was

allowed to react with rhodium(II) acetate dimer (2.2 mg) in

dry DCM (5 mL) for 3 h at room temperature under an argon

atmosphere according to the general method A to afford the

cycloadduct 26 (73 mg) in 66% yield as a colorless oil: IR (neat,

NaCl) 2976, 2940, 2875, 1770, 1503, 1467, 1445, 1395, 1103

1

2942, 2866, 1766, 1450, 1038, 987 cm^-1; H NMR (200 MHz,

1

cm^-1; H NMR (200 MHz, CDCl₃) δ 7.35 (1H, t, J ) 1.3 Hz,

CDCl₃) δ 5.90-5.65 (1H, m, dCH), 5.43 (1H, dd, J ₁) 15.2

Hz, J ₂) 6.4 Hz, dCH), 4.38 (1H, s, OCH), 4.19 (1H, d, J )

7.4 Hz, OCH), 2.10-1.35 (8H, m), 1.71 (3H, d, J ) 6.2 Hz,

CH₃), 1.11 (3H, s, CH₃); ¹³C NMR (50.3 MHz, CDCl₃) δ 213.8

(CdO), 130.7 (dCH), 128.3 (dCH), 113.0 (quat-C), 85.0 (OCH),

77.1 (OCH), 52.6 (quat-C), 31.2 (CH₂), 27.3 (CH₂), 23.5 (CH₂),

20.5 (CH₂), 18.0 (CH₃), 15.9 (CH₃); MS (FD⁺) m/z 222 (M⁺).

Anal. Calcd for C₁₃H₁₈O₃: C, 70.24; H, 8.16. Found: C, 70.26;

H, 8.13.

dCH), 6.30 (2H, d, J ) 1.3 Hz, dCH), 4.78 (1H, s, OCH), 4.60

(1H, s, OCH), 1.59 (3H, s, CH₃), 1.09 (3H, s, CH₃), 1.06 (3H, s,

CH₃); ¹³C NMR (50.3 MHz, CDCl₃) δ 213.2 (CdO), 151.9 (quat-

C), 143.1 (dCH), 114.6 (quat-C), 110.9 (dCH), 108.7 (dCH),

84.1 (OCH), 71.8 (OCH), 53.1 (quat-C), 21.0 (CH₃), 19.2 (CH₃),

15.1 (CH₃); MS (FD⁺) m/z 222 (M⁺). Anal. Calcd for C₁₂H₁₄O₄:

C, 64.85; H, 6.35. Found: C, 64.84; H, 6.32.

Rea ction of r-Dia zo Keton e 12a w ith 2-Cycloh exen -

1-on e, P r ep a r a tion of Cycloa d d u cts 29a a n d 30a . A

mixture of 2-cyclohexen-1-one (215 mg, 2.0 mmol) and diazo

ketone 12a (200 mg, 1.1 mmol) was allowed to react with

rhodium(II) acetate dimer (4.9 mg) in dry DCM (10 mL) for

3.5 h at room temperature under an argon atmosphere

according to the general method A to afford the cycloadducts

29a and 30a in 64% (175 mg) and 23% (63 mg) yield,

respectively. 29a : Colorless thick oil; IR (neat, NaCl) 2931,

2863, 1758, 1700, 1455, 1270, 1120, 1036, 995 cm^-1; ¹H NMR

(200 MHz, CDCl₃) δ 4.33 (1H, s, OCH), 2.71 (1H, d, J ) 8.7

Hz), 2.52-2.11 (5H, m), 1.94-1.25 (10H, m), 1.10 (3H, s, CH₃);

¹³C NMR (50.3 MHz, CDCl₃) δ 217.2 (CdO), 212.2 (CdO), 92.0

(quat-C), 87.1 (OCH), 54.6 (CH), 51.6 (quat-C), 42.1 (CH), 41.1

(CH₂), 31.2 (CH₂), 27.8 (CH₂), 27.5 (CH₂), 22.9 (CH₂), 21.0

(CH₂), 20.6 (CH₂), 13.0 (CH₃); MS (FD⁺) m/z 248 (M⁺). Anal.

Calcd for C₁₅H₂₀O₃: C, 72.55; H, 8.12. Found: C, 72.63; H,

8.16. 30a : Mixture of diastereomers in the ratio of 1:0.3,

colorless thick oil; IR (neat, NaCl) 2935, 2866, 1764, 1650,

Rea ction of r-Dia zo Keton e 22 w ith 18a , P r ep a r a tion

of 1,6,6-Tr im eth yl-3-styr yl-2,7-d ioxa bicyclo[2.2.1]h ep ta n -

5-on e (23a ). A mixture of 3-phenylpropenal (270 mg, 2.0

mmol) and diazo ketone 22 (155 mg, 1.0 mmol) was allowed

to react with rhodium(II) acetate dimer (4.4 mg) in dry DCM

(10 mL) for 3.5 h at room temperature under an argon

atmosphere according to the general method A to afford the

cycloadduct 23a (189 mg) in 73% yield as a colorless solid: mp

111-113 °C (CHCl₃/hexane); IR (KBr) 2983, 1766, 1500, 1454,

1

1382, 1267, 1134 cm^-1; H NMR (200 MHz, CDCl₃) δ 7.37-

7.21 (5H, m, arom-H), 6.58 (1H, d, J ) 15.8 Hz, dCH), 6.09

(1H, dd, J ₁) 15.8 Hz, J ₂) 7.1 Hz, dCH), 4.42 (1H, s, OCH),

4.36 (1H, d, J ) 7.1 Hz, OCH), 1.59 (3H, s, CH₃), 1.09 (3H, s,

CH₃), 1.06 (3H, s, CH₃); ¹³C NMR (50.3 MHz, CDCl₃) δ 213.8

(CdO), 136.5 (quat-C), 133.8 (dCH), 129.1 (dCH), 128.6 (d

CH), 127.2 (dCH), 126.4 (dCH), 113.8 (quat-C), 84.8 (OCH),

77.4 (OCH), 53.4 (quat-C), 21.0 (CH₃), 19.2 (CH₃), 15.3 (CH₃);

MS (FD⁺) m/z 258 (M⁺). Anal. Calcd for C₁₆H₁₈O₃: C, 74.40;

H, 7.02. Found: C, 74.31; H, 7.04.

1

1451, 1376, 1283, 1099, 1042, 948 cm^-1; H NMR (200 MHz,

CDCl₃) δ 5.95-5.90 (1H, m), 5.69 (1H, d, J ) 10.4 Hz), 4.24

(1H, s, OCH), 2.14-1.17 (14H, m), 1.13 (3H, s, CH₃); ¹³C NMR

(50.3 MHz, CDCl₃) δ 214.0 (CdO), 132.0 (dCH), 129.4 (dCH),

112.9 (quat-C, C-1), 87.9 (OCH), 79.8 (quat-C, C-9), 53.9 (quat-

C), 32.6 (CH₂), 30.8 (CH₂), 28.1 (CH₂), 25.3 (CH₂), 23.8 (CH₂),

20.8 (CH₂), 20.1 (CH₂), 15.5 (CH₃); MS (FD⁺) m/z 248 (M⁺).

Anal. Calcd for C₁₅H₂₀O₃: C, 72.55; H, 8.12. Found: C, 72.56;

H, 8.09.

Rea ction of r-Dia zo Keton e 22 w ith 18b, P r ep a r a tion

of 1,6,6-Tr im eth yl-3-p r op en yl-2,7-d ioxa bicyclo[2.2.1]h ep -

ta n -5-on e (23b). A mixture of but-2-enal (70 mg, 1.0 mmol)

and diazo ketone 22 (75 mg, 0.5 mmol) was allowed to react

with rhodium(II) acetate dimer (2.2 mg) in dry DCM (5 mL)

for 3.5 h at room temperature under an argon atmosphere

according to the general method A to afford the cycloadduct

23b (63 mg) in 64% yield as a colorless solid: mp 73-75 °C

J . Org. Chem, Vol. 67, No. 23, 2002 8031

Muthusamy et al.

Rea ction of r-Dia zo Keton e 12d w ith 2-Cycloh exen -

1-on e, P r ep a r a tion of Cycloa d d u cts 29b a n d 30b. A

mixture of 2-cyclohexen-1-one (155 mg, 2.0 mmol) and diazo

ketone 12d (200 mg, 0.8 mmol) was allowed to react with

rhodium(II) acetate dimer (3.5 mg) in dry benzene (10 mL)

for 8 h at reflux under an argon atmosphere according to the

general method B to afford the cycloadducts 29b and 30b in

12% (31 mg) and 67% (170 mg) yield, respectively. 29b:

Colorless thick oil; IR (neat, NaCl) 2937, 2862, 1769, 1739,

1715, 1457, 1376, 984 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 4.34

(2H, q, J ) 7.1 Hz, OCH₂), 2.75-1.97 (8H, m), 1.94-1.47 (8H,

m), 1.36 (3H, t, J ) 7.1 Hz, CH₂CH₃), 1.16 (3H, s, CH₃); ¹³C

NMR (50.3 MHz, CDCl₃) δ 218.5 (CdO), 211.0 (CdO), 161.7

(COO), 106.9 (quat-C), 90.0 (quat-C), 62.5 (OCH₂), 54.8 (CH),

51.9 (quat-C), 44.8 (CH), 41.2 (CH₂), 31.3 (CH₂), 27.0 (CH₂),

25.1 (CH₂), 22.5 (CH₂), 20.8 (CH₂), 20.3 (CH₂), 16.9 (CH₃), 14.9

(CH₃); MS (EI, 70 eV) m/z 320 (M⁺). Anal. Calcd for C₁₈H₂₄O₅:

C, 67.48; H, 7.55. Found: C, 67.51; H, 7.49. 30b: Mixture of

diastereomers in the ratio of 1:0.3 as a colorless thick oil; IR

(neat, NaCl) 2939, 2869, 1775, 1746, 1650, 1518, 1456, 1381,

1132, 1085 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 6.06-5.98 (1H,

m), 5.60 (1H, d, J ) 10.4 Hz), 4.30 (2H, q, J ) 7.1 Hz, OCH₂),

2.17-1.97 (4H, m), 1.96-1.33 (10H, m), 1.29 (3H, t, J ) 7.1

Hz, CH₂CH₃), 1.19 (3H, s, CH₃); ¹³C NMR (50.3 MHz, CDCl₃)

δ 207.4 (CdO), 163.6 (COO), 134.4 (dCH), 125.9 (dCH), 110.7

(quat-C, C-1), 93.2 (quat-C, C-8), 80.4 (quat-C, C-9), 62.4

(OCH₂), 54.1 (quat-C), 32.1 (CH₂), 30.8 (CH₂), 27.7 (CH₂), 25.2

(CH₂), 23.3 (CH₂), 20.5 (CH₂), 19.6 (CH₂), 15.6 (CH₃), 14.7

(CH₃); MS (FD⁺) m/z 320 (M⁺). Anal. Calcd for C₁₈H₂₄O₅: C,

67.48; H, 7.55. Found: C, 67.54; H, 7.54.

(8H, m), 1.35 (3H, s, CH₃); ¹³C NMR (50.3 MHz, CDCl₃) δ 214.4

(CdO), 199.2 (CdO), 141.5 (quat-C), 138.0 (quat-C), 133.6 (d

CH), 129.2 (dCH), 129.0 (dCH), 128.6 (dCH), 128.3 (dCH),

127.8 (dCH), 127.1 (dCH), 91.8 (quat-C), 84.1 (OCH), 51.9

(CH), 51.3 (quat-C), 50.7 (CH), 31.4 (CH₂), 26.9 (CH₂), 21.9

(CH₂), 20.1 (CH₂), 15.3 (CH₃); MS (EI, 70 eV) m/z 360 (M⁺).

Anal. Calcd for C₂₄H₂₄O₃: C, 79.97; H, 6.71. Found: C, 79.91;

H, 6.66.

Rea ction of r-Dia zo Keton e 12b w ith 2,3,4,5-Tetr a -

p h en ylcyclop en ta -2,4-d ien on e, P r ep a r a tion of Cycloa d -

d u ct 35a .⁵⁰A mixture of 2,3,4,5-tetraphenylcyclopenta-2,4-

dienone (575 mg, 1.5 mmol) and diazo ketone 12b (165 mg,

1.0 mmol) was allowed to react with rhodium(II) acetate dimer

(4.4 mg) in dry DCM (10 mL) for 3 h at room temperature

under an argon atmosphere according to the general method

A to afford the cycloadduct 35a (313 mg) in 60% yield as a

colorless solid: mp 157-159 °C (DCM/hexane); IR (KBr) 2962,

1

2931, 1762, 1600, 1491, 1444, 1139, 909, 734 cm^-1; H NMR

(200 MHz, CDCl₃) δ 7.25-7.00 (10H, m, arom-H), 6.98-6.75

(10H, m, arom-H), 4.72 (1H, s, OCH), 2.15-1.55 (4H, m), 1.37-

0.90 (2H, m), 0.13 (3H, s, CH₃); ¹³C NMR (50.3 MHz, CDCl₃)

δ 208.6 (CdO), 146.8 (quat-C), 145.0 (quat-C), 142.0 (quat-C),

140.4 (quat-C), 136.6 (quat-C), 134.5 (quat-C), 134.1 (quat-C),

133.7 (quat-C), 132.6 (dCH), 130.3 (dCH), 129.8 (dCH), 129.5

(dCH), 127.5 (dCH), 127.4 (dCH), 127.1 (dCH), 127.0 (dCH),

126.8 (dCH), 126.7 (dCH), 123.5 (quat-C), 96.0 (quat-C), 86.9

(OCH), 59.2 (quat-C), 33.8 (CH₂), 25.3 (CH₂), 19.6 (CH₂), 13.2

(CH₃); MS (FD⁺) m/z 522 (M⁺). Anal. Calcd for C₃₇H₃₀O₃: C,

85.03; H, 5.79. Found: C, 85.19; H, 5.89.

Rea ction of r-Dia zo Keton e 12a w ith 2,3,4,5-Tetr a -

p h en ylcyclop en ta -2,4-d ien on e, P r ep a r a tion of Cycloa d -

d u ct 35b.⁵⁰A mixture of 2,3,4,5-tetraphenylcyclopenta-2,4-

dienone (575 mg, 1.5 mmol) and diazo ketone 12a (180 mg,

1.0 mmol) was allowed to react with rhodium(II) acetate dimer

(4.4 mg) in dry DCM (10 mL) for 2.5 h at room temperature

under an argon atmosphere according to the general method

A to afford the cycloadduct 35b (348 mg) in 65% yield as a

colorless solid: mp 151-153 °C (DCM/hexane); IR (KBr) 3058,

2942, 1764, 1600, 1492, 1443, 1375, 1036 cm^-1; ¹H NMR (200

MHz, CDCl₃) δ 7.25-7.13 (10H, m, arom-H), 6.99-6.75 (10H,

m, arom-H), 4.81 (1H, s, OCH), 1.99-1.26 (8H, m), 0.25 (3H,

s, CH₃); ¹³C NMR (50.3 MHz, CDCl₃) δ 210.2 (CdO), 146.5

(quat-C), 146.0 (quat-C), 142.1 (quat-C), 140.6 (quat-C), 136.8

(quat-C), 134.5 (quat-C), 134.3 (quat-C), 133.8 (quat-C), 132.8

(dCH), 130.4 (dCH), 129.7 (dCH), 129.5 (dCH), 127.5 (dCH),

127.3 (dCH), 127.1 (dCH), 126.9 (dCH), 126.8 (dCH), 126.6

(dCH), 114.9 (quat-C), 94.5 (quat-C), 87.1 (OCH), 53.6 (quat-

C), 32.8 (CH₂), 26.1 (CH₂), 22.8 (CH₂), 19.7 (CH₂), 12.2 (CH₃);

MS (FD⁺) m/z 536 (M⁺). Anal. Calcd for C₃₈H₃₂O₃: C, 85.05;

H, 6.01. Found: C, 85.01; H, 6.04.

Rea ction of r-Dia zo Keton e 12a w ith 2-Cyclop en ten -

1-on e, P r ep a r a tion of Cycloa d d u cts 29c a n d 30c. A

mixture of 2-cyclopenten-1-one (85 mg, 1.0 mmol) and diazo

ketone 12a (90 mg, 0.5 mmol) was allowed to react with

rhodium(II) acetate dimer (2.2 mg) in dry DCM (10 mL) for

2.5 h at room temperature under an argon atmosphere

according to the general method A to afford the cycloadducts

29c and 30c in 44% (51 mg) and 6% (6 mg) yield, respectively.

29c: Colorless solid; mp 88-90 °C (DCM/hexane); IR (KBr)

2932, 2861, 1755, 1729, 1466, 1378, 1179, 988 cm^-1; ¹H NMR

(200 MHz, CDCl₃) δ 4.43 (1H, s, OCH), 2.69-2.53 (2H, m),

2.32-2.03 (4H, m), 1.84-1.29 (8H, m), 1.08 (3H, s, CH₃); ¹³C

NMR (50.3 MHz, CDCl₃) δ 217.7 (CdO), 213.8 (CdO), 91.0

(quat-C), 87.9 (CH), 54.3 (CH), 49.9 (quat-C), 41.6 (CH), 39.5

(CH₂), 30.4 (CH₂), 25.8 (CH₂), 25.3 (CH₂), 22.2 (CH₂), 20.1

(CH₂), 16.4 (CH₃); MS (EI, 70 eV) m/z 234 (M⁺). Anal. Calcd

for C₁₄H₁₈O₃: C, 71.77; H, 7.74. Found: C, 71.72; H, 7.69.

30c: Mixture of diastereomers in the ratio of 1:0.4 as a

colorless thick oil; IR (neat, NaCl) 2938, 2864, 1758, 1698,

1

1455, 1350, 1261, 1124, 1045, 984 cm^-1; H NMR (200 MHz,

CDCl₃) δ 6.03-5.99 (1H, m), 5.72 (1H, d, J ) 10.4 Hz), 4.27

(1H, s, OCH), 2.50-1.29 (12H, m), 1.23 (3H, s, CH₃); MS (FD⁺)

m/z 234 (M⁺). Anal. Calcd for C₁₄H₁₈O₃: C, 71.77; H, 7.74.

Found: C, 71.79; H, 7.79.

Rea ction of r-Dia zo Keton e 12c w ith 2,3,4,5-Tetr a -

p h en ylcyclop en ta -2,4-d ien on e, P r ep a r a tion of Cycloa d -

d u cts 35c₁/c₂.⁵⁰A mixture of 2,3,4,5-tetraphenylcyclopenta-

2,4-dienone (575 mg, 1.5 mmol) and diazo ketone 12c (180 mg,

1.0 mmol) was allowed to react with rhodium(II) acetate dimer

(4.4 mg) in dry DCM (10 mL) for 2 h at room temperature

under an argon atmosphere according to the general method

A to afford the cycloadducts 35c₁and 35c₂(316 mg) in 59%

over all yield in the ratio of 1:0.35. 35c₁: Colorless solid; mp

155-157 °C (DCM/hexane); IR (KBr) 2931, 2854, 1723, 1598,

1489, 1440 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 7.25-7.00 (10H,

m, arom-H), 6.98-6.94 (6H, m, arom-H), 6.79-6.75 (4H, m,

arom-H), 4.97 (1H, s, OCH), 1.95-1.45 (5H, m), 1.41-0.80 (6H,

m); ¹³C NMR (50.3 MHz, CDCl₃) δ 202.4 (CdO), 148.3 (quat-

C), 145.4 (quat-C), 142.2 (quat-C), 138.2 (quat-C), 135.8 (quat-

C), 134.4 (quat-C), 134.0 (quat-C), 131.4 (dCH), 130.9 (dCH),

129.7 (dCH), 127.6 (dCH), 127.4 (dCH), 127.3 (dCH), 127.2

(dCH), 127.1 (dCH), 126.8 (dCH), 126.7 (dCH), 111.8 (quat-

Rea ction of r-Dia zo Keton e 12a w ith 1,3-Dip h en yl-

p r op en on e (31), P r ep a r a tion of Cycloa d d u cts 32/33.⁴⁹

A

mixture of 1,3-diphenylpropenone (208 mg, 1.0 mmol) and

diazo ketone 12a (90 mg, 0.5 mmol) was allowed to react with

rhodium(II) acetate dimer (2.2 mg) in dry DCM (10 mL) for

3.5 h at room temperature under an argon atmosphere

according to the general method A to afford the cycloadducts

9-benzoyl-6-methyl-10-phenyl-11-oxatricyclo[6.2.1.0^1,6]undecan-

7-one (32)/10-benzoyl-6-methyl-9-phenyl-11-oxatricyclo[6.2.1.0^1,6]-

undecan-7-one (33) in 57% (103 mg) yield as a mixture of

regioisomers in the ratio of 1:2.1 as a colorless thick oil: IR

(neat, NaCl) 2937, 2801, 1758, 1675, 1594, 1449, 1369, 1273

1

cm^-1; H NMR (200 MHz, CDCl₃) δ 7.99 (2H, d, J ) 7.4 Hz,

arom-H), 7.61-7.10 (8H, m, arom-H), 4.84 (1H, d, J ) 6.3 Hz),

4.54 (1H, t, J ) 6.4 Hz), 4.30 (1H, d, J ) 6.6 Hz), 1.79-1.38

(50) A mixture of benzene-hexane was used as eluent. Initially, the

crude residue was allowed to adsorb in the silica gel column for a longer

time to obtain the pure products.

(49) Spectral data (Proton and Carbon NMR) given for the predomi-

nant isomer in the mixture.

8032 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxy-Bridged Tetrahydropyranone Frameworks

C), 94.6 (quat-C), 85.9 (OCH), 41.5 (CH₂), 40.7 (CH₂), 33.9

(CH₂), 33.8 (CH₂), 29.7 (CH₂), 27.8 (CH₂), 23.2 (CH₂); MS (FD⁺)

m/z 536 (M⁺). Anal. Calcd for C₃₈H₃₂O₃: C, 85.05; H, 6.01.

Found: C, 85.00; H, 5.99. 35c₂: Colorless solid; mp 159-161

°C (DCM/hexane); IR (KBr) 3057, 2932, 2859, 1725, 1599,

1491, 1444 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 7.25-7.20 (10H,

m, arom-H), 6.99-6.94 (6H, m, arom-H), 6.79-6.75 (4H, m,

arom-H), 4.91 (1H, s, OCH), 2.00-1.05 (8H, m), 0.87-0.62 (3H,

m); ¹³C NMR (50.3 MHz, CDCl₃) δ 202.4 (CdO), 148.5 (quat-

C), 145.5 (quat-C), 142.0 (quat-C), 138.4 (quat-C), 136.1 (quat-

C), 134.4 (quat-C), 134.3 (quat-C), 134.0 (quat-C), 131.8 (d

CH), 130.9 (dCH), 129.7 (dCH), 127.6 (dCH), 127.5 (dCH),

127.3 (dCH), 127.2 (dCH), 127.1 (dCH), 126.8 (dCH), 126.7

(dCH), 111.0 (quat-C), 95.5 (quat-C), 85.4 (OCH), 43.5 (CH₂),

39.9 (CH₂), 33.6 (CH₂), 33.8 (CH₂), 29.7 (CH₂), 25.0 (CH₂), 23.5

(CH₂); MS (FD⁺) m/z 536 (M⁺). Anal. Calcd for C₃₈H₃₂O₃: C,

85.05; H, 6.01. Found: C, 84.96; H, 6.02.

Anal. Calcd for C₃₆H₃₀O₃: C, 84.68; H, 5.92. Found: C, 84.76;

H, 5.91.

X-r a y Cr ysta l Str u ctu r e An a lyses. Crystal data for

compound 35a : C₃₇H₃₃O₃, M ) 522.64, 0.20 × 0.14 × 0.06

mm³, triclinic, P1h, a ) 11.37(2) Å, b ) 11.623(7) Å, c ) 13.455-

(13) Å, R ) 110.83(9)°, â ) 114.86(10)°, γ ) 93.10(13)°, V )

1464(3) Å³, T ) 293(2) K, R₁) 0.1176, wR₂) 0.22882 on

observed data, z ) 2, D_calcd) 1.227 g cm^-3, F(000) ) 572,

absorption coefficient ) 0.079 mm^-1, λ ) 0.7107 Å, 3822

reflections were collected on a CAD-4 diffractometer, 1438

observed reflections (I g 2σ(I)). The largest difference peak

and hole ) 0.870 and -0.450e Å^-3, respectively.

Crystal data for compound 38: C₃₆H₃₀O₃, M ) 510.63, 0.20

× 0.16 × 0.10 mm³, triclinic, P1h, a ) 11.515(3) Å, b ) 11.841-

(4) Å, c ) 13.366(3) Å, R ) 113.61(2)°, â ) 112.17(2)°, γ ) 93.78-

(2)°, V ) 1495(7) Å³, T ) 293(2) K, R₁) 0.0852, wR₂) 0.2795

on observed data, z ) 2, D_calcd) 1.041 g cm^-3, F(000) ) 492,

absorption coefficient ) 0.066 mm^-1, λ ) -0.7107 Å, 5247

reflections were collected on a CAD-4 diffractometer, 3582

observed reflections (I g 2σ(I)). The largest difference peak

and hole ) 1.013 and -0.204e Å^-3, respectively. The structures

were solved by direct methods and refined by full-matrix least

squares on F²using SHELXL-97.

Rea ction of r-Dia zo Keton e 22 w ith 2,3,4,5-Tetr a p h e-

n ylcyclop en ta -2,4-d ien on e, P r ep a r a tion of Cycloa d d u ct

38.⁵⁰A mixture of 2,3,4,5-tetraphenylcyclopenta-2,4-dienone

(575 mg, 1.5 mmol) and diazo ketone 22 (155 mg, 1.0 mmol)

was allowed to react with rhodium(II) acetate dimer (4.4 mg)

in dry DCM (10 mL) for 2.5 h at room temperature under an

argon atmosphere according to the general method A to afford

the cycloadduct 38 (271 mg) in 53% yield as a colorless solid:

mp 159-162 °C (DCM/hexane); IR (KBr) 3028, 1765, 1489,

Ack n ow led gm en t. This research was supported by

Young Scientist Scheme, CSIR, New Delhi. We thank

Dr. P. K. Ghosh, Director, and Dr. R. V. J asra, Head of

the discipline, for their encouragement of this work.

S.A.B. and C.G. thank CSIR, New Delhi for a fellowship.

1441, 1299, 1266, 1129 cm^-^{1 1}H NMR (200 MHz, CDCl₃) δ

;

7.26-7.10 (10H, m, arom-H), 6.98-6.80 (10H, m, arom-H), 4.77

(1H, s, OCH), 1.39 (3H, s, CH₃), 0.85 (3H, s, CH₃), 0.27 (3H, s,

CH₃); ¹³C NMR (50.3 MHz, CDCl₃) δ 210.8 (CdO), 147.0 (quat-

C), 146.7 (quat-C), 142.7 (quat-C), 141.2 (quat-C), 137.5 (quat-

C), 134.9 (quat-C), 134.8 (quat-C), 134.3 (quat-C), 133.2 (d

CH), 131.0 (dCH), 130.2 (dCH), 130.1 (dCH), 128.0 (dCH),

127.8 (dCH), 127.6 (dCH), 127.5 (dCH), 127.3 (dCH), 127.2

(dCH), 116.3 (quat-C), 95.9 (quat-C), 87.5 (OCH), 54.9 (quat-

C), 23.5 (CH₃), 16.0 (CH₃), 14.8 (CH₃); MS (FD⁺) m/z 510 (M⁺).

Su p p or tin g In for m a tion Ava ila ble: Tables of X-ray

crystallographic data and CIF files of spiro epoxy-bridged

tetrahydropyranone derivatives 35a and 38. This material is

available free of charge via the Internet at http://pubs.acs.org.

J O0256134

J . Org. Chem, Vol. 67, No. 23, 2002 8033

Article Doi

Tandem cyclization-cycloaddition behavior of rhodium carbenoids with carbonyl compounds: stereoselective studies on the construction of novel epoxy-bridged tetrahydropyranone frameworks.

DOI: 10.1021/jo0256134

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Full text of DOI:10.1021/jo0256134

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