Intramolecular [2 + 2] photocycloaddition of alkenes incorporated in a carbohydrate template. Synthesis of enantiopure bicyclo[3.2.0]heptanes and -[6.3.0]undecanes

Article abstract of DOI:10.1021/jo026920c

Intramolecular [2 + 2] photocycloaddition of alkenes with a furano sugar placed between them have been investigated under both copper(I)-catalyzed and sensitized conditions. The copper(I)-catalyzed photocycloaddition of the dienes 4a, 4b, and 4c led to un

Full text of DOI:10.1021/jo026920c

Intramolecular [2 + 2] Photocycloaddition of Alkenes
Incorporated in a Carbohydrate Template. Synthesis of
Enantiopure Bicyclo[3.2.0]heptanes and -[6.3.0]undecanes
Shyamapada Banerjee and Subrata Ghosh*
Department of Organic Chemistry, Indian Association for the Cultivation of Science,
Jadavpur, Kolkata 700 032, India
ocsg@mahendra.iacs.res.in
Received December 31, 2002
Intramolecular [2 + 2] photocycloaddition of alkenes with a furano sugar placed between them
have been investigated under both copper(I)-catalyzed and sensitized conditions. The copper(I)-
catalyzed photocycloaddition of the dienes 4a, 4b, and 4c led to unexpected formation of the
thermodynamically less stable cis-syn-cis 4-5-5 tricyclic adducts 5a, 5b, and 5c, respectively.
The sensitized photocycloaddition of the diene 14 also gave the cis-syn-cis adduct 15 showing
that the copper(I) catalyst does not have any influence on the stereochemical course through
coordination with the anomeric ring oxygen of the furano sugar. The identical stereochemical course
observed under both catalyzed and sensitized photoaddition reactions have been attributed to be
of steric origin. Bis(dienes) 25a and 25b, which gave an intractable mixture on copper(I)-catalyzed
irradiation, underwent smooth photocycloaddition in the presence of benzophenone, and the resulting
1,2-divinyl cyclobutanes underwent spontaneous [3.3]-rearrangement at room temperature to
produce bicyclo[6.3.0]undecanes 30a and 30b, respectively. This investigation provides an approach
for the construction of enantiopure bicyclo[3.2.0]heptanes and -[6.3.0]undecanes.
Introduction
and commercially available, have served over the years
as a source of chirality. A variety of C-C bond-forming
reactions and ring annulation have been accomplished
using carbohydrates either as chiral auxiliary6 or as
chiral building blocks.7 Cycloaddition reactions such as
Diels-Alder7b or 1,3-dipolar8 reactions have also been
investigated. The [2 + 2] photocycloaddition reaction in
pyranosugar templates has been occasionally studied.9
However, the [2 + 2] photocycloaddition reaction of al-
kenes attached to furanosugar have not been explored.
In connection to our interest in the synthesis of
cyclopentanoids,10 we had the occasion to investigate the
reactivity and stereoselectivity in intramolecular [2 + 2]
photocycloaddition of 1,6-dienes using CuOTf as catalyst.
The seminal work by Salomon et al.11 and subsequently
our own work9c,10b,c have established that the stereochem-
ical outcome in these reactions is strongly influenced by
steric and electronic effects of the alkyl and hydroxyl
substituents at the allylic position. Carbohydrates en-
The [2 + 2] photocycloaddition of alkenes offers an
excellent stereoselective1 pathway for rapid access to
systems of significant complexity incorporating cyclo-
butanes. In general, the [2 + 2] photocycloaddition of an
alkene to a conjugated system such as an enone or a diene
can be achieved either on direct irradiation or irradiation
in the presence of a photosensitizer. On the other hand,
photoaddition of an alkene to a nonconjugated alkene is
possible only in the presence of metal catalyst,2 except
in few examples3 where the reacting alkenes are either
strained or closely held in conformationally rigid mol-
ecules. The bis(copper(I)trifluoromethane sulfonate)-
benzene complex [(CuSO3CF3)2‚C6H6](CuOTf) intro-
duced by Salomon and Kochi4 has been found to be the
most efficient catalyst for accomplishing both inter- and
intramolecular additions.
Despite great synthetic utility of the [2 + 2] photo-
cycloaddition reaction,1 asymmetric induction during this
reaction using either chiral auxiliary or metal complexes
with chiral ligands as catalysts has not been very
successful.5 Carbohydrates, being highly functionalized
(5) Langer, K.; Mattay, J. J. Org. Chem. 1995, 60, 7256.
(6) Hultin, P. G.; Earle, M. A.; Sudharshan, M. Tetrahedron 1997,
53, 14823.
(7) (a) Hanessian, S. Total Synthesis of Natural Products: The
Chiron Approach; Pergamon: New York, 1983. (b) Ferrier, R. J.;
Middleton, S. Chem. Rev. 1993, 93, 2779. (c) For selected recent work,
see: (i) Contelles, J. M.; Alhambra, C.; Grau, A. M. Synlett 1998, 693.
(ii) Haque, A.; Panda, J.; Ghosh, S. Indian J. Chem. 1999, 38B, 8. (iii)
Holt, D. J.; Barker, W. D.; Jenkins, P. R.; Panda, J.; Ghosh, S. J. Org.
Chem. 2000, 65, 482 and references cited there. (iv) Nandi, A.;
Chattopadhyay, P. Tetrahedron Lett. 2002, 43, 5977 and references
cited there.
(8) For a review, see: Osborn, H. M. I.; Gemmel, N.; Harwood: L.
M. J. Chem. Soc., Perkin Trans 1 2002, 2419.
(9) (a) Tenaglia, A.; Barille, D. Synlett 1995, 776. (b) Gomez, A. M.;
Mantecon, S.; Velazquez, S.; Valverde, S.; Herczegh, P.; Lopez, J. C.
Synlett, 1998, 1402. (c) Holt, D. J.; Barker, W. D.; Jenkins, P. R.; Ghosh,
S.; Russell, D. R.; Fawcett, J. Synlett 1999, 1003.
(1) For excellent accounts on the stereoselectivity in [2 + 2] photo-
cycloaddition reactions and their synthetic utility, see: (a) Crimmins,
M. T. Chem. Rev. 1988, 1453. (b) Fleming, S. A.; Bradford, C. L.; Gao,
J. J. In Organic Photochemistry; Ramamurthy, V., Schanze, K. S., Eds.;
Marcel Dekker: New York, 1997; Vol. 1, Chapter 6, p 187. (c) Bach, T.
Synthesis 1998, 683.
(2) Salomon, R. G. Tetrahedron 1983, 39, 485.
(3) (a) Fischer, J. W.; Hollins, R. A.; Lowe-Ma, C. K.; Nissan, R. A.;
Chapman, R. D. J. Org. Chem. 1996, 61, 9340. (b) Gleiter, R.; Brand,
S. Tetrahedron Lett. 1994, 35, 4969. (c) Chou, T. C.; Yeh, Y. L.; Lin, G.
H. Tetrahedron Lett. 1996, 37, 8779.
(4) Salomon, R. G.; Kochi, J. K. J. Am. Chem. Soc. 1973, 95, 1889.
10.1021/jo026920c CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/16/2003
J. Org. Chem. 2003, 68, 3981-3989
3981

Banerjee and Ghosh
SCHEME 1a
dowed with multiple oxygen functionality are thus ex-
pected to exert profound influence on the stereochemical
course during photoaddition reaction of the alkenes
attached to them. We initiated an investigation involving
intramolecular [2 + 2] photocycloaddition of alkenes at-
tached to a furanosugar with the following objectives: to
determine the influence of the intervening sugar unit on
the stereochemical outcome, under both catalyzed and
sensitized conditions; to prepare enantiopure bicyclo-
[3.2.0]heptanes; and to employ appropriately function-
alized bicyclo[3.2.0]heptanes for the construction of bicyclo-
[6.3.0]undecanes. The results of this investigation are
presented here.12
Results and Discussion
The diene 4a with alkenes linked by a furanosugar was
initially chosen for [2 + 2] photocycloaddition. It was
expected that this would provide rapid access to the
enantiopure cis-anti-cis 4-5-5 oxatricyclic system 7
(R ) Me). The carbocyclic structure analogous to 7 is
a Reagents and conditions: (i) CH2dCHCH2MgBr, THF, rt, 80%
(for 2a); CH2dC(Me)CH2MgCl, THF, rt, 70% (for 2b); (ii) NaH,
CH3I, THF, reflux, 2 h, 90% (for 3a); NaH, BnBr, THF, reflux, 2
h, 70-80% (for 3a and 3b); (iii) (a) 75% aq AcOH, rt, 12 h, (b) I2,
PPh3, imidazole, PhMe, reflux, 2 h, 53-60%; (iv) hν, CuOTf, Et2O,
3.5h, 72-77%; (v) 10% Pd-C, H2, MeOH, AcOH, HClO4, 80-85%.
was then protected to provide the methyl ether 3a in 90%
yield. The ether 3a was then converted to the diene 4a
in 60% yield through a two-step sequence involving
selective deprotection of the 5,6-acetonide moiety followed
by conversion of the resulting diol to alkene. Cycloaddi-
tion of the diene 4a could be achieved only on irradiation
in the presence of CuOTf as catalyst, producing a single
photoadduct 5a in 60% yield as a colorless liquid. The
gross structure of the photoadduct was clearly evident
from 1H and 13C NMR spectral data. The C2-H appeared
as a doublet at δ 4.38 with J ) 5.1 Hz. It was difficult to
ascertain the stereochemistry at the 4/5 ring fusion based
on it.
present in a number of structurally novel sesquiterpenes
such as kelsoene (8)13 and sulcatine G (9),14 which in
recent years have elicited considerable interest among
the synthetic organic chemists. The diene 4 was prepared
from the known ketone 1 derived from D-glucose as
delineated in Scheme 1. Reaction of the ketone 1 with
allylmagnesium bromide provided the homoallyl alcohol
2a in 79% yield. The hydroxyl group in the alcohol 2a15
The failure to assign stereochemistry led us to search
for a crystalline analogue. Irradation of the diene 4b
having a benzyloxy group instead of OMe in the presence
of CuOTf as catalyst indeed afforded a crystalline photo-
adduct 5b in 72% yield, mp 52 °C. However, crystals of
this compound were not suitable for X-ray structure
determination. The C2-H in the 1H NMR spectrum of its
debenzylated analogue 6a, obtained through hydro-
genolysis of 5b, appeared at δ 4.15 as a doublet with a
coupling constant of 5.5 Hz. This indicates that cyclo-
addition of both the dienes 4a and 4b proceeded with
same stereochemical outcome. An attempt to distinguish
the cis-anti-cis structure 7 from the cis-syn-cis struc-
ture 5 by comparison of the observed coupling constants
for the C2-H’s in the photoadducts 5a and 5b with those
reported11a for the proton R to the OH group in a series
of exo- and endo-2-hydroxybicyclo[3.2.0]heptanes (4.5 Hz
and 6-8 Hz respectively) was not conclusive.
(10) (a) Ghosh, S.; Patra, D. Tetrahedron Lett. 1993, 34, 4565. (b)
Patra, D.; Ghosh, S. J. Org. Chem. 1995, 60, 2526. (c) Ghosh, S.; Patra,
D.; Samajdar, S. Tetrahedron Lett. 1996, 37, 2073. (d) Haque, A.;
Ghatak, A.; Ghosh, S.; Ghoshal, N. J. Org. Chem. 1997, 62, 5211. (e)
Samajdar, S.; Patra, D.; Ghosh, S. Tetrahedron 1998, 54, 1789. (f)
Ghosh, S.; Patra, D.; Saha, G. J. Chem. Soc., Chem. Commun. 1993,
783. (g) Patra, D.; Ghosh, S. J. Chem. Soc., Perkin Trans. 1 1995, 2635.
(h) Samajdar, S.; Ghatak, A.; Ghosh, S. Tetrahedron Lett. 1999, 40,
4401.
(11) (a) Salomon, R. G.; Coughlin, D. J.; Ghosh, S.; Zagorski, M. G.
J. Am. Chem. Soc. 1982, 104, 998. (b) Avasthi, K.; Raychaudhuri, S.
R.; Salomon, R. G. J. Org. Chem. 1984, 49, 4322. (c) Ghosh, S.;
Raychaudhuri, S. R.; Salomon, R. G. J. Org. Chem. 1987, 52, 83.
(12) A portion of this work appeared as a preliminary communica-
tion: Ghosh, S.; Banerjee, S. P.; Chowdhury, K.; Mukherjee, M.;
Howard, J. A. K. Tetrahedron Lett. 2001, 42, 5997.
(13) (a) For isolation, see: Konig, G.; Wright, A. D. J. Org. Chem.
1997, 62, 3837. (b) For total syntheses see: Mehta, G.; Srinivas, K.
Tetrahedron Lett. 1999, 40, 4877; Tetrahedron Lett. 2001, 42, 2855.
Piers, E.; Orellana, A. Synthesis, 2001, 2138. Fietz-Razavian, S.;
Schulz, S.; Dix, I.; Jones, P. G. J. Chem. Soc., Chem. Commun. 2001,
2154. Thorsten, B.; Anja, S. Synlett, 2002, 1305.
(14) (a) For isolation, see: Arnone, A.; Nasini, G.; de Pava, O, V. J.
Chem. Soc., Perkin Trans. 1 1993, 2723. (b) For synthesis see: Mehta,
G.; Sreenivas, K. J. Chem. Soc., Chem. Commun. 2001, 1892; Tetra-
hedron Lett. 2002, 43, 3319.
(15) Gable, K. P.; Benz, G. A. Tetrahedron Lett. 1991, 32, 3473.
3982 J. Org. Chem., Vol. 68, No. 10, 2003

Intramolecular [2 + 2] Photocycloaddition
SCHEME 2a
FIGURE 1. ORTEP diagram of the photoadduct 5c.
We next focused on the photocycloaddition of the diene
4c, as this would incorporate the angular Me group
required for the natural products. The diene 4c was
prepared by a sequence similar to that used for preparing
the diene 4b after addition of methylallylmagnesium
chloride to the ketone 1. Irradiation of the diene 4c in
the presence of CuOTf as catalyst afforded the crystalline
photoadduct 5c, mp 58 °C in 77% yield. The C2-H in the
debenzylated analogue 6b appeared as a doublet at δ 4.15
with J ) 6.3 Hz. Thus, all the three dienes, irrespective
of the substituent on the alkene or the nature of the
alkoxy groups, behaved similarly in the CuOTf-catalyzed
photocycloaddition reaction. A single-crystal X-ray struc-
ture determination16 of this photoadduct showed that it
possesses a cis-syn-cis structure (Figure 1). This es-
tablishes the cis-syn-cis structure for the phtoadducts
5a and 5b.
a Reagents and conditions: (i) OsO4, NaIO4, H2O, Et2O, 79%;
(ii) NaH, (EtO)2P(O)CH2CO2Et, THF, rt, 18 h, 67%; (iii) (a) 75%
aq AcOH, rt, 12h, (b) I2, PPh3, imidazole, PhMe, reflux, 2 h, 54%;
(iv) hν, Ph2CO, CH3CN, 6 h, 50%;(v) 10% Pd-C, H2, EtOH, AcOH,
HClO4, 65%;(vi) KOH, H2O, EtOH, reflux, 2 h, 83%; (vii) hν,
quinoline, t-BuSH, C6H6,7 h, 40%.
to the formation of the cis-syn-cis adducts. The involve-
ment of analogous tricoordinated Cu(I) complexes 11
during photocycloaddition of 3-hydroxy-1,6-heptadienes
has been invoked11a to explain the predominant formation
of endo-2-hydroxy bicyclo[3.2.0]heptanes.
Exclusive formation of a thermodynamically less stable
cis-syn-cis linearly arranged tricyclic system in a cyclo-
addition reaction is noteworthy. The formation of cis-
syn-cis adducts in a [2 + 2] photocycloaddition has been
observed17 only when the reacting alkenes are tethered
through a long chain. AM1 calculations18 (using MOPAC,
version 1.10) indicates that the cis-syn-cis adduct 5b
(E ) -4865.8857 kcal mol-1) is less stable than the
corresponding cis-anti-cis adduct 7 (R ) Bn) (E )
-4869.0894 kcal mol-1) by 3.2 kcal mol-1 in the gas
phase. Thus, one would expect the formation of the cis-
anti-cis adduct 7 (R ) Bn) from photocycloaddition of
the diene 4b. A plausible explantion for the formation of
the cis-syn-cis adducts is the involvement of the tri-
coordinated Cu(I) complex 10 formed prior to cyclo-
addition. This complex preorganizes the diene for cyclo-
addition to take place syn to the furanose ring, leading
To determine the stereochemical outcome in a [2 + 2]
photocycloaddition in the absence of Cu(I) catalyst, the
diene 14 with a conjugated ester moiety was chosen. The
diene 14 was prepared as outlined in Scheme 2. Oxidative
cleavage of the alkene unit in the benzyl derivative 3b
followed by Wittig-Horner reaction of the resulting
aldehyde 12 afforded exclusively the E-isomer 13. The
ester 13 was then converted to the diene 14 by following
a sequence similar to the transformation of the di-
acetonide 3b to the diene 4b.
The diene 14 could be made to undergo cycloaddition
on irradiation in acetonitrile with benzophenone as a
sensitizer. A single photoadduct 15 was obtained as a
liquid in 50% yield. The stereochemical assignment to
the adduct 15 was based on its transformation to the
cyclobutane derivative 6a through debenzylation, hy-
drolysis, and photodecarboxylation19 of the resulting
hydroxy acid 17. Thus, sensitized photocycloaddition of
the dienic ester 14 provided also a cis-syn-cis adduct
15.
(16) Crystallographic data for compound 5c has been deposited with
the Cambridge Crystallographic Data Centre as deposition number
CCDC 158331. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax:
+44(0) (122 3) - 336033. E-mail: deposit@ccdc.cam.ac.uk].
(17) (a) Chebolu, R.; Zhang, W.; Galoppini, E.; Gilardi, R. Tetra-
hedron Lett. 2000, 41, 2831. (b) Comins, D. L.; Lee, Y. S.; Boyle, P. D.
Tetrahedron Lett. 1998, 39, 187. (c) Winker, J. D.; Hershberger, P. M.;
Springer, J. P. Tetrahedron Lett. 1986, 27, 5177. (d) Musser, A. K.;
Fuchs, P. L. J. Org. Chem. 1982, 47, 3121.
The observed stereochemical outcome in the photo-
cycloaddition of the diene 14 may be explained by the
(18) Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P.
J. Am. Chem. Soc. 1985, 107, 3901.
(19) Okada, K.; Okubo, K.; Oda, M. Tetrahedron Lett. 1989, 30, 6733.
J. Org. Chem, Vol. 68, No. 10, 2003 3983

Banerjee and Ghosh
SCHEME 3
SCHEME 4a
well-accepted pathway,20 as delineated in Scheme 3.
Triplet sensitization of the conjugated ester 14 leads to
the biradical intermediate 18. 5-Exo-trig addition of the
high-energy â-radical to the double bond may give rise
to two new biradical intermediates, 19 and 20. Prefer-
ential formation of the biradical 20 is expected over the
biradical 19, as the later experiences severe 1,3-diaxial
interactions involving the alkoxy group and the radical-
bearing alkyl chains. The crystal structure of the photo-
adduct 5c (Figure 1) points out that such interaction in
the structure 19 is possible. Further, such 1,3-diaxial
interactions between alkoxy and alkyl groups have been
found21 to determine the stereochemistry of the product
in 5-exo-trig radical cyclizations. Ring closure of the 1,4-
biradical 20 then leads to the product 15. In the light of
this observation, it is apparent that photocycloaddition
of the diene 4 in the presence of Cu(I) catalyst may not
necessarily need formation of the sterically crowded
complex 10. Instead, it probably proceeds through photo-
excitation of the complex 21.2 Sequential bond formation,
similar to the sensitized process, preferentially leads to
the radical intermediate 22, which finally collapses to the
product. Thus, the unusual stereochemical outcome in
both the Cu(I)-catalyzed and sensitized photocycloaddi-
tions arises from the steric effect of the substituents in
the sugar template.
a Reagents and conditions: (i) allyltriphenyl phosphonium
chloride, n-BuLi, Et2O, 0 °C, 64% (for 23a); methallyltriphenyl
phosphonium chloride, n-BuLi, Et2O, 0 °C, 63% (for 23b);(ii) (a)
75% aq AcOH, rt, 12 h, (b) NaIO4, CH3CN, H2O, rt, 65%; (iii) hν,
Ph2CO, n-hexane, 6 h; (iv) rt, 20 days, 35-40% (for 26 and 27);
200 °C, sealed tube, PhMe, 22 h, 10-12% (for 28 and 29); (v) 10%
Pd-C, H2, MeOH, 81%.
triphenyl phosphonium chloride afforded the diene 23a
in 64% yield as an inseparable mixture of E and Z
isomers. The diene 23a was converted to the aldehyde
24a in 65% yield using a two-step sequence involving
selective deprotection of the 5,6-acetonide moiety followed
by cleavage of the resulting vicinal diol. A nonstereo-
selective Wittig olefination of the aldehyde 24a finally
afforded the bis(diene) 25a in 63% yield as a mixture of
geometrical isomers. Irradiation of an ether solution of
the bis(diene) 25a for 3 h in the presence of CuOTf as
catalyst led to an intractable mixture of products. How-
ever, irradiation of its hexane solution in the presence
of benzophenone as sensitizer led to complete consump-
tion of the bis(diene) 25a (Rf 0.53) in 6 h, producing a
new component (Rf 0.42), as revealed by TLC (1:19 ethyl
acetate/petroleum ether). The product was rapidly freed
from benzophenone through silica gel column chroma-
To extend the scope of this reaction, we next focused
on the [2 + 2] photocycloaddition of the bis(dienes) 25
interconnected through the same furanosugar, anticipat-
ing that the resulting 1,2-divinyl cyclobutanes would
rearrange22,23 to afford a fused 5-8 ring system. The
bis(diene) 25a was prepared as follows. Wittig olefination
of the aldehyde 12 with the ylide generated from allyl
(20) Brown, M. J. Org. Chem. 1968, 33, 162.
(21) (a) Corey, E. J.; Shih, C.; Shih, N. Y.; Shimoji, K. Tetrahedron
Lett. 1984, 25, 5013. (b) Wilcox, C. S.; Thomasco, L. M. J. Org. Chem.
1985, 50, 546.
(22) Wender, P. A.; Correia, C. R. D. J. Am. Chem. Soc. 1987, 109,
2523.
(23) Hertel, R.; Mattay, J.; Runsink, J. J. Am. Chem. Soc. 1991, 113,
657.
1
tography. H and 13C NMR spectra showed it to be a
3984 J. Org. Chem., Vol. 68, No. 10, 2003

Intramolecular [2 + 2] Photocycloaddition
mixture of several components. Purification and charac-
terization of the photoadducts became difficult as the
mixture kept on changing to produce an additional
component (Rf 0.36, 1:19 ethyl acetate/petroleum ether).
The new component was isolated as a liquid by prepara-
tive TLC and was characterized as the cyclooctadiene
derivative 30a arising from [3.3] sigmatropic rearrange-
ment of the intermediate 1,2-divinyl cyclobutanes. The
photoadducts were stored at room temperature. Isolation
of the cyclooctadiene 30a from the mixture through
preparative TLC on every alternate day was continued
until (20 days) no cyclooctadiene 30a was found to form.
In this way cyclooctadiene derivative 30a was isolated
in 35% yield. The material that remained unchanged
after separation of the cyclooctadiene derivative was
heated in toluene in a sealed tube at 200 °C for 24 h to
afford also the same cyclooctadiene 30a in 10% yield. A
small amount (5%) of material still remained unchanged.
Thus the cyclooctadiene derivative 30a was obtained in
a combined yield of 45%. From this behavior of the
photoadducts it is likely that the products that gave the
cyclootadiene derivative at room temperature are the cis-
1,2-divinyl cyclobutanes 26 and/or 27, as cis-1,2-divinyl-
cyclobutanes are known to undergo Cope rearrangement
at temperatures much lower than that required for
rearrangement of trans-1,2-divinylcyclobutanes.22 Thus
the fraction of the photoadducts that required heating
at 200 °C for rearrangement are likely the trans-1,2-
divinylcyclobutanes 28 and/or 29. Comparison of the
yields of the cyclootadiene derivative 30a obtained at
room temperature (35%) and on heating (10%) indicated
that the photoaddition of the bis(diene) 25a produced the
cis-1,2-divinylcyclobutanes predominantly.
The material that remained unchanged even on heat-
ing the photoadducts was found to be a mixture of two
components in ca. 1:1 ratio by 1H NMR. For characteriza-
tion, this mixture was hydrogenated over Pd/C to remove
the double bonds and the benzyl protecting groups to lead
to again a mixture (ca. 1:1) of two components. On the
basis of spectral and microanalytical data, the gross
structure of the hydrogenation product appeared to be
either 33 and/or 34. Hence, vinyl cyclohexenes 31 and/
or 32 were formed through [1,3] rearrangement of the
trans-1,2-divinylcyclobutanes, possibly during thermoly-
sis,24 along with the cyclooctadiene derivative.
The bis(diene) 25b followed a similar reaction course
on irradiation and subsequent thermolysis. Thus, the
cyclootadiene derivative 30b was obtained in 40% yield
after storing the photoadduct at room temperature for
20 days. Another 12% yield of the cyclooctadiene deriva-
tive was obtained on heating the residual mass, thus
indicating that cis-1,2-divinylcyclobutanes were obtained
as the major photoadduct. The stereochemical assign-
ment at the 4/5 ring fusion of the photoadducts 26-29
and hence that at 5/8 ring fusion in the tricycles 30a and
30b is based on analogy to the formation of the photo-
adducts 5 from [2 + 2] photocycloaddition of the dienes
4.
In conclusion, we have demonstrated the influence of
furanosugar on the reactivity and stereochemical course
during intramolecular [2 + 2] photocycloaddition of al-
kenes leading to unusual formation of cis-syn-cis
4-5-5 tricyclic system in enantiomerically pure form.
The stark concavity of these compounds suggests the
possibility of their use as potential building blocks for
chiral molecular clefts.25 A sequence of [2 + 2] photo-
cycloaddition of bis(diene) attached through the same
furanosugar and facile [3.3] sigmatropic rearrangement
provides an enantioselective approach for direct construc-
tion of bicyclo[6.3.0]undecanes.26
Experimental Section
All reactions were carried out under a blanket of N2. Melting
points were taken in open capillaries in a sulfuric acid bath
and are uncorrected. Petroleum ether refers to the fraction
having bp 60-80 °C. A usual workup of the reaction mixture
consists of extraction with ether, washing with brine, drying
over Na2SO4, and removal of solvent in vacuo. Column chro-
matography was carried out with silica gel (60-120 mesh).
Peak positions in 1H and 13C NMR spectra are indicated in
ppm downfield from internal TMS in δ units. NMR spectra
were taken in CDCl3 solution at 300 MHz for 1H and 75 MHz
for 13C. 13C peaks assignment is based on DEPT experiment.
IR spectra were recorded as neat for liquids and in KBr for
solids.
1:2,5:6-Di-O-isopropylidine-3-C-(2′-propenyl)-r-D-allo-
furanose 2a. To a stirred solution of allylmagnesium bromide
[prepared from allyl bromide (1.5 mL, 17.44 mmol) and Mg
(0.5 g, 23.24 mmol) in THF (30 mL)] at 0 °C was added
dropwise a solution of the ketone 1 (3.0 g, 11.62 mmol) in THF
(20 mL). After complete addition, the reaction mixture was
stirred at room temperature for 6 h. The reaction mixture was
cooled to 0 °C and quenched by adding saturated aqueous
NH4Cl solution. Usual workup of the reaction mixture followed
by column chromatography using ether-petroleum ether
(1:4) as eluent afforded the allofuranose 2a (2.79 g, 80%): mp
124 °C; [R]30 + 42.8 (c 3.0, CHCl3); 1H NMR δ 1.34 (3H, s,
D
CH3), 1.36 (3H, s, CH3), 1.45 (3H, s, CH3), 1.58 (3H, s, CH3),
2.17 (1H, dd, J ) 8.8, 14.5 Hz, CH2), 2.65 (1H, dd, J ) 6.4,
15.5 Hz, CH2), 2.69 (1H, s, OH), 3.81 (1H, d, J ) 5.4 Hz, C4-H),
3.91 (1H, m, CH), 4.13 (2H, m, CH2), 4.35 (1H, d, J ) 3.7 Hz,
C2-H), 5.15 (1H, d, J ) 16.9 Hz, dCH2), 5.19 (1H, d, J ) 10.1
Hz, dCH2), 5.67 (1H, d, J ) 3.7 Hz, C1-H), 5.99 (1H, m, dCH);
13C NMR δ 25.7 (CH3), 26.8 (CH3), 27.1 (CH3), 37.1 (CH2), 68.4
(OCH2), 73.6 (CH), 79.1 (C), 81.6 (CH), 82.5 (CH), 103.9 (CH),
110.1 (C), 112.9 (C), 119.3 (dCH2), 132.9 (dCH-). Anal. Calcd
for C15H24O6: C, 59.98; H, 8.05. Found: C, 60.34; H, 8.29.
1:2,5:6-Di-O-isopropylidine-3-C-(2′-methyl-2′-propenyl)-
r-D-allofuranose 2b. Following the above procedure, a solu-
tion of the ketone 1 (1.0 g, 3.18 mmol) in THF (10 mL) was
allowed to react with methallylmagnesium chloride [prepared
from methallyl chloride (0.4 mL, 3.82 mmol) and Mg (120 mg,
4.77 mmol)] and THF (10 mL) to afford the allofuranose 2b
1
(850 mg, 70%): mp 118 °C; [R]25 +48.2 (c 0.89, CHCl3); H
D
NMR δ 1.35 (3H, s, CH3), 1.37 (3H, s, CH3), 1.50 (3H, s, CH3),
1.59 (3H, s, CH3), 1.91 (3H, s, CH3), 2.12 (1H, d, J ) 15 Hz,
(24) Thermolysis of 1,2-divinylcyclobutanes has been the subject of
several investigations. It has been established that cis-1,2-divinyl-
cyclobutanes produce cyclooctadienes as the major product while trans-
1,2-divinyl cyclobutanes produce vinylcyclohexenes as the major
product. See: (a) Hammond, G. S.; DeBoer, C. D. J. Am. Chem. Soc.
1964, 86, 899. (b) Trecker, D. J.; Henry, J. P. J. Am. Chem. Soc. 1964,
86, 902. (c) Berson, J. A.; Dervan, P. B.; Malherbe, R.; Jenkins, J. A.
J. Am. Chem. Soc. 1976, 98, 5937. Also see refs 22 and 23.
(25) Pascal, R. A., Jr.; Mathai, M. S.; Shen, X.; Ho, D. M. Angew.
Chem., Int. Ed. 2001, 40, 4746.
(26) (a) For an account on the synthesis of 5-8 ring systems, see:
Mehta, G.; Singh, V. Chem. Rev. 1999, 99, 881. (b) For selected recent
work on the direct construction of 5-8 systems, see: (i) Stragies, R.;
Blechert, S. Synlett 1998, 169. (ii) Lo, P. C. K.; Snapper, M. L. Org.
Lett. 2001, 3, 2819. (iii) Boyer, F. D.; Hanna, I.; Ricard, L. Org. Lett.
2001, 3, 3095.
J. Org. Chem, Vol. 68, No. 10, 2003 3985

Banerjee and Ghosh
CH2), 2.54 (1H, d, J ) 12 Hz, CH2), 2.62 (1H, s, OH), 3.78 (1H,
d, J ) 9 Hz, CH), 3.91 (1H, m, CH), 4.11 (2H, m, CH2), 4.45
(1H, d, J ) 6 Hz, CH), 4.76 (1H, s, dCH2), 4.94 (1H, s, dCH2),
5.66 (1H, d, J ) 6 Hz, CH); 13C NMR δ 24.2 (CH3), 25.2 (CH3),
26.3 (CH3), 26.5 (CH3), 26.6 (CH3), 39.6 (CH2), 67.8 (CH2), 72.9
(CH), 78.9 (C), 80.6 (CH), 82.4 (CH), 103.4 (CH), 109.5 (C),
112.4 (C), 115.0 (CH2), 141.8 (C). Anal. Calcd for C16H26O6: C,
61.13; H, 8.34. Found: C, 61.28; H, 8.51.
and concentrated to afford a colorless viscous liquid (400 mg).
This diol was converted to the alkene following the procedure
developed by Gregg and Samuelsson.27 To a solution of this
liquid in toluene (20 mL) was added imidazole (400 mg, 5.83
mmol) and PPh3 (1.52 g, 5.83 mmol). This mixture was refluxed
gently and iodine (1.11 g, 4.38 mmol) was added in small
portions. Refluxing was continued for 2 h. The reaction mixture
was cooled to room temperature and aqueous NaOH solution
(5 mL, 20%) was added to it. Usual workup of this mixture
followed by column chromatography using ether-petroleum
ether (1:19) as eluent afforded the diene 4a (230 mg, 60%) as
a colorless viscous liquid: [R]25D +51.7 (c 5.4, CHCl3); 1H NMR
δ 1.27 (3H, s, CH3), 1.52 (3H, s, CH3), 2.15 (1H, dd, J ) 7.3,
15.0 Hz), 2.47 (1H, dd, J ) 6.9, 15.0 Hz), 3.34 (3H, s, OMe),
4.33 (1H, d, J ) 3.6 Hz, C2-H), 4.50 (1H, d, J ) 6.3 Hz, C4-H),
5.03-5.09 (2H, m), 5.21-5.42 (2H, m), 5.57 (1H, d, J ) 3.6
Hz, C1-H), 5.75-5.86 (2H, m); 13C NMR δ 26.8 (CH3), 27.3
(CH3), 34.5 (CH2), 52.9 (OCH3), 82.4 (2CH), 84.4 (C), 103.8
(CH), 112.9 (C), 118.8 (CH2), 119.4 (CH2), 132.8 (CH), 132.9
(CH).
1:2,5:6-Di-O-isopropylidine-3-C-(2′-propenyl)-3-O-meth-
yl r-D-allofuranose 3a. To a magnetically stirred suspension
of NaH (130 mg, 2.7 mmol, 50% in oil), freed from adhering
oil by repeated washing with petroleum, in THF (5 mL) was
added dropwise a solution of the alcohol 2a (550 mg, 1.83
mmol) in THF (5 mL). The mixture was gently refluxed for 2
h and then cooled to room temperature. To it was added HMPA
(0.5 mL) followed by CH3I (0.3 mL, 3.6 mmol). After refluxing
for 2 h, the reaction mixture was cooled to room temperature
and quenched by adding saturated NH4Cl solution (2 mL).
Usual workup of the reaction mixture followed by column
chromatography using ether-petroleum ether (1:9) as eluent
1,2-Di-O-isopropylidine-3-C-(2′-propenyl)-3-O-benzyl-
4â-ethynyl-r-D-allofuranose 4b. Following the above pro-
cedure the diacetonide 3b (1.5 g, 3.84 mmol) was converted to
afforded the methyl ether 3a (520 mg, 90%) as a colorless
1
viscous liquid: [R]25 +20.0 (c 1.56, CHCl3); H NMR δ 1.29
D
(3H, s, CH3), 1.32 (3H, s, CH3), 1.39 (3H, s, CH3), 1.54 (3H, s,
CH3), 2.25 (1H, dd, J ) 7.5, 15.2 Hz), 2.63 (1H, dd, J ) 6.3,
15.2 Hz), 3.45 (3H, s, OMe), 3.84 (1H, d, J ) 2.7 Hz), 4.03-
4.09 (3H, m), 4.36 (1H, d, J ) 3.5 Hz, C2-H), 5.10-5.16 (2H,
m), 5.52 (1H, d, J ) 3.5 Hz, C1-H), 5.85-5.99 (1H, m); 13C
NMR δ 25.8 (CH3), 26.8 (CH3), 26.9 (CH3), 27.4 (CH3), 34.5
(CH2), 53.3 (OCH3), 68.8 (CH2), 73.1 (CH), 82.3 (CH), 83.5 (CH),
83.9 (C), 103.4 (CH), 110.0 (C), 113.0 (C), 119.0 (CH2), 137.7
(CH). Anal. Calcd for C16H26O6: C, 61.13; H, 8.34. Found: C,
61.51; H,8.32
the diene 4b (470 mg, 53%) as a colorless viscous liquid: [R]25
D
+13.6 (c 0.6, CHCl3); 1H NMR δ 1.35 (3H, s, CH3), 1.60 (3H, s,
CH3), 2.33 (1H, dd, J ) 7.2, 14.7 Hz, CH2), 2.56 (1H, dd, J )
7.2, 14.7 Hz, CH2), 4.49 (1H, d, J ) 3.9 Hz, C2H), 4.67 (2H, s,
PhCH), 5.15 (2H, m, dCH2), 5.27 (1H, d, J ) 10.8 Hz, dCH2),
5.43 (1H, d, J ) 16.2 Hz, dCH2), 5.69 (1H, d, J ) 3.9 Hz, CH
C
1-H), 5.85-5.96 (1H, m, dCH), 7.23-7.45 (5H, m, ArH); 13
C
NMR δ 27.0 (CH3), 27.3 (CH3), 36.3 (CH2), 67.2 (CH2), 82.2
(CH), 82.4 (CH), 84.7(C), 104.2 (CH), 112.9(C), 118.7 (CH2),
118.8 (CH2), 127.8 (CH), 128.8 (CH), 132.6 (CH), 132.8 (CH),
133.1 (CH), 139.2 (C). Anal. Calcd for C19H24O4: C, 72.12; H,
7.64. Found: C, 72.37; H, 7.21.
1:2,5:6-Di-O-isopropylidine-3-C-(2′-propenyl)-3-O-ben-
zyl-r-D-allofuranose 3b. Following the above procedure, the
alcohol 2a (800 mg, 2.66 mmol) was alkylated with BnBr (0.4
1,2-Di-O-isopropylidine-3-C-(2′-methyl-2′-propnyl)-3-O-
benzyl-4â-ethenyl -r-D-allofuranose 4c. Following the above
procedure the diacetonide 3c (1.8 g, 4.45 mmol) was converted
to the diene 4c (840 mg, 57%) as a colorless viscous liquid:
[R]21D +13.2 (c 0.93, CHCl3); 1H NMR δ 1.34 (3H, s, CH3), 1.61
(3H, s, CH3), 1.84 (3H, s, CH3), 2.15 (1H, d, J ) 15 Hz,), 2.50
(1H, d, J ) 15 Hz,), 4.60 (1H, d, J ) 3.6 Hz, C2-H), 4.70 (1H,
d, J ) 11.5 Hz, PhCH), 4.82 (4H, m), 5.26 (1H, d, J ) 10.65
Hz, dCH2), 5.37 (1H, dt, J ) 1.5, 17.2 Hz), 5.67 (1H, d, J )
3.6 Hz, C1-H), 5.82-5.93 (1H, m, dCH-), 7.20-7.37 (5H, m,
ArH); 13C NMR δ 24.4 (CH3), 26.50 (CH3), 26.9 (CH3), 37.6
(CH2), 66.5 (CH2), 80.7 (CH), 82.2 (CH), 84.2 (C), 103.1 (CH),
112.5 (C), 115.2 (CH2), 119.2 (CH2), 127.1 (CH), 127.2 (CH),
128.2 (CH), 132.5 (CH), 138.9 (C), 141.4 (C). Anal. Calcd for
C20H26O4: C, 72.70; H, 7.93. Found: C, 72.32; H, 8.16.
mL, 3.19 mmol) to afford the benzyl ether 3 (730 mg, 70%):
1
mp 98 °C; [R]25 +20.5 (c 3.7, CHCl3); H NMR δ 1.33 (3H, s,
D
CH3), 1.34 (3H, s, CH3), 1.37 (3H, s, CH3), 1.59 (3H, s, CH3),
2.41 (1H, dd, J ) 7.2, 14.8 Hz, CH2), 2.68 (1H, dd, J ) 6.7,
14.8 Hz, CH2), 3.95 (1H, m), 4.10 (1H, m), 4.22 (2H, m), 4.8
(1H, d, J ) 3.6 Hz, C2H), 4.72 (1H, d, J ) 11.1 Hz, PhCH),
4.84 (1H, d, J ) 11.1 Hz, PhCH), 5.15 (2H, m, CH2), 5.62 (1H,
d, J ) 3.6 Hz, C1H), 6.01 (1H, m, -CH)), 7.21-7.40 (5H, m,
ArH); 13C NMR δ 25.8 (CH3), 26.9 (CH3), 27.0 (CH3), 27.4 (CH3),
36.2 (CH2), 67.3 (CH2), 68.4 (CH2), 73.4 (CH), 81.7 (CH), 83.4
(CH), 84.0(C), 103.9 (CH), 109.9(C), 113.1(C), 119.0 (CH2),
127.5 (CH), 128.4 (CH), 133.0 (CH), 139.6(C). Anal. Calcd for
C22H30O6: C, 67.67; H, 7.74. Found: C, 68.02; H, 7.24.
1:2,5:6-Di-O-isopropylidine-3-C-(2′-methyl-2′-proprenyl)-
3-O-benzyl-r-D-allofuranose 3c. Following the above pro-
cedure, the alcohol 2b (850 mg, 2.70 mmol) was alkylated with
BnBr (0.4 mL, 3.24 mmol) to afford the benzyl ether 3c (870
Photocycloaddition of the Dienes. cis-syn-cis-4r,5r-
Di-O-isopropylidine-6r-methoxy-3-oxatricyclo[3.2.0.02,6]-
decane 5a. A magnetically stirred solution of the diene 4a
(110 mg, 0.46 mmol) in dry ether (150 mL) containing CuOTf
(10 mg, 0.03 mmol) under an argon atmosphere was irradiated
with a 450 W medium-pressure mercury vapor lamp (Hanovia)
through a double-walled water-cooled quartz immersion well
for 3.5 h. The reaction mixture was then washed successively
with ice-cold NH4OH (35%, 3 × 10 mL) and water (2 × 10 mL)
and dried. After evaporation of the solvent the residual mass
was chromatographed using ether-petroleum ether (1:19) as
mg, 80%) as a colorless viscous liquid: [R]25 +14.5 (c 0.57,
D
1
CHCl3); H NMR δ 1.34 (9H, s, CH3), 1.61 (3H, s, CH3), 1.88
(3H, s, CH3), 2.17 (1H, d, J ) 15 Hz, CH2), 2.67 (1H, d, J ) 15
Hz, CH2), 3.94 (1H, m), 4.16 (2H, m), 4.36 (1H, d, J ) 6 Hz,
CH), 4.62 (1H, d, J ) 3.0 Hz, C2-H), 4.77 (1H, d, J ) 12 Hz,
PhCH), 4.90 (2H, d, J ) 18 Hz, dCH2), 5.05 (1H, d, J ) 12
Hz, PhCH), 5.61 (1H, d, J ) 6 Hz, C1-H), 7.23-7.39 (5H, m,
ArH); 13C NMR δ 24.3 (CH3), 25.2 (CH3), 26.2 (CH3), 26.4 (CH3),
27.0 (CH3), 38.5 (CH2), 67.1 (CH2), 68.4 (CH2), 72.5 (CH), 80.3
(CH), 83.1 (CH), 83.4 (C), 102.0 (CH), 109.5 (C), 112.6 (C), 115.1
(CH2), 127.0 (CH), 127.3 (CH), 128.1 (CH), 139.3 (C), 141.4
(C). Anal. Calcd for C23H32O6: C, 68.29; H, 9.79. Found: C,
68.02; H, 8.01.
1,2-Di-O-isopropylidine-3-C-(2′-propenyl)-3-O-methyl-
4â-ethynyl-r-D-allofuranose 4a. A solution of the diacet-
onide 3a (500 mg, 1.59 mmol) in aqueous acetic acid (5 mL,
75%) was stirred at room temperature for 12 h. The reaction
mixture was diluted with ethyl acetate (30 mL) and washed
repeatedly with saturated aqueous NaHCO3 solution (5 × 3
mL) to make it free from acid. The organic layer was dried
eluent to afford the cyclobutane derivative 5a (80 mg, 73%)
1
as a colorless viscous liquid: [R]25 +35.4 (c 1.05, CHCl3); H
D
NMR δ 1.37 (3H, s, CH3), 1.59 (3H, s, CH3), 1.93-2.38 (6H,
m), 2.87 (2H, m), 3.32 (3H, s, OCH3), 4.38 (1H, d, J ) 5.1 Hz,
C
C
2-H), 4.52 (1H, d, J ) 3.9 Hz, C5-H), 5.94 (1H, d, J ) 3.6 Hz,
4-H); 13C NMR δ 16.6 (CH2), 26.6 (CH3), 26.9 (CH2), 27.1
(CH3), 37.5 (CH2), 38.5 (CH), 41.0 (CH), 52.3 (OCH3), 80.4 (CH),
86.4 (CH), 98.1 (C), 106.0 (CH), 112.5 (C). Anal. Calcd for
C13H20O4: C, 64.96; H, 8.39. Found: C, 64.88; H, 8.51.
(27) Gregg, P. J.; Samuelsson, B. Synthesis 1979, 469.
3986 J. Org. Chem., Vol. 68, No. 10, 2003

Intramolecular [2 + 2] Photocycloaddition
cis-syn-cis-4r,5r-Di-O-isopropylidine-6r-benzyloxy-
3-oxatricyclo[3.2.0.02,6]decane 5b. Irradiation of a solution
of the diene 4b (470 mg, 1.48 mmol) in dry ether (250 mL)
containing CuOTf (0.05 g, 0.1 mmol) under argon using the
above-mentioned procedure afforded the cyclobutane derivative
5b (340 mg, 72%): mp 52 °C; [R]25D +6.93 (c 1.32, CHCl3); 1H
NMR δ 1.38 (3H, s, CH3), 1.60 (3H, s, CH3), 1.95-2.41 (6H,
m), 2.90 (2H, m), 4.46-4.50 (2H, m, PhCH and C2-H), 4.59
(1H, d, J ) 3.6 Hz, C5-H), 4.60 (1H, d, J ) 14.4 Hz, PhCH),
5.99 (1H, d, J ) 3.9 Hz, C4-H), 7.14-7.37 (5H, m, ArH); 13C
NMR δ 17.2 (CH2), 27.0 (CH2), 27.4 (CH3), 27.5 (CH3), 39.1
(CH2), 39.09 (CH), 41.3 (CH), 67.4 (CH2), 80.9 (CH), 87.0 (CH),
98.7(C), 106.9 (CH), 112.9(C), 127.9 (CH), 128.6 (CH), 139.1(C).
Anal. Calcd for C19H24O4: C, 72.12; H, 7.64. Found: C, 71.57;
H, 7.27.
mg, 79%) as a colorless viscous liquid: [R]30 +21.8 (c 6.4,
D
CHCl3); IR 1720.4 cm-1; 1H NMR δ 1.33 (3H, s, CH3), 1.35 (3H,
s, CH3), 1.40 (3H, s, CH3), 1.60 (3H, s, CH3), 2.65 (1H, dd, J )
2.5, 15.3 Hz), 2.79 (1H, dd, J ) 2.5, 15.3 Hz), 3.96 (1H, m),
4.10 (2H, m), 4.25 (1H, d, J ) 5.4 Hz), 4.56 (1H, d, J ) 3.9 Hz,
C2-H), 4.79 (1H, d, J ) 10.8 Hz, PhCH), 4.83 (1H, d, J ) 10.8
Hz, PhCH), 5.65 (1H, d, J ) 3.9 Hz, C1-H), 7.23-7.38 (5H, m,
ArH), 9.95 (1H, t, J ) 2.6 Hz, CHO); 13C NMR δ 25.5 (CH3),
26.93 (CH3), 26.95 (CH3), 27.2 (CH3), 45.0 (CH2), 67.9 (CH2),
68.7 (CH2), 73.6 (CH), 80.2 (CH), 83.8 (CH), 84.3 (C), 103.7
(CH), 110.4 (C), 113.5 (C), 127.6 (CH), 127.8 (CH), 128.6 (CH),
138.7 (C), 201.3 (CHO). Anal. Calcd for C21H28O7: C, 64.27; H,
7.19. Found: C, 64.54; H, 7.51.
Wittig-Horner Reaction of the Aldehyde 12. Synthe-
sis of the Unsaturated Ester 13. To a magnetically stirred
suspension of NaH (60 mg, 1.2 mmol, 50% in oil), freed from
adhering oil by repeated washing with petroleum, was added
a solution of triethyl phosphonoacetate (0.27 mL, 1.35 mmol)
in dry THF (2 mL) dropwise at room temperature. After
stirring of the resulting clear solution at room temperature
for 40 min, the aldehyde 12 (380 mg, 0.97 mmol) in dry THF
(5 mL) was added dropwise and allowed to stir for additional
12 h. The reaction mixture was cooled to 0 °C and quenched
by adding saturated aqueous NH4Cl (5 mL). Usual workup of
the mixture followed by column chromatography [ether-
petroleum ether (1:4)] afforded the unsaturated ester 13 (300
cis-syn-cis-4r,5r-Di-O-isopropylidine-6r-benzyloxy-
8r-methyl-3-oxatricyclo[3.2.0.02,6]decane 5c. Irradiation of
a solution of the diene 4c (800 mg, 2.42 mmol) in dry diethyl
ether (250 mL) containing CuOTf (0.06 g, 0.11 mmol) under
an argon atmosphere afforded the corresponding cyclobutane
derivative 5c (620 mg, 77%): mp 58 °C; [R]21 +15.1 (c 0.89,
D
1
CHCl3); H NMR δ 1.26 (3H, s, CH3), 1.36 (3H, s, CH3), 1.59
(3H, s, CH3), 1.76-2.15 (6H, m), 2.46 (1H, m), 4.47-4.57 (4H,
m, PhCH, C5-H and C2-H), 5.99 (1H, d, J ) 3.9 Hz, C4-H),
7.24-7.4 (5H, m, ArH); 13C NMR δ 13.1 (CH2), 26.9 (CH3), 27.0
(CH3), 27.8 (CH3), 34.3 (CH2), 38.1 (C), 44.6 (CH2), 46.6 (CH),
67.0 (CH2), 80.6 (CH), 87.4 (CH), 97.4 (C), 106.5 (CH), 112.5
(C), 127.4 (CH), 127.9 (CH), 128.2 (CH), 128.4 (CH), 128.8
(CH), 138.3 (C). Anal. Calcd for C20H26O4: C, 72.70; H, 7.93.
Found: C, 72.35; H, 8.25.
mg, 67%) as a colorless viscous liquid: [R]21 +17.6 (c 0.5
D
1
CHCl3); IR 1718.5, 1652.9 cm-1; H NMR δ 1.16 (3H, t, J )
7.2 Hz, COOCH2CH3), 1.21 (6H, s, CH3), 1.26 (3H, s, CH3),
1.47 (3H, s, CH3), 2.43 (1H, dd, J ) 6.3, 7.8 Hz, CH2), 2.64
(1H, dd, J ) 1.5, 6.3 Hz, CH2), 3.80 (1H, m), 4.05 (5H, m),
4.32 (1H, d, J ) 3.6 Hz, C2-H), 4.63 (1H, J ) 11 Hz, PhCH),
4.70 (1H, J ) 11 Hz, PhCH), 5.51 (1H, d, J ) 3.6 Hz, C1-H),
5.80 (1H, d, J ) 14.7 Hz, dCH), 7.02-7.28 (6H, m); 13C NMR
δ 14.6 (CH3), 25.6 (CH3), 26.91 (CH3), 26.97 (CH3), 27.3 (CH3),
34.6 (CH2), 60.8 (CH2), 67.6 (CH2), 68.8 (CH2), 73.3 (CH), 81.1
(CH), 83.6 (CH), 84.3 (C), 103.6 (CH), 110.2 (C), 113.4 (C), 125.0
(CH), 127.6 (CH), 128.0 (CH), 128.5 (CH), 139.2 (C), 143.4
(CH), 166 (CO2CH2CH3). Anal. Calcd for C25H34O8: C, 64.92;
H, 7.41. Found: C, 64.45; H, 7.68.
cis-syn-cis-4r,5r-Di-O-isopropylidine-6r-hydroxy-3-
oxatricyclo[3.2.0.02,6]decane 6a. A solution of the photo-
adduct 5b (120 mg, 0.37 mmol) in dry methanol (4 mL)
containing acetic acid (0.2 mL), perchloric acid (0.05 mL), and
Pd-C (5%) (20 mg) was stirred under hydrogen atmosphere
at room temperature for 2 h. The mixture was filtered and
treated with saturated aqueous NaHCO3 solution (2 mL) to
make it alkaline. MeOH was removed and the residue was
worked up in the usual way. The crude mass obtained was
chromatographed using ether-petroleum ether (1:4) to afford
the hydroxy compound 6a (70 mg, 80%) as a colorless viscous
Synthesis of the Diene 14. Following the procedure
described above for the conversion of the diacetonide 3a to the
diene 4a, the diacetonide 13 (1.1 g, 2.3 mmol) was transformed
liquid: [R]25 +28.5 (c 0.23, CHCl3); 1H NMR δ 1.37 (3H, s,
D
CH3), 1.57 (3H, s, CH3), 1.99-2.24 (6H, m), 2.98 (2H, m), 4.15
(1H, d, J ) 5.5 Hz, C2-H), 4.39 (1H, d, J ) 3.7 Hz, C5-H), 5.98
(1H, J ) 3.7 Hz, C4-H); 13C NMR δ 17.2 (CH2), 27.0 (CH3),
27.1 (CH2), 27.2 (CH3), 39.7 (CH), 40.9 (CH), 42.6 (CH2), 81.4
(CH), 87.7 (CH), 93.0(C), 106.2 (CH), 112.5(C). Anal. Calcd for
C12H18O4: C, 63.70; H, 8.02. Found: C, 63.84; H, 7.70.
to the diene 14 (500 mg, 54%) as a colorless viscous liquid:
1
[R]25 +9.31 (c 2.6, CHCl3); IR 1716.5, 1651.0 cm-1; H NMR
D
δ 1.27 (3H, t, J ) 6 Hz, COOCH2CH3), 1.36 (3H, s, CH3), 1.61
(3H, s, CH3), 2.45 (1H, dd, J ) 9.15 Hz, CH2), 2.66 (1H, dd, J
) 6, 15 Hz, CH2), 4.19 (2H, q, J ) 6 Hz, COOCH2CH3), 4.48
(1H, d, J ) 3 Hz, C2-H), 4.67 (3H, m), 5.32 (1H, d, J ) 10.8
Hz, dCH2), 5.46 (1H, d, J ) 17.4 Hz, CH2), 5.71 (1H, d, J )
3.9 Hz, C1-H), 5.82-5.92 (2H, m), 7.05 (1H, dt, J ) 8.4, 16
Hz, dCH), 7.24-7.39 (5H, m, ArH); 13C NMR δ 14.6 (CH3),
26.9 (CH3), 27.2 (CH3), 34.5 (CH2), 60.8 (CH2), 67.5 (CH2), 81.5
(CH), 82.4 (CH), 84.8 (C), 103.9 (CH), 113.2 (C), 119.1 (CH2),
124.9 (CH), 127.8 (CH), 128.0 (CH), 128.7 (CH), 132.2 (CH),
138.6 (C), 143.3 (CH), 166.3 (CO2CH2CH3). Anal. Calcd for
C22H28O6: C, 68.02; H, 7.26. Found: C, 67.45; H, 7.17.
cis-syn-cis-4r,5r-Di-O-isopropylidine-6r-hydroxy-8r-
methyl-3-oxatricyclo[3.2.0.02,6]decane 6b. Hydrogenolysis
of the photoadduct 5c (120 mg, 0.36 mmol) in dry methanol
(4 mL) following the above procedure afforded the hydroxy
compound 6b (75 mg, 85%) as a colorless viscous liquid: [R]25
D
+33.6 (c 0.60, CHCl3); 1H NMR δ 1.28 (3H, s, CH3), 1.36 (3H,
s, CH3), 1.54 (3H, s, CH3), 1.79-2.1 (6H, m), 2.48 (1H, m), 4.15
(1H, d, J ) 6.3 Hz, C2-H), 4.27 (1H, d, J ) 3.6 Hz, C5-H), 5.89
(1H, d, J ) 3.6 Hz, C4-H); 13C NMR δ 13.3 (CH2), 26.7 (CH3),
26.9 (CH3), 28.0 (CH3), 29.7 (C), 34.2 (CH2), 46.7 (CH), 48.8
(CH2), 81.3 (CH), 88.2 (CH), 92.0 (C), 105.8 (CH), 112.4 (C).
Anal. Calcd for C13H20O4: C, 64.97; H, 8.38. Found: C, 64.36;
H, 8.11.
cis-syn-cis-4r,5r-Di-O-isopropylidine-6r-benzyloxy-
9-carbethoxy-3-oxatricyclo[3.2.0.02,6]decane 15. A solution
of the unsaturated ester 14 (250 mg, 0.64 mmol) in acetonitrile
(200 mL) was irradiated in the presence of benzophenone (20
mg, 0.1 mmol) through a water-cooled Pyrex immersion well
with a medium-pressure mercury vapor Hanovia Lamp (450
W) for 3 h. The solvent was removed under vacuum. The
residue was chromatograhed [ether-petroleum ether (1:5)] to
afford the cyclobutane derivative 15 (125 mg, 50%) as a
colorless viscous liquid: [R]21D +12.7 (c 2.4, CHCl3); IR 1728.1
1:2,5:6-Di-O-isopropylidine-3-C-(2′-oxopropyl)-3-O-ben-
zyl-r-D-allofuranose 12. To a stirred suspension of NaIO4
(1.64 g, 7.68 mmol) in water (10 mL) was added the alkene
3b (500 mg, 1.28 mmol) in diethyl ether (20 mL). After stirring
the mixture for 15 min, a catalytic amount of OsO4 was added
and the mixture stirred at room temperature till complete
disappearance of the starting alkene. The organic layer was
separated and washed with saturated aqueous NaHCO3 solu-
tion (2 × 3 mL). The organic layer was dried and concentrated.
The residual mass was chromatographed using ether-
petroleum ether (1:4) as eluent to afford the aldehyde 12 (400
1
cm-1; H NMR δ 1.25 (3H, t, J ) 7.2 Hz, COOCH2CH3), 1.39
(3H, s, CH3), 1.61 (3H, s, CH3), 2.21-2.50 (3H, m), 2.77-2.95
(3H, m), 3.09-3.20 (1H, m), 4.13 (2H, q, J ) 7.2 Hz), 4.49 (1H,
d, J ) 11 Hz, PhCH), 4.50 (1H, d, J ) 4.8 Hz, C7-H), 4.61
(1H, d, J ) 11 Hz, PhCH), 4.62 (1H, d, J ) 3.9 Hz, C1-H),
J. Org. Chem, Vol. 68, No. 10, 2003 3987

Banerjee and Ghosh
5.98 (1H, d, J ) 3.9 Hz, C5-H), 7.14-7.36 (5H, m, ArH); 13C
NMR δ 14.6 (CH3), 21.0 (CH2), 27.2 (CH3), 38.6 (CH2), 38.7
(CH), 42.3 (CH), 45.3 (CH), 60.8 (CH2), 67.5 (CH2), 81.1 (CH),
86.0 (CH), 98.7 (C), 106.4 (CH), 113.1 (C), 127.8 (CH), 127.9
(CH), 128.7 (CH), 138.8 (C), 175.9 (CO2CH2CH3). Anal. Calcd
for C22H28O6: C, 68.02; H, 7.26. Found: C, 68.40; H, 7.33.
above procedure, the aldehyde 12 (1.8 g, 4.6 mmol) on reaction
with the ylide generated from methallyltriphenyl phosphonium
chloride (3.23 g, 9.2 mmol) with n-BuLi (5.7 mL, 6.8 mmol,
1.2M) afforded, after workup and column chromatography
[ether-petroleum ether (1:19)], the diene 23b (1.2 g, 63%) as
a colorless viscous liquid: [R]32D +6.4 (c 6.7, CHCl3); 1H NMR
δ 1.34 (6H, s, CH3), 1.39 (3H, s, CH3), 1.60 (3H, s, CH3), 1.83
(3H, s, CH3), 1.88 (3H, s, CH3), 2.49-2.79 (2H, m), 3.95 (1H,
m), 4.07-4.25 (3H, m), 4.44 (1H, d, J ) 3.7 Hz), 4.46 (1H, d,
J ) 3.7 Hz), 4.67-5.05 (5H, m), 5.62 (1H, d, J ) 3.6 Hz), 5.66
(1H, d, J ) 3.7 Hz), 5.74-5.88 (1H, m), 5.99 (1H, d, J ) 12.0
Hz), 6.24 (1H, d, J ) 15.7 Hz), 7.24-7.41 (5H, m, ArH); 13C
NMR δ 19.0 (CH2), 23.8 (CH2), 25.8 (CH3), 25.81 (CH3), 26.9
(CH3), 27.0 (CH3), 27.0 (CH3), 27.3 (CH3), 27.4 (CH3), 29.9
(CH2), 34.8 (CH2), 67.1 (CH2), 67.3 (CH2), 68.3 (CH2), 68.6
(CH2), 73.4 (CH), 81.8 (CH), 81.9 (CH), 83.6 (CH), 83.8 (CH),
84.2 (C), 84.5 (C), 103.8 (CH), 103.9 (CH), 109.8 (C), 109.9 (C),
113.18 (C), 113.19 (C), 116.0 (CH2), 116.4 (CH2), 124.4 (CH),
124.6 (CH), 127.4 (CH), 127.5 (CH), 127.6 (CH), 128.47 (CH),
128.48 (CH), 128.8 (CH), 133.7 (CH), 136.7 (CH), 139.4 (C),
139.6 (C), 141.6 (C), 142.1 (C). Anal. Calcd for C25H34O6: C,
69.74; H, 7.96. Found: C, 69.49; H, 8.18.
cis-syn-cis-4r,5r-Di-O-isopropylidine-6r-hydroxy-9-
carbethoxy-3-oxatricyclo[3.2.0.02,6]decane 16. A solution
of the benzyl ether 15 (120 mg, 0.30 mmol) in dry EtOH (4
mL) containing acetic acid (0.2 mL), perchloric acid (0.05 mL),
and Pd-C (20 mg, 5%) was stirred under hydrogen atmosphere
for 2 h. Usual workup of the reaction mixture followed by
column chromatography [ether-petroleum ether (1:4)] afforded
the hydroxy ester 16 (60 mg, 65%) as a colorless viscous
liquid: [R]21D +6.05 (c 0.79, CHCl3); IR 1728.1, 3460 cm-1; 1H
NMR δ 1.23 (3H, t, J ) 6.9 Hz, COOCH2CH3), 1.38 (3H, s,
CH3), 1.57 (3H, s, CH3), 2.14-2.38 (4H, m), 2.58 (1H, brs, OH),
2.76 (1H, m), 2.94 (1H, m), 3.21 (1H, m), 4.09-4.18 (3H, m),
4.43 (1H, d, J ) 3.9 Hz, C5-H), 5.97 (1H, d, J ) 3.9 Hz, C4-H);
13C NMR δ 14.2 (CH3), 20.6 (CH2), 26.6 (CH3), 26.8 (CH3), 38.0
(CH), 41.8 (CH2), 42.7 (CH), 44.9 (CH), 60.4 (CH2), 81.5 (CH),
86.4 (CH), 92.8 (C), 105.4 (CH), 112.4 (C), 175.4 (CO2CH2CH3).
Anal. Calcd for C15H22O6: C, 60.39; H, 7.43. Found: C, 61.01;
H, 7.73.
Transformation of the Hydroxy Ester to the Cyclo-
butane Derivative 6a. A mixture of the hydroxy ester 16
(40 mg, 0.13 mmol), EtOH (1.5 mL), KOH (40 mg, 0.67 mmol),
and water (0.2 mL) was refluxed for 2 h. The reaction mixture
was cooled to 0 °C and acidified with aqueous HCl (10%). EtOH
was removed under vacuum and the residue was extracted
with CHCl3 (2 × 5 mL). The organic extract was dried and
concentrated to afford a yellowish white viscous mass, 17 (30
mg).
1,2-Di-O-isopropylidine-3-C-(2′,4′-pentadienyl)-3-O-ben-
zyl-4â-formyl-r-D-allofuranose 24a. A solution of the di-
acetonide 23a (1.5 g, 3.6 mmol) in aqueous acetic acid (15 mL,
75%) was stirred at room temperature for 12 h. The reaction
mixture was diluted with ethyl acetate (60 mL) and washed
repeatedly with saturated aqueous NaHCO3 solution (6 × 10
mL) till it was alkaline. The organic layer was dried and
concentrated to afford a colorless viscous liquid (1.2 g). A
solution of this liquid in acetonitrile (10 mL) was added to a
magnetically stirred suspension of NaIO4 (1.02 g, 4.78 mmol)
in water (5 mL) and stirring was continued for 1 h. Usual
workup of the reaction mixture followed by column chroma-
tography [ether-petroleum ether (1:9)] afforded the aldehyde
A solution of the hydroxy acid 17 in benzene (5 mL) (30 mg,
0.1 mmol) containing quinoline (20 mg) and tBuSH (0.2 mL)
was irradiated externally with a medium-pressure 450-W
Hanovia mercury-vapor lamp (Pyrex filter) for 7 h under argon.
The mixture was then washed successively with cold 6 N HCl
(3 × 1 mL), saturated aqueous NaHCO3 solution, and brine.
Evaporation of the solvent followed by chromatography [ether-
petroleum ether (1:4)] afforded the cyclobutane derivative 6a
(10 mg, 40%).
24a (800 mg, 65%) as a colorless liquid: [R]30 +12.1 (c 3.5,
D
CHCl3); IR 1735, 1602 cm-1; 1H NMR δ 1.39 (3H, s, CH3), 1.62
(3H, s, CH3), 2.48-2.59 (1H, m, CH2), 2.71 (1H, dd, J ) 8.6,
16.1 Hz, CH2), 4.51 (1H, d, J ) 3.6 Hz), 4.67 (1H, d, J ) 5.9
Hz), 4.69-4.79 (2H, m), 5.35 (2H, m), 5.53 (1H, q, J ) 7.4 Hz,
dCH-), 5.66 91H, quintet, J ) 7.4 Hz), 5.85 (1H, d, J ) 3.6
Hz), 5.89 (1H, d, J ) 3.6 Hz), 6.13 (1H, m), 6.25-6.60 (1H,
m), 7.32-7.46 (5H, m, ArH), 9.70 (1H, d, J ) 5.4 Hz, CHO),
9.73 (1H, d, J ) 6.9 Hz, CHO); 13C NMR δ 27.03 (CH3), 27.06
(CH3), 27.36 (CH3), 27.40 (CH3), 29.35 (CH2), 34.76 (CH2), 67.70
(CH2), 67.76 (CH2), 82.95 (CH), 83.01 (CH), 85.59 (CH), 85.71
(CH), 86.98(C), 87.12(C), 104.70 (CH), 104.74 (CH), 113.89(C),
118.00 (CH2), 120.27 (CH2), 123.66 (CH), 126.41 (CH), 128.12
(CH), 128.15 (CH), 128.19 (CH), 128.19 (CH), 128.22 (CH),
128.78 (CH), 131.57 (CH), 131.57 (CH), 133.50 (CH), 136.51
(CH), 136.74 (CH), 138.13(C), 138.18(C), 198.20 (CO), 198.63
(CO). Anal. Calcd for C20H24O5: C, 69.75; H, 7.02. Found: C,
69.95; H, 7.54.
1:2,5:6-Di-O-isopropylidine-3-C-(2′,4′-pentadienyl)-3-O-
benzyl-r-D-allofuranose 23a. n-BuLi (1.22 mL, 1.90 mmol,
1.55 M) in hexane was added dropwise to a magnetically
stirred and cooled (0 °C) suspension of allyltriphenyl phos-
phonium chloride (860 mg, 2.54 mmol) in ether (10 mL) under
Ar. After stirring at 0 °C for 15 min, a solution of the aldehyde
12 (500 mg, 1.27 mmol) in ether (5 mL) was added over a
period of 10 min. After stirring for 30 min at 0 °C, the reaction
mixture was quenched by addition of cold water (5 mL). Usual
workup of the reaction mixture followed by column chroma-
tography using ether-petroleum ether (1:19) as eluent af-
forded the diene 23a (340 mg, 64%) as a colorless viscous
liquid: [R]32D +7.5 (c 7.6, CHCl3); 1H NMR δ (for both isomers)
1.33 (6H, s, CH3), 1.38 (3H, s, CH3), 1.58 (3H, s, CH3), 2.40-
2.77 (2H, m), 3.93 (1H, m), 3.96-4.23 (3H, m), 4.42 (1H, d, J
) 3.7 Hz), 4.45 (1H, d, J ) 3.7 Hz), 4.69-4.85 (2H, m), 5.01-
5.28 (2H, m), 5.60 (1H, d, J ) 3.6 Hz), 5.64 (1H, d, J ) 3.6
Hz), 5.70-5.91 (1H, m), 6.11-6.66 (2H, m), 7.23-7.39 (5H,
m, ArH); 13C NMR δ 25.88 (CH3), 25.39 (CH3), 26.53 (CH3),
25.54 (CH3), 26.6 (CH3), 26.6 (CH3), 26.9 (CH3), 29.11 (CH2),
34.53 (CH2), 66.90 (CH2), 66.99 (CH2), 68.08 (CH2), 68.11 (CH2),
73.02 (CH), 81.27 (CH), 81.29 (CH), 83.09 (CH), 83.24 (CH),
83.99, 84.09 (C), 103.46 (CH), 103.48 (CH), 109.52 (C), 109.55
(C), 112.68 (C), 112.70 (C), 116.33 (CH), 118.79 (CH), 125.32
(CH), 127.28 (CH), 128.18 (CH), 128.34 (CH), 128.53 (CH),
131.43 (CH), 131.71 (CH), 134.51 (CH), 136.62 (CH), 139.5 (C),
139.6 (C). Anal. Calcd for C24H32O6: C, 69.20; H, 7.74. Found:
C, 69.49; H, 8.04.
1,2-Di-O-isopropylidine-3-C-(4′-methyl-2′,4′-penta-
dienyl)-3-O-benzyl-4â-formyl-r-D-allofuranose 24b. Fol-
lowing the above procedure, the diacetonide 23 (1.5 g, 3.4
mmol) was transformed to the aldehyde 24b (720 mg, 56%)
as a colorless liquid: [R]30 +40.4 (c 1.6, CHCl3); IR 1733.9,
D
1
1608.5 cm-1; H NMR δ 1.40 (3H, s, CH3), 1.62 (3H, s, CH3),
1.85 (3H, s, CH3), 1.90 (3H, s, CH3), 2.50-2.88 (2H, m, CH2),
4.50 (1H, d, J ) 3.6 Hz), 4.52 (1H, d, J ) 3.6 Hz), 4.64-4.77
(3H, m), 4.96 (2H, dd, J ) 5.52-5.65 (1H, m), 5.85 (1H, d, J )
3.5 Hz), 5.89 (1H, d, J ) 3.5 Hz), 6.01 (1H, d, J ) 11.7 Hz),
6.20 (1H, d, J ) 15.6 Hz), 7.29-7.51 (5H, m, ArH); 13C NMR
δ 18.9 (CH3), 23.6 (CH3), 27.0 (CH3), 27.31 (CH3), 27.35 (CH3),
27.4 (CH3), 29.6 (CH2), 34.8 (CH2), 67.5 (CH2), 67.7 (CH2), 83.0
(CH), 83.2 (CH), 85.6 (CH), 85.7 (CH), 86.8 (C), 87.2 (C), 104.71
(CH), 104.74 (CH), 113.8 (C), 116.8 (CH2), 117.1 (CH2), 122.4
(CH), 122.7 (CH), 128.0 (CH), 128.1 (CH), 128.2 (CH), 128.76
(CH), 128.78 (CH), 135.3 (CH), 138.1 (C), 138.2 (C), 138.6 (CH),
141.4 (C), 141.6 (C), 198.1 (CHO), 198.6 (CHO). Anal. Calcd
for C21H26O5: C, 70.37; H, 7.31. Found: C, 69.95; H, 7.05.
1:2,5:6-Di-O-isoprepylidine-3-C-(4′-methyl-2′,4′-penta-
dienyl)-3-O-benzyl-r-D-allofuranose 23b. Following the
3988 J. Org. Chem., Vol. 68, No. 10, 2003

Intramolecular [2 + 2] Photocycloaddition
1,2-Di-O-isopropylidine-3-C-(2′,4′-pentadienyl)-3-O-ben-
zyl-4â-(1,3-butadienyl)-r-D-allofuranose 25a. Wittig reac-
tion of the aldehyde 24a (800 mg, 2.32 mmol) with the ylide
generated from allyltriphenyl phosphonium chloride (1.57 g,
4.65 mmol) and n-BuLi (2.5 mL, 3.48 mmol, 1.4 M) afforded
4.47 (1H, d, J ) 10.9 Hz, PhCH), 4.53 (1H, d, J ) 3.8 Hz,
5-H), 4.61 (1H, d, J ) 10.9 Hz, PhCH), 5.13 (1H, m), 5.36
(1H, m), 5.57 (1H, m), 5.75 (1H, m), 5.79 (1H, d, J ) 3.8 Hz,
4-H), 7.18-7.34 (5H, m, ArH); 13C NMR δ 27.3 (CH3), 27.4
(CH3), 27.8 (CH2), 28.3 (CH2), 41.2 (CH2), 42.1 (CH), 47.8 (CH),
67.4 (CH2), 82.3 (CH), 88.6 (CH), 91.9 (C), 106.2 (CH), 113.3
(C), 127.9 (CH), 128.0 (CH), 128.2 (CH), 128.6 (CH), 128.7
(CH), 135.4 (CH), 138.9 (C). Anal. Calcd for C23H28O4: C, 74.97;
H, 7.65. Found: C, 75.00; H, 7.62.
C
C
the tetraene 25a (540 mg, 63%) as a colorless liquid: [R]30
D
1
+6.9 (c 4.3, CHCl3); H NMR δ 1.27 (3H, s, CH3), 1.54 (3H, s,
CH3), 2.17-2.59 (2H, m, CH2), 4.35-4.42 (1H, m), 4.50-4.65
(3H, m), 4.92-5.20 (4H, m), 5.34-5.44 (1H, m), 5.49-5.90 (2H,
m), 6.00-6.29 (2H, m), 6.50-6.76 (1H, m), 7.13-7.31 (5H, m,
ArH); 13C NMR δ 27.0 (CH3), 27.02 (CH3), 27.04 (CH3), 27.34
(CH3), 27.35 (CH3), 27.39 (CH3), 29.1 (CH2), 34.5 (CH2), 35.8
(CH2), 66.9 (CH2), 67.1 (CH2), 67.3 (CH2), 78.3 (CH), 78.49
(CH), 78.51 (CH), 82.32 (CH), 82.35 (CH), 82.55 (CH), 85.5 (C),
85.9 (C), 104.1 (CH), 104.2 (CH), 104.3 (CH), 104.4 (CH),
112.92 (C), 112.97 (C), 113.01 (C), 116.7 (CH2), 118.8 (CH2),
119.1 (CH2), 120.2 (CH2), 120.3 (CH2), 125.76 (CH), 125.77
(CH), 125.8 (CH), 125.0 (CH), 127.50 (CH), 127.54 (CH), 127.61
(CH), 127.6 (CH), 127.9 (CH), 128.53 (CH), 128.55 (C), 128.6
(C), 128.7 (C), 131.85 (CH), 131.91 (CH), 132.99 (CH), 133.06
(CH), 133.10 (CH), 133.14 (CH), 134.6 (CH), 134.7 (CH), 134.74
(CH), 136.7 (CH), 137.1 (CH), 139.13 (C), 139.19 (C), 139.25
(C). Anal. Calcd for C23H28O4: C, 74.97; H, 7.65. Found: C,
75.55; H, 7.59.
Without further characterization this material was hydro-
genated over Pd-C (5 mg, 10%) in MeOH (2 mL).The catalyst
was filtered off and the solvent was removed. The residue was
purified through preparative TLC to afford the hydroxy
1
compounds 33 and 34 (12.5 mg, 81%): mp 79 °C; H NMR δ
(for both isomer) 0.74 (6H, t, J ) 7.29 Hz), 1.06-1.76 (21H,
m), 1.27 (3H, s, CH3), 1.47 (3H, s, CH3), 1.49 (3H, s, CH3), 1.91-
2.18 (4H, m), 2.22-2.49 (2H, m), 2.81-2.88 (1H, m), 3.96 (1H,
d, J ) 4.47 Hz, C2-H), 4.10 (1H, d, J ) 6.48 Hz, C2-H), 4.21
(1H, d, J ) 3.84 Hz, C5-H), 4.29 (1H, d, J ) 3.84 Hz, C5-H),
5.69 (1H, d, J ) 3.84 Hz, C4-H), 5.90 (1H, d, J ) 3.84 Hz,
C
4-H); 13C NMR δ 11.8 (CH3), 22.7 (CH2), 26.1 (CH2), 26.3
(CH2), 27.05 (CH3), 27.09 (CH3), 27.2 (CH3), 27.3 (CH3), 30.0
(CH2), 30.5 (CH2), 31.8 (CH2), 31.9 (CH2), 32.6 (CH2), 32.8 (CH),
36.6 (CH), 41.5 (CH), 42.1 (CH2), 44.1 (CH), 43.8 (CH2), 46.9
(CH), 81.0 (CH), 82.4 (CH), 85.4 (C), 87.9 (CH), 91.9 (CH), 93.3
(C), 105.4 (CH), 105.5 (CH), 112.4 (C), 112.5 (C). Anal. Calcd
for C16H26O4: C, 68.06; H, 9.28. Found: C, 68.13; H, 9.20.
1,2-Di-O-isopropylidine-3-C-(4′-methyl-2′,4′-penta-
dienyl)-3-O-benzyl-4â-(1′′,3′′-butadienyl)-r-D-allofuranose
25b. The aldehyde 24b (920 mg, 2.5 mmol) on reaction with
the ylide generated from allyltriphenyl phosphonium chloride
(1.70 g, 5.13 mmol) and n-BuLi (2.6 mL, 3.75 mmol, 1.4 M)
afforded the tetraene 25b (420 mg, 61%) as a colorless liquid:
[R]30D +14.0 (c 0.9, CHCl3); 1H NMR δ 1.37 (3H, s, CH3), 1.64
(3H, s, CH3), 1.82 (3H, s, CH3), 1.88 (3H, s, CH3), 2.37-2.89
(2H, m), 4.46-4.50 (1H, m), 4.56-4.75 (3H, m), 4.87-5.29 (5H,
m), 5.47 (1H, dd, J ) 11.9, 20.1 Hz), 5.63-5.97 (2H, m), 6.19-
cis-syn-cis-4r,5r-Di-O-isopropylidine-6r-benzyloxy-
10-methyl-3-oxatricyclo[6.6.0.02,6]tetradeca-9,13-diene 30b.
A solution of the tetraene 26b (340 mg, 0.89 mmol) in dry
hexane (90 mL) was irradiated in the presence of benzo-
phenone (30 mg, 0.18 mmol) for 6 h. The solvent was removed
under reduced pressure. Benzophenone was removed by rapid
chromatography through a short column of silica using ether-
petroleum ether (1:19) as eluent to afford a colorless viscous
liquid (230 mg) (Rf 0.54). The mixture was allowed to stand
at room temperature for 20 days when a new spot (Rf 0.38)
appeared in the TLC. The resulting mixture was purified
through preparative TLC to afford the cyclooctadiene deriva-
tive 30b (135 mg) and the unchanged component with Rf (0.54)
(80 mg). Heating a solution of this component (80 mg) in
toluene (2 mL) in a sealed tube at 200 °C for 24 h followed by
purification through preparative TLC afforded a further crop
of the cyclooctadiene derivative (40 mg) (total yield 52%). The
rest of the material (20 mg) was not characterized further.
30b: Rf 0.38 [ethyl acetate-petroleum ether (1:9)]; [R]32D +24.5
(c 3.8, CHCl3); 1H NMR δ 1.29 (3H, s, CH3), 1.52 (3H, s, CH3),
1.59 (3H, s, CH3), 1.66-1.80 (1H, m), 1.94 (1H, m), 2.36-2.52
(4H, m), 3.27 (1H, m), 3.41 (1H, m), 4.40 (1H, d, J ) 4.0 Hz,
6.40 (1H, m), 6.74-6.78 (1H, m), 7.23-7.41 (5H, m, ArH); 13
C
NMR δ 19.05 (CH3), 23.8 (CH3), 26.9 (CH3), 27.0 (CH3), 27.29
(CH3), 27.35 (CH3), 27.41 (CH3), 29.3 (CH2), 34.5 (CH2), 34.8
(CH2), 66.7 (CH2), 67.0 (CH2), 67.3 (CH2), 77.5 (C), 78.11 (CH),
78.66 (CH), 81.78 (CH), 82.43 (CH), 82.61 (CH), 82.91 (CH),
85.54 (C), 85.56 (C), 86.0 (C), 104.17 (CH), 104.19 (CH), 104.35
(CH), 112.9 (C), 113.03 (C), 113.06 (C), 115.9 (CH2), 116.2
(CH2), 116.3 (CH2), 118.39 (CH2), 120.2 (CH2), 120.3 (CH2),
124.5 (CH), 124.6 (CH), 125.6 (CH), 125.9 (CH), 126.0 (CH),
127.5 (CH), 127.55 (CH), 127.60 (CH), 127.63 (CH), 127.8 (CH),
127.9 (CH), 128.05 (CH), 128.14 (CH), 128.53 (CH), 128.6 (CH),
128.65 (CH), 132.9 (CH), 133.1 (CH), 133.4 (CH), 134.3 (CH),
134.4 (CH), 134.6 (CH), 136.5 (CH), 136.62 (CH), 136.65 (CH),
139.0 (C), 139.2 (C), 141.7 (C), 142.16 (C), 142.18 (C). Anal.
Calcd for C24H30O4: C, 75.36; H, 7.91. Found: C, 74.97; H, 7.82.
cis-syn-cis-4r,5r-Di-O-isopropylidine-6r-benzyloxy-
3-oxatricyclo[6.6.0.02,6]tetradeca-9,13-diene 30a. A solu-
tion of the tetraene 25a (370 mg, 1.0 mmol) in dry hexane (90
mL) was irradiated internally in the presence of benzophenone
(40 mg, 0.21 mmol) for 6 h. The solvent was removed under
reduced pressure. Benzophenone was removed by rapid chro-
matography through a short column of silica gel using ether-
petroleum (1:19) as eluent to afford a colorless viscous liquid
(220 mg) (Rf 0.53). The mixture was allowed to stand at room
temperature for 20 days when a new spot (Rf 0.36) appeared
in the TLC. The resulting mixture was purified through
preparative TLC to afford the cyclooctadiene derivative 30a
(130 mg) and the unchanged component with Rf 0.53 (80 mg).
Heating a solution of this component in toluene (2 mL) in a
sealed tube at 200 °C for 24 h, followed by purification through
preparative TLC, afforded the same cyclooctadiene derivative
(40 mg) (total yield 45%). Another fraction (20 mg, 5%) with
the same Rf 0.53 was also isolated which was found to be a
mixture of two components by 1H and 13C NMR. 30a: Rf 0.36
C2-H), 4.47 (1H, d, J ) 10.8 Hz, PhCH), 4.51 (1H, d, J ) 3.8
Hz, C5-H), 4.59 (1H, d, J ) 10.8 Hz, PhCH), 4.95 (1H, d, J )
6.1 Hz, C9-H), 5.49-5.58 (1H, m), 5.69 (1H, dd, J ) 3.9, 11.1
Hz, C14-H), 5.78 (1H, d, J ) 3.7 Hz, C9-H), 7.17-7.33 (5H, m,
ArH); 13C NMR δ 25.85 (CH3), 27.27 (CH2), 27.38 (CH3), 27.49
(CH3), 32.85 (CH2), 40.18 (CH2), 41.8 (CH), 47.23 (CH), 67.50
(CH2), 81.87 (CH), 88.09 (CH), 92.15 (C), 106.29 (CH), 113.24
(C), 127.35 (CH), 127.69 (CH), 127.97 (CH), 128.73 (CH), 129.0
(CH), 129.76 (CH), 136.28 (C), 138.94 (C). Anal. Calcd for
C24H30O4: C, 75.36; H, 7.91. Found: C, 75.17; H, 7.81.
Acknowledgment. Financial support from DST,
New Delhi, is gratefully acknowledged. S.P.B. thanks
CSIR, New Delhi, for a Senior Research Fellowship.
Supporting Information Available: Copies of 1H, 13C,
and DEPT NMR spectra of compounds 3a, 4a, 4b, 4c, 5a, 5b,
5c, 6a, 6b, 14, 15, 23a, 23b, 25a, 25b, 30a, 30b, 33, and 34.
This material is available free of charge via the Internet at
http://pubs.acs.org.
[ethyl acetate-petroleum ether (1:19)]; [R]32 +47.9 (c 0.61,
D
CHCl3); 1H NMR δ 1.30 (3H, s, CH3), 1.53 (3H, s, CH3), 1.91-
2.02 (2H, m), 2.40 (2H, m), 2.52 (2H, dd, J ) 8.9, 14.8 Hz),
3.28 (1H, m), 3.50 (1H, br s), 4.42 (1H, d, J ) 3.5 Hz, C2-H),
JO026920C
J. Org. Chem, Vol. 68, No. 10, 2003 3989