Role of Heteroatoms in Diastereofacial Control in Cycloaddition to a Dissymmetric Cyclohexa-1,3-diene Moiety in a Polycyclic Framework. Remarkable Stereodirecting Influence of Distal Protective Groups

Article abstract of DOI:10.1021/jo991349b

Diels-Alder cycloaddition to several derivatives of a facially dissymmetric diene, the hexacyclo-[7.5.1.0.^1,60.^6,130.^8,120. ^10,14]pentadeca-2,4-diene-7,15-dione 4a, with a variety of dienophiles such as singlet oxygen, N-phenyltriazolinedione, dimethyl acetylenedicarboxylate, maleic anhydride, and N-methylmaleimide has been studied. The stereochemistry of the resulting adducts has been unambiguously secured by ¹H and ¹³C NMR spectral data, chemical correlations, and X-ray crystal structure determination. While a variety of dienophiles undergo [4 + 2]-cycloadditions with 4a predominantly from the carbonyl face, protection of the carbonyl groups in 4a as simple mono- or bis-acetals 4b-e or thioacetals 9a,b leads to complete reversal in selectivity, favoring addition from the cyclobutane face, with heterodienophiles and acetylenic dienophiles. The reversal in selectivity observed in mono- and bis-acetals 4b-e has been attributed to unfavorable electrostatic interaction between the oxygen atom and the incoming dienophile. Whereas, in the case of thioacetals 9a,b, apart from unfavorable electrostatic interactions, Cieplak-type hyperconjugative interactions have to be given due consideration in order to account for the observed selectivities. Our studies highlight the role of simple protective groups (acetals in the present case) in modulating diastereoselection during [4 + 2]-cycloadditions.

Full text of DOI:10.1021/jo991349b

J . Org. Chem. 2000, 65, 1685-1696
1685
Role of Heter oa tom s in Dia ster eofa cia l Con tr ol in Cycloa d d ition
to a Dissym m etr ic Cycloh exa -1,3-d ien e Moiety in a P olycyclic
F r a m ew or k . Rem a r k a ble Ster eod ir ectin g In flu en ce of Dista l
P r otective Gr ou p s
Goverdhan Mehta* and R. Uma
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India, and
Department of Organic Chemistry, Indian Institute of Science, Bangalore 500 012, India
Received August 25, 1999
Diels-Alder cycloaddition to several derivatives of a facially dissymmetric diene, the hexacyclo-
[7.5.1.0.1,60.6,130.8,12010,14]pentadeca-2,4-diene-7,15-dione 4a , with a variety of dienophiles such as
singlet oxygen, N-phenyltriazolinedione, dimethyl acetylenedicarboxylate, maleic anhydride, and
N-methylmaleimide has been studied. The stereochemistry of the resulting adducts has been
unambiguously secured by 1H and 13C NMR spectral data, chemical correlations, and X-ray crystal
structure determination. While a variety of dienophiles undergo [4 + 2]-cycloadditions with 4a
predominantly from the carbonyl face, protection of the carbonyl groups in 4a as simple mono- or
bis-acetals 4b-e or thioacetals 9a ,b leads to complete reversal in selectivity, favoring addition
from the cyclobutane face, with heterodienophiles and acetylenic dienophiles. The reversal in
selectivity observed in mono- and bis-acetals 4b-e has been attributed to unfavorable electrostatic
interaction between the oxygen atom and the incoming dienophile. Whereas, in the case of
thioacetals 9a ,b, apart from unfavorable electrostatic interactions, Cieplak-type hyperconjugative
interactions have to be given due consideration in order to account for the observed selectivities.
Our studies highlight the role of simple protective groups (acetals in the present case) in modulating
diastereoselection during [4 + 2]-cycloadditions.
In tr od u ction a n d Ba ck gr ou n d
orbital mixing/tilting,9,10 secondary orbital interactions,11
hyperconjugative effects,12 electrostatic interactions,13
and nonbonded attraction between the diene and dieno-
phile14 as additional factors in determining face selectiv-
ity. Attempts have been made to evaluate critically the
relative importance of steric, orbital, and electrostatic
effects in determining the π-face preferences. In this
regard, substrates having the 1,3-diene moiety embedded
in constrained, rigid polycyclic frames constitute incisive
probe systems as electronic fine-tuning of the substitu-
ents can be achieved without concomitant conformational
ambiguities. Several polycyclic probe systems such as
1-4a have been studied in detail to glean insights into
the subtle role of stereoelectronic factors in determining
face selectivity in [4 + 2]-cycloadditions.10,15-18 Among
Among the commonly employed methods for generat-
ing stereogenic centers,1 [4π + 2π]-cycloadditions (Diels-
Alder reaction) have attracted much attention, as they
are among the most versatile and synthetically useful
reactions in which four new contiguous stereogenic
centers can be generated in a single laboratory opera-
tion.2 The influence of olefin geometry, neighboring chiral
centers, and transition state topology on product stere-
ochemistry is well-established. However, the role of
π-facial diastereoselection, which arises when the two
faces of the reacting partners, viz. the diene or the
dienophile, are nonequivalent (dissymmetric), is still a
matter of ongoing debate.3 Thus, it is important to study
either newer probe systems or modify the existing ones
to get better insights into the steric and electronic factors
that control diastereoselection in Diels-Alder reactions
of dissymmetric 1,3-dienes.
(5) (a) Poirier, R. A.; Pye, C. C.; Xidos, J . D.; Burnell, D. J . J . Org.
Chem. 1995, 60, 2328. (b) Xidos, J . D.; Poirier, R. A.; Pye, C. C.; Burnell,
D. J . J . Org. Chem. 1998, 63, 105.
(6) Angell, E. C.; Fringuelli, F.; Pizzo, B.; Taticchi, A.; Wenkert, E.
J . Org. Chem. 1986, 51, 2642.
(7) Hagenbuch, J . P.; Vogel, P.; Pinkerton, A. A.; Schwarzenbach,
D. Helv. Chim. Acta 1981, 64, 1818.
(8) Brown, F. K.; Houk, K. N. J . Am. Chem. Soc. 1985, 107, 1971.
(9) Inagaki, S.; Fujimoto, H.; Fukui, K. J . Am. Chem. Soc. 1976,
98, 4054.
Cycloaddition studies with a number of simple cyclic
dienes, wherein the conformational effects are minimal
and which allow an assessment of other factors, have
revealed the importance of steric,4,5 ground-state geo-
metric distortions,6 product stabilities,7 torsional effects,8
(10) (a) Paquette, L. A.; Carr, R. V. C.; Bohm, M. C.; Gleiter, R. J .
Am. Chem. Soc. 1980, 102, 1186. (b) Gleiter, R.; Paquette, L. A. Acc.
Chem. Res. 1983, 16, 328 and references therein.
(11) (a) Gleiter, R.; Ginsburg, D. Pure Appl. Chem. 1979, 51, 1301.
(b) Ginsburg, D. Tetrahedron 1983, 39, 2095.
(12) (a) Cieplak, A. S. J . Am. Chem. Soc. 1981, 103, 4540. (b)
Cieplak, A. S. Chem. Rev. 1999, 99, 1265. (c) Coxon, J . M.; McDonald,
D. Q. Tetrahedron Lett. 1992, 33, 651.
(13) Kahn, S. D.; Hehre, W. J . J . Am. Chem. Soc. 1987, 109, 663.
(14) Anh, N. T.; Tetrahedron 1973, 29, 3227.
(1) For a series of articles on diastereoselection, see: Thematic Issue
on Diastereoselection Chem. Rev. 1999, 99(5).
(2) (a) Carruthers, W. Cycloaddition Reactions in Organic Synthesis;
Pergamon: Oxford, 1990. (b) Fringuelli, F.; Taticchi, A. Dienes in the
Diels-Alder Reaction; J ohn Wiley and Sons: New York, 1990.
(3) (a) Fallis, A. G.; Lu, Y.-F. In Advances in Cycloaddition; Curran,
D. P., Ed.; J AI Press: London, 1993, Vol. 3, Chapter 1. (b) Mehta, G.;
Uma, R. Acc. Chem. Res., in press.
(4) (a) Burnell, D. J .; Valenta, Z. J . Chem. Soc., Chem. Commun.
1985, 1247 (b) Brown, F. K.; Houk, K. N.; Burnell, D. J .; Valenta, Z.
J . Org. Chem. 1987, 52, 3050. (c) Adam, W.; J acob, U.; Prein, M. J .
Chem. Soc., Chem. Commun. 1995, 839.
(15) (a) Fessner, W. D.; Grund, C.; Prinzbach, H. Tetrahedron Lett.
1991, 32, 5935. (b) Fessner, W. D.; Scheumann, K.; Prinzbach, H.
Tetrahedron Lett. 1991, 32, 5939.
10.1021/jo991349b CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/24/2000

1686 J . Org. Chem., Vol. 65, No. 6, 2000
Mehta and Uma
them, the hexacyclic diene 4a , embodying a [4.4.2]-
propella-2,4-diene moiety as part of its rigid structure,
To probe the role of carbonyl groups in π-facial selec-
tivities in the diene 4a , Pandey et al.18a have studied the
facial selection in corresponding diol 5, resulting from
has been more enduring because of its ready avail-
ability,19 reactivity, and ease of functional group inter-
conversion. In addition, the planarity of the diene com-
ponent was ensured on the basis of single-crystal X-ray
structure17a,d,18b of diene 4a , thereby ruling out ground-
state geometric distortion. Furthermore, the 1,3-diene
moiety in 4a is desymmetrized by the presence of an
electron-rich cyclobutane ring on one face and two
carbonyl groups at the homoallylic position on the other
and provides an opportunity to study the effect of
heteroatoms20,21 on Diels-Alder diastereoselection and
also the subtle steric and electronic factors associated
with them. Apart from the intrinsic nonequivalence in
the steric environment, the functionalities can also exert
electronic preferences such as hyperconjugative partici-
pation of the high-energy cyclobutane σ-bonds and elec-
trostatic interaction of the two carbonyl groups in the
vicinity of a polar reagent. Coxon et al.17 and Pandey et
al.18 have independently studied the π-face selectivities
exhibited by 4a and its derivatives and have found that
the diene 4a captures a variety of dienophiles from the
sterically more open carbonyl face. However, dienophiles
such as maleic anhydride (MA), benzyne, singlet oxygen
(1O2),22 N-phenyl-1,2,4-triazolinedione (PTAD), dimethyl
acetylenedicarboxylate (DMAD), and DEAD exhibit mixed
selectivity with exclusive carbonyl-face attack in the case
of MA and exclusive cyclobutane-face attack for DEAD.17a
The variation in selectivity observed in the case of azo
and alkyne dienophiles was qualitatively rationalized by
Coxon et al.17a as an interplay of three factors. (i) In MA
addition, steric interaction between the cyclobutane
hydrogens and the dienophile directs addition exclusively
from the carbonyl face. (ii) The azo and alkyne type of
dienophiles do not possess protons similarly disposed to
those in the olefinic dienophiles for steric interaction with
the cyclobutane protons. In other words, the exclusive
carbonyl-face attack observed with olefinic dienophiles
is a consequence of the steric bias inherent in the diene
4a . (iii) In the transition state for carbonyl-face attack,
the π- or nonbonding orbital electron density in the
alkyne and azo dienophiles can repulsively interact with
the electron density of the carbonyl oxygen atoms.
NaBH4 reduction of 4a , with acrylonitrile to give the
endo-product with addition exclusively from the hydroxy
face as shown. On the basis of these findings, it was
surmised that the carbonyl groups are unimportant in
determining the face selectivity in 4a .18a To substantiate
their interpretation concerning the role of carbonyl
groups, Coxon et al. replaced the carbonyl groups by
methylidene groups as in 6 and 7, thereby retaining the
π-electron configuration but replacing the lone pairs of
the carbonyl oxygens with hydrogen atoms, expecting
that this subtle variation might increase the steric
hindrance to the carbonyl-face addition and encourage
reaction from the cyclobutane face of the diene.17b
It was shown that alkene dienophiles, MA and benzo-
quinone, react with the dienes 6 and 7 with strong
preference for the carbonyl face, whereas, for DMAD,
attack from this face decreases with successive meth-
ylidene substitution. In the case of PTAD this trend was
found to be reversed. It was shown that several factors
such as ground-state geometric distortion,6 product sta-
bilities,7 σ/π-mixing,10 and steric and torsional effects8
which were earlier considered to be responsible for
governing face selectivities could not explain all the
observed selectivities in this system. Apart from orbital
tilting and transition state steric and torsional interac-
tions, unfavorable orbital interaction of the closed shells
of the carbonyl(s) and methylidene(s) syn to the incoming
orthogonal π-orbital of DMAD was also considered
important.17b
(16) Mehta, G.; Padma, S.; Reddy, H. K.; Nethaji, M. J . Chem. Soc.,
Perkin Trans. 1 1994, 2049.
(17) (a) Coxon, J . M.; O’Connell, M. J .; Steel, P. J . J . Org. Chem.
1987, 52, 4726. (b) Coxon, J . M.; Maclagan, R. G. A. R.; McDonald, D.
Q.; Steel, P. J . ibid. 1991, 56, 2542. (c) Coxon, J . M.; Fong, S. T.;
McDonald, D. Q.; Steel, P. J . Tetrahedron Lett. 1993, 34, 163. (d) Coxon,
J . M.; O′Connell, M. J .; Steel, P. J . Acta Crystallogr. 1986, C42, 1773.
(18) (a) Pandey, B.; Zope, U. R.; Ayyangar, N. R. Synth. Commun.
1989, 19, 585. (b) Dhaneshwar, N. N.; Tavale, S. S.; Guru Row: T. N.;
Zope, U. R.; Pandey, B.; Ayyanger, N. R. Acta Crystallogr. 1988, C44,
2191.
(19) (a) Fillipesen, N.; Menter, J . M. J . Chem. Soc., B 1969, 616. (b)
Kushner, A. S. Tetrahedron Lett. 1971, 12, 3275. (c) Mehta, G.; Singh,
V.; Rao, K. S. Tetrahedron Lett. 1980, 21, 1369.
(20) Macaulay, J . B.; Fallis, A. G. J . Am. Chem. Soc. 1990, 112, 1136.
(21) Paquette, L. A.; Branan, B. M.; Rogers, R. D.; Bond, A. H.;
Lange, H.; Gleiter, R. J . Am. Chem. Soc. 1995, 117, 5992 and references
therein.
To validate this proposition, Coxon et al.17c investigated
the π-face preferences in a related cage ether 8, wherein
a lone pair of the ether oxygen is positioned centrally so
as to interact with the π-orbital of the acetylenic dieno-
phile or n-orbitals of an azo dienophile. It was reasoned
that if this electronic effect were important, acetylenic
and azo dienophiles would react from the cyclobutane
face and alkene dienophiles from the less hindered ether
face. Indeed, such a variation in face selectivities with
(22) Mehta, G.; Uma, R.; Pramanik, A.; Chandrasekhar, J .; Nethaji,
M. J . Chem. Soc., Chem. Commun. 1995, 677.

Role of Heteroatoms in Diastereofacial Control
Ta ble 1. P r od u ct Distr ibu tion (%)a a n d Yield (%) in Cycloa d d ition s of Va r iou s Dien op h iles to 4a -e
singlet oxygen PTAD DMAD MA
carbonyl face cyclobutane face carbonyl face cyclobutane face carbonyl face cyclobutane face carbonyl face cyclobutane face
J . Org. Chem., Vol. 65, No. 6, 2000 1687
substrate
10a -e
11a -e
12a ,c
13a ,c
14a -e
15a -e
16a -e
17a -e
4a
4b
4c
4d
4e
78
14
22 (88)
86 (92)
100 (98)
100 (70)
97 (91)
64
36 (80)
55
17
05
06
18
45 (85)
83 (91)
95 (92)
94 (75)
82 (83)
100 (98)
100 (98)
100 (98)
100 (98)
100 (98)
100 (85)
03
a
The product ratios were obtained from the analyses of the 1H NMR spectra of the crude reaction mixture as well as from isolated
yields of pure compounds.
Sch em e 1
three representative dienophiles, viz. MA, DMAD, and
PTAD, was observed. MO calculations at the AM1 level
reproduced the observed selectivities. Additionally, on the
basis of these calculations, an unfavorable interaction in
the transition state between the filled π-orbital of acety-
lene (disposed orthogonal to the forming σ-bonds) and the
lone pair on the ether oxygen was computed during
approach from the ether face. Coxon et al. have recog-
nized this factor for undermining addition from the ether
face.17c
Resu lts a n d Discu ssion
On the basis of earlier studies on system 4a , it was
reasoned that rehybridization of the carbonyl carbon(s)
in 4a and strategic disposition of hetero (O, S etc.)
functionalities on the newly generated sp3 center(s)
should enable alteration of face selectivity in a profound
way. In a practical sense, this expedience could be simply
implemented by protecting the carbonyl groups in 4a as
corresponding acetals or thioacetals, which represents a
simple modification of a carbonyl group through a protec-
tive group. Thus, without substantially altering the steric
environment or sacrificing the skeletal identity of the
dominantly from the carbonyl face,22 in the acetals 4b-e
the addition was found to be uniformly from the cyclo-
substrate, simple protective groups could function as
butane face and the diastereomeric ratios are indicated
stereodirectors by turning on the electrostatic effects. The
in Table 1.
expectation was that with hetero and acetylenic dieno-
Addition of PTAD, generated by the oxidation of
philes the speculated repulsive interactions between the
N-phenylurazole to acetal 4c, followed the same trend
acetal oxygens and the lone pair or filled π-orbital of the
dienophiles would be operative and reverse the face
selectivity.
Further, to make the study comprehensive, dienophiles
representing three important types were employed: (a)
MA and N-methylmaleimide (NMM), as representative
alkene dienophile, wherein, the two olefinic protons could
as observed for 1O2 addition, and a single crystalline
adduct 13c, arising from cyclobutane-face attack, was
realized. The carbonyl-face adduct 12c could not be
detected in the crude reaction mixture (1H NMR spec-
trum) (Table 1). Acetals 4b, 4d , and 4e did not furnish
readily characterizable products on reaction with PTAD.
It is known17a that PTAD is captured predominantly from
induce a steric bias; (b) DMAD, a representative acety-
the carbonyl face in the dione 4a to furnish adducts 12a
and 13a (Scheme 1).
The acetals 4b -e underwent smooth [4 + 2]-cyclo-
addition with DMAD in refluxing benzene to afford
1
lenic dienophile with filled π-orbitals; and (c) O2 and
PTAD, representing heterodienophiles with filled n-
orbitals which can interact with the diene substrate.
Cycloa d d ition s to Aceta ls 4b-e. The hexacyclic
adducts 14b-e and 15b-e, with preponderant attack
dione 4a was readily transformed to the corresponding
1
from the cyclobutane face, in analogy with O2 and PTAD
mono- and bis-acetals (4b-e) or thioacetals (9a ,b),
additions (Scheme 1). In sharp contrast to this observa-
through simple protective group modification of the
tion, the dione 4a is known17a to afford adducts 14a and
carbonyl groups.23 The mono- and bis-acetals of 4a were
15a , with modest excess of addition from the carbonyl-
obtained using the appropriate alcohol/diol in benzene
face (Table 1).
As a control, we also studied the addition of MA to
and employing PTSA as the catalyst.
The dione 4a and acetals 4b-e readily underwent
photooxygenation when irradiated with a 500 W tungsten
acetals 4b-e to rule out any significant contribution from
steric factors. The addition of MA to acetals 4b-e was
lamp using methylene blue as the sensitizer to furnish
effected in refluxing benzene to furnish adducts 16b-e
endoperoxides 10a -e and 11a -e, respectively (Scheme
(Scheme 1). The series of adducts 17b-e could not be
1). While in the dione 4a 1O2 addition occurred pre-
detected in any of the reaction mixtures. We were
gratified to note that the addition indeed occurred
exclusively from the carbonyl face, effectively eliminating
(23) A portion of this work dealing with the cycloadditions to acetals
has been published as a preliminary communication, see: Mehta, G.;
Uma, R. Tetrahedron Lett. 1995, 36, 4873.
any steric intervention by the acetal groups (Table 1).

1688 J . Org. Chem., Vol. 65, No. 6, 2000
Mehta and Uma
acetal 15e were hydrolyzed to dione 15a 17a and mono-
acetal 15b, respectively. Alternately, the dione 14a 17a was
acetalized to furnish 14b, 14c, and 14e. In addition,
mono-acetal 16d and bis-acetal 16e were converted to
dione 16a 17a and mono-acetal 16b, respectively. Last, the
dione 16a 17a was transformed into mono-acetals 16b and
16c.
In ter p r eta tion of Dia ster eoselectivities. For ac-
etals 4b -e, addition of 1O2, PTAD, and DMAD is
overwhelmingly preferred from the cyclobutane face, in
dramatic contrast to the carbonyl-face addition in 4a .17a
There is no marked change in the π-face selectivity in
addition of MA to 4b-e, clearly indicating that the
observed preferences are dienophile specific. The fine-
tuning of the face selectivity as a function of the acetal
protecting group (Table 1) further reflects the effect of
subtle variations in the positioning of the oxygen atoms
on the extent of repulsive interactions. Interestingly,
higher selectivities have been observed for the more
flexible mono-acetals 4c and 4d . Since there is no marked
change in the π-face selectivity of MA to acetals 4b-e
when compared with the dione 4a , it is reasonable to rule
out any steric intervention due to the acetal groups. In
fact, the predominant cyclobutane-face selectivity in
4b-e is a contrasteric outcome.
F igu r e 1. Molecular structure of 11e.
The yields in the various cycloadditions studied ranged
between 70 and 100% and are displayed in Table 1. The
product ratios were obtained from the analyses of the H
NMR integration of the crude reaction mixture as well
as from isolated yields of pure compounds and are
summarized in Table 1. The diastereomers were carefully
separated using silica gel column chromatography and
fully characterized. Interestingly, the cyclobutane-face
adducts in most of the cases eluted out first from the
column.
1
Several factors such as product stability,7 ground-state
geometric distortion,6 σ/π-mixing,10 and torsional interac-
tions,8 which have been previously considered to account
for face selectivity in [4 + 2]-cycloaddition, are not ap-
plicable for this system. According to the Cieplak model,12a
the addition should occur from the side opposite to the
most electron rich bond, as shown for 4a ; see 18.
Ster eoch em ica l Assign m en ts of th e Dia ster eo-
m er ic Ad d ition P r od u cts. Stereostructures of all the
cycloadducts were determined on the basis of detailed
NMR spectral analyses, particularly 1H NMR data;
chemical correlation; and X-ray crystal structure deter-
mination of key compounds.
1
An a lyses of H NMR Sp ectr a l Da ta . The formation
of [4 + 2]-cycloaddition products was indicated by the
disappearance of signals due to cyclohexadiene moiety
in the region δ 5.4-6.0 and appearance of signals due to
the bicyclo[2.2.2] moiety; particularly, the allylic bridge-
head protons and olefinic protons in the region δ 6.4-
6.8 were of diagnostic value.
In most of the adducts, the cyclobutane protons served
as a stereochemical handle, as they are deshielded by a
syn transannular heteroatom bridge. On the other hand,
the cyclobutane hydrogens are substantially shielded by
a syn double bond. However, in the case of DMAD
addition products, the cyclobutane hydrogens were no
longer of any diagnostic value and hence we resorted to
other methods for assigning stereostructures.
Ch em ica l Cor r ela tion a n d X-r a y Cr ysta l Str u c-
tu r e Deter m in a tion . The stereostructures were unam-
biguously secured by chemical transformation of each of
the diastereomer into a known compound whose struc-
ture was established by single-crystal X-ray diffraction
studies.17a,d,22 While the crystal structure of 11a has been
reported previously22 by us, that of 11e is included here
and the molecular structure is shown in Figure 1. The
chemical correlations involved routine protection-depro-
tection protocols. Unmasking the acetal groups in the
adducts 11d , 11e, 13c, 15c, 15d , 15e, 16d , and 16e
converted them into the adducts derived from 4a , whose
stereostructure has been previously established. Alter-
natively, the adducts of known derivatives of 4a could
be converted into the corresponding acetal derivatives.
Thus, the endoperoxides 11d and 11e were hydrolyzed
to dione 11a 22 and mono-acetal 11b, respectively. Like-
wise, the mono-acetal 13c was hydrolyzed into the dione
13a .17a Further, the mono-acetals 15c and 15d and bis-
This model can readily rationalize the predominant
carbonyl-face attack (addition opposite to electron rich
cyclobutane bonds) in MA, but it fails to rationalize the
contrasteric approach of 1O2, PTAD, and DMAD in
acetals 4b-e. In particular, the key hyperconjugative
interaction in the cycloaddition transition state should
become more important when the newly formed bonds
involve highly electronegative groups. Hence, addition of
1O2 or PTAD to the carbonyl face of the diene is predicted
to be strongly preferred on the basis of the Cieplak model;
nevertheless, the observed selectivities are reversed for
acetals 4b-e.
The observed selectivities can be rationalized as fol-
lows: when the addition occurs from the face of the diene
bearing the acetal functionality in 4b-e, a repulsive
nonbonded interaction between the lone pair on the
acetal oxygen with the π-orbital of DMAD or n-orbitals
1
of PTAD or O2 (which are orthogonal to forming σ-bonds)
is turned on, resulting in destabilization of the transition
state. Further, the variation in diastereoselectivity, with
respect to the dienophile employed (Table 1), reaffirms
our surmise that the repulsive nonbonded interactions
between the incoming dienophile and the acetal oxygens
in 4b-e govern the π-facial selectivities in these systems.

Role of Heteroatoms in Diastereofacial Control
Ta ble 2. P r od u ct Distr ibu tion (%)a a n d Yield (%) in Cycloa d d ition s of Va r iou s Dien op h iles to 9a ,b
singlet oxygen DMAD MA NMM
PTADb
carb face carb face
J . Org. Chem., Vol. 65, No. 6, 2000 1689
carbc face
19a ,b
cyb face
carb face
cyb face
carb face
23a ,b
cyb face
cyb face
cyb face
substrate
20a ,b
21a ,b
22a ,b
24a ,b
25a ,b
26a ,b
27a ,b
28a ,b
9a
9b
100 (15)
100 (81)
09
11
91 (75)
89 (80)
100 (92)
100 (91)
100 (98)
100 (98)
100 (98)
100 (98)
a
The product ratios were obtained either from the analyses of the 1H NMR spectra of the crude reaction mixture or from isolated
b
yields of pure compounds. The adducts 21a ,b and 22a ,b underwent in situ dethioacetalization to furnish 12a and 13a , respectively.
c Carb face, carbonyl face; Cyb face, cyclobutane face.
Sch em e 2
In addition, these results also provide an unprecedented
illustration of the stereodirecting effect of simple remote
protective groups. Since acetal protection and deprotec-
tion are fairly routine manipulations, we feel that this
tactic can be employed for controlling diastereoselection
in certain systems.
Cycloa d d ition to Th ioa ceta ls 9a ,b. To further ex-
tend the scope of our findings on the acetals 4b-e, we
directed our study to their sulfur counterparts 9a ,b,
expecting to gauge the effect of the change in the
heteroatom on diastereoselection in these systems. Al-
though considerable efforts have been made to under-
stand the influence of a heteroatom on [4 + 2]-cyclo-
additions, experimental data available to illustrate the
role of allylic/homoallylic sulfur substituents is rather
limited.20,21 Apart from this, the following distinctive
features make studies employing sulfur as a heteroatom
particularly interesting:
If the Cieplak hyperconjugative model12 is operative,
it is reasonable to speculate that a preference should exist
for addition anti to the best σ-donor (C-S bond) when
the competition is between a C-C and a C-S bond.
If the electrostatic model is the principal determinant
of face selectivity, oxygen atoms will experience greater
nonbonded lone pair repulsion in the vicinity of a het-
1
erodienophile such as O2 or PTAD because of the better
match in their 2p energy levels as compared to that of
sulfur.21,24 Hence, addition syn to sulfur may not be
disfavored. However, progression from oxygen to sulfur
face and the adducts 19a ,b due to carbonyl face attack
were not encountered (Table 2).
is accompanied by substantial changes in atomic radii
Addition of PTAD to thioacetals 9a ,b was brought
(van der Waals radii for oxygen is 1.4 Å and that of sulfur
about in dichloromethane at 0-5 °C. The 1H NMR
is 1.85 Å) and bond length (C-S bond is 2.0 Å and C-O
spectral features of the resulting adducts clearly indi-
bond is 1.45 Å). Taking both the bond length and atomic
cated that they were in fact PTAD addition products 12a
and 13a of the hexacyclic dione 4a and their identity was
further confirmed by comparing the 1H and 13C NMR
spectra with authentic samples. Our speculation was that
during PTAD addition to 9a ,b the resultant [4 + 2]-
radii into consideration, the net steric factor favors
addition opposite to sulfur.3
To evaluate the relative contribution of the above-
mentioned effects, we ventured to investigate the π-facial
selectivities of mono-thioacetals 9a ,b which were readily
adducts 21a ,b and 22a ,b underwent smooth in situ
prepared from 4a employing the appropriate dithiol,
dethioacetalization to furnish adducts 12a and 13a ,
respectively, corresponding to those derived from hexa-
viz.1,2-ethanedithiol or 1,3-propanedithiol and PTSA as
the catalyst. However, the bis-thioacetals were not
cyclic dione 4a . The issue that needed to be settled at
this juncture was whether dethioacetalization preceded
or followed the addition of PTAD to thioacetals 9a ,b. The
answer was forthcoming from the fact that the major
(∼90%) diastereomer obtained in the case of 9a ,b cor-
responded to 22a ,b (not isolated) through the cyclo-
butane-face addition (cf. ∼36% observed in the case of
hexacyclic dione 4a ), which established beyond doubt that
dethioacetalization followed PTAD addition (Scheme 2).
Therefore, the diastereoselectivities observed during
PTAD additions reported herein correspond to that of
thioacetals 9a ,b.25 Addition of PTAD to thioacetals 9a ,b
follows the same trend as in 1O2 addition, albeit with
slight decrease in selectivity (Table 2).
formed under these reaction conditions. The crystalline
mono-thioacetals 9a ,b were fully characterized on the
basis of their 1H and 13C NMR spectral data. The 13C
NMR spectra indicated loss of symmetry in consonance
with the mono-thioacetal structure.
The thioacetal 9b readily underwent photooxygenation
to furnish a single crystalline endoperoxide 20b in near
quantitative yield (Scheme 2). However, in 9a , photo-
oxygenation was not clean (probably due to other com-
peting reactions such as oxidation at sulfur) and resulted
1
in poor yield of endoperoxide 20a . In both 9a and 9b O2
addition is uniformly, exclusively from the cyclobutane-
(24) Bohm, M.; Gleiter, R. Tetrahedron 1980, 36, 3209.

1690 J . Org. Chem., Vol. 65, No. 6, 2000
Mehta and Uma
Further, thioacetals 9a ,b underwent smooth [4 + 2]-
selectivity in the case of MA, NMM, 1O2, and DMAD with
the introduction of barely a single thioacetal functional-
ity. The addition of 1O2 and DMAD to 9a ,b occurs
exclusively from the cyclobutane face, while PTAD ex-
hibits ∼90% selectivity for this face. Last, MA and NMM
almost exclusively add from the carbonyl face. For olefinic
dienophiles, viz. MA and NMM, possessing an intrinsic
steric bias, the addition is expected from the face of the
diene which is sterically least hindered.
cycloaddition with DMAD exclusively from the cyclo-
1
butane face, in accord with O2 and PTAD addition. The
crude reaction mixture did not indicate the presence of
carbonyl-face adducts 23a ,b (Table 2).
As a control, we also studied the addition of MA and
NMM to thioacetals 9a ,b, to gauge contribution from
steric bias exerted by the thioacetal functionality. The
addition of MA and NMM to thioacetals 9a ,b was effected
in refluxing benzene to furnish adducts 25a ,b and 27a ,b,
respectively (Table 2). In each case, addition indeed
occurred exclusively from the carbonyl face, without any
trace of the corresponding cyclobutane-face adducts
(26a ,b and 28a ,b) (Scheme 2).
Considering the preferences observed for MA and
NMM, it is not unreasonable to conclude that carbonyl
face is still sterically less demanding as compared to
cyclobutane face even after the introduction of thioacetal
groups in dienes 9a ,b. Therefore, the observed preference
for cyclobutane face during 1O2, PTAD, and DMAD
addition to thioacetals 9a ,b is a contrasteric outcome.
Nonetheless, heterodienophiles do not have hydrogens,
as in the case of MA or NMM, which can experience steric
interaction during the cyclobutane-face attack. Consider-
The yields in cycloadditions ranged between 90 and
100% and are displayed in Table 2. The product ratios
1
were obtained from the analyses of the H NMR integra-
tion of the crude reaction mixture as well as from iso-
lated yields of pure compounds and are summarized in
Table 2.
1
ing these factors, the observed preferences during O2,
PTAD, and DMAD addition to thioacetals 9a ,b can be
attributed to electronic factors such as orbital or electro-
static interactions.
Ster eoch em ica l Assign m en ts of th e Dia ster eo-
m er ic Cycloa d d ition P r od u cts. An a lyses of 1H NMR
Sp ectr a l Da ta . The formation of the [4 + 2]-cycloaddi-
tion products 19a ,b-28a ,b was fully in consonance with
the 1H and 13C NMR spectral data. All the cycloadditions
reported herein afforded only Alder adducts. The disap-
pearance of signals due to the cyclohexadiene moiety in
the region δ 5.6-6.0 and appearance of signals due to
the bicyclo[2.2.2] moiety were readily identifiable. Par-
ticularly, allylic bridgehead and olefinic protons in the
region δ 6.4-6.8 were diagnostic. However, the stereo-
structures of adducts 24a ,b, 25a ,b, 27a ,b could not be
assigned on the basis of the 1H NMR spectral data alone.
The signals for the diagnostic cyclobutane protons were
often obscured by overlap with the multiplets due to the
thioacetal group. The only exception being endoperoxide
20b, where there was a discernible downfield shift of (ca.
0.3 ppm) for the cyclobutane protons, indicating a syn
relationship to the transannular peroxo bridge.
Ch em ica l Cor r ela tion s. The stereostructures were
unambiguously secured by chemical transformation of
each of the diastereomer into a compound of known
stereostructure. This was accomplished by either un-
masking the thioacetal groups in the adducts or convert-
ing the adducts of known stereostructures into the
corresponding thioacetal derivatives by protecting with
appropriate dithiol. These chemical correlations involved
unexceptional but tricky protection-deprotection proto-
cols. Accordingly, the mono-thioacetals 24a ,b were de-
thioacetalized to the dione 15a , whose structure has been
previously established.17a Alternately, The dione 15a 17a
was converted into mono-thioacetals 24a and 24b. Like-
wise, the dione 16a 17a was transformed into mono-
thioacetals 25a and 25b. In addition, the dione 2917a was
converted into mono-thioacetals 27a and 27b.
The observed preferences for heterodienophiles and
acetylenic dienophiles may be reconciled in terms of the
Cieplak hyperconjugative model, according to which the
preferred face of addition is anti to the most electron rich
bond. In the substrates 9a ,b, the choice is between
cyclobutane bonds and C-C bonds R to a thioacetal and
a carbonyl group, as we are dealing with unsymmetrical
mono-thioacetals; see 30. Interestingly, it is evident from
the trends in Table 2 that such a hyperconjugative
contribution should be operative. On the other hand,
unfavorable nonbonded interactions between the hetero-
dienophiles and the lone pairs on sulfur should also
encourage addition from the cyclobutane face. However,
in thioacetals 9a ,b the relative contribution from such
interactions is expected to decrease as compared to their
oxygen variants 4b-e, where there is better match of
2p energy levels. If this were the major determining
factor, it is reasonable to speculate that the observed
trends for cyclobutane-face addition would be reduced or
comparable with the acetal series (4b-e).
In light of these arguments, it is reasonable to consider
that both electrostatic and orbital interactions act coop-
eratively during addition of heterodienophiles and acety-
lenic dienophiles, whereas, unfavorable steric interac-
tions between cyclobutane and the olefinic hydrogens are
the principal determining factors during addition of MA
and NMM to thioacetals 9a ,b.
In ter p r eta tion of Dia ster eoselectivities. The re-
sults in Table 2 clearly indicate that the thioacetal
functionality has a profound bearing on the π-facial
selectivity and is generally consistent with the observed
trends in the acetals 4b-e, most noteworthy being total
Con clu d in g Rem a r k s
(25) The concomitant dethioacetalization in 21a ,b and 22a ,b can
be rationalized as follows. Preparation of PTAD involved oxidation26
of N-phenylurazole with “oxides of nitogen”27 and this invariably leaves
residual amounts of the oxidizing reagent dissolved in DCM along with
PTAD. We have shown that DCM solution of “oxides of nitrogen”
effectively effects dethioacetalizations.28
Employing hexacyclo[7.5.1.0.1,60.6,130.8,12010,14]pentadeca-
2,4-diene-7,15-dione (4a ), a unique polycycle, embodying
a [4.4.2]propella-2,4-diene moiety as part of its rigid

Role of Heteroatoms in Diastereofacial Control
J . Org. Chem., Vol. 65, No. 6, 2000 1691
δ 123.6 (2C), 114.6, 67.2, 63.7, 53.7, 49.3, 48.8, 45.7, 32.8. Anal.
Calcd for C19H20O4: C, 73.06; H, 6.45. Found: C, 73.15; H, 6.49.
(ii) Reaction with 2,2-dimethylpropane-1,3-diol gave 4c.
Elution with 30% ethyl acetate-hexane furnished the
mono-acetal 5,5-dimethylspiro[dihydro-4H-[1,3]dioxane-2,7′-
hexacyclo[7.5.1.0.1,60.6,130.8,12010,14]pentadeca-2′,4′-diene]-15′-
one (4c) (85%), which was recrystallized from DCM-hexane:
structure, we have illustrated the profound influence of
heteroatoms, viz. oxygen and sulfur, on π-facial diaste-
reoselection in these systems by exploiting the distal
carbonyl groups as a handle for electronic fine-tuning.
Employing this tactic, we have shown that simple
modification of carbonyl groups into mono- or bis-acetals
(4b-e) or thioacetals (9a ,b) can reverse the carbonyl face
selectivity in [4 + 2]-cycloaddition with certain dieno-
philes. In other words, the reversal in diastereoselectivity
in these systems has been accomplished through a
routine protective group maneuver. With the demonstra-
tion of an unprecedented stereodirecting effect of simple,
remote, protecting groups, we expect that this tactic
would find useful synthetic applications in achieving
diastereoselection in related systems, as acetal protection
and deprotection is a fairly routine manipulation. The
observed reversals in diastereoselectivities has been
primarily attributed to unfavorable nonbonded interac-
tions between acetal oxygens and filled orbitals on the
dienophiles.
On replacement of oxygen by sulfur, as in the thio-
acetal system (9a ,b), the expectation was that the
magnitude of through-space interactions would be
reduced and hence attack from the carbonyl face would
be promoted. However, the total selectivity for the
cyclobutane face, as observed in these systems, suggests
the need for Cieplak-type hyperconjugative interactions
to be considered in addition to through-space electrostatic
interactions.
mp 203 °C; IR (KBr) 1740, 1581 cm-1 1H NMR (200 MHz,
;
CDCl3) δ 5.94-5.88 (2H, m), 5.74-5.69 (1H, m), 5.50-5.44 (1H,
m), 3.63 (1H, 1/2 ABq, J ) 11.2 Hz), 3.46-3.40 (3H, m) 3.39
(1H, 1/2 ABq, J ) 11.4 Hz), 3.10-3.03 (1H, m), 2.94-2.86 (1H,
m), 2.77-2.73 (1H, m), 2.66-2.62 (1H, m), 2.50-2.43 (1H, m),
1.76 (1H, 1/2 ABq, J ) 11.6 Hz), 1.40 (1H, 1/2 ABq, J ) 10.8
Hz), 1.07 (3H, s), 0.71 (3H, s); 13C NMR (50 MHz, CDCl3)
δ 212.5, 123.8, 123.4, 122.2, 120.8, 103.7, 73.0, 71.1, 53.7, 52.4,
49.9, 49.5, 47.0, 46.4, 45.6, 42.6, 36.7, 29.9, 22.7, 21.8. Anal.
Calcd for C20H22O3: C, 77.39; H, 7.14. Found: C, 77.45; H,
7.16.
(iii) Reaction with methanol gave 4d . Elution with 30% ethyl
acetate-hexane afforded the mono-acetal 15,15-Dimethoxy-
hexacyclo[7.5.1.0.1,60.6,130.8,12010,14]pentadeca-2,4-diene-7-one 4d
(91%): mp 88-89 °C; IR (KBr) 1734, 1580 cm-1; 1H NMR (200
MHz, CDCl3) δ 5.91 (1H, dd, J 1 ) 9.8 Hz, J 2 ) 4.8 Hz), 5.84-
5.71 (2H, m), 5.54 (1H, d, J ) 9.8 Hz), 3.23 (3H, s), 3.13 (3H,
s), 2.99-2.96 (1H, m), 2.92-2.84 (2H, m), 2.70-2.60 (2H, m),
1
2.53-2.46 (1H, m) 1.72 (1H, /2 ABq, J ) 11.4 Hz), 1.33 (1H,
1/2 ABq, J ) 11.4 Hz), 13C NMR (50 MHz, CDCl3) δ 212.5, 125.0,
123.80, 121.2, 120.8, 105.9, 56.4, 51.9, 51.5, 50.4(2C), 50.1,
48.2, 46.5, 44.1, 42.3, 36.2. Anal. Calcd for C17H18O3: C, 75.53;
H, 6.71. Found: C, 75.66; H, 6.74.
(iv) Reaction with 1,2-ethanedithiol gave 9a . Elution with
10% ethyl acetate-hexane furnished the mono-thioacetal
spiro[dihydro[1,3]dithiolane-2,7′-hexacyclo[7.5.1.0.1,60.6,130.8,12010,14]-
pentadeca-2′,4′-diene]-15′-one (9a ) (50%), which was recrystal-
lized from DCM-hexane: mp 157 °C; IR (KBr) 1732, 1583
1
cm-1; H NMR (200 MHz, CDCl3) δ 5.99-5.92 (2H, series of
Exp er im en ta l Section
m), 5.85-5.77 (1H, m), 5.60-5.51 (1H, m), 3.35-3.11 (4H, m),
3.08-3.01 (2H, m), 2.94-2.86 (2H, m), 2.72-2.64 (2H, m), 1.84
(1H, 1/2 ABq, J ) 11.1 Hz), 1.40 (1H, 1/2 ABq, J ) 11.6 Hz);
13C NMR (50 MHz, CDCl3) δ 214.1, 125.5, 124.4, 123.8, 121.4,
61.4, 56.7, 56.3, 53.4, 50.7, 49.2, 48.3, 43.2, 40.1, 39.4, 23.3;
MS m/z 300 (M+). Anal. Calcd for C17H16OS2: C, 67.96; H, 5.37.
Found: C, 67.92; H, 5.35.
All melting points are uncorrected. Microanalyses were
performed on a Perkin-Elmer 240C CHN analyzer at the
University of Hyderabad. Column chromatography was per-
formed with Acme’s silica gel (100-200 mesh). All nonhalo-
genated solvents were dried over sodium wire. Dichloro-
methane and chloroform were distilled over P2O5.
Aceta liza tion /Th ioa ceta liza tion of Dion e 4a . Gen er a l
P r oced u r e. In a round-bottomed flask fitted with a Dean-
Stark water separator were placed dione 4a 19 (500 mg, 2.23
mmol), alcohol/diol/thiol (∼2.5 equiv), PTSA (5-7 mg), and dry
benzene (25 mL). The contents of the flask were refluxed
overnight with stirring. The reaction mixture was cooled,
diluted with ethyl acetate (20 mL), washed with water (3 mL)
and saturated NaHCO3 solution (5 mL), and dried. Removal
of solvent furnished crude acetals/thioacetals which were
purified on a silica gel column.
(v) Reaction with 1,3-propanedithiol gave 9b. Elution with
25% ethyl acetate-hexane furnished mono-thioacetal spiro-
[dihydro-4H-[1,3]dithiane-2,7′-hexacyclo[7.5.1.0.1,60.6,130.8,12010,14]-
pentadeca-2′,4′-diene]-15-one (9b) (80%), which was recrys-
tallized from DCM-hexane: mp 186 °C; IR (KBr) 1723, 1583
1
cm-1; H NMR (200 MHz, CDCl3) δ 6.07-5.63 (4H, series of
m), 3.41-3.35 (1H, m), 3.21-3.17 (2H, m), 3.07-2.76 (5H, m),
1
2.71-2.59 (2H, m), 2.10-1.73 (2H, series of m), 1.81 (1H, /2
1
ABq, J ) 11.2 Hz), 1.37 (1H, /2 ABq, J ) 11.3 Hz); 13C NMR
(50 MHz, CDCl3) δ 211.4, 124.2, 123.9, 123.3, 122.2, 62.2, 57.6,
56.4, 55.9, 51.4, 48.9, 48.5, 48.3, 43.0, 35.1, 27.9, 27.1, 24.6;
MS m/z 314 (M+). Anal. Calcd for C18H18OS2: C, 68.75; H, 5.77.
Found: C, 68.82; H, 5.74.
(i) Reaction with ethylene glycol gave a mixture of 4b and
4e. Elution with 30% ethyl acetate-hexane initially furnished
the mono-acetal spiro[dihydro[1,3]dioxolane-2,7′-hexacyclo-
[7.5.1.0.1,60.6,130.8,12010,14]pentadeca-2′,4′-diene]-15′-one (4b) (45%),
which was recrystallized from DCM-hexane: mp 128-129 °C;
IR (KBr) 1734, 1585 cm-1; 1H NMR (200 MHz, CDCl3) δ 5.96-
5.84 (2H, m), 5.53-5.46 (2H, m), 3.96-3.93 (4H, m), 3.16-
3.09 (1H, m), 3.01-2.94 (1H, m), 2.86 (1H, bs), 2.69-2.66 (1H,
P h otooxygen a tion of d ien es. Gen er a l P r oced u r e. In a
small irradiation vessel fitted with an outer jacket for cold
water circulation were placed diene (0.35 mmol), methylene
blue (5 mg), and 25 mL of dry chloroform. The solution was
irradiated with a 500 W tungsten lamp, placed about a foot
away, under a slow stream of bubbling oxygen for 3-6 h.
Reactions were continuously monitored by TLC and continued
until most of the starting material was consumed. At the end
of the reaction, chloroform was removed under vacuum at room
temperature to give a diastereomeric mixture of endoperoxides
in good yield. The product ratios were determined by 1H NMR
analyses of the crude reaction mixture by comparing the
integrations of appropriate protons.
P h otooxygen a tion of 4a . The reaction was performed as
described in the general procedure to furnish 10a :11a (78:22)
in 88% yield (based on starting material recovery). The minor
isomer 11a had almost the same Rf as that of the starting
material. Therefore, monitoring the completion of reaction and
separation were done carefully. The isomers were separated
1
m), 2.57-2.55 (2H, m), 1.79 (1H, /2 ABq, J ) 10.8 Hz), 1.43
(1H, 1/2 ABq, J ) 11.4 Hz); 13C NMR (50 MHz, CDCl3) δ 212.8,
123.8 (2C), 122.4, 121.0, 113.8, 66.1, 65.8, 54.6, 53.5, 51.0, 50.0,
47.4, 45.3, 42.7, 36.9. Anal. Calcd for C17H16O3: C, 76.10; H,
6.01. Found: C, 76.17; H, 6.11.
Further elution of the column with 35% ethyl acetate-
hexane furnished the bis-acetal dispiro[dihydro[1,3]dioxolane-
2,7′-hexacyclo[7.5.1.0.1,60.6,130.8,12010,14]pentadeca-2′,4′-diene-
15′, 2′′-(dihydro[1,3]dioxolane)] (4e) (33%), which was recrystal-
lized from DCM-hexane: mp 148-149 °C; IR (KBr) 1581
cm-1; 1H NMR (200 MHz, CDCl3) δ 5.89-5.84 (2H, m), 5.57-
5.51 (2H, m), 4.12-4.07 (4H, m), 3.87-3.80 (4H, m), 2.84 (2H,
bs), 2.69 (2H, bs), 2.29 (2H, bs), 1.52 (1H, 1/2 ABq, J ) 11.0
Hz), 1.07 (1H, 1/2 ABq, J ) 10.9 Hz); 13C NMR (50 MHz, CDCl3)

1692 J . Org. Chem., Vol. 65, No. 6, 2000
Mehta and Uma
by column chromatography using silica gel, and elution with
20% ethyl acetate-hexane initially provided unreacted 4a and
further elution gave minor isomer 11a , which was recrystal-
lized from DCM-hexane: mp 240 °C (chars); IR (KBr) 1726,
1298, 1105, 908 cm-1; 1H NMR (200 MHz, CDCl3) δ 6.78 (2H,
dd as t, J ) 3.9 Hz), 4.70 (2H, dd as t, J ) 3.9 Hz), 3.45 (2H,
bs), 3.09-3.07 (2H, m), 2.72 (2H, bs), 2.11 (2H, bs); 13C NMR
(50 MHz, CDCl3) δ 208.4, 131.6, 70.9, 55.3, 44.3, 42.0, 39.2;
MS m/z 256 (M+). Anal. Calcd for C15H12O4: C, 70.31; H, 4.72.
Found: C, 69.52; H, 4.62.
35% ethyl acetate-hexane. 11e: mp >230 °C (sublimes); IR
(KBr) 1316, 1157, 1026 cm-1 1H NMR (200 MHz, CDCl3) δ
;
6.73 (2H, dd as t, J ) 3.5 Hz), 4.65 (2H, dd as t, J ) 3.5 Hz),
3.99-3.91 (4H, m), 3.87-3.73 (4H, m), 2.95 (2H, bs), 2.67 (2H,
bs), 2.26 (2H, bs), 1.63 (1H, 1/2 ABq, J ) 10.7 Hz), 1.42 (1H, 1/2
ABq, J ) 10.7 Hz); 13C NMR (50 MHz, CDCl3) δ 131.1, 112.5,
72.3, 66.6, 63.1, 50.9, 48.9, 44.1, 40.4, 36.0; MS m/z 344 (M+).
Anal. Calcd for C19H20O6: C, 66.27; H, 5.85. Found: C, 66.35;
H, 5.88.
P h otooxygen a tion of 9b. The reaction was performed as
described in the general procedure to furnish 20b (single
isomer) in 81% yield, and it was purified by column chroma-
tography over silica gel with 25% ethyl acetate-hexane as the
solvent system: mp 213 °C (DCM-hexane); IR (KBr) 1728,
1277, 737 cm-1; 1H NMR (200 MHz, CDCl3) δ 6.81 (2H, dd as
t, J ) 3.8 Hz), 4.95-4.88 (1H, m), 4.78-4.75 (1H, m), 3.71-
3.62 (1H, m), 3.47-3.39 (1H, m), 3.22-2.58 (8H, series of m),
2.11-2.01 (1H, m), 2.00 (1H, 1/2 ABq, J ) 12.4 Hz), 1.85-1.60
Further elution with 50% ethyl acetate-hexane furnished
the pure major isomer 10a , which was recrystallized from
DCM-hexane: mp 243 °C; IR (KBr) 1728, 1225, 1105 cm-1
;
)
1H NMR (200 MHz, CDCl3) δ 6.83 (2H, dd, J 1 ) 4.5 Hz, J 2
3.4 Hz), 4.94 (2H, dd, J 1 ) 4.4 Hz, J 2 ) 3.4 Hz), 2.94 (2H, bs),
2.86 (2H, bs), 2.73 (2H, bs), 2.03 (1H, 1/2 ABq, J ) 11.3 Hz),
1
1.82 (1H, /2 ABq, J ) 11.5 Hz); 13C NMR (50 MHz, CDCl3) δ
208.1, 131.4, 69.5, 55.4, 48.0, 43.6, 40.6, 40.4; MS m/z 256 (M+).
Anal. Cald for C15H12O4: C, 70.31; H, 4.72. Found: C, 70.22;
H, 4.75.
1
(1H, m), 1.77 (1H, /2 ABq, J ) 10.8 Hz); 13C NMR (50 MHz,
CDCl3) δ 210.2, 132.0, 131.2, 73.2, 71.0, 58.1, 57.9, 52.0, 51.1,
46.9, 44.4, 42.1, 38.9, 36.2, 28.6, 26.5, 24.8; MS m/z 346 (M+).
Anal. Calcd for C18H18O3S2: C, 62.40; H, 5.24. Found: C, 62.50;
H, 5.28.
P h otooxygen a tion of 4b. The reaction was performed as
described in the general procedure to furnish 10b:11b (14:86)
in 92% yield. The two stereoisomers were separated by column
chromatography using silica gel and elution with 35% ethyl
acetate-hexane. 10b: mp 133-134 °C (from DCM-hexane);
IR (KBr) 1744, 1319, 1051 cm-1; 1H NMR (200 MHz, CDCl3) δ
6.88-6.73 (2H, m), 4.98-4.91 (1H, m), 4.82-4.77 (1H, m),
4.18-3.90 (4H, m), 2.75-2.71 (1H, m), 2.63 (3H, bs), 2.51-
2.44(1H, m), 2.37-2.30 (1H, m), 1.83 (1H, 1/2 ABq, J ) 11.2
Hz), 1.50 (1H, 1/2 ABq, J ) 10.8 Hz); 13C NMR (50 MHz, CDCl3)
δ 210.9, 132.5, 131.1, 113.3, 70.9, 69.4, 66.4, 66.1, 55.6, 51.7,
48.1, 45.9, 43.4(2C), 42.1, 39.0, 38.7; MS m/z 300 (M+). Anal.
Calcd for C17H16O5: C, 67.99; H, 5.37. Found: C, 68.15; H,
5.40. 11b: mp 150-151 °C (DCM-hexane); IR (KBr) 1738,
1321, 1069 cm-1; 1H NMR (200 MHz, CDCl3) δ 6.83-6.75 (1H,
m), 6.67-6.59 (1H, m), 4.69 (2H, t, J ) 5.8 Hz), 3.96-3.77 (4H,
m), 3.35-3.25 (1H, m), 3.12-3.04 (1H, m), 2.88-2.83 (1H, m),
2.78-2.73 (1H, m), 2.61-2.53, (1H, m), 2.48-2.41 (1H, m), 1.93
[4 + 2]-Cycloa d d ition s w ith P TAD. Gen er a l P r oce-
d u r e. PTAD was prepared as follows: To a stirred suspension
of N-phenylurazole (0.5 mmol) in DCM cooled in an ice bath
(0-5 °C) was added a solution of “oxides of nitrogen” (usually
regarded as a mixture of N2O4, N2O3 and NO2)27 in DCM. This
was prepared according to the literature procedure26 by
treating arsenious oxide with concentrated HNO3, and the
resulting gaseous mixture was bubbled through
a DCM
solution cooled in an ice bath (0-5 °C). The reaction mixture
turned red and was stirred for additional 30 min to get a clear
homogeneous red solution of N-phenyl-1,2,4-triazoline-3,5-
dione (PTAD) in DCM, which was used for the cycloadditions.
To an ice-cooled solution of diene (0.35 mmol) in DCM (10
mL) was slowly added, dropwise, a solution of PTAD (0.40
mmol) in DCM (5 mL). The solution was stirred at 0-5 °C for
1 h until the red color had disappeared and completion of the
reaction was monitored by TLC analysis. DCM was removed
at room temperature under reduced pressure to give a solid
residue, which was analyzed using 1H NMR spectroscopy to
determine the product ratios.
(1H, 1/2 ABq, J ) 10.9 Hz), 1.79 (1H, 1/2 ABq, J ) 11.3 Hz); 13
C
NMR (50 MHz, CDCl3) δ 211.2, 131.0, 130.9, 111.4, 71.8, 71.1,
65.8, 65.1, 54.8, 52.9, 51.5, 50.9, 43.9, 42.3, 42.1, 40.1, 36.9.
MS m/z 300 (M+). Anal. Calcd for C17H16O5: C, 67.99; H, 5.37.
Found: C, 67.85; H, 5.35.
P h otooxygen a tion of 4c. The reaction was performed as
described in the general procedure to furnish 11c (single
isomer) in 98% yield and was purified by column chromatog-
raphy over silica gel with 30% ethyl acetate-hexane as the
solvent system. 11c: mp 222-223 °C (DCM-hexane); IR (KBr)
P TAD Ad d ition to 4c. The reaction was performed as
described in the general procedure to furnish 13c (single
isomer) in 85% yield and was purified by column chromatog-
raphy over silica gel with 25% ethyl acetate-hexane as the
solvent system. 13c: mp 240 °C (DCM-hexane); IR (KBr)
1744, 1325, 1121, 1032 cm-1 1H NMR (200 MHz, CDCl3) δ
;
1750, 1715, 1399, 1125 cm-1 1H NMR (200 MHz, CDCl3) δ
;
6.69 (2H, t, J ) 3.7 Hz), 4.84-4.79 (1H, m), 4.68-4.65 (1H,
m), 3.59 (1H, d, J ) 11.4 Hz), 3.49-3.23 (5H, m), 3.06-2.98
7.47-7.38 (5H, m), 6.53 (2H, t, J ) 4.0 Hz), 5.26 (1H, t, J ) 4
Hz), 5.03 (1H, t, J ) 4 Hz), 3.64 (1H, d, J ) 11.2 Hz), 3.53-
3.30 (4H, m), 3.27-3.20 (1H, m), 3.03-2.97 (1H, m), 2.83-
1
(1H, m), 2.78-2.71 (2H, m), 2.40-2.32 (1H, m), 1.90 (1H, /2
1
1
ABq, J ) 11.2 Hz), 1.76 (1H, /2 ABq, J ) 10.9 Hz), 1.06 (3H,
2.72 (2H, m), 2.49-2.42 (1H, m), 1.94 (1H, /2 ABq, J ) 12.8
s), 0.69 (3H, s); 13C NMR (50 MHz, CDCl3) δ 210.6, 132.0,
129.5, 101.4, 72.9, 71.8, 71.2, 71.0, 54.6, 50.2, 48.0, 44.0, 42.0,
41.9, 39.8, 36.9, 29.8, 22.8, 21.7. Anal. Calcd for C20H22O5: C,
70.16; H, 6.48. Found: C, 70.20; H, 6.50.
Hz), 1.75 (1H, 1/2 ABq, J ) 10.9 Hz), 1.10 (3H, s), 0.73 (3H, s);
13C NMR (50 MHz, CDCl3) δ 209.1, 156.2(2C), 131.5, 130.4,
129.1(2C), 128.2, 127.8, 125.6 (2C), 101.5, 73.0, 71.1, 56.1, 51.7,
51.5, 51.0, 50.2, 47.9, 44.3, 42.8, 42.0, 39.7, 37.7, 29.8, 22.9,
21.7. Anal. Calcd for C28H27N3O5: C, 69.26; H, 5.61; N, 8.65.
Found: C, 69.31; H, 5.59; N, 8.70.
P h otooxygen a tion of 4d . The reaction was performed as
described in the general procedure to furnish 4d (single isomer)
in 70% yield (based on starting material recovery) and was
purified by column chromatography over silica gel with 25%
ethyl acetate-hexane as the solvent system. 4d : mp 151 °C
(DCM-hexane); IR (KBr) 1738, 1121, 1059 cm-1; 1H NMR (200
MHz, CDCl3) δ 6.78-6.64 (2H, m), 4.83 (1H, d, J ) 5.7 Hz),
4.66 (1H, d with st, J ) 5.7 Hz), 3.26 (4H, bs), 3.16 (3H, s),
3.08-3.00 (1H, m), 2.87-2.69 (3H, m), 2.41-2.33 (1H, m), 1.89
P TAD Ad d ition to 9a a n d 9b. The reaction was performed
as described in the general procedure to furnish 12a :13a
(9:91) in 75% overall yield in the case of 9a and (11:89) in 80%
overall yield for 9b. Addition of PTAD accompanied by
concomitant dethioacetalization furnished 12a and 13a , which
were separated by column chromatography using neutral
alumina and elution with 70% ethyl acetate-chloroform. The
two products 12a and 13a were found to be identical with the
products obtained from PTAD addition to 4a .17a
(1H, 1/2 ABq, J ) 10.8 Hz), 1.75 (1H, 1/2 ABq, J ) 11.3 Hz); 13
C
NMR (50 MHz, CDCl3) δ 210.6, 130.8, 130.5, 105.2, 72.8, 70.9,
55.6, 53.8, 52.4, 50.9, 50.5, 49.5, 44.1, 42.9, 42.0, 39.8, 36.7.
Anal. Calcd for C17H18O5: C, 67.54; H, 6.00. Found: C, 67.58;
H, 6.02.
[4 + 2]-Cycloa d d ition s w ith DMAD. Gen er a l P r oce-
d u r e. A solution of diene (0.30 mmol) and DMAD (0.31 mmol)
P h otooxygen a tion of 4e. The reaction was performed as
described in the general procedure to furnish 10e:11e (3:97)
in 91% yield. The major diastereomer 11e was separated
by column chromatography using silica gel and elution with
(26) Dox, A. W. Organic Synthesis; Wiley: New York, 1941; Collect.
Vol. 1, p 266.
(27) Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; J ohn-
Wiley: New York, 1967; p 737.

Role of Heteroatoms in Diastereofacial Control
J . Org. Chem., Vol. 65, No. 6, 2000 1693
in dry benzene was refluxed for 12-18 h. Benzene was
removed under vacuum to give a diastereomeric mixture of
adducts. The product ratios were determined by 1H NMR
analyses of the crude reaction mixture by comparing the
integrations of appropriate protons.
38.7, 37.8. Anal. Calcd for C23H24O7: C, 66.98; H, 5.87.
Found: C, 67.05; H, 5.90.
DMAD Ad d ition to 4e. The reaction was performed as
described in the general procedure to furnish 14e:15e (18:82)
in 83% yield. The diastereomers were separated by column
chromatography using silica gel and elution with 40% ethyl
acetate-hexane. 14e: mp 247 °C (darkens), 253 °C (melts);
DMAD Ad d ition to 4b. The reaction was performed as
described in the general procedure to furnish 14b:15b (17:83)
in 91% yield. The diastereomers were separated by column
chromatography using silica gel and elution with 35% ethyl
acetate-hexane. 14b: mp 184 °C; IR (KBr) 1742, 1711, 1437,
IR (KBr) 1728, 1437, 1254, 1063 cm-1 1H NMR (200 MHz,
;
CDCl3) δ 6.63 (2H, t, J ) 4 Hz), 4.07-3.81 (10H, series of m),
3.74 (6H, s), 2.53 (2H, bs), 2.14 (2H, bs), 2.07 (2H, bs), 1.51
(1H, 1/2 ABq, J ) 10.8 Hz), 1.19 (1H, 1/2 ABq, J ) 10.7 Hz); 13
C
1
1265, 1065 cm-1; H NMR (200 MHz, CDCl3) δ 6.63 (2H, t, J
NMR (50 MHz, CDCl3) δ 166.5, 143.7, 135.7, 113.8, 66.9, 63.4,
56.8, 51.9, 48.4, 44.1, 41.6, 40.5, 35.7. Anal. Calcd for
C25H26O8: C, 66.07; H, 5.77. Found: C, 66.14; H, 5.80. 15e:
) 2.7 Hz), 4.10-3.90 (6H, m), 3.82 (3H, s), 3.69 (3H, s), 2.75-
2.14 (6H, series of multiplets), 1.78 (1H, 1/2 ABq, J ) 10.9 Hz),
1
1.55 (1H, /2 ABq, J ) 10.9 Hz); 13C NMR (50 MHz, CDCl3) δ
mp 192-193 °C; IR (KBr) 1721, 1645, 1260, 1073 cm-1 1H
;
212.7, 166.3, 166.1, 143.2, 142.5, 135.2, 135.0, 112.4, 66.1, 64.9,
59.0, 56.1, 53.1, 52.2, 51.9, 50.8, 44.0, 43.0, 42.2, 40.2, 39.6,
39.3, 38.2. Anal. Calcd for C23H22O7: C, 67.31; H, 5.40.
Found: C, 67.45; H, 5.40. 15b: mp 159 °C; IR (KBr) 1738,
NMR (200 MHz, CDCl3) δ 6.53 (2H, t, J ) 3.2 Hz), 4.03-3.83
(10H, series of m), 3.80 (6H, s), 2.55 (2H, bs), 2.19 (4H, bs),
1.51 (1H, 1/2 ABq, J ) 11.0 Hz), 1.22 (1H, 1/2 ABq, J ) 11.1
Hz); 13C NMR (50 MHz, CDCl3) δ 166.6, 144.3, 133.3, 114.1,
66.7, 63.1, 55.8, 52.2, 48.7, 44.1, 41.7, 40.3, 35.7. Anal. Calcd
for C25H26O8: C, 66.07; H, 5.77. Found: C, 66.00; H, 5.79.
DMAD Ad d ition to 9a . The reaction was performed as
described in the general procedure to furnish 24a (single
isomer) in 93% yield and was purified by column chromatog-
raphy over silica gel with 20% ethyl acetate-hexane as the
solvent system. 24a : mp 139 °C (DCM-hexane); IR (KBr)
1736, 1709, 1333, 1254, 1057 cm-1; 1H NMR (200 MHz, CDCl3)
δ 6.56 (2H, t, J ) 3.6 Hz), 4.39 (1H, dd, J 1 ) 4.6 Hz, J 2 ) 3.1
Hz), 4.02 (1H, dd, J 1 ) 4.6 Hz, J 2 ) 3.1 Hz), 3.84 (3H, s), 3.81
(3H, s), 3.32-3.15 (4H, m), 3.06-2.97 (1H, m), 2.92-2.86(1H,
1
1262, 1076 cm-1; H NMR (200 MHz, CDCl3) δ 6.52 (1H, t, J
) 6.4 Hz), 6.32 (1H, t, J ) 6.4 Hz), 3.98-3.72 (6H, m), 3.77
(3H, s), 3.75 (3H, s), 2.68-2.25 (6H, series of multiplets), 1.75
(1H, 1/2 ABq, J ) 10.8 Hz), 1.54 (1H, 1/2 ABq, J ) 10.8 Hz); 13
C
NMR (50 MHz, CDCl3) δ 212.7, 166.4, 166.2, 143.7, 143.1,
133.2, 132.6, 113.0, 65.8, 65.1, 58.3, 55.5, 53.9, 52.3(2C), 50.9,
43.7, 43.1, 42.1, 40.1, 39.7, 39.0, 38.0. Anal. Calcd for
C
23H22O7: C, 67.31; H, 5.40. Found: C, 67.35; H, 5.40.
DMAD Ad d ition to 4c. The reaction was performed as
described in the general procedure to furnish 14c:15c (5:95)
in 92% yield. The diastereomers were separated by column
chromatography using silica gel and elution with 30% ethyl
acetate-hexane. 14c: mp 190-191 °C; IR (KBr) 1748, 1709,
1281, 1119 cm-1; 1H NMR (200 MHz, CDCl3) δ 6.70-6.59 (2H,
m), 4.34 (1H, d, J ) 4.5 Hz), 3.94 (1H, d, J ) 4.5 Hz), 3.80
(3H, s), 3.69 (3H, s), 3.67 (1H, d, J ) 9.3 Hz), 3.43-3.31 (4H,
1
m), 2.70-2.45 (3H, m), 2.31-2.24 (1H, m), 1.86 (1H, /2 ABq,
J ) 10.9 Hz), 1.58 (1H, 1/2 ABq, J ) 10.5 Hz); 13C NMR (50
MHz, CDCl3) δ 213.7, 166.4, 166.3, 144.6, 143.3, 135.6, 131.7,
64.2, 64.0, 57.9, 52.9, 52.4 (2C), 47.0, 45.9, 43.5, 42.4, 39.8,
39.3 (2C), 38.9, 37.5; MS m/z 442 (M+). Anal. Calcd for
m), 2.62-2.57 (2H, m), 2.45 (1H, t, J ) 6 Hz), 2.33 (1H, dd, J 1
C
23H22O5S2: C, 62.42; H, 5.01. Found: C, 62.52; H, 5.05.
1
) 10 Hz, J 2 ) 2 Hz), 2.12 (1H, t, J ) 6.5 Hz), 1.77 (1H,
/
2
DMAD Ad d ition to 9b. The reaction was performed as
1
ABq, J ) 10.8 Hz), 1.52 (1H, /2 ABq, J ) 10.9 Hz), 1.05 (3H,
s), 0.70 (3H, s); 13C NMR (50 MHz, CDCl3) δ 211.2, 166.7,
165.5, 144.2, 142.1, 135.9, 135.2, 102.8, 73.2, 70.8, 60.7, 54.8,
52.1, 51.7, 49.6, 46.6, 43.8, 43.3, 42.0, 39.7, 39.3, 39.1, 38.4,
29.5, 23.4, 22.5. Anal. Calcd for C26H28O7: C, 69.01; H, 6.24.
Found: C, 69.12; H, 6.28. 15c: mp 181-182 °C; IR (KBr) 1730,
described in the general procedure to furnish 24b (single
isomer) in 91% yield and was purified by column chromatog-
raphy over silica gel with 15% ethyl acetate-hexane as the
solvent system. 24b: mp 204-205 °C (DCM-hexane); IR
(KBr) 1736, 1717, 1337, 1254, 1057 cm-1; 1H NMR (200 MHz,
CDCl3) δ 6.61-6.56 (2H, m), 4.35 (1H, dd, J 1 ) 5.0 Hz, J 2
)
1709, 1260, 1082 cm-1; H NMR (200 MHz, CDCl3) δ 6.51-
1
1.8 Hz), 4.05 (1H, dd, J 1 ) 5.1 Hz, J 2 ) 2.2 Hz), 3.81 (3H, s),
3.78 (3H, s), 3.61-3.52 (1H, m), 3.18-2.50 (8H, series of
multiplets), 2.27-2.19 (1H, m), 2.11-2.01 (1H, m), 1.88-1.73
6.41 (2H, m), 4.20 (1H, dd, J 1 ) 4.0 Hz, J 2 ) 2.0 Hz), 3.98-
3.94 (1H, m), 3.79 (3H, s), 3.77 (3H, s), 3.61 (1H, d, J ) 11.2
Hz), 3.44-3.36 (4H, m), 2.61-2.53 (3H, m), 2.34-2.27 (2H,
1
1
(1H, m), 1.85 (1H,
/ ABq, J ) 11.4 Hz), 1.56 (1H, / ABq,
2 2
1
1
m), 1.76 (1H,
/ ABq, J ) 11.1 Hz), 1.55 (1H, / ABq, J )
2 2
J ) 11.3 Hz); 13C NMR (50 MHz, CDCl3) δ 211.7, 166.4, 166.0,
144.8, 142.3, 134.8, 133.1, 63.7, 60.9, 57.3, 55.8, 52.4 (2C), 51.5,
47.1, 45.7, 42.0 (2C), 38.9, 38.7, 37.5, 29.0, 26.6, 25.0; MS m/z
456 (M+). Anal. Calcd for C24H24O5S2: C, 63.13; H, 5.30.
Found: C, 63.10; H, 5.29.
10.8 Hz), 1.12 (3H, s), 0.70 (3H, s); 13C NMR (50 MHz, CDCl3)
δ 212.1, 166.4(2C), 143.8, 143.7, 134.0, 131.7, 102.8, 72.9, 71.0,
60.1, 54.8, 52.2(2C), 49.9, 47.1, 43.8, 43.1, 41.9, 40.0, 39.4, 38.9,
38.0, 29.8, 22.9, 21.7. Anal. Calcd for C26H28O7: C, 69.01; H,
6.24. Found: C, 69.00; H, 6.28.
[4 + 2]-Cycloa d d ition s w ith MA. Gen er a l P r oced u r e.
A solution of diene (0.40 mmol) and MA (0.41 mmol) in dry
benzene was refluxed for 12-18 h. Benzene was removed
under vacuum to give a single diastereomer and was further
confirmed by analyzing the 1H NMR of crude reaction mixture.
MA Ad d ition to 4b. The reaction was performed as
described in the general procedure to furnish 16b (single
isomer) in near quantitative yield, and the crude adduct was
directly crystallized from DCM-hexane. 16b: mp 279-280
°C; IR (KBr) 1860, 1834, 1779,1736, 1229, 1078 cm-1; 1H NMR
(200 MHz, CDCl3) δ 6.55-6.41 (2H, m), 4.09-3.92 (4H, m),
3.62 (1H, dd, J 1 ) 4.4 Hz, J 2 ) 2.9 Hz), 3.50 (1H, dd, J 1 ) 8.8
Hz, J 2 ) 3.3 Hz), 3.42-3.37 (1H, m), 3.32-3.27 (1H, m), 2.70-
2.59 (3H, m), 2.53-2.44 (2H, m), 2.31-2.23 (1H, m), 1.80 (1H,
DMAD Ad d ition to 4d . The reaction was performed as
described in the general procedure to furnish 14d :15d (4:96)
in 75% yield. The diastereomers were separated by column
chromatography using silica gel and elution with 30% ethyl
acetate-hexane. 14d : mp 134 °C; IR (KBr) 1742, 1707, 1282,
1123, 1059 cm-1; 1H NMR (200 MHz, CDCl3) δ 6.68-6.58 (2H,
m), 4.26-4.23 (1H, m), 3.98-3.94 (1H, m), 3.81 (3H, s), 3.72
(3H, s), 3.44 (3H, s), 3.17 (3H, s), 2.78-2.69 (2H, m), 2.58-
2.53 (1H, m), 2.47-2.39 (1H, m), 2.32-2.25 (1H, m), 2.13-
1
2.04 (1H, m), 1.75 (1H,
/ ABq, J ) 10.9 Hz), 1.52 (1H,
2
1/2 ABq, J ) 11.3 Hz); 13C NMR (50 MHz, CDCl3) δ 211.5, 166.3
(2C), 143.3, 142.5, 135.7, 135.0, 106.2, 62.0, 55.5, 53.1, 52.3,
52.1, 51.9, 50.8, 50.2, 44.7, 44.0, 42.0, 41.0, 39.24, 39.18, 38.1.
Anal. Calcd for C23H24O7: C, 66.98; H, 5.87. Found: C, 67.00;
H, 5.90. 15d : mp 119-120 °C; IR (KBr) 1736, 1271, 1123, 1074
1
1
/
ABq, J ) 11.1 Hz), 1.52 (1H, /
ABq, J ) 11.1 Hz); 13C
2
2
NMR (50 MHz, CDCl3) δ 212.5, 173.2, 172.6, 134.0, 132.6,
113.1, 65.4, 64.9, 54.2, 51.7, 51.5, 49.3, 44.3, 43.5, 42.0, 40.8,
40.3, 39.8, 39.0, 32.8, 32.4. Anal. Calcd for C21H18O6: C, 68.85;
H, 4.95. Found: C, 68.90; H, 4.98.
MA Ad d ition to 4c. The reaction was performed as
described in the general procedure to furnish 16c (single
isomer) in near quantitative yield, and the crude adduct was
directly crystallized from DCM-hexane. 16c: mp 251 °C; IR
cm-1; H NMR (200 MHz, CDCl3) δ 6.49-6.34 (2H, m), 4.13
1
(1H, d, J ) 5.8 Hz), 3.89 (1H, d, J ) 5.8 Hz), 3.76 (3H, s), 3.74
(3H, s), 3.37 (3H, s), 3.10 (3H, s), 2.71-2.65 (2H, m), 2.53-
1
2.47 (2H, m), 2.27-2.17 (2H, m), 1.71 (1H, /2 ABq, J ) 10.8
Hz), 1.51 (1H, 1/2 ABq, J ) 11.1 Hz); 13C NMR (50 MHz, CDCl3)
δ 211.7, 166.4, 166.1, 144.8, 142.2, 133.3, 131.8, 106.4, 60.4,
54.7, 52.9, 52.4, 52.2 (2C), 50.3(2C), 44.0(2C), 41.7, 40.9, 39.4,

1694 J . Org. Chem., Vol. 65, No. 6, 2000
Mehta and Uma
1
(KBr) 1860, 1836, 1777,1738, 1227, 1086 cm-1; H NMR (200
MHz, CDCl3) δ 6.55-6.40 (2H, m), 3.95 (1H, dd, J 1 ) 8.8 Hz,
J 2 ) 3.7 Hz), 3.70 (1H, d, J ) 11.6 Hz), 3.60-3.39 (6H, m),
3.32-3.26 (1H, m), 2.66-2.58 (2H, m), 2.50-2.39 (2H, m),
3.65-3.60 (1H, m), 3.43-3.25 (6H, m), 3.09-3.03 (1H, m), 2.88
(3H, s), 2.80-2.75 (1H, m), 2.62-2.48 (3H, m), 2.20-2.13 (1H,
1
1
m), 1.84 (1H,
/ ABq, J ) 11.3 Hz), 1.46 (1H, / ABq, J )
2 2
11.1 Hz); 13C NMR (50 MHz, CDCl3) δ 214.3, 178.9, 178.5,
133.7, 132.3, 75.2, 66.0, 57.7, 53.9, 53.1, 47.0, 46.4, 42.3, 41.4,
40.5, 39.7, 38.9, 38.5, 38.3, 36.2, 32.4, 24.5. Anal. Calcd for
C22H21NO3S2: C, 64.20; H, 5.14; N, 3.40. Found: C, 64.25; H,
5.12; N, 3.98.
1
2.27-2.19 (1H, m), 1.80 (1H, /2 ABq, J ) 11.2 Hz), 1.51 (1H,
1/2 ABq, J ) 10.8 Hz), 1.18 (3H, s), 0.77 (3H, s); 13C NMR (50
MHz, CDCl3) δ 211.7, 173.2, 172.9, 134.2, 132.5, 103.6, 73.6,
70.9, 54.1, 50.2, 48.5, 48.3, 44.3, 43.6, 41.9, 40.8, 40.5, 39.7,
38.7, 32.5, 32.4, 29.9, 23.7, 21.9. Anal. Calcd for C24H24O6: C,
70.58; H, 5.92. Found: C, 70.65; H, 5.95.
NMM Ad d ition to 9b. The reaction was performed as
described in the general procedure to furnish 27b (single
isomer) in near quantitative yield, and the crude adduct was
directly crystallized from DCM-hexane. 27b: mp >280 °C;
MA Ad d ition to 4d . The reaction was performed as
described in the general procedure to furnish 16d (single
isomer) in near quantitative yield, and the crude adduct was
directly crystallized from DCM-hexane. 16d : mp 241-242
°C; IR (KBr) 1856, 1833, 1771, 1738, 1231, 1086 cm-1; 1H NMR
(200 MHz, CDCl3) δ 6.45-6.41 (2H, m), 3.81 (1H, dd, J 1 ) 8.8
Hz, J 2 ) 3.1 Hz), 3.55-3.47 (2H, m), 3.46 (3H, s), 3.31 (3H, s),
3.26-3.21 (1H, m), 2.93-2.85 (1H, m), 2.77-2.72 (1H, m),
2.60-2.55 (1H, m), 2.48-2.36 (2H, m), 2.22-2.16 (1H, m), 1.77
IR (KBr) 1775, 1725, 1696, 1279 cm-1 1H NMR (200 MHz,
;
CDCl3) δ 6.41-6.28 (2H, m), 4.03-3.96 (1H, m), 3.73-3.58 (2H,
m), 3.32-3.28 (1H, m), 3.24-2.99 (4H, series of multiplets),
2.89 (3H, s), 2.80-2.53 (5H, series of multiplets), 2.18-2.05
1
(2H, m), 1.96-1.81 (1H, m), 1.86 (1H, /2 ABq, J ) 10.5 Hz),
1
1.48 (1H, /2 ABq, J ) 10.8 Hz); 13C NMR (50 MHz, CDCl3) δ
211.1, 178.5, 178.4, 133.5, 132.3, 59.8, 59.0, 57.5, 52.3, 51.3,
47.3, 46.0, 42.2, 40.5, 40.0, 39.4, 37.6, 35.2, 32.0, 28.9, 26.4,
24.8, 24.6; MS m/z 425 (M+). Anal. Calcd for C23H23NO3S2: C,
64.91; H, 5.45; N, 3.29. Found: C, 65.00; H, 5.46; N, 3.29.
Hyd r olysis of Eth ylen e Aceta l of 11e; Con ver sion of
11e to 11b. A mixture of bis-acetal 11e (30 mg, 0.09 mmol)
and CSA (catalytic, 2 mg) in moist acetone (2 mL) was stirred
at room temperature for 30 min. Acetone was removed under
vacuum to furnish a residue which was charged on a silica
gel column. Elution with 30% ethyl acetate-hexane furnished
mono-acetal 11b (25 mg, 95%). This was found to be identical
(1H, 1/2 ABq, J ) 11.3 Hz), 1.49 (1H, 1/2 ABq, J ) 11.1 Hz); 13
C
NMR (50 MHz, CDCl3) δ 211.9, 173.2, 172.6, 133.7, 132.7,
107.3, 56.0, 53.7, 53.4, 50.9, 50.6, 49.4, 45.1, 44.2, 41.8, 41.1,
40.5, 39.4, 38.7, 33.8, 32.1. Anal. Calcd for C21H20O6: C, 68.47;
H, 5.47. Found: C, 68.55; H, 5.42.
MA Ad d ition to 4e. The reaction was performed as
described in the general procedure to furnish 16e (single
isomer) in near quantitative yield, and the crude adduct was
directly crystallized from DCM-hexane. 16e: mp 268 °C; IR
(KBr) 1860, 1834, 1775, 1236, 1074 cm-1; 1H NMR (200 MHz,
CDCl3) δ 6.48-6.42 (2H, m), 4.09-3.89 (8H, m), 3.77 (2H, bs),
3.35 (2H, bs), 2.51 (2H, bs), 2.28 (2H, bs), 2.12 (2H, bs), 1.51
1
(mp, IR, and H NMR) to the sample 11b derived from mono-
acetal 4b.
(1H, 1/2 ABq, J ) 10.8 Hz), 1.14 (1H, 1/2 ABq, J ) 10.7 Hz); 13
NMR (50 MHz, CDCl3) δ 173.8, 133.6, 114.5, 66.6, 63.2, 49.4,
48.9, 43.8, 43.0, 41.0, 34.8, 33.3. Anal. Calcd for C23H22O7: C,
67.31; H, 5.40. Found: C, 67.25; H, 5.42.
C
Hyd r olysis of Dim eth yl Aceta l of 11d ; Con ver sion of
11d to 11a . A mixture of mono-acetal 11d (25 mg, 0.08 mmol)
and Amberlyst-15 (10 mg) in moist acetone (2 mL) was stirred
at room temperature for 15 min. Amberlyst resin was filtered
and the solvent was removed under vacuum to furnish a
residue which was charged on a silica gel column. Elution with
chloroform furnished dione 11a (20 mg, 94%). This was found
to be identical (mp, IR, and 1H NMR) to the sample 11a
derived from dione 4a .
MA Ad d ition to 9a . The reaction was performed as
described in the general procedure to furnish 25a (single
isomer) in near quantitative yield, and the crude adduct was
directly crystallized from DCM-hexane. 25a : mp > 280 °C;
IR (KBr) 1860, 1777, 1725, 1225, 1084 cm-1 1H NMR (200
;
MHz, CDCl3) δ 6.62-6.45 (2H, m), 4.21 (1H, dd, J 1 ) 8.8 Hz,
J 2 ) 3.9 Hz), 3.72-3.63 (2H, m), 3.43-3.27 (5H, m), 3.13-
3.06 (1H, m), 2.83-2.78 (1H, m), 2.66-2.52 (3H, m), 2.24-
Aceta liza tion of 14a ; Con ver sion of 14a to 14b a n d 14e.
A mixture of dione 14a (60 mg, 0.16 mmol), ethylene glycol
(0.03 mL, 0.49 mmol), PTSA (3 mg), and benzene (20 mL) was
refluxed for 12 h with a Dean-Stark water separator. The
reaction was cooled and quenched by adding saturated NaH-
CO3 solution (2 mL) and extracted with ethyl acetate (3 × 5
mL). The combined organic extract was washed and dried.
Removal of solvent furnished a mixture of acetals, which were
separated by column chromatography using silica gel. Elution
with 40% ethyl acetate-hexane first furnished mono-acetal
14b (30 mg, 45%), and on further elution pure bis-acetal 14e
(26 mg, 35%) was obtained. Both 14b and 14e were found to
1
1
2.17 (1H, m), 1.87 (1H,
/ ABq, J ) 11.5 Hz), 1.49 (1H, /
2 2
ABq, J ) 11.7 Hz); 13C NMR (50 MHz, CDCl3) δ 213.9, 172.9,
172.3, 134.9, 133.0, 75.0, 66.1, 56.9, 53.7, 52.5, 47.0, 46.4, 42.3,
41.4(2C), 40.4, 38.9, 38.6, 38.3, 36.1, 32.4; MS m/z 398 (M+).
Anal. Calcd for C21H18O4S2: C, 63.29; H, 4.55. Found: C, 63.35;
H, 4.58.
MA Ad d ition to 9b. The reaction was performed as
described in the general procedure to furnish 25b (single
isomer) in near quantitative yield, and the crude adduct was
directly crystallized from DCM-hexane. 25b: mp >280 °C;
1
be identical (mp, IR, and H NMR) to the sample derived from
mono-acetal 4b and bis-acetal 4e, respectively.
IR (KBr) 1838, 1775, 1721, 1231, 1096 cm-1
;
1H NMR (200
MHz, CDCl3) δ 6.58-6.45 (2H, m), 4.30 (1H, dd, J 1 ) 8.8 Hz,
J 2 ) 3.7 Hz), 3.73-3.62 (2H, m), 3.49 (1H, dd, J 1 ) 8.8 Hz, J 2
) 2.9 Hz), 3.40-3.35 (1H, m), 3.19-3.00 (3H, m), 2.84-2.57
Aceta liza tion of 14a ; Con ver sion of 14a to 14c. A
mixture of dione 14a (30 mg, 0.08 mmol), 2,2-dimethylpropane-
1,3-diol (25 mg, 0.24 mmol), PTSA (3 mg), and benzene (10
mL) was refluxed for 12 h with a Dean-Stark water separator.
Usual workup and removal of solvent furnished a residue,
which was purified by column chromatography using silica gel.
Elution with 35% ethyl acetate-hexane furnished mono-acetal
14c (35 mg, 95%). This sample was found to be identical (mp,
1
(5H, m), 2.21-2.10 (2H, m), 1.98-1.76 (1H, m), 1.88 (1H, /2
1
ABq, J ) 11.1 Hz), 1.50 (1H, /2 ABq, J ) 11.0 Hz); 13C NMR
(50 MHz, CDCl3) δ 210.6, 172.4, 172.2, 134.6, 132.9, 59.5, 59.0,
56.9, 52.1, 50.7, 47.2, 46.1, 42.1, 41.5, 40.6, 39.4, 37.5, 35.0,
32.1, 28.9, 26.4, 24.7; MS m/z 412 (M+). Anal. Calcd for
1
C
22H20O4S2: C, 64.05; H, 4.89. Found: C, 64.10; H, 4.87.
IR, and H NMR) to the sample 14c derived from mono-acetal
[4 + 2]-Cycloa d d ition s w ith NMM. Gen er a l P r oced u r e.
4c.
A solution of diene (0.30 mmol) and NMM (0.31 mmol) in dry
benzene was refluxed for 12-18 h. Benzene was removed
under vacuum to give a single diastereomer (> 96%) and was
Hyd r olysis of Neop en tyl Aceta l of 15c; Con ver sion of
15c to 15a . To a stirred solution of NaI (25 mg, 0.17 mmol) in
dry acetonitrile (2 mL) was added successively trimethylchloro-
silane (0.02 mL, 0.16 mmol) and mono-acetal 15c (30 mg, 0.07
mmol) under a dry nitrogen atmosphere. Iodine color formation
appeared instantaneously. The reaction was stirred for 45 min
and then quenched with water and extracted with DCM (3 ×
10 mL), and the organic layer was washed successively with
aqueous sodium thiosulfate, water, and brine and was dried.
Removal of solvent and filtration through silica gel (elution
with 25% ethyl acetate-hexane) afforded the dione 15a (17
1
further confirmed by analyzing the H NMR of crude reaction
mixture.
NMM Ad d ition to 9a . The reaction was performed as
described in the general procedure to furnish 27a (single
isomer) in near quantitative yield, and the crude adduct was
directly crystallized from DCM-hexane. 27a : mp 280 °C; IR
(KBr) 1769, 1728, 1694, 1277 cm-1; 1H NMR (200 MHz, CDCl3)
δ 6.44-6.27 (2H, m), 3.86 (1H, dd, J 1 ) 7.9 Hz, J 2 ) 3.2 Hz),

Role of Heteroatoms in Diastereofacial Control
J . Org. Chem., Vol. 65, No. 6, 2000 1695
mg, 70%). This sample was found to be identical (mp, IR, and
Aceta liza tion of 16a ; Con ver sion of 16a to 16b. A
mixture of dione 16a (33 mg, 0.1 mmol), ethylene glycol (0.01
mL, 0.20 mmol), PPTS (3 mg), and benzene (10 mL)
was refluxed for 6 h with a Dean-Stark water separator.
Usual workup and removal of solvent furnished a residue,
which was purified by column chromatography using silica gel.
Elution with 40% ethyl acetate-hexane furnished mono-acetal
16b (30 mg, 80%). This sample was found to be identical (mp,
1H NMR) to the sample 15a derived from dione 4a .
Hyd r olysis of Dim eth yl Aceta l of 15d ; Con ver sion of
15d to 15a . A mixture of mono-acetal 15d (33 mg, 0.08 mmol)
and Amberlyst-15 (10 mg) in moist acetone (2 mL) was stirred
at room temperature for 30 min. Amberlyst resin was filtered
and the solvent was removed under vacuum to furnish a
residue, which was charged on a silica gel column. Elution with
25% ethyl acetate-hexane furnished dione 15a (28 mg, 95%).
1
IR, and H NMR) to the sample 16b derived from mono-acetal
4b.
1
This sample was found to be identical (mp, IR, and H NMR)
Aceta liza tion of 16a ; Con ver sion of 16a to 16c. A
mixture of dione 16a (20 mg, 0.06 mmol), 2,2-dimethylpropane-
1,3-diol (8 mg, 0.08 mmol), PTSA (3 mg), and benzene (10 mL)
was refluxed for 12 h with a Dean-Stark water separator.
Usual workup and removal of solvent furnished a residue,
which was purified by column chromatography using silica gel.
Elution with 35% ethyl acetate-hexane furnished mono-acetal
16c (23 mg, 91%). This sample was found to be identical (mp,
to the sample 15a derived from dione 4a .
Hyd r olysis of Eth ylen e Aceta l of 15e; Con ver sion of
15e to 15b. A mixture of bis-acetal 15e (35 mg, 0.08 mmol)
and Amberlyst-15 (10 mg) in moist acetone (3 mL) was stirred
at room temperature for 45 min. Amberlyst resin was filtered
and the solvent was removed under vacuum to furnish a
residue which was charged on a silica gel column. Elution with
30% ethyl acetate-hexane furnished mono-acetal 15b (30 mg,
95%). This sample was found to be identical (mp, IR, and 1H
NMR) to the sample 15b derived from mono-acetal 4b.
1
IR, and H NMR) to the sample 16c derived from mono-acetal
4c.
Hyd r olysis of Dim eth yl Aceta l of 16d ; Con ver sion of
16d to 16a . A mixture of mono-acetal 16d (30 mg, 0.08 mmol)
and Amberlyst-15 (10 mg) in moist acetone (3 mL) was stirred
at room temperature for 30 min. Amberlyst resin was filtered
and the solvent was removed under vacuum to furnish a
residue which was charged on a silica gel column. Elution with
40% ethyl acetate-hexane furnished dione 16a (25 mg, 96%).
Th ioa ceta liza tion of 15a ; Con ver sion of 15a to 24a . A
mixture of dione 15a (37 mg, 0.1 mmol), 1,2-ethanedithiol (0.02
mL, 0.2 mmol), PTSA (3 mg) in DCM (10 mL) was stirred for
4 h. Usual workup and removal of solvent furnished a residue,
which was purified by column chromatography using silica gel.
Elution with 20% ethyl acetate-hexane furnished mono-
thioacetal 24a (38 mg, 85%). This sample was found to be
identical (mp, IR, and 1H NMR) to the sample 24a derived
from mono-thioacetal 9a .
1
This sample was found to be identical (mp, IR, and H NMR)
to the sample 16a derived from dione 4a .
Hyd r olysis of Eth ylen e Aceta l of 16e; Con ver sion of
16e to 16b. A mixture of bis-acetal 16e (29 mg, 0.07 mmol)
and PTSA (catalytic, 2 mg) in moist acetone (2 mL) was stirred
at room temperature for 30 min. Acetone was removed under
vacuum to furnish a residue, which was charged on a silica
gel column. Elution with 40% ethyl acetate-hexane furnished
mono-acetal 16b (24 mg, 93%). This sample was found to be
identical (mp, IR, and 1H NMR) to the sample 16b derived
from mono-acetal 4b.
Th ioa ceta liza tion of 15a ; Con ver sion of 15a to 24b. A
mixture of dione 15a (37 mg, 0.1 mmol), 1,3-propanedithiol
(0.02 mL, 0.2 mmol), PTSA (3 mg), and benzene (10 mL) was
refluxed for 12 h with a Dean-Stark water separator. Usual
workup and removal of solvent furnished a residue, which was
purified by column chromatography using silica gel. Elution
with 30% ethyl acetate-hexane furnished mono-thioacetal
24b (41 mg, 90%). This sample was found to be identical (mp,
IR, and 1H NMR) to the sample 24b derived from mono-
thioacetal 9b.
Th ioa ceta liza tion of 16a ; Con ver sion of 16a to 25a . A
mixture of dione 16a (29 mg, 0.09 mmol), 1,2-ethanedithiol
(0.02 mL, 0.2 mmol), PTSA (3 mg), and benzene (10 mL) was
refluxed for 6 h with a Dean-Stark water separator. Usual
workup and removal of solvent furnished a residue, which was
purified by column chromatography using silica gel. Elution
with 30% ethyl acetate-hexane furnished mono-thioacetal 25a
(30 mg, 84%). This sample was found to be identical (mp, IR,
Deth ioa ceta liza tion of 24a ; Con ver sion of 24a to 15a .
[Bis(trifluroacetoxy)iodo]benzene (47 mg, 0.11 mmol) was
added at room temperature to a stirred solution of mono-
thioacetal 24a (30 mg, 0.07 mmol) in MeOH:H2O (10 mL, 9:1).
The mixture was stirred for an additional 10 min and
quenched with saturated solution of NaHCO3 and extracted
with DCM (3 × 5 mL). Removal of solvent and filtration
through silica gel pad (elution with 25% ethyl acetate-hexane)
furnished dione 15a (15 mg, 60%). This sample was found to
1
and H NMR) to the sample 25a derived from mono-thioacetal
9a .
Th ioa ceta liza tion of 16a ; Con ver sion of 16a to 25b. A
mixture of dione 16a (32 mg, 0.1 mmol), 1,3-propanedithiol
(0.02 mL, 0.2 mmol), PTSA (3 mg), and benzene (10 mL) was
refluxed for 6 h with a Dean-Stark water separator. Usual
workup and removal of solvent furnished a residue, which was
purified by column chromatography using silica gel. Elution
with 35% ethyl acetate-hexane furnished mono-thioacetal 25b
(37 mg, 90%). This sample was found to be identical (mp, IR,
1
be identical (mp, IR, and H NMR) to the sample 15a derived
from dione 4a .
Deth ioa ceta liza tion of 24b; Con ver sion of 24b to 15a .
To a stirred solution of the mono-thioacetal 24b (30 mg, 0.07
mmol) in DCM (10 mL), cooled in an ice bath (0-5 °C), was
added dropwise a solution of “nitrogen oxides” in DCM until
the pink color was discharged. After stirring for 5 min, the
reaction was quenched with ice-cold aqueous NaHCO3 and
extracted with DCM (3 × 5 mL). Removal of solvent and
filtration through silica gel pad (elution with 25% ethyl
acetate-hexane) furnished dione 15a (17 mg, 70%). This
sample was found to be identical (mp, IR, and 1H NMR) to
the sample 15a derived from dione 4a .
1
and H NMR) to the sample 25b derived from mono-thioacetal
9b.
Th ioa ceta liza tion of 29; Con ver sion of 29 to 27a . A
mixture of dione 29 (34 mg, 0.1 mmol), 1,2-ethanedithiol (0.02
mL, 0.2 mmol), PTSA (3 mg), and benzene (10 mL) was
refluxed for 6 h with a Dean-Stark water separator. Usual
workup and removal of solvent furnished a residue, which was
purified by column chromatography using silica gel. Elution
with 40% ethyl acetate-hexane furnished mono-thioacetal 27a
(38 mg, 90%). This sample was found to be identical (mp, IR,
Hyd r olysis of Neop en tyl Aceta l of 13c; Con ver sion of
13c to 13a . To a stirred solution of NaI (12 mg, 0.08 mmol)
in dry acetonitrile (2 mL) was added successively trimethyl-
chlorosilane (0.01 mL, 0.08 mmol) and mono-acetal 13c (15
mg, 0.03 mmol) under a dry nitrogen atmosphere. The reaction
was stirred for 45 min and then quenched with water and
extracted with DCM (3 × 10 mL), and the organic layer was
washed successively with aqueous sodium thiosulfate, water,
and brine and then dried. Removal of solvent and filtration
through neutral alumina (elution with 70% ethyl acetate-
chloroform) afforded the dione 13a (8 mg, 65%). This sample
1
and H NMR) to the sample 27a derived from mono-thioacetal
9a .
Th ioa ceta liza tion of 29; Con ver sion of 29 to 27b. A
mixture of dione 29 (34 mg, 0.1 mmol), 1,3-propanedithiol (0.02
mL, 0.2 mmol), PTSA (3 mg), and benzene (10 mL) was reflux-
ed for 6 h with a Dean-Stark water separator. Usual workup
and removal of solvent furnished a residue, which was purified
by column chromatography using silica gel. Elution with 40%
ethyl acetate-hexane furnished mono-thioacetal 27b (41 mg,
1
was found to be identical (mp, IR, and H NMR) to the sample
13a derived from dione 4a .

1696 J . Org. Chem., Vol. 65, No. 6, 2000
Mehta and Uma
95%). This sample was found to be identical (mp, IR, and 1H
NMR) to the sample 27b derived from mono-thioacetal 9b.
matrix least-squares on F2 with all non-H atoms anisotropic
and H atoms isotropic.29b
X-r a y cr ysta l str u ctu r e d a ta of 11e:
C19H20O6, Mr )
344.40, colorless crystals from DCM-hexane, orthorhombic,
Ack n ow led gm en t. G.M. thanks J NCASR for a
research grant and R.U. wishes to thank CSIR for a
research fellowship. We thank Dr. M. Nethaji of Indian
Institute of Science, Bangalore, for the X-ray crystal
structure determination.
space group P212121, a ) 8.889(2) Å, b ) 9.011(4) Å, c )
19.369(6) Å, V ) 1551.4(9) Å3, Z ) 4, Dcalcd ) 1.731 Mg m-3
,
T ) 293 °K, F(000) ) 848, µ(Mo KR) ) 0.125 mm-1. Data were
collected on Enraf-Nonius CAD-4 diffractometer, with graphite-
monochromated Mo-KR radiation (λ ) 0.71070 Å), by the ω/2θ
scan method in the range 2 e θ e 25°. At final convergence
R1 [I > 2σ(I)] ) 0.0517, wR2 ) 0.1491 for 306 parameters, GOF
) 1.393, ∆Fmax ) 0.293 e Å-3, ∆Fmin ) -0.252 e Å-3. The
structure was solved by direct methods,29a refined by full-
Su p p or tin g In for m a tion Ava ila ble: All the chemical
correlations in a schematic form and Crystallographic experi-
mental sections and tables of X-ray crystal data, bond lengths
and angles, final fractional coordinates, and thermal param-
eters for 11e. This material is available free of charge via the
Internet at http://pubs.acs.org.
(28) Mehta, G.; Uma, R. Tetrahedron Lett. 1996, 37, 1897.
(29) (a) Sheldrick, G. M. SHELX 86 program for the solution of
crystal structures; University of Go¨ttingen, Germany, 1986. (b) Shel-
drick, G. M. SHELX76, program for crystal structure determination,
University of Cambridge, England, 1976.
J O991349B