Synthesis and Diels-Alder reactions of 4-substituted-1,3-diphenoxy-2-[(tert-butyldimethylsilyl)oxy]-1,3-butadienes: Application to the synthesis of triaryl ethers

Article abstract of DOI:10.1021/jo960105d

A novel class of tetrahetero-substituted 1,3-dienes 1a-d having aryl ether substituents at the 1,3-positions were synthesized by enol silylation of 4-substituted 1,3-diphenoxy-3-buten-2-ones 3a-c. The 1Z,3Z configuration of 1b has been assigned by X-ray crystallography. The synthesis of triaryl ethers utilizing a Diels-Alder approach involved reaction of diene 1a with methyl acrylate to furnish a 3:1 mixture of endo- and exo-adducts. Conversion of the adducts to cyclohexenone 8 and aromatization with DDQ gave triaryl ether 9. Cycloaddition reactions of 1a, 1b with some conjugated alkenes exhibited excellent regiospecificity and endo stereoselectivity.

Full text of DOI:10.1021/jo960105d

5852
J . Org. Chem. 1996, 61, 5852-5856
Syn th esis a n d Diels-Ald er Rea ction s of 4-Su bstitu ted -
1,3-d ip h en oxy-2-[(ter t-bu tyld im eth ylsilyl)oxy]-1,3-bu ta d ien es:
Ap p lica tion to th e Syn th esis of Tr ia r yl Eth er s
Richard K. Olsen* and Rui-lian Shao
Department of Chemistry and Biochemistry, Utah State University, Logan, Utah 84322
Received J anuary 17, 1996X
A novel class of tetrahetero-substituted 1,3-dienes 1a -d having aryl ether substituents at the 1,3-
positions were synthesized by enol silylation of 4-substituted 1,3-diphenoxy-3-buten-2-ones 3a -c.
The 1Z,3Z configuration of 1b has been assigned by X-ray crystallography. The synthesis of triaryl
ethers utilizing a Diels-Alder approach involved reaction of diene 1a with methyl acrylate to furnish
a 3:1 mixture of endo- and exo-adducts. Conversion of the adducts to cyclohexenone 8 and
aromatization with DDQ gave triaryl ether 9. Cycloaddition reactions of 1a , 1b with some
conjugated alkenes exhibited excellent regiospecificity and endo stereoselectivity.
Sch em e 1
1,3-Dienes with hetero substituents have proven to be
versatile reactants for the synthesis of highly function-
alized ring systems via the Diels-Alder cycloaddition
reaction. In addition, the heteroatoms in the substituent
groups are known to impart enhanced reactivity, regio-
selectivity, and stereoselectivity to these dienes in the
cycloaddition.1 In preceding communications,2-4 we re-
ported the preparation of functionalized aryloxy 1,3-
dienes and their use in a Diels-Alder approach to diaryl
ethers related to isodityrosine. As a natural outgrowth
of these studies, we were stimulated to effect the syn-
thesis of a new class of diaryloxy 1,3-dienes that incor-
porate an additional oxygen substituent, which could lead
to the triarylether components in glycopeptides of van-
comycin.5 Although the preparation and cycloaddition
chemistry of dienes containing aryloxy and sulfur sub-
stituents have been examined in some detail,1b,4,6 dienes
containing four substituents have not, to the best of our
knowledge, received significant study. In this paper, we
describe a convenient synthesis of 4-substituted-1,3-
diphenoxy-2-[(tert-butyldimethylsilyl)oxy]-1,3-butadi-
ene (1), as also studies of their configuration and of the
stereochemistry of their Diels-Alder cycloaddition prod-
ucts. A Diels-Alder approach using these dienes for the
preparation of triaryl ethers is also described.
fide diene 1a could be oxidized with MCPBA to give the
corresponding 4-(butylsulfinyl)-1,3-butadiene 1d . These
new tetrahetero-substituted dienes appear to be stable
and could be kept for 2-3 months at -20 °C.
Each diene was obtained as only one stereoisomer, as
1
determined by their H NMR spectra, in which the proton
at C4 is seen in each case as a singlet. The sulfide dienes
1a and 1b are crystalline solids, (mp 1a 50 °C, 1b 66
°C), which are well suited for X-ray crystallography. The
X-ray analysis assigned diene 1b to be the 1Z,3Z config-
uration and to exist in the s-trans conformation in the
crystalline state.7
Enaminone 2 was readily converted into the corre-
sponding enone or thioenone 3a -c upon acid-catalyzed
exchange.4 The tetrahetero-substituted dienes 1a -c
were prepared by enol silylation of the enone or thioenone
with tert-butyldimethylsilyl triflate in ether containing
2.5 equiv of triethylamine. Of significance, in comparison
with the [(trimethylsilyl)oxy]-1,3-butadiene reported in
our preliminary work,4 these new dienes could be purified
on silica gel in excellent yield and exhibited higher
thermal stability during Diels-Alder cycloaddition. Sul-
Prior studies3,4 suggested that cycloaddition of tetra-
substituted dienes 1 with acetylenic dienophiles would
generate triaryl ethers and serve as a model for the
preparation of the triaryl ether unit present in vanco-
mycin.5 Reaction of diene 1a with methyl propiolate in
a sealed tube at 150 °C for 66 h gave, however, the diaryl
ether 4 in 81% yield resulting from the elimination of
butylmercaptan and one of the phenol groups, rather
than the desired triaryl ether 5.
Dienes 1c and 1d , having methoxy and sulfoxide
substituents at the 4 position, gave similar results with
no apparent triaryl ether product being formed. Varia-
tion in reaction conditions also did not result in triaryl
ether formation. Thus, double elimination is a favored
X Abstract published in Advance ACS Abstracts, August 1, 1996.
(1) For views, see: (a) Petrizilka, M.; Grayson, J . I. Synthesis 1981,
753. (b) Trost, B. M., Fleming, I., Eds. Comprehensive Organic
Synthesis; Pergamon Press: Oxford, 1991; Vol. 5 (Paquette, L., Ed.),
Chapter 4.1, pp 329-337.
(2) Olsen, R. K.; Feng, X. Tetrahedron Lett. 1991, 32, 5721.
(3) Feng, X.; Olsen, R. K. J . Org. Chem. 1992, 57, 5811.
(4) Olsen, R. K.; Feng, X.; Campbell, M.; Shao, R.-L.; Math, S. J .
Org. Chem. 1995, 60, 6025.
(5) Evans, D. A.; Ellman, J . A.; DeVries, K. M. J . Am. Chem. Soc.
1989, 111, 8912. Pearson, A. J .; Bignan, G. Tetrahedron Lett. 1996,
37, 735.
(6) Moreau, P.; Guillaumet, G.; Coudert, G. Tetrahedron 1994, 50,
3407.
(7) The authors have deposited atomic coordinates, bond lengths,
and angles for structure 1b with the Cambridge Crystallographic Data
Centre, the data for which can be obtained, upon request, from the
Director, Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, UK.
S0022-3263(96)00105-3 CCC: $12.00 © 1996 American Chemical Society

Diels-Alder Reaction of 1,3-Diphenoxy 1,3-Butadienes
J . Org. Chem., Vol. 61, No. 17, 1996 5853
Sch em e 2
Sch em e 4
adducts,8 since H4 tends toward eclipsing H5 when these
hydrogens are cis. The pseudoequatorial C5 methine
hydrogen of the endo stereoisomers 6 was observed as a
doublet of doublet of doublets and occurred further
downfield than in the corresponding exo-stereoisomer.8
This downfield shift of the pseudoequatorial H5 has been
observed in other 4,5-disubstituted 2-cyclohexenes.9,10
Transformation of cycloadducts 6a , 7a to an aromatic
ring was performed by a oxidation:dehydrogenation
procedure using reagents such as peroxycarboxylic acids
and dichlorodicyanoquinone (DDQ). However, the yields
of products varied greatly, and the elimination of a
phenoxy group was frequently a problem. For example,
oxidation of a mixture of cycladducts 6a , 7a with MCPBA
at -78 °C, followed by aromatization with DDQ gave
diaryl ether 4 and triaryl ether 5 in yields of 62% and
13%, respectively.
The synthesis of the target triaryl ether 9 in acceptable
yield finally was achieved with the transformation of the
cyclohexene adducts to the R,â-unsaturated ketone 8
followed by dehydrogenation with DDQ. Deprotection of
6a , 7a with n-Bu4NF effected removal of the silyl ether,
ketolization, and elimination of the alkyl mercaptan to
give 8 in 86% yield. Treatment of 8 with DDQ at reflux
in dioxane afforded the triaryl ether 9 in 60% yield.
The thermal cycloaddition of diene 1a or 1b with
maleic anhydride and N-phenylmaleimide also was stud-
ied. Maleic anhydride was caused to react with 1a at
120 °C for 25 h to give the tetrahydrophthalic anhydride
adduct 10a .
Sch em e 3
process that likely occurs during the aromatization of the
cyclohexadiene Diels-Alder cycloadduct. The mecha-
nism of this elimination process has not been studied,
but is observed with various C-4 substituents as alkyl-
thio, alkoxy, and sulfinyl, present in dienes 1a ,c,d . An
attempt to effect cycloaddition under Lewis acid catalysis
at low temperature (1a , methyl propiolate, TiCl4 or tert-
butyldimethylsilyl triflate, -78 °C) resulted in transfor-
mation of diene to thioenone 3 (66-70%) with no appar-
ent cyclic product being formed.
Our attention now was focused on application of Diels-
Alder reactions of diene 1 with dienophilic alkenes, which
would lead to cyclohexene cycloadducts that should not
directly undergo elimination to form a benzene ring,
thereby allowing other procedures to be studied to effect
formation of the aromatic ring. Our studies have been
mainly concerned with 1a ,b that bear a butylthio or
phenylthio group at position 4. This group conferred
higher reactivity to the diene in its reactions with
electrophilic dienophiles and functioned to control the
regiochemistry of the cycloaddition step.
Cycloaddition of dienes 1a ,b with excess methyl acry-
late was carried out at 150 °C for 72 h in a sealed tube.
The products were isolated by column chromatography
as a 3:1 mixture of endo-6 and exo-7 stereoisomers. Other
regioisomers were not detected by TLC.
The cycloaddition was highly regiospecific and occurred
with preferential endo-addition. The allylic hydrogen H4
to the SR substituent was coupled to the acyl methine
hydrogen H5. This hydrogen was observed as a doublet
both in the endo and exo isomers and collapsed to a
singlet upon irradiation at the frequency of the methine
hydrogen H5. The complete regiocontrol exercised by the
SR substituent demonstrates the excellent regiodirecting
ability of these sulfur groups. As expected, the coupling
constant between H4 and H5 showed a larger value for
endo adducts, 6a and 6b, in each isomeric pair of
The stereochemistry of the adduct was assigned on the
1
basis of analysis of the H NMR spectrum, with appropri-
ate decoupling, and comparing those data with that of
other related compounds.9,11 The 1H NMR data are
consistent with the stereochemistry in 10a having re-
sulted from endo cycloaddition. Both of the coupling
constants between the ring juncture hydrogens and the
allylic methine hydrogens at C1 and C4 are typical gauche
couplings. Thus, J 1,1a ) 5.50 Hz and J 4,4a ) 8.20 Hz; the
latter value is indicative for a more eclipsed interaction
between H4 and H4a as observed in related cases involving
a somewhat deformed “extended” boat form.11 However,
analysis of the NMR data, coupled with the more highly
substituted nature of compound 10a compared to other
(8) 6a : δH5 ) 3.15 ppm, δH4 ) 3.87 ppm, J H4,H5 ) 8.2 Hz. 7a : δH5
)
3.08 ppm, δH4 ) 3.76 ppm, J H4,H5 ) 4.0 Hz. 6b: δH5 ) 3.12 ppm, δH4
) 4.27 ppm, J H4,H5 ) 7.1 Hz. 7b: δH5 ) 3.05 ppm, δH4 ) 4.19 ppm,
J H4,H5 ) 3.6 Hz.
(9) Overman, L. E.; Taylor, G. F.; Houk, K. N.; Demelsmith, L. N.
J . Am. Chem. Soc. 1978, 100, 3182 and references cited therein.
(10) Overman, L. E.; Freerks, R. L.; Petty, C. B.; Clizbe, L. A.; Oho,
R. K.; Taylor, G. F.; J essup, P. J . J . Am. Chem. Soc. 1981, 103, 2816.
(11) Danishefsky, S.; Yan, C.-F.; Singh, R. K.; Gammill, R. B.;
MuCurry, P. M.; Fritsch, N.; Clardy, J . J . Am. Chem. Soc. 1979, 101,
7001.

5854 J . Org. Chem., Vol. 61, No. 17, 1996
Olsen and Shao
p-toluenesulfonic acid monohydrate (10 mmol), and the re-
quired thio or alcohol (36 mmol) in benzene (60 mL) was heated
at reflux under nitrogen for 5 h until the enaminone disap-
peared on TLC. The solvent was removed in vacuo, and the
residue was purified by flash chromatography on silica gel with
elution by 15% EtOAc in hexane to afford product.
Sch em e 5
4-(Bu tylth io)-1,3-d ip h en oxy-3-bu ten -2-on e (3a ). The
product was obtained as a pale yellow solid in 81% yield: mp
56-58 °C (EtOAc/hexane); IR (CCl4,cm-1) 3068, 3042, 2959,
1
1703, 690; H NMR (400 MHz, CDCl3) δ 0.92 (t, 3H, J ) 7.4
Hz), 1.41 (m, 2H), 1.66 (m, 2H), 2.82 (t, 2H, J ) 7.4 Hz), 4.81
(s, 2H), 6.79-7.33 (m, 10H), 7.63 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 13.4, 21.3, 32.3, 34.1, 70.4, 114.7, 114.9, 121.4, 122.7,
129.4, 129.8, 134.8, 143.0, 155.6, 157.8, 188.3. Anal. Calcd
for C20H22O3S: C, 70.15; H, 6.48; S, 9.36. Found: C, 70.36;
H, 6.35; S, 9.51.
1,3-Dip h en oxy-4-(p h en ylth io)-3-bu ten -2-on e (3b). The
product was obtained as a pale-yellow solid in 78% yield: mp
1
79-80 °C; IR (CHCl3, cm-1) 3060, 2914, 1695, 1671, 690; H
NMR (400 MHz, CDCl3) δ 4.84 (s, 2H), 6.80-7.44 (m, 15H),
7.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 70.5, 114.7, 115.0,
121.6, 123.0, 128.5, 129.5, 129.6, 130.0, 130.8, 132.5, 133.9,
143.0, 155.7, 157.8, 188.6. Anal. Calcd for C22H18O3S: C,
72.91; H, 5.01; S, 8.85. Found: C, 72.77; H, 5.23; S, 8.59.
1,3-Diph en oxy-4-m eth oxy-3-bu ten -2-on e (3c). The prod-
uct was obtained as a colorless viscous oil in 72.2% yield; IR
(neat, cm-1) 3402, 3042, 2944, 1704, 1685; 1H NMR (400 MHz,
CDCl3) δ 3.86 (s, 3H), 4.81 (s, 2H), 6.81-7.31 (m, 10H), 7.45
(s, 1H); 13C NMR (100 MHz, CDCl3) δ 62.6, 70.3, 114.5, 114.7,
121.5, 122.5, 129.4, 129.7, 131.6, 150.8, 156.8, 157.8, 191.8.
Anal. Calcd for C17H16O4: C, 71.82; H, 5.67. Found: C, 71.69;
H, 5.69.
described cyclohexenes, does not allow a definitive dif-
ferentiation between possible “extended” and “folded”
conformations. In contrast, if an exo product had been
formed, 10a would be expected to show either a large anti
coupling for an extended boat or very small J value due
to the coupling hydrogens being nearly perpendicular in
a folded conformation.
Gen er a l P r oced u r e for P r ep a r a tion of 4-Su bstitu ted -
2-[(ter t-bu tyld im eth ylsilyl)oxy]-1,3-d ip h en oxy-1,3-bu ta -
d ien e (1). To a stirred solution of enone 3 (3 mmol) in dry
ether (4 mL) under nitrogen at 0 °C was added triethylamine
(7.5 mmol), and the resulting mixture was stirred at 0 °C for
30 min. tert-Butyldimethylsilyl trifluoromethanesulfonate (4.5
mmol) was added dropwise, and the reaction mixture was
stirred at 0 °C for 2 h. Hexane (30 mL) was added, the mixture
swirled, and the top layer decanted. Two more 30 mL portion
of hexane were added to the reaction mixture and swirled, and
the top layer was decanted each time. The combined hexane
layer was dried over MgSO4 and purified by flash chromatog-
raphy on silica gel using 10% EtOAc in hexane to give 1,3-
butadiene.
2-[(ter t-Bu tyldim eth ylsilyl)oxy]-4-(bu tylth io)-1,3-diph e-
n oxy-1,3-bu ta d ien e (1a ). The product was obtained as a
white crystalline solid in 96% yield: mp 50 °C (CH3OH); IR
(CCl4, cm-1) 3077, 3042, 2958, 1655, 1592; 1H NMR (400 MHz,
CDCl3) δ 0.20 (s, 4H), 0.93 (t, 3H, J ) 7.4), 1.02 (s, 9H), 1.40
(m, 2H), 1.63 (m, 2H), 2.68 (t, 2H, J ) 7.4), 6.26 (s, 1H), 6.38
(s, 1H), 6.80-7.31 (m, 10H); 13C NMR (100 MHz, CDCl3) δ
-4.2, 13.6, 18.6, 21.6, 26.0, 32.5, 33.7, 113.5, 115.2, 115.8,
122.0, 122.5, 126.7, 129.6, 129.7, 133.9, 143.5, 156.6, 157.1.
Anal. Calcd for C26H36O3SSi: C, 68.83; H, 7.95; S, 7.02.
Found: C, 68.50; H, 7.95; S, 6.82.
Reaction of 1b with N-phenylmaleimide was conducted
in xylene under reflux for 48 h to afford the cyclohexene
11b. The value of the coupling constants (J 1,1a ) 5.1 Hz,
J 4,4a ) 8.1 Hz, J 1a,4a ) 10.6 Hz) established an all cis
configuration of the adducts, consistent with reaction via
an endo-transition state. Furthermore, the large cou-
pling constant between the bridgehead hydrogens (10.6
Hz) also suggested the “extended” boat conformation for
the cyclohexene ring.9,12
In conclusion, 1,3-diaryloxy tetrahetero-substituted
dienes reacted with several active dienophiles to provide
access to a variety of aryloxy-functionalized cyclic sys-
tems. A most significant feature contributing to the
synthetic applications of dienes 1a , 1b is the high
regiospecificity and endo-selectivity observed in their
thermal cycloaddition reactions. A method has been
developed that effects the synthesis of triaryl ether
products by Diels-Alder reaction of 1 with methyl
acrylate, subsequent deprotection of the silyl ether with
concurrent elimination of the sulfur substituent, and
aromatization of the resulting enone with DDQ. This
represents the first entry, utilizing a Diels-Alder ap-
proach, to the triaryl ether class of compounds; the
method should have application to the synthesis of triaryl
ether amino acid units as found in the glycopeptide
vancomycin.
2-[(t er t -B u t y ld im e t h y ls ily l)o x y ]-1,3-d ip h e n o x y -4-
(p h en ylth io)-1,3-bu ta d ien e (1b). The product was obtained
as a white crystal solid in 92% yield: mp 66-66.5 °C (CH3-
OH); IR (CHCl3, cm-1) 3075, 3041, 2930, 1655, 1066; 1H NMR
(400 MHz, CDCl3) δ 0.21 (s, 6H), 0.99 (s, 9H), 6.47 (s, 1H),
6.56 (s, 1H), 6.82-7.38 (m, 10H); 13C NMR (100 MHz, CDCl3)
δ -4.2, 18.5, 26.0, 111.4, 115.2, 115.9, 122.2, 122.7, 126.6,
127.8, 129.0, 129.1, 129.6, 129.7, 133.6, 135.5, 145.4, 156.8,
156.9. Anal. Calcd for C28H32O3SSi: C, 70.55; H, 6.77; S, 6.73.
Found: C, 70.61; H, 6.73; S, 6.66.
Exp er im en ta l Section
General procedures and methods for characterization have
been described previously.4 X-ray crystal diffraction was
performed on a Siemens P4 Autodiffractometer. Melting
points were uncorrected. All solvents were purified when
necessary according to standard procedures.
Gen er a l P r oced u r es for P r ep a r a tion of 4-Su bstitu ted
1,3-Dip h en oxy-3-bu ten -2-on e (3). A stirred mixture of
4-(dimethylamino)-1,3-diphenoxy-3-buten-2-one (2) (12 mmol),
2-[(ter t-Bu tyld im eth ylsilyl)oxy]-1,3-d ip h en oxy-4-m eth -
oxy-1,3-bu ta d ien e (1c). The product was obtained as a plae
yellow oil in 68% yield: IR (neat, cm-1) 3065, 2930, 2857, 1647,
1
1076; H NMR (400 MHz, CDCl3) δ 0.2 (s, 6H), 1.01 (s, 9H),
3.67 (s, 3H), 6.25 (s, 1H), 6.44 (s, 1H), 6.82-7.30 (m, 10H); 13
C
NMR (100 MHz, CDCl3) δ -4.3, 18.6, 26.0, 60.9, 114.9, 115.7,
121.7, 122.3, 124.7, 129.4, 129.5, 130.6, 133.3, 137.6, 157.2,
157.4. Anal. Calcd for C23H30O4Si: C, 69.31; H, 7.59.
Found: C, 69.42; H, 7.45.
(12) Arce, E.; Carren˜o, M. C.; Cid, M. B.; Garc´ıa Ruano, J . L. J . Org.
Chem. 1994, 59, 3421.

Diels-Alder Reaction of 1,3-Diphenoxy 1,3-Butadienes
J . Org. Chem., Vol. 61, No. 17, 1996 5855
2-[(ter t-Bu t yld im et h ylsilyl)oxy]-4-b u t ylsu lfin yl-1,3-
d ip h en oxy-1,3-bu ta d ien e (1d ). To a solution of diene 1a
(550 mg, 1.2 mmol) in dichloromethane (12 mL) was added
dropwise a solution of m-chloroperbenzoic acid (413 mg, of 50-
60% mixture, 1.2 mmol) in dichloromethane (10 mL) at -78
°C. The reaction mixture was allowed to warm slowly to room
temperature. TLC analysis (30% EtOAc in hexane) showed
complete loss of starting material. The reaction mixture was
partitioned between ether (40 mL) and 10% aqueous potassium
carbonate solution (20 mL). The ether layer was washed twice
with 10% aqueous potassium carbonate solution (2 mL), dried
over MgSO4, and purified by flash chromatography on silica
gel with 30% EtOAc in hexane to yield 500 mg of sulfoxide
(88%) as a pale yellow viscous oil: IR (neat, cm-1) 3063, 2943,
J ) 9.4, 13.5 and 13.7 Hz, 1H), 2.60 (ddd, J ) 2.6, 6.8 and
13.7 Hz, 1H), 3.05 (ddd, J ) 2.6, 3.6 and 13.5 Hz, 1H), 3.20 (s,
3H), 4.19 (d, J ) 3.6 Hz, 1H), 4.98 (dd, J ) 6.8 and 9.4 Hz,
1H), 6.92-7.30 (m, 15H); 13C NMR (100 MHz, CDCl3) major
isomer 6b, δ -4.4, 18.2, 25.6, 28.6, 43.0, 47.6, 52.1, 72.3, 115.8,
116.5, 121.1, 122.0, 127.6, 128.8, 129.2, 129.5, 133.2, 133.4,
133.7, 140.4, 155.7, 157.4, 173.3; minor isomer 7b, δ -4.2,
-4.1, 18.4, 25.7, 26.7, 42.7, 49.8, 51.3, 72.9, 116.5, 116.6, 121.4,
122.2, 127.2, 128.6, 129.4, 129.5, 129.6, 132.8, 134.3, 140.5,
155.7, 157.5, 170.6. Anal. Calcd for C32H38O5SSi (major
isomer 6b): C, 68.29; H, 6.81; S, 5.69. Found: C, 68.46; H,
6.59; S, 5.44.
Ar om a tiza tion of Diels-Ald er Cycloa d d u ct 6a w ith
MCP BA a n d DDQ. To a solution of cyclic adduct 6a (136
mg, 0.25 mmol) in dichloromethane (3 mL) was added dropwise
a solution of MCPBA (86 mg 50-60%, 0.25 mmol) in CH2Cl2
(2 mL) at -78 °C. The reaction mixture was stirred for 30
min, allowed to warm to 0 °C, and partitioned between ether
(20 mL) and 10% aqueous K2CO3 (5 mL). The ether layer was
dried over MgSO4 and concentrated in vacuo. The resulting
sulfoxide was heated with DDQ (113 mg, 0.5 mmol) at 50 °C
in benzene (3 mL) for 1 h. The reaction mixture was separated
by flash chromatography on silica gel. The products were
again subjected to TLC plate on silica gel using 15% EtOAc
in hexane to provide 55 mg of 4 (61%) and 13 mg of methyl
3,5-diphenoxy-4-[(tert-butyldimethylsilyl)oxy]benzoate (5) as a
1
1649, 1367, 1067; H NMR (400 MHz, CDCl3) δ 0.23 (d, 6H),
0.91 (t, 3H), 1.03 (s, 9H), 1.41 (m, 2H), 1.68 (m, 2H), 2.68 (m,
1H), 2.82 (m, 1H), 6.42 (s, 1H), 6.68 (s, 1H), 6.78 (m, 10H); 13
C
NMR (100 MHz, CDCl3) δ -4.3, 13.5, 18.3, 21.7, 24.2, 25.7,
54.0, 115.5, 115.9, 119.5, 123.0, 123.3, 129.6, 129.8, 131.4,
132.6, 154.1, 156.3, 157.5. Anal. Calcd for C26H36O4SSi: C,
66.06; H, 7.68; S, 6.78. Found: C, 65.97; H, 7.57; S, 7.00.
Rea ction of 1a w ith Meth yl P r op iola te. A mixture of
diene 1a (456 mg, 1 mmol) and methyl propiolate (178 mg, 2
mmol) in xylene (1 mL) was heated in a sealed tube at 150 °C
for 66 h. The solvent and excess methyl propiolate were
removed in vacuo to give an oil which was purified by flash
chromatography on silica gel with elution by 15% ethyl acetate
in hexane to afford methyl 3-phenoxy-4-[(tert-butyldimethyl-
silyl)oxy]benzoate (4) (290 mg, 81%) as a clear liquid: IR
(neat,cm-1) 3041, 2954, 1724, 1608, 1024. 1H NMR (400 MHz,
CDCl3) δ 0.16 (s, 6H), 0.87 (s, 9H), 3.85 (s, 3H), 6.87-7.77 (m,
8H); 13CNMR (100 MHz, CDCl3) δ -4.6, 18.2, 25.4, 51.9, 116.9,
121.1, 122.5, 122.9, 124.0, 126.7, 129.5, 146.5, 152.0, 157.4,
166.3. Anal. Calcd for C20H26O4Si: C, 67.01; H, 7.31.
Found: C, 67.00; H, 7.13.
Diels-Ald er R ea ct ion of 1a w it h Met h yl Acr yla t e.
P r ep a r a tion of Cycloa d d u cts 6a a n d 7a . A mixture of
diene 1a (456 mg, 1.0 mmol) and methyl acrylate (344 mg,
4.0 mmol) in xylene (1.5 mL) was heated in a sealed tube at
150 °C for 72 h. The solvent and excess methyl acrylate were
removed in vacuo, and the adducts were isolated as a 3:1
mixture of diastereoisomers after flash chromatography on
silica gel (ethyl acetate-hexane, 9:1, major isomer 320 mg and
minor isomer 120 mg, yield 81%): 1H NMR (400 MHz, CDCl3)
major isomer 6a , δ 0.07 (d, 6H), 0.72 (s, 9H), 0.87 (t, J ) 7.3
Hz, 3H), 1.35 (m, 2H), 1.49 (m, 2H), 2.16 (ddd, J ) 4.1, 10.6,
and 13.8 Hz, 1H), 2.31 (ddd, J ) 4.1, 3.5, and 13.8 Hz, 1H),
2.55 (t, J ) 7.3 Hz, 2H), 3.15 (ddd, J ) 3.5, 8.2 and 10.6 Hz,
1H), 3.68 (s, 3H), 3.87 (d, J ) 8.2 Hz, 1H), 4.96 (t, J ) 4.1 Hz,
1H), 6.92-7.32 (m, 10H); minor isomer 7a , δ 0.08 (s, 6H), 0.73
(s, 9H), 0.83 (t, J ) 7.3 Hz, 3H), 1.30 (m, 2H), 1.44 (m, 2H),
2.10 (ddd, J ) 9.2, 13.5 and 13.7, 1H), 2.52 (m, 2H), 2.63 (ddd,
J ) 2.6, 7.0, and 13.7 Hz, 1H), 3.08 (ddd, J ) 2.6, 4.0, and
13.5 Hz, 1H), 3.66 (s, 3H), 3.76 (d, J ) 4.0 Hz, 1H), 4.98 (dd,
J ) 7.0 and 9.2, Hz, 1H), 6.94-7.32 (m, 10H); 13C NMR (100
MHz, CDCl3) major isomer 6a , δ -4.5, 13.5, 18.1, 21.9, 25.5,
29.3, 30.6, 31.6, 43.3, 43.7, 51.9, 72.7, 115.8, 116.2, 121.2, 121.8,
129.2, 129.5, 134.2, 139.7, 155.8, 157.4, 173.6; minor isomer
7a , δ -4.2, -4.1, 13.6, 18.3, 21.8, 25.6, 26.9, 32.0, 33.0, 43.3,
44.0, 51.8, 72.8, 116.2, 116.3, 121.3, 122.0, 129.4, 129.5, 134.9,
139.5, 155.7, 157.4, 171.1. Anal. Calcd for C30H42O5SSi (major
isomer 6a ): C, 66.38; H, 7.80; S, 5.91. Found: C, 66.41; H,
7.59; S, 6.17.
white solid: mp 102-103 °C (MeOH); IR (CHCl3
, cm-1) 3020,
2954, 1718, 1592, 1042; 1H NMR (400 MHz, CDCl3) δ 0.16 (s,
6H), 0.83 (s, 9H), 3.78 (s, 3H), 6.97-7.44 (m, 12H); 13CNMR
(100 MHz, CDCl3) δ -4.4, 18.5, 25.4, 52.0, 116.9, 117.8, 123.0,
123.1, 129.8, 144.0, 148.5, 156.8, 166.0. Anal. Calcd for
C26H30O5Si: C, 69.30; H, 6.71. Found: C, 69.44; H, 6.79.
P r ep a r a tion of Meth yl 4-Oxo-3,5-d ip h en oxy-2-cyclo-
h exen e-1-ca r b oxyla t e (8). Tetrabutylammonium fluoride
(0.25 mL, 1.0 M in THF, 0.25 mmol) was added dropwise to a
solution of mixture of 6a and 7a (109 mg, 0.2 mmol) in THF
(2 mL) at -78 °C. The reaction mixture was stirred for 20
min at -78 °C and diluted with an equal mixture of ether and
hexane (20 mL). The cooled reaction solution was washed with
saturated aqueous NH4Cl (5 mL containing 2 drops 1 N HCl)
and extracted with ether. The ether layer was washed with
saturated aqueous NaHCO3 and dried over MgSO4. The
solvent was removed in vacuo to give the crude product which
was washed with ether to afford 8 as a white solid, 58 mg (86%)
mp 120-121 °C. 1H NMR (400 MHz, CDCl3) δ 2.53 (ddd J )
10.1, 11.8, and 13.2 Hz, 1H), 2.77 (ddd J ) 4.5, 4.8, and 13.2
Hz, 1H), 3.63 (ddd J ) 3.1, 4.8, and 10.1 Hz, 1H), 3.74 (s, 1H),
4.84 (dd J ) 4.5 and 11.8 Hz, 1H), 6.33 (d J ) 3.1 Hz, 1H)
6.95-7.32 (m, 10H). 13C NMR (100 MHz, CDCl3) δ 32.2, 39.0,
52.7, 77.8, 116.2, 118.8, 122.2, 124.0, 124.2, 129.5, 129.8, 149.5,
155.5, 157.8, 171.3, 189.8. Compound 8 appeared to be
somewhat unstable, and an attempt to obtain elemental
analysis did not give acceptable results.
P r ep a r a tion of Meth yl 3,5-Dip h en oxy-4-h yd r oxyben -
zoa te (9). The mixture of enone 8 (135 mg, 0.4 mmol) and
DDQ (182 mg, 0.8 mmol) in 1,4-dioxane (8 mL) was heated at
reflux under nitrogen for 18 h. The reaction mixture was
diluted with EtOAc (20 mL) and washed with 10% K2
CO3 and
saturated aqueous NaCl. The organic layer was dried over
MgSO4. The product was purified by flash chromatography
on silica gel to yield triaryl ether 9 as a white solid: 80 mg
(60%), mp 140-141 °C (EtOAc/hexane); IR (CDCl3, cm-1) 3308,
2949, 1698, 1587, 1218; 1H NMR (400 MHz, CDCl3) δ 3.78 (s,
3H), 6.05 (s, 1H), 7.05-7.43 (m, 12H); 13C NMR (100 MHz,
CDCl3) δ 52.1, 116.2, 118.2, 122.0, 123.9, 130.0, 143.7, 144.5,
156.5, 165.9. Anal. Calcd for C20H16O5: C, 71.42; H, 4.80.
Found: C, 71.56; H, 4.71.
Diels-Ald er R ea ct ion of 1b w it h Met h yl Acr yla t e.
P r ep a r a tion of Cycloa d d u cts 6b a n d 7b. A mixture of
diene 1b (476 mg, 1.0 mmol) and methyl acrylate (344 mg,
4.0 mmol) in dioxane (1.5 mL) was heated in a sealed tube at
140-150 °C for 90 h. The solvent and excess methyl acrylate
were removed in vacuo. The adducts were isolated as a 3:1
mixture of diastereoisomers after flash chromatography to
yield cycloadduct (200 mg, 40%) and to recover 270 mg of diene
1b (56%). 1H NMR (400 MHz, CDCl3) major isomer 6b, δ 0.04
(s, 6H), 0.71 (s, 9H), 2.29 (m, J ) 4.0, 8.6 and 4.8, 13.8 Hz,
2H), 3.12 (ddd, J ) 4.0, 7.1 and 8.6 Hz, 1H), 3.64 (s, 3H), 4.27
(d, J ) 7.1 Hz, 1H), 4.98 (t, J ) 4.8 Hz, 1H), 6.92-7.27 (m,
15H); minor isomer 7b, δ 0.09 (d, 6H), 0.75 (t, 9H), 2.23 (ddd,
Diels-Ald er Rea ction of Dien e 1a w ith Ma leic An h y-
d r id e. P r ep a r a tion of Ad d u ct (10a ). A solution of diene
1a (456 mg, 1 mmol) and maleic anhydride (108 mg, 1.1 mmol)
in xylene (1 mL) was heated at 120 °C for 24 h. After cooling
to room temperature, the solvent was removed in vacuo. The
crude product was purified by chromatography on a column
of silica gel using 25% EtOAc in hexane to yield cycloadduct
10a (290 mg) as a colorless liquid (60.2%): IR (neat, cm-1
3065, 3041, 2931, 1785, 1023; H NMR (400 MHz, CDCl3) δ
)
1

5856 J . Org. Chem., Vol. 61, No. 17, 1996
Olsen and Shao
0.03 (s, 6H), 0.72 (s, 9H), 0.77 (t, J ) 7.3 Hz, 3H), 1.26 (m,
2H), 1.37 (m, 2H), 2.53 (m, 1H), 2.62 (m, 1H), 3.80 (d, J ) 8.2
Hz, 1H), 3.84 (dd, J ) 5.5 and 11.5 Hz, 1H), 4.08 (dd, J ) 8.2
and 11.5 Hz, 1H), 5.09 (d, J ) 5.5 Hz, 1H), 6.84-7.28 (m, 10H);
13C NMR (100 MHz, CDCl3) δ -4.5, -4.3, 13.5, 17.9, 21.6, 25.3,
31.6, 35.9, 41.3, 46.7, 47.6, 75.2, 116.6, 117.8, 122.6, 122.8,
129.3, 129.5, 136.1, 137.7, 155.0, 157.4, 168.6, 169.0. Anal.
Calcd for C30H38O6SSi: C, 64.95; H, 6.90; S, 5.78. Found: C,
65.15; H, 6.70; S, 5.60.
C36H43NO5SSi: C, 68.65; H, 6.88; N, 2.22. Found: C, 68.79;
H, 6.95; N, 2.26.
Diels-Ald er R ea ct ion of Dien e 1b w it h N-P h en yl-
m a leim id e. P r ep a r a tion of Ad d u ct (11b). Compound 11b
was obtained as a white solid in 67% yield; mp 198-200 °C;
IR (CHCl3, cm-1) 3476, 3067, 2928, 1718, 1595; 1H NMR (400
MHz, CDCl3) δ 0.05 (d, 6H), 0.75 (s, 9H), 3.69 (dd, J ) 5.1 and
10.6 Hz, 1H), 3.91 (dd, J ) 8.4 and 10.6 Hz, 1H), 4.25 (d, J )
8.4 Hz, 1H), 5.23 (d, J ) 5.1 Hz, 1H), 6.85-7.50 (m, 20H); 13
C
Diels-Ald er R ea ct ion of Dien e 1a w it h N-P h en yl-
m a leim id e. P r ep a r a tion of Ad d u ct (11a ). To a solution
of diene 1a (456 mg, 1.0 mmol) in 2.0 mL of xylene was added
N-phenylmaleimide (208 mg, 1.2 mmol). The mixture was
heated in a sealed tube at 150 °C for 48 h. The solvent was
evaporated in vacuo, and the resulting mixture was separated
by flash chromatography on silica gel (ethyl acetate-hexane
1:4). Adduct 11a was obtained as a white foam (520 mg,
83%): mp 52-54 °C; IR (CHCl3, cm-1) 3480, 3068, 2931, 1718,
NMR (100 Hz, CDCl3) δ -4.4, -4.2, 17.9, 25.3, 44.9, 47.0, 48.9,
75.8, 116.7, 117.6, 122.3, 122.6, 126.8, 127.4, 128.6, 128.8,
129.2, 129.3, 129.4, 132.1, 132.9, 137.1, 138.0, 138.4, 155.1,
157.6, 173.7, 174.1. Anal. Calcd for C38H39NO5SSi: C, 70.23;
H, 6.05; N, 2.16. Found: C, 70.38; H, 6.14; N, 1.96.
Ack n ow led gm en t. This work was generously sup-
ported by a grant from the National Institutes of Health
(Grant No. GM47360). We thank Professor J . Hubbard
of this department for the X-ray crystallography deter-
mination. We acknowledge the NSF (CHE-9002379)
and the Utah State University Research Office for
jointly funding the purchase of the USU X-ray diffrac-
tion facilities.
1
1595; H NMR (400 Hz, CDCl3) δ 0.02 (d, 6H), 0.73 (s, 9H),
0.74 (t, J ) 7.4, 3H), 1.21 (m, 2H), 1.35 (m, 2H), 2.49 (m, 1H),
2.64 (m, 1H), 3.67 (dd, J ) 5.4 and 13.1 Hz, 1H), 3.88 (dd, J )
8.0 and 13.1 Hz, 1H), 3.89 (d, J ) 8.0 Hz, 1H), 5.17 (d, J ) 5.4
Hz, 1H), 6.87-7.48 (m, 15H); 13C NMR (100 Hz, CDCl3) δ -4.4,
-4.3, 13.5, 17.9, 21.6, 25.3, 31.8, 35.8, 42.1, 45.4, 46.8, 75.7,
116.6, 117.8, 122.2, 122.5, 126.7, 128.6, 129.1, 129.4, 132.1,
136.7, 138.3, 155.2, 157.8, 173.8, 174.6. Anal. Calcd for
J O960105D