Cyclization pathways of a (Z)-stilbene-derived bis(orthoquinone monoketal)

Article abstract of DOI:10.1021/jo9704220

Lead tetraacetate mediated oxidation of a (Z)-bisphenolic stilbene derivative affords a bis(orthoquinone monoketal) product. Thermolysis studies of this highly unsaturated dione reveal that sigmatropic hydrogen shifts, followed by either of two distinct solvolytic ring closures, constitute the predominate reaction pathways under heating. No evidence for a desired 6π electron electrocyclization was forthcoming.

Full text of DOI:10.1021/jo9704220

J . Org. Chem. 1997, 62, 4983-4990
4983
Cycliza tion P a th w a ys of a (Z)-Stilben e-Der ived Bis(or th oqu in on e
m on ok eta l)
Ken S. Feldman
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802
Received March 7, 1997X
Lead tetraacetate mediated oxidation of a (Z)-bisphenolic stilbene derivative affords a bis-
(orthoquinone monoketal) product. Thermolysis studies of this highly unsaturated dione reveal
that sigmatropic hydrogen shifts, followed by either of two distinct solvolytic ring closures, constitute
the predominate reaction pathways under heating. No evidence for a desired 6π electron
electrocyclization was forthcoming.
Sch em e 1
Success in approaches to the synthesis of morphinan
alkaloids which utilize a biomimetic C(12)-C(13) ring
closure (cf. 3, morphine numbering) hinges on controlling
the ortho-para coupling regiochemistry in ring A.1
A
host of direct and indirect solutions to this problem of
regiocontrol have been explored, and to date a high-
yielding, completely selective strategy remains elusive.2
An alternative to the typical oxidative phenolic coupling
chemistry can be envisioned which completely eliminates
the ambiguity in the site of A-ring attachment (Scheme
1). This strategy would rely on a 6π electron electrocy-
clization of a trienic system specifically spanning the
C(12)-C(13) gap to deliver only the correctly substituted
phenanthrene skeleton of the morphinan alkaloids (cf. 1
f 2). However, other cyclization pathways are available
to this highly functionalized substrate which lead to non-
phenanthrene polycycles, as described below.
The desired electrocyclization 1 f 2 would likely face
stiff competition from an alternative pericyclic process,
the [1,7] sigmatropic shift interconnecting 1 with 4. The
outcome of this competition would determine the feasibil-
ity of this approach for morphinan construction. Numer-
ous studies on relatively unfunctionalized trienic systems
have documented the kinetic advantages of the [1,7]
H-shift over 6π electrocyclization.3 However, coupling
the electrocyclization with an essentially irreversible
process, the strain-driven [1,5] sigmatropic H-shift within
2 to provide 3,4 may thwart this kinetic preference.5
Thus, the ready reversibility of the [1,7] shift and the
presumed driving force of converting 2 into 3 suggested
that this strategy was worthy of experimental inquiry.
In a structurally related but much less oxidized system,
Fehr et al. provided precedent that the products of 6π
electrocyclization (with some subsequent [1,5] H-shift)
can predominate over [1,7] H-shift products (ca. 18:1)
when both reaction channels are available.6a The syn-
thesis of (Z)-stilbene 1a , and characterization of the
chemistry emerging from heating or irradiation of this
species or its (E)-isomer 15, is described herein. To-
gether, these studies delineate the isomerization chem-
istry of this highly functionalized polyenyldione.
(4) Molecular mechanics calculations were performed with Macro-
model V4.5 on a Silicon Graphics Indigo2XZ workstation. Structures
2 and 3 (R ) H, R1 ) R2 ) CH3) were subjected to a directed Monte
Carlo search of conformational space. The relative strain energies of
the “global” minima indicated that 3 is more stable than 2 by 6 kcal/
mol. See: Mohamadi, F.; Richards, N. G. J .; Guida, W. C.; Liskamp,
R.; Caulfield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J . Comput.
Chem. 1990, 11, 440.
(5) Other examples of thermal 6π electrocyclizations followed by [1,5]
sigmatropic H-shifts have been reported; see: Darcy, P. J .; Hart, R.
J .; Heller, H. G. J . Chem. Soc., Perkin Trans. 1 1978, 571.
(6) (a) Fehr, C.; Galindo, J .; Guntern, O. Tetrahedron Lett. 1990,
31, 4021. (b) Paquette et al. have reported that trienedione i electro-
cyclizes and then undergoes H-shift at 110 °C: Paquette, L. A.; Bzowej,
E. I.; Branan, B. M.; Stanton, K. J . J . Org. Chem. 1995, 60, 7277.
X Abstract published in Advance ACS Abstracts, J uly 1, 1997.
(1) Hudlicky, T.; Butora, G.; Fearnley, S. P.; Gum, A. G.; Stabile,
M. R. In Studies in Natural Products Chemistry, Vol. 18; Rahman A.,
Ed., Elsevier: Amsterdam, 1996; p 43.
(2) (a) Grewe, R.; Friedrichsen, W. Chem. Ber. 1967, 100, 1550. (b)
Barton, D. H. R.; Kirby, G. W.; Steglich, W.; Thomas, G. M. Proc. Chem.
Soc. 1963, 203. (c) Kametani, T; Ihara, M.; Fukumoto, K.; Yagi, H. J .
Chem. Soc. C 1969, 2030. (d) Schwartz, M. A.; Mami, I. S. J . Am. Chem.
Soc. 1975, 97, 1239. (e) Lie, T. S.; Maat, L.; Beyerman, H. C. Recl.
Trav. Chim. Pays-Bas 1979, 98, 419. (f) Rice, K. C. J . Org. Chem. 1980,
45, 3135. (g) White, J . D.; Caravatti, G.; Kline, T. B.; Edstrom, E.; Rice,
K. C.; Brossi, A. Tetrahedron 1983, 39, 2393. (h) Ludwig, W.; Scha¨fer,
H. J . Angew. Chem., Int. Ed. Engl. 1986, 25, 1025. (i) Morrison, G. C.;
Waite, R. O.; Shavel, J ., J r. Tetrahedron Lett. 1967, 4055.
(3) (a) Mella, M.; Freccero, M.; Albini, A. J . Am. Chem. Soc. 1996,
118, 10311. (b) Baldwin, J . E.; Reddy, V. P. J . Am. Chem. Soc. 1987,
109, 8051. (c) Curtin, M. L.; Okamura, W. H. J . Am. Chem. Soc. 1991,
113, 6958. (d) Okamura, W. H.; Elnagar, H. Y.; Ruther, M.; Dobreff,
S. J . Org Chem. 1993, 58, 600 and references cited therein. (e) Bakulev,
V. A. Russ. Chem. Rev. 1995, 64, 99.
S0022-3263(97)00422-2 CCC: $14.00 © 1997 American Chemical Society

4984 J . Org. Chem., Vol. 62, No. 15, 1997
Feldman
Sch em e 2
Sch em e 3
10 in CH3OH provided 1a with no evidence for dimethoxy
ketal-containing products, but in an inferior yield com-
pared with using CH2Cl2 as solvent. The bright orange
bis(orthoquinone monoketal) 1a was subject to decom-
position both upon standing under ambient conditions
and upon contact with unpassivated silica gel. Conse-
quently, purification of this and all subsequent ortho-
quinone monoketal species was best accomplished by
rapid chromatography on silica gel deactivated by 10-
20% H2O.
The corresponding (E)-alkenyl isomer 15 was unex-
pectedly available also, as a consequence of a normally
(Z) selective Wittig alkenylation reaction9 proceeding
with high (E) selectivity on the congested aldehyde 11,
Scheme 3. Coupling of the stannylated A-ring precursor
13 with the hindered iodide 12 under either Farina/
Liebeskind’s Ph3As/Pd(0)-based protocol10a or Liebe-
skind’s copper salt alternative10b afforded only modest
yields of the (E)-stilbene derivative 14. In these trans-
formations, the sensitive aryl tin coupling partner was
rapidly consumed in processes which did not lead to
stilbene product. The related (Z)-alkenyl bromide 16 did
not couple with 13 under either set of conditions. Oxida-
tion of the (E)-bis(phenol) derived by desilylation of 14
occurred without event under Wessely conditions to
furnish the corresponding (E)-bis(orthoquinone monoket-
al) 15 in good yield as an inseparable mixture of stereo-
isomers.
Warming a dilute (ca. 1 mM) solution of (Z)-alkenyl
bis(orthoquinone monoketal) 1a in benzene at reflux
effected clean conversion of the starting material into a
mixture of three rearrangement products in approxi-
mately equal proportions (Scheme 4). Chromatographic
purification on deactivated silica gel afforded a less polar
off-white solid and a more polar yellow-orange solid. The
first-eluting solid appeared by 1H NMR to be a 1:1
mixture of compounds with similar structures. Further
The preparation of bis(orthoquinone monoketal) 1a
relies on the Pb(OAc)4-mediated oxidation of the ap-
propriate precursor bis(phenol) 10 (Scheme 2). The (Z)-
stilbene derivative 10 was assembled from the known
salicylaldehyde derivative 57 and guaiacol acetate (7)
utilizing precedented chemistry. Lindlar semi-hydroge-
nation of either the sterically hindered alkynyl phenol
9a or its silyl ether derivative 9b proved problematic and
required extensive optimization. Eventually adherence
to the carefully defined conditions indicated permitted
reproducibly high yields of the isomerically pure (Z)-
alkene 10 to be obtained from either substrate. Bis-
(phenol) 10 was exposed to several established phenolic
oxidants (e.g., Pb(OAc)4, Tl(NO3)3, PhI(OAc)2, PhI-
(OTFA)2), but only Wessely conditions (Pb(OAc)4 in CH2-
Cl2)8 furnished the desired bis(orthoquinone monoketal)
1a (1:1 mixture of diastereomers) in good yield and free
of difficultly removable impurities. Similar oxidation of
(7) Ishii, H.; Ishikawa, T.; Wada, H.; Miyazaki, H.; Kaneko, Y.;
Harayama, T. Chem. Pharm. Bull. 1992, 40, 2614.
(8) (a) Wessely, F.; Swoboda, J .; Guth, V. Monatsh. 1964, 95, 649
and references cited therein. (b) Bubb, W. A.; Sternhell, S. Tetrahedron
Lett. 1970, 4499.
(9) Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 2173.
(10) Farina, V.; Kapadia, S.; Krishnan, R.; Wang, C.; Liebeskind,
L. S. J . Org. Chem. 1994, 59, 5905. (b) Allred, G. D.; Liebeskind, L. S.
J . Am. Chem. Soc. 1996, 118, 2748.

Cyclization Pathways of a Bis(orthoquinone monoketal)
J . Org. Chem., Vol. 62, No. 15, 1997 4985
Sch em e 4
discussed earlier. A subsequent [1,5] H-shift within 17
delivers a reactive species 18 poised for intramolecular
cyclization. Solvolysis of the dienol ether-dienyl acetate
unit of 18, followed by aromatization of the A-ring,
completes the synthesis of 20. Apparently, the lability
of pentaene 18 and the opportunity to aromatize 19
conspire to provide a low-energy pathway which con-
sumes intermediate 18.
Unraveling the structures of the compounds constitut-
ing the less polar off-white mixture proved more chal-
lenging than that of 20 but eventual recourse to HMQC/
HMBC NMR techniques allowed complete assignment of
proton and carbon resonances (see Supporting Informa-
tion) and led to the structural proposals 23a /b. As with
20, initial analysis of the MS and IR data confirmed that
(1) a molecule of acetic acid had been lost, (2) one of the
original carbonyls was now a phenolic hydroxyl, and (3)
the remaining carbonyl was no longer adjacent to an
1
alkene. The H and 13C spectra of each compound in the
mixture provided similar evidence for (1) an exo meth-
ylene, (2) one methoxy-acetoxy ketal unit, and (3) a
3
disubstituted alkene whose J H-H value (5.5 Hz in both
compounds) was suggestive of a cyclopentene ring. HM-
QC/HMBC spectra of the less polar of the two compounds
provided unambiguous support for the proposed struc-
3
tures 23a /b (key J C-H are given in the Supporting
Information). The spiro carbons’ 13C resonances (72.4
and 69.4 for the two compounds) were unexpectedly far
downfield, but nevertheless consistent with cognate
model compounds of known structure.11 Two uncoupled
aromatic proton resonances on the A-ring permit assign-
ment of regiochemistry as shown.
A mechanistic pathway which connects 1a to these
diastereomeric indene derivatives 23a /b is proposed in
Scheme 4. The key intermediate 18 is a likely branch
point from which chemistry leading to 23a /b diverges
from that leading to 20. Thus, the most direct route
which links 18 to 23a /b would involve enolization to
provide the nucleophilic entity which traps an electro-
philic A-ring species generated by acetate solvolysis, 18
f 21 f 22. Aromatization of 22 then completes the
conversion to 23 a /b. An alternative scheme for forming
enol 21 from ketone 18 which relies on sigmatropic
H-shifts also can be envisioned.12 It is noteworthy that
the dienolic nucleophile of 21 apparently favors addition
(from C(14)) to C(1) (morphinan numbering) of the
ambident electrophile generated by A-ring acetate sol-
volysis, while the dienolic nucleophile of 18 prefers
addition to C(12) of that same electrophilic species. A
rationale for this dichotomy is at present obscure.
purification of this mixture by HPLC led to fractions
enriched in each compound (ca. 80% pure). The spectral
data from these enriched mixtures could be interpreted.
In addition, partial decomposition of this mixture upon
HPLC afforded a new, more polar homogeneous yellow
oil.
(11) P. Maslak, unpublished results, Penn State University.
The yellow-orange solid displayed spectral data con-
sistent with the structural assignment 20. In particular,
interpretation of IR and mass spectral data indicated that
one orthoquinone monoketal moiety in 1a suffered loss
of acetic acid with concomitant aromatization while the
remaining oxidized ring survived intact. 1H and 13C
NMR spectra revealed the key resonances of the central
cycloheptatriene ring and furthermore allowed assign-
ment of the regiochemistry of the A-ring by observation
of an ortho hydrogen-hydrogen coupling. A plausible
mechanism of formation of 20 from 1a is detailed in
Scheme 4. The conversion of the allylic methyl in 1a into
the exomethylene of 17 implicates the [1,7] H-shift
(12)

4986 J . Org. Chem., Vol. 62, No. 15, 1997
Feldman
Partial hydrolysis of the mixture 23a /b accompanied
HPLC purification, eq 1. A more polar yellow oil was
isolated and assigned the structure 24 on the basis of
analysis of spectral data. This unstable dienedione
decomposes to unidentified material upon standing at
ambient conditions for a few hours. Further evidence for
the lability of the dienyl ketal moiety of 23a /b can be
gleaned from the results of attempted acylation, eq 1.
When a 1:1 mixture of 23a /23b was subjected to AcCl/
DMAP, a new dienyl chloride species 25 was formed to
the exclusion of any direct ketal-containing acetylated
products. Apparently, the DMAP‚HCl formed as an
acylation byproduct is a potent enough acid to promote
ketal solvolysis with Sn2′ capture of chloride.
has not been realized. Competitive sigmatropic hydrogen
shifts intervene, and these isomerizations are rendered
irreversible by facile acetate solvolyses which afford a
suite of unusual tricyclic dienone derivatives. One dia-
stereomeric set of tricyclic products featuring a spiroin-
dene framework is quite sensitive to a second acetate
solvolysis, leading to ketonic or dienyl chloride products
depending on conditions.
Exp er im en ta l Section
THF, DME, and diethyl ether (Et2O) were dried by distil-
lation from sodium/benzophenone under Ar. Benzene and
CH2Cl2 were dried by distillation from CaH2 under Ar. Liquid
(flash)14 chromatography was carried out using 32-63 µm
silica gel and the indicated solvent system. Hexane and Et2O
used in flash chromatography were distilled from CaH2 prior
to use. All moisture and air sensitive reactions were carried
out in predried glassware under an inert atmosphere of Ar.
All melting points are uncorrected. Chemical ionization mass
spectra (CIMS) were obtained with isobutane as the reagent
gas. Combustion analyses were performed by Midwest Mi-
crolabs, Indianapolis, IN. 1H and 13C NMR spectra are
provided in the Supporting Information to establish purity for
those compounds which were not subject to combustion
analyses.
2-Meth oxy-5-iodoph en ol (8a). This procedure was adapted
from the method of Bushby.15 A stirring solution of guaiacol
(10.0 g, 80.6 mmol) and pyridine (15.0 mL, 186 mmol) in 200
mL of CH2Cl2 was cooled in an ice bath and treated with acetyl
chloride (6.4 mL, 90 mmol). After 5 min, TLC (1:1 Et2O/
hexane) indicated consumption of guaiacol, and the reaction
solution was poured into ice cold 1 M H3PO4. The organic
phase was extracted with 50 mL of CH2Cl2, and the combined
organic layers were washed with brine, dried with Na2SO4,
filtered, and concentrated in vacuo to afford a light yellow oil.
This oil in 200 mL of CH2Cl2 was cooled in an ice bath, and
with vigorous stirring a solution of ICl (15.5 g, 96 mmol) in
100 mL of CH2Cl2 was added dropwise over 2 h. TLC analysis
(PhH) indicated consumption of acetate, and the reaction
solution was poured into an ice cold saturated Na2S2O3
solution. The aqueous layer was extracted with 50 mL of CH2-
Cl2, and the combined organic phases were washed with brine,
dried with Na2SO4, filtered, and concentrated to yield 20.5 g
of a light yellow solid. This solid was dissolved in 60 mL of
CH3OH, 60 mL of THF, and 20 mL of H2O, and LiOH‚H2O
(11.8 g, 280 mmol) was added in one portion. After vigorous
stirring at rt for 3.5 h, TLC (1:1 Et2O/hexane) indicated
consumption of the starting iodoacetate. The reaction solution
was poured into ice cold 1 M HCl, and this mixture was
extracted with 3 × 100 mL of Et2O. The combined ethereal
layers were washed with brine, dried with Na2SO4, filtered,
and concentrated in vacuo to furnish an off-white solid.
Crystallization from 50 mL of hexane and 3 mL of Et2O
(concentrated by boiling to ∼20 mL, then cooled to rt) yielded
11.8 g (59% from guaiacol) of iodophenol 8a as chunky off-
white crystals upon filtration. An analytical sample could be
prepared by vapor diffusion crystallization from THF/hexane,
The thermal rearrangement pathway taken by 1a
appears to be sensitive to concentration. Heating a 28
1
mM solution of 1a in C6D6 in 10 °C increments with H
NMR monitoring revealed that the signals for the bis-
(orthoquinone monoketal) had disappeared after 9 h at
82-84 °C, but the rearrangement/solvolysis products 20/
23a /b comprised only about 20% of the product mixture.
The major component (ca. 80%) of the species present was
isolated following chromatography and assigned struc-
ture 27 on the basis of analysis of spectral data, eq 2.
The tetrasubstituted A-ring of 27 might plausibly result
from initial 1,3-acetate shift within 1a to furnish tran-
sient dienone 26, followed by aromatization. In an
independent experiment, a 1 mM solution of 1a in C6D6
was charged with 3 equiv of acetic acid and warmed at
reflux for 2.5 h. At that time, starting bis(orthoquinone
monoketal) 1a was consumed, and a mixture containing
approximately 15% of 27 and 85% of the solvolysis
products 20/23a /b was present. No 27 was seen in the
original 1 mM thermolysis without added acid. It is
possible, then, that the concentration of acetic acid plays
a role in determining the facility of the 1,3-acetate shift.13
The higher concentration run (28 mM) produces a
proportionately higher concentration of acetic acid as a
byproduct from 20/23a /b formation, and this acid might
then catalyze the conversion of 1a into 27. As a final
control experiment, heating the (E)-alkenyl bis(ortho-
quinone monoketal) isomer 15 (ca. 23 mM solution in
C6D6) led to formation of a similar 1,3-acetate shift
product at 90 °C.
The possibility of photochemically redirecting the peri-
cyclic chemistry of 1a toward electrocyclization was
explored in a few scouting experiments. Irradiation of a
C6D6 solution of 1a with 350 nm light furnished the (E)-
alkene isomer 15 cleanly. Similarly, 15 survived 350 nm
irradiation unchanged. In no case was even a trace
amount of cyclization products detected.
The goal of preparing oxidized phenanthrene systems
related to the morphinan skeleton by electrocyclization
(13) Acetic acid and p-nitrobenzoic acid catalysis of 1,3 acetate shifts
have been reported: (a) Braude, E. A.; Turner, D. W.; Waight, E. S. J .
Chem. Soc. 1958, 2396. (b) Pocker, Y. J . Chem. Soc. 1958, 4318.
(14) Still, W. C. Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(15) Boden, N.; Bushby, R. J .; Cammidge, A. N. J . Am. Chem. Soc.
1995, 117, 924.

Cyclization Pathways of a Bis(orthoquinone monoketal)
J . Org. Chem., Vol. 62, No. 15, 1997 4987
mp 87-88 °C: IR (CCl4) 3351 cm-1; 1H NMR (CDCl3, 200 MHz)
7.22 (d, J ) 2.1 Hz, 1H), 7.14 (dd, J ) 8.4, 2.1 Hz, 1H), 6.57
(d, J ) 8.4 Hz, 1H), 5.62 (s, 1H), 3.84 (s, 3H); 13C NMR (CDCl3,
50 MHz) 146.6, 146.5, 129.0, 123.4, 112.5, 82.9, 55.9; CIMS
m/z (relative intensity) 250 (M+, 100). Anal. Calcd for C7H7-
IO2: C, 33.63; H, 2.82; I, 50.75. Found: C, 33.51; H, 2.76; I,
50.97.
the dibromide from above (1.00 g, 2.1 mmol) and Pd(PPh3)4
(121 mg, 0.105 mmol) in 20 mL of benzene was treated with
n-Bu3SnH (706 uL, 2.63 mmol). TLC analysis (2:1 hexane/
CH2Cl2 on SiO2 plates impregnated with AgNO3 (dipped in 10%
AgNO3/CH3CN solution)) revealed that some dibromide re-
mained after 18 h. Additional aliquots of n-Bu3SnH were
added at 18 h (250 uL, 0.93 mmol) and 24 h (100 uL, 0.37
mmol), and TLC analysis indicated almost complete consump-
tion of starting dibromide after 29 h. The reaction mixture
was poured into saturated NaHCO3 solution and extracted
with 2 × 25 mL of hexane. The combined organic phases were
washed with brine, dried with Na2SO4, filtered, and concen-
trated in vacuo. The residue was purified by flash chroma-
tography with 99:1 hexane/Et2O f 50:1 hexane/Et2O as eluent
to furnish 852 mg of (Z)-bromide 16 (93%) as a viscous,
colorless oil. An analytical sample could be prepared by
crystallization from hexane at -10 °C, mp 52-53 °C: 1H NMR
(CDCl3, 200 MHz) 7.02 (d, J ) 7.5 Hz, 1H), 6.51 (d, J ) 7.3
Hz, 1H), 6.43 (s, 1H), 3.85 (s, 3H), 3.73 (s, 3H), 2.22 (s, 3H),
0.98 (s, 9H), 0.16 (s, 6H); 13C NMR (CDCl3, 90 MHz) 152.7,
146.7, 137.8, 131.6, 131.1, 121.0, 111.5, 106.6, 60.4, 55.7, 26.0,
20.2, 18.6, -3.1; CIMS m/z (relative intensity) 387 MH+, 50).
Anal. Calcd for C17H27BrO3Si: C, 52.71; H, 7.03; Br, 20.63.
Found: C, 53.11; H, 7.17; Br, 20.28.
3-(ter t-Bu t yld im et h ylsiloxy)-4-m et h oxyiod ob en zen e
(8b). A stirring solution of phenol 8a (2.01 g, 8.0 mmol) and
tert-butyldimethylsilyl chloride (1.46 gm, 9.6 mmol) in 10 mL
of DMF was treated with diisopropylethylamine (1.94 mL, 11.6
mmol). After 30 min at rt, TLC (3:1 hexane/Et2O) indicated
complete consumption of starting alcohol. The reaction solu-
tion was poured into ice cold 1 M H3PO4, and this mixture
was extracted with 2 × 25 mL of Et2O. The combined ethereal
layers were washed with brine, dried with Na2SO4, filtered,
and concentrated in vacuo. The oily residue so obtained was
purified by flash chromatography on SiO2 with 19:1 hexane/
Et2O as eluent to furnish 2.65 g of the silyl ether 8b as a
colorless oil (91%). An analytical sample could be prepared
by crystallization from hexane at -10 °C, mp 36 °C: 1H NMR
(CDCl3, 360 MHz), 7.20 (dd, J ) 8.4, 2.2 Hz, 1 H), 7.14 (d, J )
2.2 Hz, 1H), 6.58 (d, J ) 8.5 Hz, 1 H), 3.77 (s, 3H), 0.98 (s,
9H), 0.15 (s, 6H); 13C NMR (CDCl3, 90 MHz) 151.3, 146.1,
130.6, 129.8, 114.0, 82.1, 55.5, 25.7, 18.4, -2.6; CIMS m/z
(relative intensity) 365 (M+, 18); HRMS calcd for C13H21IO2Si
364.0357, found 364.0327.
2-(ter t-Bu tyld im eth ylsiloxy)-3,4-d im eth oxy-6-m eth yl-
ben za ld eh yd e (11). A stirring solution of phenol 57 (4.87 g,
24.8 mmol) and tert-butyldimethylsilyl chloride (4.88 gm, 32.3
mmol) in 20 mL of DMF was treated with diisopropylethyl-
amine (6.47 mL, 32.7 mmol). After 15 min, TLC (3:1 hexane/
Et2O) indicated complete consumption of starting alcohol. The
reaction solution was poured into ice cold 1 M H3PO4, and this
mixture was extracted with 2 × 50 mL of Et2O. The combined
ethereal layers were washed with brine, dried with Na2SO4,
filtered, and concentrated in vacuo. The residue was purified
by flash chromatography on SiO2 with 4:1 hexane/Et2O as
eluent to furnish 7.04 g (92%) of silyl ether 11 as a white solid.
An analytical sample could be prepared by recrystallization
1-(ter t-Bu tyld im eth ylsiloxy)-2,3-d im eth oxy-6-eth yn yl-
5-m eth ylben zen e (6). As per the method of Corey and
Fuchs,16 a stirring, -78 °C solution of the dibromide from
above (803 mg, 1.72 mmol) in 10 mL of THF was treated with
a 2.5 M n-BuLi solution in hexane (1.70 mL, 4.25 mmol) to
furnish a yellow solution. TLC (3:1 hexane/CH2Cl2 on AgNO3-
impregnated SiO2 plates) indicated complete consumption of
starting dibromide after 10 min. The reaction solution was
poured into ice cold 1 M H3PO4, and this mixture was extracted
with 2 × 10 mL of Et2O. The combined organic phases were
washed with brine, dried over Na2SO4, filtered, and concen-
trated in vacuo. The residue was purified by flash chroma-
tography on SiO2 with 9:1 hexane/Et2O as eluent to afford 503
mg of alkyne 6 (96%) as a colorless oil. An analytical sample
could be prepared by crystallization from hexane at -10 °C,
1
mp 50-51 °C: IR (CCl4) 3311, 2104 cm-1; H NMR (CDCl3,
from hexane at -10 °C, mp 62-64 °C: IR (CCl4) 1683 cm-1
;
360 MHz) 6.41 (s, 1H), 3.85 (s, 3H), 3.71 (s, 3H), 3.34 (s, 1H),
1.04 (s, 9H), 0.23 (s, 6H); 13C NMR (CDCl3, 90 MHz) 153.7,
151.2, 137.9, 137.5, 108.6, 106.5, 84.1, 80.1, 60.3, 55.8, 25.9,
21.0, 18.6, -3.1; CIMS m/z (relative intensity) 307 (MH+, 75).
Anal. Calcd for C17H26O3Si: C, 66.62; H, 8.55. Found: C,
67.06; H, 8.64.
1H NMR (CDCl3, 360 MHz) 10.47 (s, 1H), 6.40 (s, 1H), 3.92 (s,
3H), 3.75 (s, 3H), 2.56 (s, 3H), 1.01 (s, 9H), 0.22 (s, 6H); 13C
NMR (CDCl3, 90 MHz) 191.2, 157.3, 154.2, 138.0, 137.7, 120.7,
108.5, 60.5, 55.9, 25.9, 21.9, 18.8, -2.8; CIMS m/z (relative
intensity) 311 (M+, 100). Anal. Calcd for C16H26O4Si: C,
61.90; H, 8.44. Found: C, 62.20; H, 8.62.
(E)-1-Iodo-2-(2-ter t-bu tyldim eth ylsiloxy)-3,4-dim eth oxy-
6-m eth ylp h en yleth en e (12). As per the method of Stork,9
a 1 M solution of TMS2NNa in THF (2.50 mL, 2.50 mmol) was
added dropwise to a stirring, rt suspension of Ph3PCH2I2 (1.33
gm, 2.5 mmol) in 5 mL of THF. This homogeneous orange
solution was cooled in a dry ice-acetone bath, and 0.75 mL of
HMPA followed by aldehyde 11 (620 mg, 2.00 mmol) in 7 mL
of THF was added, resulting in a cloudy yellow solution. After
30 min, TLC analysis (3:1 hexane/Et2O) indicated complete
consumption of aldehyde. The reaction solution was poured
into 100 mL of vigorously stirring hexane, and the mixture
was filtered through SiO2. Concentration of the filtrate and
purification of the resulting yellow oil via flash chromatogra-
phy on SiO2 with 19:1 hexane/Et2O as eluent furnished 512
mg of iodide 12 (59%, 13:1 E/Z) as a colorless oil. An analytical
sample of the E isomer could be prepared by crystallization
from hexane at -10 °C, mp 63-64 °C: 1H NMR (CDCl3, 360
MHz) 7.40 (d, J ) 15.0 Hz, 1H), 6.48 (d, J ) 15.0 Hz, 1H),
6.38 (s, 1H), 3.84 (s, 3H), 3.72 (s, 3H), 2.27 (s, 3H), 1.00 (s,
9H), 0.17 (s, 6H); 13C NMR (CDCl3, 90 MHz) 152.5, 147.1,
140.2, 138.2, 131.3, 123.4, 107.3, 80.5, 60.4, 55.8, 26.0, 21.3,
18.6, -4.0; CIMS m/z (relative intensity) 435 (MH+, 55). Anal.
Calcd for C17H27IO3Si: C, 47.01; H, 6.27; I, 29.21. Found: C,
47.16; H, 6.38; I, 29.00.
1,1-Dibr om o-2-[2-(ter t-bu tyldim eth ylsiloxy)-3,4-dim eth -
oxy-6-m eth ylp h en yleth en e. As per the method of Corey
and Fuchs,16 CBr4 (3.32 g, 10 mmol) in 15 mL of CH2Cl2 was
added dropwise to a stirring, ice-cooled solution of PPh3 (5.25
g, 20 mmol) in 40 mL of CH2Cl2. Aldehyde 11 (1.55 g, 5 mmol)
in 10 mL of CH2Cl2 was added to this homogeneous orange
ylide solution, and the mixture was allowed to warm to rt over
2 h, at which time TLC (9:1 hexane/Et2O) indicated complete
consumption of aldehyde. The reaction solution was poured
into 200 mL of vigorously stirring hexane, and this mixture
was filtered through SiO2 to remove a beige solid. The filtrate
was concentrated in vacuo, and the residue obtained was
purified by flash chromatography on SiO2 with 50:1 hexane/
Et2O f 25:1 hexane/Et2O as eluent to furnish 1.88 g (81%) of
dibromide product as a colorless viscous oil. An analytical
sample could be prepared by crystallization from hexane at
-10 °C, mp 67-69 °C: 1H NMR (CDCl3, 360 MHz) 7.26 (s,
1H under CHCl3 signal), 6.41 (s, 1H), 3.85 (s, 3H), 3.71 (s, 3H),
2.22 (s, 3H), 1.02 (s, 9H), 0.18 (s, 6H); 13C NMR (CDCl3, 90
MHz) 153.1, 146.5, 138.0, 135.3, 131.6, 121.9, 106.7, 93.8, 60.4,
55.7, 25.9, 20.1, 18.6, -2.8; CIMS m/z (relative intensity) 467
(MH+, 100); HRMS calcd for C17H26Br2O3Si 464.0019, found
464.0010.
(Z)-1-Br om o-2-[2-(ter t-bu tyldim eth ylsiloxy)-3,4-dim eth -
oxy-6-m eth ylp h en yleth en e (16).17 A stirring rt solution of
1-(ter t-Bu t yld im et h ylsiloxy)-2,3-d im et h oxy-6-[(3-h y-
d r oxy-4-m eth oxyp h en yl)eth yn yl]-5-m eth ylben zen e (9a ).
A stirring solution of alkyne 6 (1.68 g, 5.49 mmol), phenolic
iodide 8a (1.51 g, 6.04 mmol,), (Ph3P)2PdCl2 (115 mg, 0.16
mmol), and CuI (61 mg, 0.32 mmol) in 15 mL of triethylamine
(16) Corey, E. J .; Fuchs, P. L. Tetrahedron Lett. 1972, 3769.
(17) Uenishi, J .; Kawahama, R.; Shiga, Y.; Yonemitsu, U.; Tsuji, J .
Tetrahedron Lett. 1996, 37, 6759.

4988 J . Org. Chem., Vol. 62, No. 15, 1997
Feldman
was purged with Ar and maintained at rt with TLC monitor-
ing. After 1 h, TLC (1:1 hexane/Et2O) indicated that iodide
8a was consumed while alkyne 6 remained. An additional
portion of iodide (100 mg, 0.4 mmol) was added. After 30 min,
TLC indicated that alkyne was consumed. The reaction
solution was poured into ice cold 1 M H3PO4 and extracted
with 2 × 50 mL of Et2O. The combined organic phases were
washed with brine, dried with Na2SO4, filtered, and concen-
trated in vacuo to give an orange oil. This oil was purified by
flash chromatography with 1:4 Et2O/hexane as eluent to
furnish 1.89 g of alkyne 9a (80%) as a white fine powder. An
analytical sample could be prepared by vapor diffusion crystal-
lization from THF/hexane, mp 134-135 °C: IR (CCl4) 3556,
OH under a balloon of hydrogen. Workup as described above,
followed by desilylation with a 1 M n-Bu4NF solution (2.0 mL,
2.0 mmol), furnished 450 mg (84%) of bis(phenol) 10 as a white
solid following chromatography.
(Z)-1-[6-Acet oxy-5,6-d im et h oxy-3-m et h yl-1-oxocyclo-
h exa -2,4-d ien -2-yl]-2-[6-a cet oxy-6-m et h oxy-1-oxocyclo-
h exa -2,4-d ien -3-yl]eth en e (1a ). A solution of bis(phenol) 10
(190 mg, 0.60 mmol) in 5 mL of CH2Cl2 was added dropwise
to a stirring, -78 °C solution/suspension of Pb(OAc)4 (586 mg,
1.32 mmol) in 25 mL of CH2Cl2. An immediate bright yellow-
orange solution resulted. After 30 min, TLC indicated com-
plete consumption of 10. The reaction solution was poured
into 20 mL of ice cold H2O containing 1 mL of a saturated
NaHCO3 solution, and the layers were separated. The aqueous
phase was extracted with CH2Cl2, and the combined organic
layers were washed with brine, dried with Na2SO4, filtered,
and concentrated in vacuo. The residue was purified by flash
chromatography on SiO2 deactivated with 15% by wt H2O
using 2:1 Et2O/hexane f 3:1 Et2O/hexane as eluent to yield
182 mg (1:1 mixture of diastereomers A and B, 70%) of bis-
(quinone monoketal) 1a as an orange foam. Chromatography
of SiO2 without H2O deactivation led to significant decomposi-
2240 cm-1 1H NMR (CDCl3, 360 MHz) 7.08 (d, J ) 1.9 Hz,
;
1H), 7.04 (dd, J ) 8.3, 2.0 Hz, 1H), 6.81 (d, J ) 8.4 Hz, 1H),
6.44 (s, 1H), 5.58 (s, 1H), 3.91 (s, 3H), 3.86 (s, 3H), 3.73 (s,
3H), 2.43 (s, 3H), 1.06 (s, 9H), 0.25 (s, 6H); 13C NMR (CDCl3,
90 MHz) 153.3, 150.1, 146.6, 145.3, 138.0, 137.0, 123.8, 117.3,
110.5, 109.8, 106.6, 96.0, 84.7, 60.4, 55.9, 55.8, 26.0, 21.2, 18.7,
-3.1; CIMS m/z (relative intensity) 429 (MH+, 100). Anal.
Calcd for C24H32O5Si: C, 67.26; H, 7.53. Found: C, 67.19; H,
7.62.
1
1-(ter t-Bu tyld im eth ylsiloxy)-6-[3-(ter t-bu tyld im eth ysi-
loxy)-4-(m eth oxyp h en yl)eth yn yl]-2,3-d im eth oxy-6-m eth -
ylben zen e (9b). In a manner analogous to the synthesis of
9a , alkyne 6 (503 mg, 1.64 mmol), iodide 8b (657 mg, 1.8
mmol), (Ph3P)2PdCl2 (35 mg, 0.05 mmol), and CuI (19 mg, 0.1
mmol) were combined in 5 mL of triethylamine. Workup as
described for 9a (no additional iodide was required) yielded
648 mg (84%) of alkyne 9b as a white solid following flash
chromatography on SiO2 with 4:1 hexane/Et2O as eluent. An
analytical sample could be prepared by recrystallization from
hexane at -10 °C, mp 130 °C: 1H NMR (CDCl3, 360 MHz)
7.09 (dd, J ) 8.3, 2.0 Hz, 1H), 7.01 (d, J ) 2.0 Hz, 1H), 6.79
(d, J ) 8.4 Hz, 1H), 6.44 (s, 1H), 3.86 (s, 3H), 3.82 (s, 3H),
3.73 (s, 3H), 2.43 (s, 3H), 1.06 (s, 9H), 1.01 (s, 9H), 0.25 (s,
6H), 0.17 (s, 6H); 13C NMR (CDCl3, 360 MHz) 153.2, 150.6,
149.3, 144.7, 137.7, 136.9, 125.4, 123.7, 116.7, 111.9, 109.4,
106.6, 96.3, 84.4, 60.4, 55.8, 55.5, 26.0, 25.7, 21.2, 18.7, 18.4,
-2.6, -3.1; CIMS m/z (relative intensity) 543 (MH+, 100).
Anal. Calcd for C30H46O5Si2: C, 66.36; H, 8.56. Found: C,
65.94; H, 8.68.
(Z)-1-(3,4-Dim eth oxy-2-h yd r oxy-5-m eth ylp h en yl)-2-(3-
h yd r oxy-4-m eth oxyp h en yl)eth en e (10). F r om Bis(silyl
eth er ) 9b. A stirring solution of alkyne 9b (377 mg, 0.69
mmol) and quinoline (1.56 mL of a 0.071 M quinoline/CH3OH
solution, 0.11 mmol) in 50 mL of CH3OH was charged with
Lindlar’s catalyst (471 mg), purged with Ar and then H2, and
brought to reflux under a balloon filled with H2. After 1.5 h,
TLC analysis (9:1 hexane/Et2O) indicated complete consump-
tion of starting material. The reaction solution was cooled to
rt, purged with Ar, filtered through Celite, and concentrated
in vacuo. The residue was taken up in 30 mL of THF and
cooled in an ice bath, and n-Bu4NF (1.72 mL of a 1 M THF
solution, 1.72 mmol) was added with stirring. After 5 min,
TLC (1:1 hexane/Et2O) indicated consumption of bis-silyl ether.
The reaction solution was poured into ice cold 1M H3PO4 and
extracted with 2 × 20 mL of Et2O. The combined organic
phases were washed with brine, dried with Na2SO4, filtered,
and concentrated in vacuo. The residue was purified by flash
chromatography on SiO2 with 2:1 hexane/Et2O f 1:1 hexane/
Et2O to furnish 191 mg (88% from alkyne 9b) of the bis(phenol)
10 as a white solid. An analytical sample could be prepared
by vapor diffusion crystallization with THF/hexane, mp 136-
138 °C: IR (CCl4) 3557, 3525 cm-1; 1H NMR (CDCl3, 360 MHz)
6.73 (s, 1H), 6.66 (d, J ) 1.1 Hz, 1H), 6.61 (d, J ) 12.0 Hz,
1H), 6.32 (d, J ) 13.5 Hz, 1H), 5.69 (s, 1H), 5.43 (s, 1H), 3.86
(s, 3H), 3.85 (s, 3H), 3.83 (s, 3H), 2.10 (s, 3H); 13C NMR (CDCl3,
90 MHz) 151.3, 146.4, 145.9, 145.1, 133.8, 132.0, 131.9, 131.0,
122.3, 120.7, 117.2, 114.2, 110.2, 105.6, 61.0, 55.8, 55.7, 20.0;
CIMS m/z (relative intensity) 317 (MH+, 100). Anal. Calcd
for C18H20O5: C, 68.34; H, 6.37. Found: C, 68.38; H, 6.49.
F r om Mon op h en ol 9a . In a manner analogous to that
described above, alkyne 9a (730 mg, 1.70 mmol), 950 mg of
Lindlar’s catalyst, and quinoline (3.59 mL of a 0.071 M solution
in CH3OH, 0.25 mmol) were stirred at reflux in 50 mL of CH3-
tion: IR (CCl4) 1743, 1673 cm-1; H NMR (C6D6, 360 MHz),
6.73 (dd, J ) 10.1, 1.5 Hz, 1H A), 6.65 (dd, J ) 10.1, 1.6 Hz,
1H B), 6.50 (d, J ) 11.9 Hz, 1H A), 6.45 (d, J ) 11.8 Hz, 1H
B), 6.11 (dd, J ) 10.0, 0.5 Hz, 1H A), 6.07 (dd, J ) 10.6, 0.5
Hz, 1H B), 6.03 (s, 1H A), 6.02 (s, 1H B), 5.95 (d, J ) 11.9 Hz,
1H A), 5.91 (d, J ) 11.9 Hz, 1H B), 4.89 (s, 1H A), 4.85 (s, 1H
B), 3.44 (s, 2 × 3H A and B), 3.37 (s, 3H A), 3.33 (s, 3H B),
2.99 (s, 3H A), 2.97 (s, 3H B), 1.86 (d, J ) 1.1 Hz, 3H A), 1.80
(d, J ) 1.1 Hz, 3H B), 1.71 (s, 3H A), 1.70 (s, 3H B), 1.60 (s,
3H A), 1.59 (s, 3H B); 13C NMR (C6D6, 90 MHz) 191.1, 191.0,
188.4, 188.3, 169.5, 169.3, 169.0, 168.9, 161.5, 161.3, 152.4,
152.1, 149.0, 148.9, 134.7, 134.5, 131.4, 131.3, 126.9, 126.7,
124.8, 124.6, 124.4, 100.4, 100.3, 93.7, 93.6, 93.3, 93.2, 55.4,
55.3, 51.8, 50.8, 22.4, 20.2, 20.1, 20.0; FABMS m/z (relative
intensity) 432 (M+, 6); HRMS calcd for C22H24O9 432.1420,
found 432.1429.
[3-(ter t-Bu tyld im eth ylsiloxy)-4-m eth oxyp h en yl]tr i-n -
bu tylsta n n a n e (13). Aryl iodide 8b (2.61 g, 7.2 mmol) in 15
mL of THF was added dropwise to a rt suspension of Mg° (190
mg, 7.9 g-atom) in n-Bu3SnCl (2.1 mL, 7.9 mmol) with vigorous
stirring. The solution began refluxing and was maintained
at this temperature by gentle warming. After 5 h, most of
the Mg was consumed and the mixture was cooled to rt, poured
into ice cold 1 M H3PO4, and extracted with 2 × 50 mL of
hexane. The combined organic phases were washed with
brine, dried with Na2SO4, filtered, and concentrated in vacuo
to afford 4.24 g of a colorless mobile oil. 1H NMR analysis
revealed a 3:1 mixture of arylstannane to starting iodide. A
portion of this mixture (3.66 g) was purified by flash chroma-
tography on SiO2 deactivated with 25 wt % H2O, using 98:1:1
hexane/benzene/triethylamine as eluent, to furnish 1.02 g
(27%) of stannane 13 as a colorless, mobile oil. The remainder
of the recovered material consisted of a mixture of stannane
13, iodide 8b, and destannylated TBDS‚guaiacol. 13: 1H NMR
(CDCl3, 360 MHz) 6.97 (dd, J ) 7.7, 1.2 Hz, 1H), 6.92 (d, J )
1.2 Hz, 1H), 6.85 (d, J ) 7.8 Hz, 1H), 3.79 (s, 3H), 1.5 (m, 6H),
1.3 (m, 6H), 1.0 (m, 6H), 0.99 (s, 9H), 0.88 (t, J ) 7.3 Hz, 9H),
0.15 (s, 6H); 13C NMR (CDCl3, 90 MHz) 151.0, 144.9, 132.4,
129.8, 128.7, 107.9, 55.4, 29.1, 27.4, 25.8, 18.5, 13.6, 9.6, -2.7;
CIMS m/z (relative intensity) 529 (MH+, 19); HRMS calcd for
C25H48SiSnO2 528.2459, found 528.2462.
(E)-1-(6-Acet oxy-5,6-d im et h oxy-3-m et h yl-1-oxocyclo-
h exa -2,4-d ien -2-yl)-2-(6-a cet oxy-6-m et h oxy-1-oxocyclo-
h exa -2,4-d ien -3-yl)eth en e (15). Meth od A. As per the
method of Liebeskind,10b iodide 12 (247 mg, 0.57 mmol) and
stannane 13 (300 mg, 0.57 mmol) in 3 mL of N-methylpyr-
rolidone were cooled to 0 °C and treated with copper 2-thiene-
carboxylate (163 mg, 0.85 mmol) with vigorous stirring. TLC
analysis (4:1 hexane/Et2O) indicated consumption of stannane
after 15 min, but iodide 12 remained. After 5 h, TLC revealed
a new compound along with iodide 12. The reaction solution
was poured into 50 mL of Et2O, filtered through a plug of SiO2,
concentrated, and purified by flash chromatography on SiO2
with 50:1 hexane/Et2O f 25:1 hexane/Et2O as eluent to furnish

Cyclization Pathways of a Bis(orthoquinone monoketal)
J . Org. Chem., Vol. 62, No. 15, 1997 4989
54 mg (18%) of (E)-biaryl alkene 14 as a colorless oil which
crystallized upon standing: 1H NMR (CDCl3, 200 MHz) 7.0
(m, 2H), 6.92 (d, J ) 17.4 Hz, 1H), 6.82 (d, J ) 8.4 Hz, 1H),
6.68 (d, J ) 18.0 Hz, 1H), 6.44 (s, 1H), 3.86 (s, 3H), 3.83 (s,
3H), 3.75 (s, 3H), 2.39 (s, 3H), 1.02 (s, 9H), 0.96 (s, 9H), 0.18
(s, 6H), 0.13, (s, 6H).
vacuo, and purified by flash chromatography on SiO2 deacti-
vated with 20 wt % H2O, using 2:1 hexane/Et2O f 1:1 hexane/
Et2O as eluent, to afford 33 mg (47%) of the less polar off-
white compounds 23a /b as an inseparable mixture followed
by 15 mg (21%) of the more polar species 20 as a yellow/orange
solid.
20: IR (CCl4) 3551, 1747, 1678 cm-1; 1H NMR (CDCl3, 360
MHz) 6.98 (d, J ) 11.5 Hz, 1H), 6.91 (d, J ) 11.8 Hz, 1H),
6.80 (d, J ) 8.4 Hz, 1H), 6.77 (d, J ) 8.4 Hz, 1H), 5.70 (s, 1H),
5.54 (s, 1H), 3.90 (s, 3H), 3.79 (s, 3H), 3.60 (d, J ) 12.5 Hz,
1H), 3.41 (s, 3H), 3.32 (d, J ) 12.5 Hz, 1H), 2.14 (s, 3H); 13C
NMR (CDCl3, 90 MHz) 188.5, 169.3, 160.9, 147.6, 147.0, 141.8,
132.1, 131.3, 123.0, 122.6, 120.4, 119.1, 108.8, 100.9, 93.6, 56.3,
56.2, 52.4, 33.1, 20.4; FABMS m/z (relative intensity) 372 (45),
313 (80); HRFABMS calcd for C20H20O7 372.1209, found
372.1205.
HPLC purification (1:1 Et2O/hexane as solvent) of the
mixture 23a /b led to enriched fractions of 23a and 23b
consisting of ca. 80% of the title compound and 20% of a
mixture of its diastereomer and unidentified material.
23a : IR (CCl4) 3351, 1737 cm-1; 1H NMR (CDCl3, 360 MHz)
6.96 (s, 1H), 6.81 (s, 1H), 6.64 (d, J ) 5.4 Hz, 1H), 6.51 (d, J
) 5.5 Hz, 1H), 5.91 (s, 1H), 5.69 (s, 1H), 4.76 (s, 1H), 4.25 (s,
1H), 3.90 (s, 3H), 3.78 (s, 3H), 3.33 (s, 3H), 2.14 (s, 3H); 13C
NMR (CDCl3, 90 MH3) 194.4, 169.1, 151.6, 145.8, 145.5, 139.3,
137.9, 136.2, 135.9, 131.4, 110.1, 108.7, 108.2, 105.4, 96.2, 72.4,
56.4, 55.9 53.0 20.4; CIMS m/z (relative intensity) 372 (M+,
65); HRMS calcd for C20H20O7 372.1209, found 372.1206.
Meth od B. As per the method of Farina,10a stannane 13
(321 mg, 0.61 mmol), iodide 12 (265 mg, 0.61 mmol), (PhCN)
2PdCl2 (8 mg, 0.03 mmol), CuI (6 mg, 0.03 mmol), and Ph3As
(37 mg, 0.12 mmol) in 4 mL of DMF were warmed to 58 °C
with vigorous stirring. After 1 h, TLC indicated consumption
of stannane, and the solution was worked up as described in
method A to afford 63 mg (19%) of (E)-alkene 14.
The combined silyl ether samples from three coupling runs
(135 mg, 0.24 mmol) in 5 mL of THF were treated with a 1 M
solution of n-Bu4NF in THF (600 uL, 0.6 mmol) at 0 °C with
stirring. TLC analysis (1:1 Et2O/hexane) indicated complete
consumption of starting material after 5 min. The reaction
mixture was poured into ice cold 1 M H3PO4 and extracted
with 2 × 10 mL of Et2O. The combined ethereal layers were
washed with brine, dried with Na2SO4, filtered, and concen-
trated in vacuo. The residue was purified by flash chroma-
tography on SiO2 with 1:1 hexane/Et2O as eluent to yield 66
mg (88%) of bis(phenol) as a white solid: 1H NMR (CDCl3, 200
MHz) 7.24 (d, J ) 14.8 Hz, 1H), 7.18 (d, J ) 3.1 Hz, 1H), 6.99
(d, J ) 15.5 Hz, 1H), 6.97 (dd, J ) 9.0, 3.0 Hz, 1H), 6.82 (d, J
) 8.8 Hz, 1H), 6.37 (s, 1H), 6.27 (s, 1H), 5.52 (s, 1H), 3.92 (s,
6H), 3.87 (s, 3H), 2.38 (s, 3H).
This bis(phenol) (64 mg, 0.20 mmol) in 2 mL of CH2Cl2 was
added dropwise to a stirring solution/suspension of Pb(OAc) 4
(194 mg, 0.44 mmol) in 3 mL of CHCl2 at -78 °C. An
immediate bright orange solution with a white precipitate
resulted. After 5 min at -78 °C, TLC (1:1 hexane/Et2O)
indicated that starting bis(phenol) was consumed. The reac-
tion solution was poured into ice cold water containing 1 mL
of saturated NaHCO3 solution, and the layers were separated.
The aqueous phase was extracted with 2 × 10 mL of Et2O,
and the combined organic layers were washed with brine, dried
over Na2SO4, filtered, and concentrated in vacuo. The reside
was purified by flash chromatography on SiO2 using Et2O as
eluent to furnish 65 mg (75%, 1:1 mixture of diastereomers A
23b: IR (CCl4) 3553, 1748, 1730 cm-1; 1H NMR (CDCl3, 360
MHz) 7.05 (s, 1H), 6.87 (s, 1H), 6.85 (d, J ) 5.5 Hz, 1H), 6.41
(d, J ) 5.5 Hz, 1H), 5.97 (s, 1H), 5.60 (s, 1H), 4.80 (s, 1H),
4.73 (s, 1H) 3.84 (s, 3H) 3.81 (s, 3H), 3.26 (s, 3H), 2.13 (s, 3H);
13C NMR (CDCl3, 90 MHz) 194.5, 169.4, 151.6, 145.7, 144.8,
139.5, 138.6, 138.0, 137.0, 133.5, 110.7, 108.2, 106.9, 105.5,
95.4, 69.5, 56.4, 55.9, 53.0, 20.5; CIMS m/z (relative intensity)
372 (60); HRMS calcd for C20H20O7 372.1209, found 372.1229.
Further elution afforded the ketal hydrolysis product 24:
1
IR (CCl4) 3551, 1697 cm-1; H NMR (CDCl3, 360 MHz) 6.97
(s, 1H), 6.82 (d, J ) 5.6 Hz, 1H), 6.81 (s, 1H), 6.41 (d, J ) 5.5
Hz, 1H), 5.71 (s, 1H), 5.15 (s, 1H), 5.04 (s, 1H), 3.90 (s, 3H),
3.88 (s, 3H); 13C NMR (CDCl3, 90 MH3) 190.6, 177.1, 153.0,
146.4, 145.5, 137.3, 134.4, 134.3, 133.6, 122.1, 116.2, 109.1,
107.3, 74.4, 56.3, 55.9; CIMS m/z (relative intensity) 298 (16);
HRCIMS calcd for C17H14O5 298.0841, found 298.1063.
and B) of 15 as an orange solid: IR (CCl4) 1746, 1670 cm-1
;
1H NMR (C6D6, 360 MHz) 7.30 (d, J ) 16.2 Hz, 1H A), 7.28 (d,
J ) 16.3 Hz, 1H B), 6.84 (d, J ) 16.5 Hz, 1H A), 6.83 (d, J )
16.2 Hz, 1H B), 6.44 (dd, J ) 10.3, 1.4 Hz, 1H A), 6.42 (dd, J
) 10.2, 1.4 Hz, 1H B), 6.14 (m, 2H A and B), 4.83 (s, 1H A and
B), 3.42 (s, 3H A and B), 3.39 (s, 3H A), 3.38 (s, 3H B), 3.10 (s,
3H A and B), 1.77 (s, 3H A), 1.76 (s, 3H B), 1.664 (s, 3H A),
1.660 (s, 3H B), 1.55 (s, 3H A and B); 13C NMR (C6D6, 90 MHz)
191.0, 189.9, 188.9, 169.2, 168.9, 162.05, 162.02, 155.3, 153.3,
147.7, 147.6, 135.4, 135.3, 130.3, 130.2, 128.65, 128.60, 124.3,
124.2, 124.1, 122.8, 122.6, 122.5, 101.56, 101.55, 94.4, 94.3,
93.6, 55.6, 52.15, 52.13, 51.0, 21.8, 21.7, 20.2, 20.1; FABMS
m/z (relative intensity) 432 (10), 373 (82); HRFABMS calcd
for C22H24O9 432.1420, found 432.1436.
Acetyla tion of 23a /b. A stirring solution of 23a /b (ca. 1:1
mixture) (8 mg, 21 µmol) in 1 mL of CH2Cl2 at rt was treated
sequentially with DMAP (10 mg, 82 µmol) and AcCl (3 µL, 42
µmol). After 22 h at rt, TLC analysis (4:1 hexane/Et2O)
indicated that 23a /b was consumed. The solution was poured
into ice cold 1 M H3PO4, and the layers were separated. The
aqueous phase was extracted wtih 10 mL of CH2Cl2, and the
combined organic layers were washed with brine, dried over
Na2SO4, filtered, and concentrated in vacuo. The residue was
purified by flash chromatography on SiO2 with 4:1 hexane/
Et2O as eluent to furnish 8 mg (95%) of dienone 25 as a yellow
solid: IR (CCl4) 1776, 1660 cm-1; 1H NMR (CDCl3, 360 MHz)
7.07 (s, 1H), 7.02 (d, J ) 5.4 Hz, 1H), 6.71 (t, J ) 1.3 Hz, 1H),
6.69 (s, 1H), 6.13 (d, J ) 5.4 Hz, 1H), 4.17 (s, 3H), 3.77 (s,
3H), 3.73 (s, 3H), 3.62 (dd, J ) 14.3, 1.4 Hz, 1H), 3.56 (dd, J
) 14.3, 1.4 Hz, 1H), 2.31 (s, 3H); 13C NMR (CDCl3, 90 MHz)
190.7, 168.8, 158.3, 143.0, 142.2, 140.3, 137.9, 136.6, 135.9,
135.0, 120.7, 116.7, 107.2, 71.3, 60.3, 58.8, 56.3, 42.0, 20.7;
CIMS m/z (relative intensity) 391 (MH+, 65); HRMS calcd for
C20H19C1O6 390.0870, found 390.0881.
Ir r a d ia tion of (Z)-Bis(or th oqu in on e m on ok eta l) 1a .
(Z)-Bis(orthoquinone monoketal) 1a (9 mg, 0.02 mmol) in 1.5
mL of C6D6 was deoxygenated by three freeze-thaw cycles in
a resealable NMR tube and placed in a Rayonet photoreactor
equipped with 350 nm bulbs. After 2 h, 1H NMR analysis
indicated an approximately 3:1 mixture of (E)-alkene 15 and
(Z) starting material 1a . No evidence for other compounds
could be discerned.
Ir r a d ia tion of (E)-Bis(or th oqu in on e m on ok eta l) 15.
(E)-Bis(orthoquinone monoketal) 15 (12 mg, 0.028 mmol) in
1.5 mL of C6D6 was deoxygenated by three freeze-thaw cycles
in a resealable NMR tube and placed in a Rayonet photoreactor
equipped with 300 nm bulbs. After a 6 h irradiation, 1H NMR
analysis indicated that no new compounds were evident.
Th er m olysis of (Z)-Bis(or th oqu in on e m on ok eta l) 1a in
Ben zen e, 0.94 m M Con cen tr a tion . (Z)-Bis(orthoquinone
monoketal) 1a (82 mg, 0.19 mmol) in 200 mL of benzene was
heated to reflux and held there for 4.5 h. At that time, TLC
analysis (3:1 Et2O/hexane) indicated that starting bis(ortho-
quinone) 1a was consumed, and two new less polar compounds
were evident. The solution was cooled to rt, concentrated in
Th er m olysis of (Z)-Bis(or th oqu in on e m on ok eta l) 1a in
Ben zen e, 27.8 m M Con cen tr a tion . (Z)-Bis(orthoquinone
monoketal) 1a (18 mg, 0.041 mmol) in 1.5 mL C6D6 was frozen
and evacuated in a resealable NMR tube. This tube was
1
placed in a 82-84 °C oil bath with H NMR monitoring. After
9.5 h, 1H NMR analysis indicated that starting material 1a
was consumed. One major new compound 27 was evident,
along with small amounts (∼7% each of 20 and 23a /b). Flash
chromatography on SiO2 with 1:1 hexane/Et2O f 1:2 hexane/
Et2O as eluent yielded 2 mg (11%) of quinone monoketal 27
as a yellow/orange solid: IR (CCl4) 3561, 1767, 1747, 1671

4990 J . Org. Chem., Vol. 62, No. 15, 1997
cm-1 1H NMR (CDCl3, 360 MHz) 6.92 (s, 1H), 6.54 (d, J )
12.1 Hz, 1H), 6.52 (s, 1H), 6.14 (d, J ) 11.9 Hz, 1H), 6.11 (d,
J ) 1.1 Hz, 1H), 5.96 (s, 1H), 5.19 (s, 1H), 3.84 (s, 3H), 3.74 (s,
3H), 3.47 (s, 3H), 2.31 (s, 3H), 2.18 (s, 3H), 1.81 (s, 3H); FABMS
m/z (relative intensity) 432 (M+, 60); HRFABMS calcd for
C22H24O9 432.1420, found 432.1429.
Feldman
;
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for 1a , 8b, 13, 15, 20, 23a /b, 24, 25, and 27 and
HMQC/HMBC spectra with interpretation for 23a (15 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
Ack n ow led gm en t. Support from the NIH (GM
35727) is gratefully acknowledged.
J O9704220