o-quinone methides from 4-allenylcyclobutenones: Synthesis and chemistry

Article abstract of DOI:10.1021/jo951445m

Selected 4-allenylcyclobutenones ring expand to the corresponding o-quinone methides upon thermolysis in refluxing toluene or benzene. These reactive intermediates were not isolated but trapped to give stable products. The reaction has synthetic potential as a route to highly-substituted phenols, benzofurans, and aryl analogs of hexahydrocannabinol. In addition, a unique rearrangement involving a methyl migration from silicon to carbon of selected 4-[3,3-bis(trimethylsilyl)-1,2-propadienyl]cyclobutenones to give 1,2-benzoxasilols is described. Finally, data are presented that show rapid rotation around the alkylidene bond of o-quinone methides at 30°C and that 2-(1-methylethenyl)phenols are in equilibrium with the corresponding o-quinone methides.

Full text of DOI:10.1021/jo951445m

J . Org. Chem. 1996, 61, 329-340
329
o-Qu in on e Meth id es fr om 4-Allen ylcyclobu ten on es: Syn th esis a n d
Ch em istr y
Meng Taing and Harold W. Moore*
Department of Chemistry, University of California, Irvine, California 92717
Received August 4, 1995X
Selected 4-allenylcyclobutenones ring expand to the corresponding o-quinone methides upon
thermolysis in refluxing toluene or benzene. These reactive intermediates were not isolated but
trapped to give stable products. The reaction has synthetic potential as a route to highly-substituted
phenols, benzofurans, and aryl analogs of hexahydrocannabinol. In addition, a unique rearrange-
ment involving a methyl migration from silicon to carbon of selected 4-[3,3-bis(trimethylsilyl)-1,2-
propadienyl]cyclobutenones to give 1,2-benzoxasilols is described. Finally, data are presented that
show rapid rotation around the alkylidene bond of o-quinone methides at 30 °C and that 2-(1-
methylethenyl)phenols are in equilibrium with the corresponding o-quinone methides.
Reported here are a number of studies associated with
the thermally induced rearrangements of selected 4-al-
lenylcyclobutenones. These rearrangements lead to ring-
expanded products and proceed via o-quinone methides,
a synthetically useful class of reactive intermediates that
previously were not readily available by a general route
with the control of regiochemistry that is inherent in the
method outlined herein.1-3 This new route to o-quinone
methides along with the fact that the ring expansions
proceed under neutral conditions allows synthetic studies
and mechanistic investigations that would be difficult or
impossible to approach by other methods. Examples of
such studies are presented herein as follows: (1) vinyl
quinones, available from o-quinone methides bearing at
least one alkyl group on the alkylidene terminus, undergo
a previously unknown isomerization to benzofurans
(Scheme 1); (2) selected o-quinone methides bearing a
trimethylsilyl group on the alkylidene terminus proceed
to benzoxasilols by an unusual reaction involving methyl
migration from silicon to carbon (Scheme 3); (3) a tandem
ring expansion/intramolecular Diels-Alder cycloaddition
route to enantiomerically pure aryl analogs of hexahy-
drocannabinol is presented (Scheme 4); (4) mechanistic
data showing a facile (30 °C) configurational equilibration
of o-quinone methides bearing two alkyl groups at the
alkylidene terminus were obtained; (5) finally, data are
provided that establish an equilibrium between selected
2-(1-methylethenyl)-1,4-benzenediols and the correspond-
ing o-quinone methides.
R egiosp ecific Syn t h esis of H igh ly-Su b st it u t ed
2-Alk en ylp h en ols: A New Ben zofu r a n Syn th esis. A
potentially general regiospecific route to highly-substi-
tuted 2-alkenylphenols is outlined in Scheme 1. Here,
the starting cyclobutenones 1a -d were prepared as
mixtures of diastereomers by the addition of 1-lithio-1-
methoxy-3-(trimethylsilyl)-1,2-hexadiene to the corre-
sponding cyclobutenedione at -78 °C in THF.1,4 Ther-
molysis of these adducts at 110 °C (toluene) gave 1-(tri-
methylsilyl)-1(E)-butenyl-substituted hydroquinones 3a-d
in good yields (75-90%). Such transformations docu-
ment an efficient route to synthetically useful 2-(1-(tri-
methylsilyl)ethenyl)phenols and further license regio-
control in the synthesis of highly-substituted aromatic
compounds from cyclobutenones.5,6 The structures of the
phenol derivatives, including the (E) stereochemistry of
the alkene moiety, were established on the basis of their
spectral properties as well as a complete X-ray crystal
structure of 3a .7
The above rearrangements are envisaged to involve
ring expansion of the cyclobutenones 1 to the correspond-
ing o-quinone methides 2. These, in turn, suffer a 1,5-
hydrogen shift thus leading to the 2-ethenylphenols 3.
It is of interest that even though precedents exist for the
1,5-hydrogen shift within o-quinone methides, the reac-
tion has not been generally employed as a synthetically
viable reaction.8,9 This is likely due to the fact that until
now no general regiospecific route to these intermediates
was available.
X Abstract published in Advance ACS Abstracts, December 15, 1995.
(1) For lead references concerning the synthesis of substituted
cyclobutenones, see: Schmidt, A. H.; Ried, W. Synthesis 1978, 1. Knorr,
H.; Ried, W. Synthesis 1978, 649. Schmidt, A. H.; Ried, W. Synthesis
1978, 869. Reed, M. W.; Pollart, D. J .; Perri, S. T.; Foland, L. D.; Moore,
H. W. J . Org. Chem. 1988, 53, 2477. Liebeskind, L. S.; Fengl, R. W.;
Wirtz, K. R.; Shawe, T. T. J . Org. Chem. 1988, 53, 2482. Liebeskind,
L. S.; Fengl, R. W. J . Org. Chem. 1990, 55, 5359. Liebeskind, L. S.;
Wirtz, K. R. J . Org. Chem. 1990, 55, 5350. Liebeskind, L. S.; Wang, J .
Tetrahedron Lett. 1990, 4293.
The ring expansion reaction also provides a useful
route to alkyl quinones, i.e., oxidation of the initially
formed 2-alkenylphenols (hydroquinones). A syntheti-
cally useful and mechanistically interesting reaction of
(2) Excellent reviews of allene chemistry are the following: Moreau,
J . L. In The Chemistry of Ketenes, Allenes and Related Compounds;
Patai, S., Ed.; Wiley: New York, 1980; p 363. Schuster, H. E.; Coppola,
G. M. Allenes In Organic Synthesis; Wiley: New York, 1984. For a
specific reference to 1-lithio-1-methoxyallene, see: Hoff, S.; Brandsma,
L.; Arens, J . F. Recl. Trav. Chim. Pays-Bas 1968, 87, 916. Weiberth,
F. J .; Hall, S. S. J . Org. Chem. 1985, 50, 5308.
(3) For reviews on the chemistry of quinone methides, see: Veciana,
J .; Martinez, A. D.; Armet, O. Rev. Chem. Intermed. 1988, 10 (1), 35-
70. Volod’kin, A. A.; Ershov, V. V. Usp. Khim. 1988, 57 (4), 595-624.
Also see the following and references cited therein; Angle, S. R.; Arnaiz,
D. O. J . Org. Chem. 1990, 55, 3708-10. Angle, S. R.; Turnbull, K. D.
J . Am. Chem. Soc. 1990, 112, 3698-700. Angle, S. R.; Yang, W. J .
Am. Chem. Soc. 1990, 112, 4524-8. Angle, S. R.; Louie, M. S.; Mattson,
H. L.; Yang, W. Tetrahedron Lett. 1989, 30, 1193-6. Angle, S. R.;
Turnbull, K. D. J . Am. Chem. Soc. 1989, 111, 1136-8.
(4) Allenes in this series are conveniently prepared from readily
available propargyl ethers. See for examples: Corey, E. J .; Terashim,
S. Tetrahedron Lett. 1972, 1819. Leroux, Y.; Roman, C. Tetrahedron
Lett. 1973, 2585. Mantione, R.; Leroux, Y. Tetrahedron Lett. 1971, 593.
(5) For a recent detailed reviews on related ring expansions of
cyclobutenones, see: Moore, H. W.; Yerxa, B. R. Chemtracts: Org.
Chem. 1992, 5, 273. Moore, H. W.; Yerxa, B. R. Advances in Strain in
Organic Chemistry; J AI: London, 1995; Vol. 4.
(6) For reviews on the synthetic utility of vinylsilanes, see: Fleming,
I. Kem. Kemi 1982, 9(5), 365. Huang, Z. Huaxue Shiji 1991, 13 (1), 32.
Overman, L. E. Lect. Heterocycl. Chem. 1985, 8, 59.
(7) The authors have deposited atomic coordinates for compound 3a
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
0022-3263/96/1961-0329$12.00/0 © 1996 American Chemical Society

330 J . Org. Chem., Vol. 61, No. 1, 1996
Taing and Moore
Sch em e 1
Sch em e 2
A modification of the above procedure allows the
silylbenzofurans to be prepared in reasonable overall
yields from the corresponding vinyl hydroquinones. For
example, when the hydroquinones 3b and 3d were
subjected to oxidation (Ag2O) and benzene solutions of
the resulting crude quinone products 4b and 4d were
refluxed in the presence of silica gel, the silylbenzofurans
8b and 8d were obtained in 54 and 55% yields, respec-
tively.
The potential generality of the vinylhydroquinone/
vinylquinone/benzofuran synthesis is further illustrated
by the observation that the starting vinyl quinones are
readily available from 4-allenylcyclobutenones as il-
lustrated by the examples outlined in Scheme 2. Specif-
ically, the cyclobutenones 9a (70%), 9b (70%), and 12
(34%) were prepared from dimethyl squarate and the
corresponding allenyllithium reagents. The vinyl hyd-
roquinones 10 and 11 were obtained in nearly quantita-
tive yields from 9a and 9b, respectively (toluene, 110 °C).
In an analogous manner, thermolysis of 12 gave the
quinone 13 (75%) after subsequent oxidation of the
initially formed hydroquinone.
Gen er a tion a n d Rea r r a n gem en t of Selected Tr i-
m eth ylsilyl-Su bstitu ted o-Qu in on e Meth id es: Syn -
th esis of Ben zoxa silols. The convergent synthesis of
4-allenylcyclobutenones and the propensity of these cy-
clobutenones to rearrange provide a potentially general
route to o-quinone methides having unique or unusual
structures. In this regard, an example showing interest-
ing chemistry associated with a previously unknown class
of o-quinone methide is found in a new carbon-carbon
bond forming reaction (Scheme 3). Specifically, the
cyclobutenone 14 [40% yield from dimethyl squarate and
1-lithio-1-tert-butoxy-3,3-bis(trimethylsilyl)propadiene] was
initially targeted as a potential precursor to the quinone
methide 15, a sterically hindered and thus possibly
isolable example. However, under the thermolysis condi-
tions employed (toluene, 110 °C), 14 undergoes an
unusual intramolecular rearrangement to 17 (>90%). In
a similar fashion, the analogous phenyl analog 18 gives
20 (94%) via the o-quinone methide 19. The spectral and
such quinones is illustrated by the isomerization of the
quinone 4a to benzofuran 8 and ultimately to the desilyl-
ated analog 5. This was accomplished in 75% overall
yield starting from the hydroquinone 3a , i.e., oxidation
(Ag2O) of 3a to quinone 4a (90%) followed by its treat-
ment with trifluoroacetic acid (TFA). The transformation
is envisaged to involve formation of cation 6 upon
protonation of 4a , ring closure to 7, and finally proton
loss. The resulting trimethylsilyl-substituted benzofuran
8 then undergoes protiodesilylation to give 5.
(8) For examples of 1,5-hydrogen shift involving o-quinone methides,
see: Yamashita, A.; Toy, A.; Scahill, T. A. J . Org. Chem. 1989, 54,
3625. Yamashita, A. J . Am. Chem. Soc. 1985, 107, 5823. Yamashita,
A.; Scahill, T. A.; Chidester, C. G. Tetrahedron Lett. 1985, 1159. Arduni,
A.; Pochini, A.; Ungaro, R. Synthesis 1984, 950. J urd, D. Aust. J . Chem.
1978, 31, 347. Casnati, G.; Pochini, A.; Terenghi, G. M.; Ungaro, R. J .
Org. Chem. 1983, 48, 3783.
(9) Boger, D. L.; Weinreb, S. N. Hetero Diels-Alder Methodology in
Organic Synthesis; Academic Press Inc.: London, 1987; pp 193-199.

o-Quinone Methides from 4-Allenylcyclobutenones
J . Org. Chem., Vol. 61, No. 1, 1996 331
Sch em e 3
annulated products via subsequent intramolecular het-
ero-Diels-Alder cycloadditions. In this regard, work
outlining a potentially general route to enantiomerically
pure aryl analogs of hexahydrocannabinol is presented
here. Since the cannabinoids have been observed to show
marked antinausea activity new routes to analogs are
important.
The natural cannabinoids, ∆8-tetrahydrocannabinol
(THC) (21) and ∆9-THC (22), are the major psychoactive
constituents of marijuana (hashish). These and related
analogs have attracted medical interest since they show
promising biological activities that include antiemetic,
analgesic, and psychotropic effects.11,12 The enantiomeri-
cally pure hexahydrocannabinoid analog 23 [(9R)-(-)-
HHC] has attracted much attention since clinical evalu-
ations showed it to have psychotropic activity similar to
that of natural ∆8-THC, 21.13
The cyclobutenone/o-quinone methide rearrangement
is an attractive method for the synthesis of enantiomeri-
cally pure aryl analogs of cannabinoids having the
general structure 24. A tandem ring expansion/cycload-
dition sequence was employed for the synthesis of the
hexahydrocannabinol analogs 33a , 33b (Scheme 5), and
38 (Scheme 6). This method is potentially general and
could conceivably be used to prepare a large number of
HHC analogs. It is particularly attractive for aryl
analogs since the aromatic moiety translates to the
cyclobutenones’ ring, and a variety of methods are now
available for their regiospecific synthesis.1,5
The synthesis initiates from (R)-5,9-dimethyl-3-(tri-
methylsilyl)-1-decyn-8-ene, 28, which was prepared in
32% overall yield starting with commercially available
(R)-(-)-citronellyl bromide (25) (Scheme 4). Treatment
of this with lithio(trimethylsilyl)ethyne in a mixed solvent
system of THF and DMSO gave the alkyne 26 in 70%
isolated yield. This was lithiated at the propargylic
position using tert-butyllithium in THF at -23 °C.
Quenching the reaction with chlorotrimethylsilane gave
27 which was immediately deprotected [AgNO3 in C2H5-
OH(aq) followed by KCN(aq)] to give 28 (45%).
analytical data for 17 and 20 are in accord with their
assigned structures; particularly revealing is their 1H
NMR spectra which show the C-CH3 absorption at 1.59
ppm for 17 and 1.85 ppm for 20.
These rearrangements apparently involve hypervalent
silicate intermediates (“ate complex”) such as 16 which
lead to 17 upon methyl migration from silicon to carbon.
Analogies for this rearrangement appear to be rare; one
example is the thermal rearrangement of R-acetoxy
silanes to the corresponding silyl acetates with concur-
rent migration of an alkyl or aryl group from silicon to
carbon.10
For comparison, it is of interest to note that o-quinone
methides bearing an alkyl group and a trimethylsilyl
group (2a ,b) at the alkylidene terminus undergo the 1,5-
hydrogen shift while those such as 15 and 19 undergo
methyl migration.
E n a n t iosp ecific Syn t h esis of Ar yl An a logs of
Hexa h yd r oca n n a bin ol. The cyclobutenone/o-quinone
methide rearrangement is an attractive method for the
synthesis of a variety of annulated ring systems. For
example, it is ideally suited for the generation of ap-
propriately substituted o-quinone methides that lead to
(11) Makriyannis, A; Rapaka, R. S. Life Sci. 1990, 47, 2173.
(12) (a) Cannabinoids as Therapeutic Agents; Mechoulam, R., Ed.;
CRC Press, Inc.: Boca Raton, FL, 1986. (b) Little, P. J .; Compton, D.
R.; J ohnson, M. R.; Melvin, L. S.; Martin, B. R. J . Pharmacol. Exp.
Ther. 1988, 247, 1046. (c) Feigenbaum, J . J .; Richmond, S. A.;
Weissman, Y.; Mechoulam, R. Eur. J . Pharmacol. 1989, 169, 159. (d)
Tius, M. A.; Busch-Petersen, J . Tetrahedron Lett. 1994, 35, 5181. (e)
Tius, M. A.; Kannangara, G. S. K. J . Org. Chem. 1990, 55, 5711. (f)
Yan, G.; Yan, G.; Yin, D.; Khanolka, A. D.; Compton, D. R.; Martin, B.
R.; Makriyannis, A. J . Med. Chem. 1994, 37, 2619.
(10) Buynak, J . D.; Strickland, J . B.; Lamb, G. W.; Khasnis, D.; Modi,
S.; Williams, D.; Zhang, H. J . Org. Chem. 1991, 56, 7076. Bassindale,
A. R.; Brook, A. G.; J ones, P. F.; Lennon, J . M. Can. J . Chem. 1975,
53, 332. Reetz, M. T.; Greif, N. Angew. Chem., Int. Ed. Engl. 1977, 16,
712. Tacke, R.; Lange, H. Chem. Ber. 1983, 116, 3585.
(13) Mechoulam, R.; Lander, N.; Varkony, T. H.; Kimmel, I.; Becker,
O.; Ben-Zri, Z. J . Med. Chem. 1980, 23, 1068.

332 J . Org. Chem., Vol. 61, No. 1, 1996
Taing and Moore
Sch em e 4
Sch em e 5
Addition of the lithium salt of 28 to the cyclobutene-
diones 29a,b gave the corresponding 4-alkynylcyclobuten-
ones 30a ,b in 71-80% yield. The desired allenylcy-
clobutenones 31a ,b were then readily obtained (80-84%)
upon treatment of 30a ,b with tetra-n-butylammonium
fluoride (TBAF) in THF. Heating a benzene solution of
31a at 50 °C for 36 h gave 33a (85%) via the o-quinone
methide 32a . In comparison, 31b rearranged under
similar conditions (40 °C, 7 h) to the cannabinoid 33b in
79% isolated yield.
In a manner analogous to the above, (S)-(-)-citronellyl
bromide provided the (S)-isomer of the propargyl silane
36, and this led to the (S)-enantiomer of hexahydrocan-
nabinol 38 in 67% overall yield (Scheme 6).
The stereochemistry of 33a was determined by the
following spectroscopic experiments. The assignment of
the chemical shifts for different protons in the ring
1
system was established by H NMR and confirmed by a
2-D COSY experiment. From the analysis of the 1H NMR
spectrum, both H10a and H6a appear as a doublet of
triplets at δ 2.34 (J ) 11.4, 3.7 Hz) and 1.36 (J ) 11.7,
2.6 Hz), respectively. The observed coupling constants
are the result of trans-diaxial coupling between H10a and
the adjacent protons (H10â, H6a) and the axial-equatorial
coupling between H10a and H10R. Similarly, H6a is coupled
to the axial protons (H10a, H7R) and the equatorial proton
(H7â).13 Further evidence of the trans-fused juncture was
revealed by a NOESY experiment. The appearance of
the NOE between H10a-H9 and H6a-H10â confirms the
relative 1,3-diaxial positions of those pairs of protons as
indicated in the three-dimensional structure of 33a
(Scheme 5). Analogous stereochemistry is assumed for
33b and 38.
A mechanism accounting for the above stereostructures
is based upon a chair transition state, 35, having the
methyl group at position 9 in an equatorial position. This
postulate is in strict agreement with the work of Marino
and Dax who reported a related synthesis of hexahydro-
cannabinol via a method utilizing an intramolecular
hetero-Diels-Alder cycloaddition to an o-quinone me-
thide.14,15
o-Qu in on e Meth id e Con figu r a tion a l Equ ilibr a -
tion a n d Equ ilibr a tion betw een Selected 2-(1-Me-
th yleth en yl)-1,4-ben zen ed iols a n d o-Qu in on e Me-
th id es. The thermally induced 4-allenylcyclobutenone
ring expansion as described herein is ideally suited to
probe mechanistic questions concerning the reactivity
and structure of o-quinone methide intermediates. For
example, the rearrangement is accomplished under neu-
tral conditions while most other routes to o-quinone
methides require oxidation or reaction conditions that
induce elimination reactions. As a result, reagents are
often present that trap the quinone methide intermedi-
ates at low concentrations.
One question of interest, for which no clear answer has
previously been reported, concerns the facility of con-
figurational equilibrium around the alkylidene group of
o-quinone methides. The answer was sought by inves-
tigating the thermolysis of 39 and determining the extent
of deuterium scrambling (Scheme 7). This study revealed
the presence of an equilibration between the o-quinone
(14) Marino, J . P.; Dax, S. L. J . Org. Chem. 1984, 49, 3671.
(15) For a related synthesis of hexahydrocannabanol itself, see:
Tietze, L.-F.; Kiedrowski, G.; Harms, K.; Clegg, W.; Sheldrick, G.
Angew. Chem., Int. Ed. Engl. 1980, 19, 134. Archer, R. A.; Boyd, D.
B.; Demarco, P. V.; Tyminski, I. J .; Allinger, N. L. J . Am. Chem. Soc.
1990, 92, 5200.

o-Quinone Methides from 4-Allenylcyclobutenones
J . Org. Chem., Vol. 61, No. 1, 1996 333
Sch em e 6
deuterated 2-ethenylphenols in >95% overall yield. This
mixture was observed to be composed of phenols contain-
ing one, two, three, and four deuterium atoms. As
revealed by mass spectrometric analysis, after correction
for the 13C satellite peak, the ratio of the D1:D2:D3:D4
products was 7 (D1):30 (D2):53 (D3):10 (D4). [It is noted
that none of the deuterium is associated with the
exchangeable phenolic hydroxyl group since the mixture
of vinylphenols was subjected to chromatographic puri-
fication (SiO2) prior to mass spectral analysis.] Since the
size of CH3 and CD3 are effectively the same, it is
assumed that the o-quinone methides 40 and 41 are
initially formed in equal amounts. It is also assumed
that no significant secondary isotope effect is operative
in the electrocyclic ring closure of the ketene intermedi-
ates to the corresponding o-quinone methides. With
these assumptions in mind, the above results provide the
foundation for the following conclusions:
1. Since 45 (D4) and 49 (D1) are formed in the reaction,
an equilibrium between the o-quinone methides and the
vinylphenols must exist.
Sch em e 7
2. The fact that 45 and 49 are formed in nearly equal
amounts suggests the presence of a significant isotope
effect in the 1,5-hydrogen shift reaction leading to the
vinylphenols from the quinone methides. That is, a
primary isotope effect would significantly reduce the
amount of 49 relative to that of 45, and apparently does
to the extent that 45 and 49 are formed in nearly equal
amounts. Indeed, if a primary isotope effect was not
present, the amount of 49 (D1) should be significantly
greater than that of 45 (D4) since there are more sources
of exchangable protons than deuterons, i.e., proton
sources for D1 (49) include 42, 43, 45, 46, 47, and 49 (nine
protons) while deuteron sources for D4 (45) are 43, 46
and 49 (3 deuterons).
3. The above proposed isotope effect which seemingly
reduces the amount of 49 (D1) along with the observations
that D3 (42 + 43) is significantly greater than D2 (46 +
47) shows that the quinone methides, e.g., 40 and 41,
are in equilibrium under the conditions of the reaction.
Trapping experiments that confirm the vinylphenol/o-
quinone methide equilibration are outlined below. Specif-
ically, when an ethanolic solution of the ethenylphenol
50 was refluxed for 24 h, a mixture composed of ap-
proximately 25% starting material and 75% of the
ethanol adduct 52 was realized (1H NMR analysis)
(Scheme 8). Michael addition of ethanol to the enone of
the o-quinone methide accounts for the observed product
52.
Further evidence was gained from a related experiment
showing deuterium incorporation when a benzene solu-
tion containing 10 equiv of C2H5OD and 1 equiv of
ethenylphenol 50 was held at 30 °C for 12 h (Scheme 8).
Under these conditions, the ethenylphenol-O-d would
be generated in situ and is apparently in equilibrium
with the deuterated quinone methide which leads to the
deuterated phenol 53. The mass spectrum of the product
showed a 10% (corrected) enhancement of the m + 1 peak
at m/z 285 associated with the monodeuterated ethe-
nylphenol 53.
Mech a n ism . Inspection of the reactions involving
o-quinone methides as outlined in this paper reveals an
apparent common selectivity. Specifically, for those
o-quinone methides bearing two different groups on the
alkylidene terminus, the products appear to arise from
the intermediate having the larger group disposed trans
to the carbonyl moiety, i.e., presumably the countrath-
methides (40 and 41) as well as between quinone methides
and 2-ethenylphenols (e.g., 40 and 42) even at 30 °C.
Specifically, when a benzene solution of 39 (1:1 mixture
of diastereomers as revealed by H NMR) was allowed
to stand at 30 °C for 12 h, it rearranged to a mixture of
1

334 J . Org. Chem., Vol. 61, No. 1, 1996
Taing and Moore
Sch em e 8
56a . Thus, steric interactions between the substituents
(RS and RL) and the ketene carbonyl group are more
important than analogous interactions involving the ring-
based group (R). As a result, the alkylidene group in the
o-quinone methide product would be formed by a rotation
mode in which the larger group (RL) rotates away from
the carbonyl group and toward the R group, thus result-
ing in the quinone methides generally represented by
56a , even for those cases leading to the countrathermo-
dynamic isomer. This process is further complimented
by the configurational equilibration of the o-quinone
methides (56a /56b), a process shown herein to be facile
for a specific example, i.e., 40/41. Thus, even though the
reactions outlined above can be rationalized as being
dictated by the “birth” of the specific configurational
isomer of the o-quinone methide (56a ), this assumption
is not necessarily valid for all cases. Rather, for those
transformations experiencing a rapid equilibrium be-
tween the E- and Z-isomers (56a and 56b), product
formation would be controlled by subsequent and slower
rate events.
Sch em e 9
Con clu sion s
In conclusion, the following significant points are
noted: 1) the reactions presented here add to the growing
importance of the ring expansions of cyclobutenones to
a variety of other ring systems including benzo- and
naphthoquinones, chlorophenols, benzofurans, methyl-
enebenzofurans, bicyclo[3.2.0]heptenones, indolizines, in-
dolizine-5,8-diones, [3.2.2]cyclazines, 2-alkylidene-1,3-
cyclopentenediones, spiroepoxycyclohexadienones, and
p-quinone methides;5 (2) the route to o-quinone methides
presented here is arguably the most versatile method for
the generation of highly-substituted examples; (3) utiliza-
tion of o-quinone methides as a regiospecific route to
highly-substituted 2-alkenylphenols and benzofurans is
presented as a useful synthetic reaction; (4) a new
carbon-carbon bond-forming reaction is described which
involves an unprecedented reaction of trimethylsilyl-
substituted o-quinone methides; (5) a potentially general
route to highly-substituted aryl analogs of hexahydro-
cannabinol is presented; (6) data are presented that
establish a low barrier to rotation around the alkylidene
group of selected o-quinone methides; and (7) an equi-
librium between 2-(1-methylethenyl)-1,4-benzenediols
and the corresponding o-quinone methides was estab-
lished.
ermodynamic o-quinone methide for 2 and 19 and the
thermodynamic isomer for 32. For example, the trim-
ethylsilyl group (A ) 2.5 kcal mol-1) in 2 is larger than
the propyl (A ) approximately 1.79 kcal mol-1), and thus
hydrogen transfer is available from the E-isomer; like-
wise, the phenyl group (A ) 2.8 kcal mol-1) in the quinone
methide 19 is slightly larger than the trimethylsilyl
substituent, thus allowing formation of the “ate” complex
and ultimate methyl migration to give 20.16 Finally, the
alkyl group in 32 is significantly larger than the proton,
and the indicated E-isomer is required to account for the
observed stereochemistry in the hexahydrocannabinoids
33a ,b and 38.
A mechanistic paradigm accounting for the above
reactions is outlined in Scheme 9. Here, the cyclobuten-
one 54 undergoes torquoselective17 electrocyclic ring
opening with outward rotation of the 4-hydroxy group
to generate the trienylketene 55. It is reasonable to
assume that an early transition state for the electrocyclic
ring closure of the reactive ketene intermediate dictates
the structure of the initially formed o-quinone methide
Exp er im en ta l Section
Gen er a l P r oced u r e. All reactions were carried out in
flame-dried glassware under a positive pressure of dry nitro-
gen. Tetrahydrofuran (THF) was distilled from sodium (ben-
zophenone indicator). Benzene, toluene, and p-xylene were
distilled from calcium hydride. Solvents were removed by a
Buchi rotary evaporator at 15-30 Torr. All reactions were
followed by TLC using E. Merck silica gel 60 F-254. Flash
column chromatography was performed by using E. Merck
silica gel (230-400 mesh).
Many of the cyclobutenone derivatives described here are
mixtures of diastereomers. These are generally unstable
compounds and tend to readily rearrange via the ring expan-
sion pathways outlined in this paper. As a result, it is not
possible to purify the individual diastereomers. Thus, spectral
properties are presented for the mixtures. When obvious, the
1H NMR absorptions for analogous protons of the individual
diastereomers are presented in brackets, and the proton count
is recorded for the sum of the peaks within the brackets. When
(16) A values were taken from the following reference: Eliel, E. L.;
Wilen, S. H. Stereochemistry of Organic Compounds; Wiley and Sons,
Inc: New York, 1994.
(17) Kirmse, W.; Rondam, N. G.; Houk, K. N. J . Am. Chem. Soc.
1989, 111, 975. Niwayama, S.; Kallel, E. A.; Houk, K. N. J . Org. Chem.,
in press.

o-Quinone Methides from 4-Allenylcyclobutenones
J . Org. Chem., Vol. 61, No. 1, 1996 335
the mixture shows an enhancement of one isomer over the
other, the first peak listed in the brackets is for the major
isomer.
128.3, 125.5, 125.4, 122.2, 110.3, 93.6, 93.6, 90.1, 75.7, 60.9,
60.8, 56.5, 56.4, 34.4, 34.3, 22.2, 22.1, 14.1, 14.0, -1.80, -1.73;
IR (neat) 3372, 2955, 1933, 1761, 1620 cm-1; MS (CI) m/ z calcd
for C23H28O4Si 396.1757, found 396.1742; 399 (7), 398 (22), 397
(64), 396 (100), 382 (6), 366 (10), 355 (8).
3,5,6-Tr im et h oxy-2-(1-(t r im et h ylsilyl)-1(E)-b u t en yl)-
1,4-ben zen ed iol (3a ). A solution of 1a (56.4 mg, 0.173 mmol)
in freshly distilled toluene (50 mL) was heated at reflux for 4
h. The solvent was then removed, and the crude product was
2,3-Dim eth oxy-4-h yd r oxy-4-(1-m eth oxy-3-(tr im eth ylsi-
lyl)-1,2-h exa d ien yl)-2-cyclobu ten -1-on e (1a ) [Mixtu r e of
Dia ster eom er s]. n-Butyllithium (0.845 mmol, 1.6 M, 0.5 mL)
was added (syringe) to a solution of 1-methoxy-3-(trimethyl-
silyl)-1,2-hexadiene18 (0.170 g, 0.922 mmol) in freshly distilled
THF (10 mL) at -78 °C. After 30 min (stirring), the resulting
yellow solution was transferred via cannula to a flask contain-
ing a solution of dimethyl squarate (0.100 g, 0.705 mmol) in
20 mL of THF at -78 °C. The resulting solution was stirred
for another 10 min followed by the addition of a mixture of
distilled water and ether (25 + 20 mL). The aqueous portion
was extracted with ether (3 × 10 mL). The combined organic
layers were washed with brine (3 × 20 mL) and dried over
anhyd MgSO4. Purification was achieved by flash column
chromatography (SiO2, Hexane:EtOAc, 4:1) to afford 0.160 g
(70%) of 1a as a yellow oil (mixture of diastereomers 1:1): Rf
0.12 (Hexane:EtOAc, 4:1); 1H NMR (500 MHz, CDCl3) δ [4.05/
4.06] (s, 3H), 3.94 (s, 3H), [3.37/3.38] (s, 3H), [2.84/2.94] (s,
1H), 2.09-2.13 (m, 2H), 1.42-1.53 (m, 2H), 0.90-0.94 (m, 3H),
[0.09/0.12] (s, 9H); 13C NMR (125 MHz, CDCl3) δ 192.9, 192.7,
183.1, 164.3, 164.0, 135.5, 129.6, 129.3, 124.7, 124.4, 85.2, 85.1,
59.6, 59.5, 58.4, 56.4, 56.3, 34.4, 34.3, 22.1, 22.0, 14.0, 13.9,
purified by flash column chromatography (SiO2
, Hexane:
EtOAc, 4:1) to afford 51 mg (90%) of 3a as a yellow oil: Rf
1
0.25 (Hexane:EtOAc, 4:1); H NMR (500 MHz, CDCl3) δ 6.15
(t, J ) 6.9 Hz, 1H), 5.31 (s, 1H), 4.97 (s, 1H), 3.94 (s, 3H), 3.86
(s, 3H), 3.63 (s, 3H), 1.95-2.00 (m, 2H), 0.96 (t, J ) 7.3 Hz,
3H), 0.046 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 147.4, 139.6,
138.4, 137.4, 136.1, 135.3, 134.8, 117.1, 61.0, 60.9, 24.4, 13.1,
-1.02; IR (neat) 3439, 2959, 2838, 1610 cm-1; MS (EI) m/ z
calcd for C16H26O5Si 326.1549, found 326.1553; 326 (36), 309
(6), 296 (25), 279 (37), 265 (20), 251 (43), 237 (8), 221 (12), 207
(11), 193 (9), 179 (5), 109 (11), 89 (28), 73 (100), 59 (36).
3,5-Dim eth oxy-6-ph en yl-2-(1-(tr im eth ylsilyl)-1(E)-bu te-
n yl)-1,4-ben zen ed iol (3b). In a manner similar to the above,
1b (60.0 mg, 0.161 mmol) gave 45 mg (75%) of 3b as a yellow
1
oil: Rf 0.28 (Hexane:EtOAc, 6:1); H NMR (500 MHz, CDCl3)
δ 7.42-7.48 (m, 4H), 7.34-7.36 (m, 1H), 6.30 (t, J ) 6.97 Hz,
1H), 5.37 (s, 1H), 4.70 (s, 1H), 3.77 (s, 3H), 3.47 (s, 3H), 2.04-
2.07 (m, 2H), 1.0 (t, J ) 7.7 Hz, 3H), 0.11 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ 148.9, 143.6, 143.1, 141.0, 135.8, 135.5,
133.6, 130.5, 128.1, 127.1, 116.9, 60.6, 60.4, 24.5, 13.2, -1.01;
IR (neat) 3517, 2960, 2896, 2834, 1614 cm-1; MS (EI) m/ z calcd
for C21H28O4Si 372.1757, found 372.1754; 374 (6), 373 (26), 372
(100), 370 (7), 357 (8), 329 (21), 315 (6), 161 (14).
-1.76, -1.86; IR (neat) 3414, 2955, 1931, 1777, 1643 cm-1
;
MS (CI) m/ z calcd for C16H26O5Si 326.1549, found 326.1518;
327 (100), 309 (54), 295 (60), 253 (1), 237 (10), 223 (12).
4-H yd r oxy-3-m et h oxy-2-p h en yl-4-(1-m et h oxy-3-(t r i-
m eth ylsilyl)-1,2-h exadien yl)-2-cyclobu ten -1-on e (1b) [Mix-
tu r e of Dia ster eom er s]. In a manner analogous to that used
for the preparation and purification of 1a , 1-methoxy-3-
(trimethylsilyl)-1,2-hexadiene (120 mg, 0.64 mmol) and 3-meth-
oxy-4-phenyl-3-cyclobutene-1,2-dione (0.100 g, 0.530 mmol)
gave 0.13 g (65%) of 1b as a yellow oil (mixture of diastereo-
mers 6:1): 1H NMR (500 MHz, CDCl3) δ 7.74-7.76 (m, 2H),
7.34 (t, J ) 7.50 Hz, 2H), 7.24-7.27 (m, 1H), [4.23/4.21] (s,
3H), [3.41/3.42] (s, 3H), 3.07 (s, 1H), 2.13-2.16 (m, 2H), 1.46-
5-n -Bu tyl-3,5-dim eth oxy-2-(1-(tr im eth ylsilyl)-1(E)-bu te-
n yl)-1,4-ben zen ed iol (3c). In a manner similar to the above,
1c (59.5 mg, 0.168 mmol) gave 57 mg (95%) of 3c as a light
1
yellow oil: Rf 0.43 (Hexane:EtOAc, 4:1); H NMR (500 MHz,
CDCl3) δ 6.31 (t, J ) 6.97 Hz, 1H), 5.21 (s, 1H), 4.65 (s, 1H),
3.85 (s, 3H), 3.65 (s, 3H), 2.60 (t, J ) 7.7 Hz, 2H), 2.00 (dt, J
) 2.57, 7.33 Hz, 2H), 1.50-1.53 (m, 2H), 1.34-1.39 (m, 2H),
0.98 (t, J ) 7.33 Hz, 3H), 0.91 (t, J ) 7.33 Hz, 3H), 0.06 (s,
9H); 13C NMR (125 MHz, CDCl3) δ 149.1, 144.4, 141.8, 141.6,
136.3, 135.3, 117.6, 115.9, 61.0, 60.4, 32.0, 24.3, 23.9, 22.8, 13.9,
13.1, -1.13; IR (neat) 3531, 2956, 2872, 1619 cm-1; MS (EI)
m/ z calcd for C19H32O4Si 352.2070, found 352.2055; 354 (7),
353 (30), 352 (100), 350 (9), 337 (7), 310 (17), 309 (91), 294 (5),
279 (5), 277 (11).
3,5-Dim eth oxy-6-(p h en yleth yn yl)-2-(1-(tr im eth ylsilyl)-
1(E)-bu ten yl)-1,4-ben zen ed iol (3d ). In a manner similar
to the above, 1d (62.0 mg, 0.156 mmol) gave 58 mg (90%) of
3d as a slightly red oil: Rf 0.30 (Hexane:EtOAc, 4:1); 1H NMR
(500 MHz, CDCl3) δ 7.54-7.56 (m, 2H), 7.32-7.36 (m, 3H),
6.23 (t, J ) 6.90 Hz, 1H), 5.37 (s, 1H), 5.28 (s, 1H), 4.10 (s,
3H), 3.75 (s, 3H), 1.98-2.02 (m, 2H), 1.00 (t, J ) 7.3 Hz, 3H),
0.09 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 148.2, 146.1, 145.7,
145.1, 135.3, 134.9, 131.4, 128.3, 123.1, 116.9, 98.7, 98.2, 81.0,
61.2, 60.4, 24.5, 13.2, -0.95; IR (neat) 3512, 2960, 2207, 1596,
1495 cm-1; MS (CI) 397 (100) m/ z calcd for C23H28O4Si
396.1757, found 396.1753; MS (EI) m/ z 396 (7), 379 (2), 364
(14), 349 (10), 105 (8), 73 (100).
1.51 (m, 2H), 0.93 (t, J ) 7.30 Hz, 3H), [0.13/0.12] (s, 9H); 13
C
NMR (125 MHz, CDCl3) δ 192.3, 186.5, 178.6, 129.9, 128.7,
128.4, 128.0, 127.1, 126.8, 125.8, 90.4, 59.6, 56.5, 34.5, 22.2,
14.0, -1.80; IR (neat) 3535, 2959, 1927, 1758, 1638 cm-1; MS
(CI) m/ z calcd for C21H28O4Si 372.1757, found 372.1758; 373
(100), 359 (9), 341 (22), 329 (1), 285 (4), 269 (5), 146 (6).
2-n -Bu t yl-4-h yd r oxy-3-m et h oxy-4-(1-m et h oxy-3-(t r i-
m eth ylsilyl)-1,2-h exadien yl)-2-cyclobu ten -1-on e (1c) [Mix-
tu r e of Dia ster eom er s]. In a manner similar to the above,
1-methoxy-3-(trimethylsilyl)-1,2-hexadiene (300 mg, 1.60 mmol)
and 2-n-butyl-3-methoxy-3-cyclobutene-1,2-dione (139 mg, 1.39
mmol) gave 0.22 g (45%) of 1c as a colorless oil (mixture of
diastereomers 3:2): 1H NMR (500 MHz, CDCl3) δ [4.04/4.05]
(s, 3H), [3.37/3.36] (s, 3H), [3.06/2.94] (s, 1H), 2.06-2.12 (m,
4H), 1.45-1.49 (m, 4H), 1.30 (sextet, J ) 7.7 Hz, 2H), 0.91
(dt, J ) 10.3, 7.33 Hz, 3H), 0.86 (t, J ) 7.33 Hz, 3H), [0.12/
0.08] (s, 9H); 13C NMR (125 MHz, CDCl3) δ 192.8, 192.6, 189.1,
180.0, 179.9, 140.2, 138.1, 130.5, 130.4, 129.8, 129.4, 124.9,
124.7, 89.4, 89.3, 59.1, 58.9, 56.3, 34.5, 34.4, 29.2, 22.4, 22.1,
21.7, 14.0, 13.9, 13.7, -1.72, -1.84; IR (neat) 3531, 2956, 2872,
1930, 1754, 1619, cm-1; MS (CI) m/ z calcd for C19H32O4Si
352.2069, found 352.2055; 354 (24), 353 (87), 352 (100), 337
(10), 322 (9), 321 (21), 311 (11), 309 (26).
3,5,6-Tr im et h oxy-2-(1-(t r im et h ylsilyl)-1(E)-b u t en yl)-
2,5-cycloh exa d ien e-1,4-d ion e (4a ). Compound 1a (51.8 mg,
0.16 mmol) was converted to 3a as described above. The crude
product was dissolved in anhyd benzene (10 mL), and Ag2O
(0.15 g, 0.65 mmol) and K2CO3 (0.10 g, 0.72 mmol) were added.
After 3 h of stirring at ambient temperature, the mixture was
filtered through a pad of Celite and rinsed with several
portions of ether. Purification was achieved by flash column
chromatography (hex:EtOAc, 4:1) to afford 47.3 mg (90%) of
4a as a red oil: Rf 0.33 (hex:EtOAc, 4:1); 1H NMR (500 MHz,
CDCl3) δ 6.01 (t, J ) 7.0 Hz, 1H), 3.97 (s, 6H), 3.83 (s, 3H),
4-Hydr oxy-3-m eth oxy-2-(ph en yleth yn yl)-4-(1-m eth oxy-
3-(tr im eth ylsilyl)-1,2-h exadien yl)-2-cyclobu ten -1-on e (1d)
(Mixtu r e of Dia ster eom er s). In a manner similar to the
above, 1-methoxy-3-(trimethylsilyl)-1,2-hexadiene (0.613 mmol,
0.113 g) and 3-methoxy-4-(phenylethynyl)-3-cyclobutene-1,2-
dione (0.111 g, 0.524 mmol) gave 0.1 g (46%) of 1d as a yellow
oil (mixture of diastereomers 3:2): Rf 0.17 (Hexane:EtOAc,
1
4:1); H NMR (500 MHz, CDCl3) δ 7.43-7.45 (m, 2H), 7.30-
7.33 (m, 3H), [4.36/4.35] (s, 3H), 3.41 (s, 3H), [3.00/2.98] (s,
1H), 2.12-2.16 (m, 2H), 1.49-1.52 (m, 2H), 0.95 (q, J ) 7.33
Hz, 3H), [0.15/0.13] (s, 9H); 13C NMR (125 MHz, CDCl3) δ
192.2, 192.1, 185.9, 185.8, 182.6, 182.4, 131.6, 128.9, 128.5,
1.85-1.88 (m, 2H), 0.92 (t, J ) 7.5 Hz, 3H), 0.044 (s, 9H); 13
C
NMR (125 MHz, CDCl3) δ 183.4, 180.1, 151.6, 146.8, 144.1,
142.5, 132.7, 129.1, 61.2, 61.1, 60.6, 25.1, 13.1, -1.06; IR (neat)
2954, 1661, 1614, 1588 cm-1; MS (CI) m/ z calcd for C16H24O5-
Si 324.1393, found 324.1382; 325 (83), 324 (53), 310 (32), 309
(65), 295 (20), 294 (100), 285 (13), 279 (24), 95 (10), 79 (10).
(18) (a) Mantione, R.; Leroux, Y. Tetrahedron Lett. 1971, 593. (b)
Mantione, R.; Leroux, Y. J . Organomet. Chem. 1971, 31, 15.

336 J . Org. Chem., Vol. 61, No. 1, 1996
Taing and Moore
2-Eth yl-5-h yd r oxy-4,6,7-tr im eth oxyben zofu r a n (5). To
a solution of quinone 4a (22.6 mg, 0.07 mmol) in anhyd CH2-
Cl2 (5 mL) was added TFA in excess (approximately 0.4 mL)
at 0 °C with stirring. The solution was allowed to stir at
ambient temperature for 2 days after which the solvent was
removed and the crude product purified by flash chromatog-
raphy (SiO2, hex:EtOAc, 4:1) to afford 13.2 mg (75%) of 5a as
a light brown oil: Rf 0.2 (hex:EtOAc, 4:1); 1H NMR (300 MHz,
CDCl3) δ 6.41 (s, 1H), 5.50 (s, 1H), 4.10 (s, 3H), 3.98 (s, 3H),
3.96 (s, 3H), 2.76 (q, J ) 7.40 Hz, 2H), 1.31 (t, J ) 7.50 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 160.4, 140.2, 136.9, 136.4,
133.8, 133.2, 117.9, 98.4, 61.6, 60.9, 60.5, 21.6, 11.8; IR (neat)
3423, 3118, 2974, 2938, 2836, 1610, 1500 cm-1; MS (CI) m/ z
calcd for C13H16O5 252.0998, found 252.0970; 253 (61), 252
(100), 238 (24).
2-E t h yl-7-p h en yl-5-h yd r oxy-4,6-d im et h oxy-3-(t r im e-
th ysilyl)ben zofu r a n (8b). Thermolysis of 1b (45.3 mg, 0.122
mmol) gave quinone 4b as a red oil after oxidation of the
hydroquinone 3b (Ag2O). The crude quinone product was
dissolved with benzene (30 mL), and silica gel (0.50 g) was
added. The mixture was refluxed overnight. The red solution
turned yellow in color during the reflux time. After filtration
and removal of the solvent, the residue was purified by flash
column chromatography (SiO2, hex:EtOAc, 8:1) to give 24.3
mg (54%) of compound 8b as a brown oil: 1H NMR (500 MHz,
CDCl3) δ 7.72 (d, J ) 7.0 Hz, 2H), 7.46-7.49 (m, 2H), 7.26-
7.38 (m, 1H), 5.66 (s, 1H), 4.11 (s, 3H), 3.46 (s, 3H), 2.75 (q, J
) 7.44 Hz, 2H), 1.22 (t, J ) 7.41 Hz, 3H), 0.38 (s, 9H); 13C
NMR (125 MHz, CDCl3) δ 165.1, 146.2, 142.6, 139.0, 136.7,
132.9, 130.0, 128.3, 127.3, 122.5, 112.4, 105.9, 61.3, 60.1, 22.3,
14.1, 1.01; IR (neat) 3511, 2937, 1617, 1559 cm-1; HRMS (EI)
calcd for C22H26O4Si 370.1600, found 370.1617; m/ z 371 (76),
370 (100), 355 (57), 340 (27), 325 (12), 308 (11), 170 (8), 113
(5), 89 (10).
chromatography (SiO2, Hexanes) to afford 0.276 g (60%) of the
allene as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.40 (d, J
) 7.5 Hz, 2H), 7.30 (t, J ) 7.5 Hz, 2H), 7.20 (t, J ) 7.5 Hz,
1H), 5.60 (s, 1H), 2.10-2.30 (m, 4H), 1.40-1.70 (m, 6H); IR
(neat) 3058, 2929, 2853, 1949, 1582 cm-1
.
2,3-Dim et h oxy-4-h yd r oxy-4-(1-(p h en ylt h io)-3,3-(p en -
ta m eth ylen e)-1,2-p r op a d ien yl)-2-cyclobu ten -1-on e (9a ).
In a manner analogous to that used for the preparation of 1a ,
dimethyl squarate (0.104 g, 0.703 mmol) and 1-(phenylthio)-
3,3-(pentamethylene)allene (0.160 g, 0.738 mmol) gave 0.175
1
g (70%) of 9a as a light yellow solid: mp 94-95 °C; H NMR
(500 MHz, CDCl3) δ 7.42-7.48 (m, 2H), 7.22-7.32 (m, 3H),
3.96 (s, 3H), 3.93 (s, 3H), 3.16 (s, 1H), 2.00-2.20 (m, 4H), 1.35-
1.60 (m, 6H); 13C NMR (125 MHz, CDCl3) δ 197.4, 183.0, 164.2,
135.9, 134.3, 132.0, 128.8, 127.5, 113.0, 99.5, 87.2, 76.9, 59.6,
58.5, 31.1, 31.0, 27.1, 27.0, 25.5; IR (neat) 3376, 2930, 2853,
1949, 1774, 1629 cm-1; HRMS (EI) calcd for C20H22O4S
358.1238, found 358.1232; m/ z 358 (100), 343 (11), 281 (28),
249 (53). Anal. Calcd: C, 67.02; H, 6.19. Found: C, 67.00;
H, 6.32.
6-(1-Cycloh exen yl)-2,3-d im et h oxy-5-(p h en ylt h io)-1,4-
ben zen ed iol (10). In a manner analogous to that used for
the preparation of 2, the cyclobutenone 9a (52.9 mg, 0.148
mmol) gave 51.2 mg (97%) of 10 as a light brown oil: 1H NMR
(500 MHz, CDCl3) δ 7.19 (t, J ) 7.70 Hz, 2H), 7.10 (t, J ) 7.70
Hz, 1H), 7.00 (d, J ) 7.70 Hz, 2H), 6.30 (s, 1H), 5.39 (s, 1H),
5.34 (s, 1H), 4.02 (s, 3H), 3.95 (s, 3H), 2.00-2.01 (m, 4H), 1.58-
1.70 (m, 4H); 13C NMR (125 MHz, CDCl3) δ 145.0, 142.3, 139.6,
138.8, 137.2, 133.2, 130.4, 128.9, 128.8, 126.6, 125.6, 110.2,
61.1, 60.9, 29.2, 25.2, 22.7, 21.8; IR (neat) 3406, 2932, 2831,
1579 cm-1; HRMS (EI) calcd for C20H22O4S 358.1238, found
358.1248; m/ z 358 (100), 343 (12), 281 (31), 250 (11), 249 (61),
234 (10).
6-(1-Cycloh exen yl)-2,3-d im et h oxy-5-(p h en ylt h io)-2,5-
cycloh exa d ien e-1,4-d ion e. To a solution of 10 (46.6 mg, 0.13
mmol) in anhyd benzene (5 mL) were added K2CO3 (0.10 g,
0.78 mmol) and Ag2O (0.12 g, 0.52 mmol). After 10 min of
stirring at ambient temperature, the reaction mixture was
filtered through a pad of Celite and rinsed with several
portions of ether. Purification was achieved by flash column
chromatography (hex:EtOAc, 2:1) to afford 44.8 mg (95%) of
the quinone as a red oil: 1H NMR (500 MHz, CDCl3) δ 7.20-
7.35 (m, 5H), 5.59 (s, 1H), 4.00 (s, 3H), 3.85 (s, 3H), 2.04-2.12
(m, 4H), 1.54-1.64 (m, 4H); 13C NMR (125 MHz, CDCl3) δ
181.5, 180.2, 147.1, 145.0, 144.8, 141.0, 134.1, 132.0, 131.5,
131.2, 129.0, 127.5, 61.2, 27.9, 25.1, 22.2, 21.4; IR (neat) 2933,
2856, 1654, 1629, 1560 cm-1; HRMS (EI) calcd for C20H20O4S
356.1082, found 356.1074; m/ z 358 (23), 357 (23), 356 (100),
341 (18), 328 (29), 279 (17), 247 (22), 215 (16), 165 (15).
3-Meth yl-1-(p h en ylth io)-1,2-bu ta d ien e. n-Butyllithium
(13.4 mL, 21.5 mmol) was added to a solution of 2-chloro-2-
methyl-3-butyne (2.0 g, 19.5 mmol) in freshly distilled THF
(30 mL) at -78 °C. The mixture was stirred for 20 min.
Thiophenol (2.14 g, 19.5 mmol) in THF (30 mL) was added to
a solution of n-BuLi (13.4 mL, 21.5 mmol) at -78 °C, and the
mixture was stirred for 20 min. The resulting lithium
thiophenoxide solution was transferred via cannula to the
lithiated propagyl chloride solution, and the mixture was
allowed to stir for 1 h. The solution temperature was raised
to -23 °C (CCl4/dry ice). After another hour, the reaction was
quenched with distilled water (50 mL). The aqueous portion
was extracted with ether (3 × 30 mL). The combined organic
layers were washed with brine and dried over anhyd MgSO4.
Purification was achieved by flash column chromatography
(SiO2, hexanes) to afford 2.0 g (58%) of the allene as a light
yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.40 (d, J ) 7.0 Hz,
2H), 7.30 (t, J ) 7.0 Hz, 2H), 7.02 (t, J ) 7.0 Hz, 1H), 5.80 (m,
1H), 1.80 (s, 6H); IR (neat) 3058, 2982, 2910, 1952, 1872, 1795,
2-Eth yl-5-h yd r oxy-4,6-d im eth oxy-7-(p h en yleth yn yl)-3-
(tr im eth ysilyl)ben zofu r a n (8d ). In a manner similar to the
preparation of 8b quinone 4d (26.5 mg, 0.067 mmol) and silica
gel (73 mg) gave 14.6 mg (55%) of 8d as a yellow oil: 1H NMR
(500 MHz, CDCl3) δ 7.59-7.61 (m, 2H), 7.26-7.37 (m, 3H),
5.56 (s, 1H), 4.15 (s, 3H), 4.10 (s, 3H), 2.81 (q, J ) 7.49 Hz,
2H), 1.31 (t, J ) 7.57 Hz, 3H), 0.35 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 165.1, 149.0, 146.1, 140.8, 140.3, 136.1, 131.4, 128.3,
128.2, 123.5, 122.0, 106.4, 97.0, 94.2, 80.6, 61.9, 60.1, 22.3, 14.2,
1.50; IR (neat) 3510, 2939, 2195, 1507 cm-1; HRMS (EI) calcd
for C23H26O4Si 394.1600, found 394.1598; m/ z 396 (9), 395 (31),
394 (100), 379 (17), 364 (12), 349 (8), 190 (3), 175 (6), 159 (3),
73 (32).
1-(P h en ylsu lfin yl)-3,3-(p en ta m eth ylen e)a llen e. Ben-
zenethiol (0.54 mL) was slowly added at ambient temperature
to a slurry of N-chlorosuccinimide (2.0 g, 15.3 mmol) in freshly
distilled methylene chloride (12 mL). Once the reaction
initiated, as evidenced by an intense red color, the remaining
benzenethiol (a total of 1.65 g, 15 mmol) was added over a
period of 5-10 min (caution! exothermic reaction). The
resulting red-colored solution was stirred for another 30 min
and then transferred in 10 portions over a period of 10 min
via cannula to a solution of 1-ethynyl-1-cyclohexanol in ether
(50 mL) and triethylamine (4 mL) at -78 °C. The reaction
mixture was allowed to stir for 2 h at -78 °C and then 1.5 h
at ambient temperature. The reaction was quenched with
water (30 mL) and then extracted with ether (3 × 20 mL).
The combined organic layers were washed with 1 N hydro-
chloric acid (3 × 20 mL), 10% potassium carbonate solution
(3 × 10 mL), and brine and dried over magnesium sulfate.
Purification was achieved by flash chromatography (SiO2, hex:
EtOAc, 2:1) to afford 1.85 g (53%) of the title compound as a
light yellow oil. It solidified upon refrigeration: 1H NMR (300
MHz, CDCl3) δ 7.60-7.70 (m, 2H), 7.45-7.55 (m, 3H), 5.92 (s,
1H), 2.10-2.30 (m, 4H), 1.45-1.65 (m, 6H); IR (neat) 3054,
1729 cm-1
2,3-Dim eth oxy-4-h yd r oxy-4-(3-m eth yl-1-(p h en ylth io)-
1,2-bu ta d ien yl)-2-cyclobu ten -1-on e (9b). In manner
.
2931, 2853, 1949 cm-1
.
1-(P h en ylth io)-3,3-(p en ta m eth ylen e)a llen e. Pyridine
(0.68 g, 8.6 mmol) followed by P2S5 (0.24 g, 1.08 mmol) was
added to a solution of (phenylsulfonyl)vinylidenecyclohexane
(0.500 g, 2.15 mmol) in freshly distilled methylene chloride
(30 mL). The solution was stirred for 2.5 h, the solvent was
removed, and the residue was purified by flash column
a
analogous to the preparation of 1a , butyllithium (0.45 mL, 1.6
M, 0.737 mmol), 3-methyl-1-(phenylthio)-1,2-butadiene (0.130
g, 0.737 mmol) in THF (10 mL), and dimethyl squarate (0.100
g, 0.704 mmol) in THF (20 mL) gave 0.159 g (71%) of 9b as a
white solid: mp 105-106 °C; 1H NMR (500 MHz, CDCl3) δ

o-Quinone Methides from 4-Allenylcyclobutenones
J . Org. Chem., Vol. 61, No. 1, 1996 337
7.41 (d, J ) 6.97 Hz, 2H), 7.24-7.30 (m, 3H), 3.94 (s, 3H),
3.91 (s, 3H), 3.12 (s, 1H), 1.70 (s, 3H), 1.69 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 201.6, 182.8, 164.1, 138.2, 135.9, 134.4,
131.8, 128.7, 127.4, 105.8, 99.3, 87.4, 59.6, 58.5, 20.3, 20.2; IR
(CDCl3) 3376, 2982, 2948, 2857, 1954, 1774, 1629 cm-1; HRMS
(EI) calcd for C17H18O4S 318.0926, found 318.0933; m/ z 318
(56), 286 (19), 271 (54), 241 (39), 209 (100), 175 (15), 121 (35),
106 (64), 91 (40).
2,3-Dim et h oxy-4-h yd r oxy-4-(1-ter t-b u t oxy-3,3-b is(t r i-
m eth ylsilyl)-1,2-p r op a d ien yl)-2-cyclobu ten -1-on e (14). n-
Butyllithium (0.94 mL, 1.6 M, 1.50 mmol) was slowly added
(syringe) to a solution of 1-tert-butoxy-3,3-bis(trimethylsilyl)-
1,2-propadiene (0.385 g, 1.50 mmol) in 20 mL of anhyd THF
at -78 °C (N2). The resulting light yellow solution was stirred
for 30 min and then transferred via cannula to a flask
containing a solution of dimethyl squarate (0.200 g, 1.41 mmol)
in 40 mL of THF at -78 °C. The solution was allowed to stir
for an additional 15 min, and then equal portions of H2O and
ether (20 + 20 mL) were added. After warming to ambient
temperature, the aqueous portion was extracted twice with
ether (2 × 10 mL), and the combined organic layers were
washed with brine and dried over anhyd MgSO4. The solvent
was removed to give a white solid which decomposes at room
temperature upon prolonged exposure to air. Purification was
achieved by flash column chromatography (silica gel, hexane:
EtOAc, 4:1) to afford 0.23 g (40%) of 14 as a white sticky
solid: 1H NMR (300 MHz, CDCl3) δ 4.05 (s, 3H), 3.94 (s, 3H),
3.28 (s, 1H), 1.31 (s, 9H), 0.18 (s, 9H), 0.16 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ 207.8, 183.8, 164.6, 135.5, 115.7, 113.9,
85.3, 78.8, 59.6, 58.4, 2.40, -0.15, -0.05; IR (CDCl3) 3535,
2956, 2901, 1917, 1776, 1640 cm-1; MS (EI) m/ z calcd for
C19H34O5Si2 398.1945; M+ - OH, 381 (9), 367 (6), 325 (3), 306
(63), 253 (100), 239 (11), 125 (2), 91 (28).
2,3-Dim eth oxy-6-(1-m eth yleth en yl)-5-(p h en ylth io)-1,4-
ben zen ed iol (11). A solution of 9b (52.6 mmol, 0.165 mmol)
in freshly distilled toluene (25 mL) was heated to reflux for 1
h. Purification was achieved by flash chromatography (SiO2,
hex:EtOAc, 2:1) to afford a quantitative yield of 11 as a yellow
oil: 1H NMR (500 MHz, CDCl3) δ 7.20 (t, J ) 7.70 Hz, 2H),
7.10 (t, J ) 7.33 Hz, 1H), 7.02 (d, J ) 7.33 Hz, 2H), 6.31 (s,
1H), 5.47 (s, 1H), 5.25 (s, 1H), 4.74 (s, 1H), 4.04 (s, 3H), 3.95
(s, 3H), 1.69 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 145.1, 142.3,
140.4, 139.1, 138.9, 136.8, 129.8, 128.9, 125.9, 125.5, 117.0,
108.8, 61.2, 60.9, 23.7; IR (neat) 3409, 3076, 2941, 1582 cm-1
;
HRMS (EI) calcd for C17H18O4S 318.0925, found 318.0921; m/ z
318 (100), 303 (15), 241 (15), 209 (71).
2,3-Dim eth oxy-4-h yd r oxy-4-(3-m eth yl-1-((tr im eth ylsi-
lyl)eth yn yl)-1,2-bu ta d ien yl)-2-cyclobu ten -1-on e (12).
A
solution of 1-methyl-6-(trimethylsilyl)-4-(triphenylstannyl)-2,3-
hexadien-5-yne19 in THF (40 mL) was cooled to -78 °C, and
methyllithium (0.55 mL, 1.4 M) was added. The resulting
yellow solution was stirred for 30 min. Then dimethyl
squarate (0.10 g, 0.7 mmol) in THF (10 mL) was transferred
at -78 °C via cannula to the lithiated allene solution. The
mixture turned a light yellow color, and after 10 min, the
reaction was quenched with a mixture of H2O and ether (15
+ 10 mL). The aqueous layer was extracted with ether (3 ×
30 mL). The combined organic layers were washed with brine
and dried over anhyd MgSO4. Concentration in vacuo afforded
the crude product which was partially purified by flash column
chromatography (SiO2, hex:EtOAc, 4:1) to afford 74.3 mg of
12 as an orange-colored oil (34%). This was used without
further purification: 1H NMR (300 MHz, CDCl3) δ 0.16 (s, 9H),
1.78 (s, 3H), 1.81 (s, 3H), 3.95 (s, 3H), 4.10 (s, 3H); IR (neat)
3-P h e n yl-1-m e t h oxy-3-(t r im e t h ylsilyl)-1,2-p r op a d i-
en e. To a solution of 1-methoxy-3-phenyl-2-propyne (0.52 g,
3.56 mmol) in freshly distilled ether (15 mL) was added n-BuLi
(4.44 mL, 7.11 mmol) at -78 °C. The resulting green solution
was stirred for 30 min, and the reaction was quenched with
chlorotrimethylsilane (0.39 g, 3.58 mmol). After an additional
20 min, a solution of ammonium chloride (5%) was added. The
aqueous portion was extracted with ether. The combined
organic layers were washed with brine and dried over anhyd
MgSO4. The crude product was purified by flash chromatog-
raphy (SiO2, Hexanes) to afford 0.46 g (60%) of 3-phenyl-1-
methoxy-3-(trimethylsilyl)-1,2-propadiene as a yellow oil: 1H
NMR (500 MHz, CDCl3) δ 7.40 (d, J ) 6.5 Hz, 2H), 7.35 (t, J
) 7.5 Hz, 2H), 7.25 (t, J ) 7.5 Hz, 1H), 6.90 (s, 1H), 3.40 (s,
3384, 2956, 2144, 1952, 1776, 1630 cm-1
.
3H), 0.30 (s, 9H); IR (neat) 2955, 1915, 1679 cm-1
.
2,3-Dim et h oxy-6-isop r op en yl-5-((t r im et h ylsilyl)et h y-
n yl)-2,5-cycloh exa d ien e-1,4-d ion e (13). A solution of 12
(38.1 mg, 0.124 mmol) in freshly distilled toluene (30 mL) was
refluxed under nitrogen for 60 min. The colorless solution
turned light yellow during the reflux period. The solvent was
removed in vacuo, and the crude hydroquinone was oxidized
with Ag2O (0.30 g) and K2CO3 (0.70 g) in benzene (15 mL).
The mixture was stirred for 4.5 h and filtered through a pad
of Celite. The solvent was removed under reduced pressure.
Purification was achieved by flash chromatography (SiO2, hex:
EtOAc, 4:1) to obtain 28.2 mg (75%) of 13 as a red oil: 1H NMR
(500 MHz, CDCl3) δ 5.38 (s, 1H), 5.07 (s, 1H), 4.02 (s, 3H),
3.98 (s, 3H), 1.98 (s, 3H), 0.22 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 182.0, 180.4, 148.9, 145.6, 143.7, 137.4, 125.2, 119.5,
113.7, 96.8, 61.3, 61.2, 21.9, -0.6; IR (neat) 2957, 2849, 2151,
1665, 1628 cm-1; HRMS (EI) calcd for C16H20O4Si 304.1131,
found 304.1146; m/ z 304 (3), 275 (2.8), 261 (2), 246 (2.2), 231
(2.3), 218 (5.2), 203 (2.8), 190 (2.2), 175 (3.4), 162 (2.4), 147
(13), 73 (100).
2,3-Diisop r op oxy-4-h yd r oxy-4-(1-m eth oxy-3-p h en yl-3-
(tr im eth ylsilyl)-1,2-p r op a d ien yl)-2-cyclobu ten -1-on e (18)
(Mixtu r e of Dia ster eom er s). In a manner similar to the
preparation of 14, 1-methoxy-3-phenyl-3-(trimethylsilyl)-1,2-
propadiene (0.54 mmol, 0.118 g) and diisopropyl squarate
(0.097 g, 0.49 mmol) gave 0.148 g (72%) of 18 as a yellow oil
1
(mixture of diastereomers 1:1): Rf 0.39 (hex:EtOAc, 2:1); H
NMR (500 MHz, CDCl3) δ 7.20-7.50 (m, 5H), 4.75-4.95 (m,
2H), [3.45/3.50] (s, 3H), [3.18/2.92] (s, 1H), 1.15-1.40 (m, 12H),
[0.30/0.25] (s, 9H); 13C NMR (125 MHz, CDCl3) δ 198.1, 198.0,
182.6, 163.7, 162.9, 137.7, 137.3, 133.6, 133.6, 130.8, 130.4,
128.4, 127.7, 127.5, 127.3, 127.21, 123.9, 123.3, 85.0, 84.9, 76.8,
56.5, 22.6, 22.6, 22.5, 22.3, 22.1, -0.44, -0.47; IR (Neat) 3406,
2979, 2899, 2834, 1921, 1772, 1631 cm-1; MS (EI) m/ z calcd
for C23H32O5Si 416.2019, found 416.2010; 416 (18), 401 (17),
359 (20), 331 (26), 317 (100), 300 (15), 240 (14), 227 (23), 158
(59), 115 (9), 73 (84).
4-(1,1-Dim eth yleth oxy)-2,3-dih ydr o-6,7-dim eth oxy-2,2,3-
tr im eth yl-3-(tr im eth ylsilyl)-1,2-ben zoxa silol-5-ol (17). A
solution of 14 (52.1 mg, 0.131 mmol) in freshly distilled
p-xylene (50 mL) was refluxed under nitrogen for 40 min. The
clear solution turned light yellow during the reflux period.
Removal of the solvent gave a yellow oil which was purified
by flash column chromatography (SiO2, Hexane:EtOAc, 9:1)
to give a quantitative yield of 17 as a colorless oil: Rf 0.45
(Hexane:EtOAc, 4:1); 1H NMR (500 MHz, CDCl3) δ 5.39 (s,
1H), 3.92 (s, 3H), 3.83 (s, 3H), 1.59 (s, 3H), 1.45 (s, 9H), 0.51
(S, 3H), 0.18 (s, 3H), -0.04 (s, 9H); 13C NMR (125 MHz, CDCl3)
δ 143.0, 138.9, 137.7, 136.1, 135.1, 123.4, 80.6, 61.3, 60.7, 29.7,
21.6, 15.9, -0.98, -1.84, -3.29; IR (CDCl3) 3515, 2974, 1603
cm-1; MS (CI) m/ z calcd for C19H34O5Si2 398.1945, found
398.1942; MS (EI) 398 (4), 342 (13), 327 (100), 311 (12), 296
(32), 279 (6), 259 (9), 237 (12), 192 (8), 133 (9), 97 (7), 73 (92),
57 (78); DEPT C (quaternary) 142.99, 138.86, 137.69, 136.12,
135.13, 123.40, 80.62, 21.60; (CH3) 61.33, 60.70, 29.67, 15.93,
-0.98, -1.84, -3.29.
1-ter t-Bu toxy-3,3-bis(tr im eth ylsilyl)-1,2-pr opadien e. n-
Butyllithium (7.50 mL, 11.9 mmol) was added (syringe) to a
solution of 1-tert-butoxy-3-(trimethylsilyl)-2-propyne (1.00 g,
5.94 mmol) in freshly distilled ether (3 mL) at -78 °C. After
30 min (stirring), the reaction was quenched with chlorotri-
methylsilane (0.75 mL, 5.94 mmol). The mixture was stirred
for 1 h, and the reaction was quenched with aqueous am-
monium chloride (5%). The aqueous portion was extracted
with ether. The combined organic layers were washed with
brine and dried over anhyd MgSO4. The crude product was
purified by flash chromatography (SiO2, Hexanes) to afford
0.860 g (56%) of 1-tert-butoxy-3,3-bis(trimethylsilyl)-1,2-pro-
padiene as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 6.22 (s,
1H), 1.26 (s, 9H), 0.13 (s, 18H); IR (neat) 2973, 1921 cm-1
.
(19) (a) Ruitenberg, K.; Westmijze, H.; Kleijn, H.; Vermeer, P. J .
Organomet. Chem. 1984, 277, 227. (b) Lequan, M.; Guillerm, G. J .
Organomet. Chem. 1973, 54, 153.

338 J . Org. Chem., Vol. 61, No. 1, 1996
Taing and Moore
4-Meth oxy-2,3-dih ydr o-6,7-diisopr opoxy-2,2,3-tr im eth yl-
3-p h en yl-1,2-ben zoxa silol-5-ol (20). In a manner similar
to the above, 18 (50.6 mg, 0.121 mmol) gave 47.6 mg (94%) of
20 as a light yellow oil: Rf 0.53 (hex:EtOAc, 2:1); 1H NMR
(500 MHz, CDCl3) δ 7.20-7.23 (m, 2H), 7.07-7.00 (m, 3H),
5.26 (s, 1H), 4.74-4.79 (m, 1H), 4.44-4.48 (m, 1H), 3.32 (s,
3H), 1.85 (s, 3H), 1.29-1.32 (m, 12H), 0.35 (s, 3H), -0.13 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 147.1, 144.8, 141.3, 138.3,
137.4, 133.8, 128.0, 125.7, 125.1, 124.3, 75.2, 75.0, 59.5, 36.9,
22.6, 22.5, 22.4, 20.5, -2.30, -2.84; IR (Neat) 3521, 2973, 2934,
1597 cm-1; MS (EI) m/ z calcd for C23H32O5Si 416.2019, found
416.2019; 416 (100), 373 (19), 331 (73), 316 (34), 240 (43), 75
(10).
MgSO4. The crude product was purified by flash column
chromatography (SiO2, hex:EtOAc, 4:1) to afford 30a (0.19 g,
71%) as a yellow oil (mixture of diastereomers): Rf 0.47 (hex:
1
EtOAc, 2:1); H NMR (500 MHz, CDCl3) δ 5.10 (m, 1H), 4.16
(s, 3H), 3.93 (s, 3H), 3.10 (m, 1H), 1.85-2.05 (m, 2H), 1.75-
1.80 (m, 1H), 1.67 (s, 3H), 1.59 (s, 3H), 1.15-1.50 (m, 4H),
0.95-1.10 (m, 1H), [0.83 /0.85] (d and d, J ) 6.6 Hz, 3H), 0.06
(s, 9H); 13C NMR (125 MHz, CDCl3) δ 181.4, 165.2, 135.2,
131.0, 124.8, 93.4, 93.1, 79.0, 74.9, 59.6, 58.4, 37.7, 36.0, 35.8,
35.1, 32.1, 31.8, 25.5, 25.1, 20.1, 18.3, 17.7, 17.5, -3.3; IR
(Neat) 3333, 2955, 2917, 2857, 2216, 1778, 1634 cm-1; MS (CI)
m/ z calcd for C21H34O4Si 378.2226, found 378.2211; 379 (26),
361 (31) 347 (100), 331 (27), 319 (16), 303 (18), 291 (28), 275
(21), 267 (16), 251 (16), 225 (22).
(R)-5,9-Dim eth yl-1-(tr im eth ylsilyl)-d ec-8-en -1-yn e (26).
n-Butyllithium (4.4 mL, 1.6 M, 11 mmol) was added dropwise
to a solution of trimethylsilyacetylene (1.10 g, 11 mmol) in THF
(8 mL) at -78 °C. After 25 min, the dry ice/acetone bath was
replaced with an ice bath (0 °C). To this solution was slowly
added (R)-citronellyl bromide (2.0 g, 9.13 mmol) followed by
anhyd DMSO (33 mL). After 10 min, the resulting slurry was
allowed to warm to ambient temperature and was stirred for
4 h. The reaction mixture was then poured into ice cold water
(30 mL). The aqueous portion was extracted with ether (4 ×
10 mL). The combined extracts were washed with brine and
dried over MgSO4. The crude oil was filtered through a short
path of silica gel, eluting with a solvent mixture of petroleum
ether and diethylether (20:1) to afford 1.51 g (70%, >90% pure)
of 26 as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 5.09 (t,
J ) 7.0 Hz, 1H), 2.14-2.28 (m, 2H), 1.90-2.04 (m, 2H), 1.67
(s, 3H), 1.60 (s, 3H), 1.50-1.58 (m, 2H), 1.28-1.38 (m, 2H),
4-Hyd r oxy-3-isop r op oxy-2-p h en yl-4-(3-(tr im eth ylsilyl)-
5,9-d im et h yld ec-8-en -1-yn yl)-2-cyclob u t en -1-on e (30b )
(Mixtu r e of Dia ster eom er s). In a manner similar to the
above, 3-isopropoxy-4-phenyl-3-cyclobutene-1,2-dione (0.462
mmol, 0.100 g) and (5R)-3-(trimethylsilyl)-5,9-dimethyldec-8-
en-1-ynyl (0.508 mmol, 0.12 g) gave 0.169 g (80%) of 30b
(mixture of diastereomers): Rf 0.28 (hex:EtOAc, 6:1); 1H NMR
(500 MHz, CDCl3) δ 7.75 (d, J ) 8.43 Hz, 2H), 7.35 (t, J )
7.70 Hz, 2H), 7.25 (t, J ) 7.30 Hz, 1H), 5.30-5.40 (m, 1H),
5.05 (s, 1H), 4.00-4.20 (m, 1H), 0.95-2.00 (m, 20H), [0.85
/0.90] (dd, dd, J ) 7.4, 3.7 Hz, 3H), 0.02 (s, 9H); 13
C NMR (125
MHz, CDCl3) δ 185.4, 185.3, 185.2, 178.1, 178.0, 131.0, 129.1,
128.3, 127.9, 126.9, 125.0, 124.9, 124.8, 94.5, 94.3, 94.2, 84.1,
79.3, 75.0, 37.8, 36.1, 35.8, 35.0, 32.0, 31.7, 25.6, 25.1, 25.0,
23.3, 23.2, 23.0, 20.2, 18.2, 17.8, 17.7, 17.5, -3.2, -3.3; IR
(Neat) 3277, 2959, 2919, 2214, 1748, 1628 cm-1; MS (CI) m/ z
calcd for C28H40O3Si 452.2747, found 452.2747; 453 (100), 435
(12), 411 (40), 395 (13), 381 (10), 329 (10), 287 (16).
1.10-1.18 (m, 1H), 0.87 (d, J ) 6.6 Hz, 3 Hz), 0.13 (s, 9H); 13
C
NMR (75 MHz, CDCl3) δ 131.2, 124.8, 107.9, 84.2, 36.7, 35.8,
31.7, 25.8, 25.5, 19.2, 17.7, 17.6, 0.21; IR (neat) 2961, 2927,
2871, 2175 cm-1; HRMS (CI) calcd for C15H28Si 236.1960, found
236.1967; m/ z 236 (16), 221 (21), 163 (40), 162 (100), 147 (28),
107 (31).
2,3-Dim eth oxy-4-h ydr oxy-4-(5,9-dim eth yldec-8-en e-1,2-
d ien yl)-2-cyclobu ten -1-on e (31a ) (Mixtu r e of Dia ster eo-
m er s). A solution of 30a (0.114 mmol, 43.3 mg) in THF (4
mL) was treated with TBAF (0.172 mmol, 0.17 mL, 1 M in
THF) with stirring at ambient temperature. After 15 min, the
reaction was quenched with distilled H2O (5 mL). The aqueous
portion was separated and extracted with ether (3 × 5 mL).
The combined organic layers were washed with brine, dried
over anhyd MgSO4, and then concentrated under vacuum to
afford a crude product which was purified by flash column
chromatography (SiO2, hex:EtOAc, 2:1) to afford 30.8 mg (88%)
of 31a as a light yellow oil (mixture of diastereomers): Rf 0.28
5,9-Dim eth yl-3-(tr im eth ylsilyl)-dec-8-en -1-yn e (28) (Mix-
tu r e of Dia ster eom er s). tert-Butyllithium (4.2 mL, 1.7 M,
7.10 mmol) was added to a solution of 26 (1.40 g, 5.92 mmol)
in THF (10 mL) at -23 °C. After 2 h of stirring, this solution
was cooled to -78 °C, and the reaction was quenched with
chlorotrimethylsilane (0.80 g, 7.40 mmol). After 10 min, the
cold bath was removed to allow the solution to warm to
ambient temperature. An aqueous workup was accomplished
according to a reported procedure to afford the crude product
27 which was used without further purification.20 Desilylation
of the terminal acetylene was accomplished as described in
the literature20 to afford 28 (0.63 g, 45%) as a colorless oil: 1H
NMR (500 MHz, CDCl3) δ 5.10 (m, 1H), 1.90-2.05 (m, 3H),
1.70-1.80 (m, 2H), 1.68 (s, 3H), 1.61 (s, 3H), 1.45-1.55 (m,
1H), 1.20-1.40 (m, 2H), 0.95-1.05 (m, 1H), 0.94, 0.87 (d, J )
7.0 Hz, 3H), 0.08 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 131.0,
125.0, 124.9, 86.9, 68.1, 37.9, 36.2, 35.8, 34.8, 31.7, 31.4, 25.7,
25.2, 20.3, 18.2, 17.7, 17.0, -3.4; IR (neat) 3315, 2959, 2918,
2852, 2099 cm-1; HRMS (CI) calcd for C15H28Si 236.1960, found
236.1970; m/ z 236 (6), 221 (40), 163 (43), 162 (100), 147 (42).
2,3-Dim et h oxy-4-h yd r oxy-4-(3-(t r im et h ylsilyl)-5,9-d i-
m eth yld ec-8-en -1-yn yl)-2-cyclobu ten -1-on e (30a ) (Mix-
tu r e of Dia ster eom er s). n-Butyllithium (0.83 mmol, 0.52
mL, 1.6 M) was added dropwise to a solution of (5R)-3-
(trimethylsilyl)-5,9-dimethyldec-8-en-1-ynyl (28) (0.83 mmol,
0.20 g) in THF (10 mL) at -78 °C, and the resulting reaction
mixture was allowed to stir for 30 min. Then a solution of
dimethyl squarate (0.703 mmol, 0.100 g) in THF (10 mL) at
-78 °C was transferred via cannula to the lithiated alkyne
solution. After an additional 10 min of stirring, the reaction
was quenched with 2 mL of ammonium chloride (10%). The
solution was allowed to warmed up to ambient temperature
and was poured into a separatory funnel containing NH4Cl
(10%) and ether (5 + 5 mL). The aqueous portion was
extracted with ether (3 × 5 mL). The combined organic layers
were washed with brine (3 × 5 mL) and dried over anhyd
1
(hex:EtOAc, 2:1); H NMR (500 MHz, CDCl3) δ 5.40-5.5 (m,
1H), 5.30 (m, 1H), 5.05-5.10 (m, 1H), 3.90 (s, 3H), 4.30 (s, 3H),
3.15 (s, 1H), 1.90-2.15 (m, 4H), 1.65 (s, 3H), 1.60 (s, 3H), 1.50-
1.60 (m, 1H), 1.30-1.40 (m, 1H), 1.10-1.20 (m, 1H), 0.88-
0.94 (m, 3H); 13C NMR (125 MHz, CDCl3) δ 203.2, 184.6, 184.5,
166.3, 134.1, 131.4, 124.5, 95.9, 95.7, 91.0, 90.8, 84.3, 59.9, 59.8,
58.5, 36.5, 36.5, 36.2, 36.2, 32.7, 32.6, 25.7, 25.5, 19.3, 17.7;
IR (Neat) 3373, 2956, 2921, 2855, 1962, 1774, 1627 cm-1; MS
(EI) m/ z calcd for C18H26O4 306.1831, found 306.1827; 306 (37),
263 (19), 221 (13), 196 (17), 183 (100), 167 (11), 159 (21), 109
(19), 81 (21), 69 (65).
(6aR,9R,10aR)-6,6,9-Tr im eth yl-2-h ydr oxy-3,4-dim eth oxy-
6a ,7,8,9,10,10a -h exa h yd r o-6H-d iben zo[b,d ]p yr a n (33a ). A
solution of 31a (0.0863 mmol, 26.6 mg) in benzene (5 mL) was
heated (oil bath) at 50 °C for 36 h. Purification was achieved
by flash chromatography (SiO2, hex:EtOAc, 6:1) to afford 22.9
mg (86%) of 33a as a yellow oil: [R]D ) -37.9° (c ) 1, CHCl3),
1
T ) 23 °C; H NMR (500 MHz, CDCl3) and 2-D COSY (500
MHz, CDCl3) δ 6.58 (s, H-1), 5.31 (s, -OH), 3.92 (s, -OCH3),
3.86 (s, -OCH3), 2.34 (dt, J 10a,6a ) J 10a,10â ) 11.4, J 10a,10R ) 3.7
Hz, H-10a), 2.27-2.32 (m, H-10R), 1.79-1.85 (m, H-7â, H-8R),
1.50-1.60 (m, H-9), 1.42 (s, CH3â-6), 1.36 (td, J 6a,10a ) J 6a,7R
)
11.7, J 6a,7â ) 2.57 Hz, H-6a), 1.13 (s, CH3-6R), 1.00-1.05 (m,
H-7R, H-8â), 0.97 (d, J ) 6.6 Hz, CH3-9), 0.80-0.90 (q, J 10â,10R
) J 10â,10a ) J 10â,H9 ) 11.9 Hz, H-10â); 13C NMR (125 MHz,
CDCl3) δ 141.5, 141.1, 140.3, 138.5, 121.5, 105.9, 77.2, 61.3,
60.7, 46.9, 39.7, 35.6, 34.8, 32.4, 28.0, 27.5, 22.5, 19.8; IR (Neat)
3427, 2928, 2864, 1590 cm-1; MS (EI) m/ z calcd for C18H26O4
306.1831, found 306.1828; 306 (100), 263 (23), 221 (9), 183 (46).
(6a R,9R,10a R)-6,6,9-Tr im et h yl-2-h yd r oxy-3-m et h oxy-
4-p h en yl-6a ,7,8,9,10,10a -h exa h yd r o-6H -d ib en zo[b,d ]p y-
r a n (33b). To a solution of 30b (0.0667 mmol, 30.2 mg) in
(20) (a) Colvin, E. W. Silicon Reagents in Organic Synthesis (Best
Synthetic Methods); Academic Press: San Diego, 1988. (b) Rajagopalan,
S.; Zweifel, G. Synthesis 1984, 1120.

o-Quinone Methides from 4-Allenylcyclobutenones
J . Org. Chem., Vol. 61, No. 1, 1996 339
Ta ble 1. P er cen t Com p osition of Com p ou n d s 45, 42, 47,
a n d 49
undistilled THF (3 mL) was added tetra-n-butylammonium
fluoride (TBAF) (0.09 mmol, 0.09 mL, 1 M) with stirring at
ambient temperature. The reaction was completed in 5 min,
and the workup was done in the same manner as above. The
crude product was placed under vacuum to remove all traces
of solvents. It was then heated in anhyd benzene (10 mL) at
40 °C (oil bath) for 7 h. The crude product was purified by
chromatotron chromatography (hex:EtOAc, 10:1) to afford 20
mg (79%) of 33b as a light yellow oil: [R]D ) -18.8° (c ) 1,
correction for
m/ z
the 13C satellite
peak (20%)
%
compd
(relative intensity)
composition
45
42
47
49
288 (36)
287 (100)
286 (53)
18
90
50.5
12.3
10
53
30
7
285 (12.3)
1
CHCl3), T ) 23 °C; Rf 0.33 (hex:EtOAc, 10:1); H NMR (500
MHz, CDCl3) δ 7.40 (d, J ) 8.43 Hz, 2H), 7.30 (t, J ) 7.70 Hz,
2H), 7.20 (t, J ) 7.33 Hz, 1H), 6.84 (s, 1H), 5.43 (s, 1H), 3.50-
3.54 (m, 1H), 2.35-2.45 (m, 2H), 1.75-1.85 (m, 2H), 0.9-1.6
(m, 20H); 13C NMR (125 MHz, CDCl3) δ 143.7, 142.6, 140.8,
134.7, 130.9, 127.4, 126.5, 122.9, 121.4, 110.3, 75.3, 46.9, 39.8,
36.0, 34.8, 32.5, 27.8, 27.5, 22.6, 22.1, 20.0; IR (Neat) 3534,
2973, 2927, 2866, 1468, 991, 911, 733, 697 cm-1; MS (EI) m/ z
calcd for C25H32O3 380.2351, found 380.2357; 380 (57), 338
(100), 337 (10), 295 (10), 215 (14).
4-Hydr oxy-3-isop r opoxy-2-p h en yl-4-[3-m eth yl-d 3-3-(tr i-
m eth ylsilyl)-1-bu tyn yl]-2-cyclobu ten -1-on e (Mixtu r e of
Dia ster eom er s). Using standard conditions, 3-isopropoxy-
2-phenyl-2-cyclobutene-1,2-diones (0.22 g), propargyl silane
(0.763 g), and n-butyllithium (0.90 mL, 1.6 M, 1.4 mmol) gave
0.283 g (79%) of product as a white solid: mp 146-148 °C; 1H
NMR (500 MHz, CDCl3) δ 7.75 (d, J ) 7.0 Hz, 2H), 7.35 (t, J
) 7.7 Hz, 2H), 7.24-7.27 (m, 1H), 5.38 (septet, J ) 6.2 Hz,
1H), 4.17 (s, 1H), 1.56 (d, J ) 6.2 Hz, 3H), 1.54 (d, J ) 5.9 Hz,
3H), [1.14/1.13] (s, 3H), 0.04 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 185.4, 178.2, 129.1, 128.4, 128.0, 126.9, 124.9, 99.3,
84.1, 79.4, 74.5, 23.5, 23.3, 22.9, 17.2, -4.5; IR (CH2Cl2) 3564,
2960, 2214, 1758, 1629, 1598 cm-1; HRMS (EI) calcd for
C21H25D3O3Si 359.1996, found 359.1995; m/ z 360 (9), 359 (33),
318 (24), 317 (100), 316 (44), 303 (11), 302 (38), 301 (43), 300
(27), 272 (14), 271 (44).
4-H yd r oxy-3-isop r op oxy-2-p h en yl-4-(3-m et h yl-d 3-1,2-
bu ta d ien yl)-2-cyclobu ten -1-on e (39) (Mixtu r e of Dia ster -
eom er s). Using standard conditions, 4-hydroxy-3-isopropoxy-
2-ph en yl-4-[3-m et h yl-d 3-3-(t r im et h ylsilyl)-1-bu t yn yl]-2-
cyclobuten-1-one (50 mg, 0.17 mmol) and TBAF (0.20 mL, 0.20
mmol) gave 34 mg (85%) of 39 as a white solid (mixture of
diastereomers 1:1): mp 106-107 °C; 1H NMR (500 MHz,
CDCl3) δ 7.73-7.76 (m, 2H), 7.33-7.36 (m, 2H), 7.24-7.27 (m,
1H), 5.38 (q, J ) 3 Hz, 1H), 5.15 (septet, J ) 6.2 Hz, 1H), 4.10
(s, 1H), [1.78/1.73] (d, J ) 2.9 Hz, 3H), 1.52 (d, J ) 6.2 Hz,
3H), 1.48 (d, J ) 6.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
200.4, 189.2, 180.0, 128.9, 128.3, 127.8, 126.9, 123.4, 102.5,
90.1, 90.0, 78.6, 23.2, 23.0, 20.4, 20.1; IR (neat) 3319, 2982,
1965, 1741, 1623, 1595 cm-1; HRMS (CI) calcd for C18H17D3O3
287.1598, found 287.1595; m/ z 289 (26), 288 (100), 287 (76),
286 (21), 246 (16), 245 (58), 244 (44), 243 (22).
3-Isop r op oxy-6-(1-m eth yl-d 4-eth en yl-d 1)-2-p h en yl-1,4-
ben zen ed iol (45), 3-Isop r op oxy-6-(1-m eth yl-d 3-eth en yl)-
2-p h en yl-1,4-ben zen ed iol (42), 3-Isop r op oxy-6-(1-m eth -
ylet h en yl-d 2)-2-p h en yl-1,4-b en zen ed iol (47), a n d 3-Iso-
p r op oxy-6-(1-m et h ylet h en yl-d 1)-2-p h en yl-1,4-b en zen e-
d iol (49). A solution of 39 (13 mg, 0.045 mmol) in benzene (4
mL) was heated to 30 °C for 12 h. Purification of the crude
product was achieved by flash column chromatography (SiO2,
Hexanes:EtOAc 3:1) to give >95% of a mixture of 45, 42, 47,
and 49 as a yellow oil. See Table 1 for percent compositions:
1H NMR (500 MHz, CDCl3) δ 7.45-7.50 (m, 4H), 7.36-7.41
(m, 1H), 6.80 (s, 1H), 5.43 (s, CdCH2), 5.30 (s, CdCH2), 5.23
(s, 1H), 5.18 (s, 1H), 3.60 (septet, J ) 6.2 Hz, 1H), 2.12 (s,
-CH3), 0.98 (d, J ) 6.2 Hz, 6H); 13C NMR (125 MHz, CDCl3)
δ 143.5, 143.4, 143.2, 142.1, 134.3, 131.2, 129.3, 128.4, 125.7,
122.8, 116.2, 114.1, 76.5, 24.4, 22.7; IR (CH2Cl2) 3513, 3060,
2974, 2931, 1466 cm-1; HRMS (EI) calcd for C18H16O3D4
288.1663, found 288.1642; calcd for C18H17O3D3 287.1601,
found 287.1596; calcd for C18H18O3D2 286.1538, found 286.1536;
calcd for C18H19O3D1 285.1476, found 285.1472.
3-Isop r op oxy-6-(1-m et h ylet h en yl)-2-p h en yl-1,4-b en -
zen ed iol (50). n-Butyllithium (0.75 mL, 1.2 mmol, 1.6 M) was
added to a solution of 3-methyl-1,2-butadiene (0.123 mg, 1.85
mmol) in THF (5 mL) at -78 °C. After 1 h, it was transferred
via cannula to a solution of 2-phenyl-3-isopropoxy-2-cyclobutene-
1,2-dione in THF (10 mL) at -78 °C. The reaction was
quenched with a 5% solution of ammonium chloride followed
by a standard aqueous workup. The crude product was flashed
through a short column of silica gel and washed with ether.
The solvent was removed in vacuo to afford the crude product.
This was dissolved in anhyd benzene (30 mL), and the
resulting solution was refluxed for 2 h. The solvent was
removed in vacuo, and the crude product was purified by
4-H yd r oxy-3,4-d iisop r op oxy-4-[3-(t r im et h ylsilyl)-5,9-
d im eth yld ec-8-en -yn yl)]-2-cyclobu ten -1-on e (Mixtu r e of
Dia ster eom er s). In a manner similar to that used for the
preparation of 30a, 3,4-diisoproxy-3-cyclobutene-1,2-dione (0.504
mmol, 0.143 g), (S)-5,9-dimethyl-3-(trimethylsilyl)dec-8-en-1-
yne (0.605 mmol, 0.12 g), and n-butyllithium (0.36 mL, 0.58
mmol, 1.6 M) gave 0.178 g (81%) of the title compound as a
yellow oil: 1H NMR (500 MHz, CDCl3) δ 5.05-5.10 (m, 1H),
4.95-5.00 (m, 1H), 4.80-4.85 (m, 1H), 3.00-3.10 (m, 1H),
1.80-2.00 (m, 2H), 1.73-1.78 (m, 1H), 1.65 (s, 3H), 1.58 (s,
3H), 1.40 (dd, J ) 9.38, 6.25 Hz, 6H), 1.25 (dd, J ) 7.81, 6.25
Hz, 6H), 1.1-1.4 (m, 4H), 0.95-1.05 (m, 1H), [0.90 /0.82] (d
and d, J ) 6.25 Hz, 3H), 0.05 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 181.7, 165.2, 133.3, 133.2, 131.1, 131.0, 124.9, 124.8,
92.4, 92.3, 92.1, 78.9, 77.4, 75.2, 75.1, 73.7, 37.8, 36.0, 35.7,
35.0, 32.0, 31.7, 25.7, 25.6, 25.1, 22.6, 22.5, 20.2, 18.3, 18.2,
17.6, 17.5, 17.4, 3.3; IR (neat) 3324, 2978, 2923, 2218, 1778,
1621 cm-1; HRMS (EI) calcd for C25H42O4Si 434.2852, found
434.2839; m/ z 434 (3), 275 (4), 223 (16), 197 (6), 109 (3), 73
(100).
4-Hyd r oxy-2,3-d iisop r op oxy-4-(5,9-d im eth yld ec-8-en e-
1,2-d ien yl)-2-cyclobu ten -1-on e (Mixtu r e of Dia ster eo-
m er s). In a manner similar to that used to prepare 31a , the
above alkynylcyclobutenone (79.3 mg, 0.182 mmol) and TBAF
(0.27 mL, 0.27 mmol, 1 M) gave 60.3 mg (91%) of the title
compound as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 5.40-
5.50 (m, 1H), 5.25-5.32 (m, 1H), 5.05-5.10 (m, 1H), 4.85-
4.90 (m, 2H), [2.80/2.85] (s, 1H), 1.85-2.15 (m, 4H), 1.67 (s,
3H), 1.59 (s, 3H), 1.50-1.55 (m, 1H), 1.37-1.39 (m, 6H), 1.28
(d, J ) 6.23 Hz, 3H), 1.26 (d, J ) 6.23 Hz, 3H), 1.10-1.20 (m,
2H), 0.90 (d, J ) 6.60 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
203.1, 184.4, 184.2, 166.0, 165.8, 140.3, 132.3, 131.3, 124.6,
124.5, 95.8, 95.7, 95.6, 95.5, 91.2, 91.0, 83.9, 83.8, 73.6, 36.6,
36.5, 36.4, 36.3, 36.1, 36.0, 32.7, 32.6, 25.7, 25.5, 25.4, 22.7,
22.6, 22.5, 22.4, 19.3, 19.2, 17.6; IR (neat) 3373, 2978, 2927,
1962, 1769, 1613 cm-1; HRMS (EI) calcd for C22H34O4 362.2457,
found 362.2449; m/ z 362 (8), 320 (5), 278 (50), 235 (40), 209
(11), 193 (28), 168 (29), 156 (39), 155 (97), 154 (45), 139 (9),
123 (23), 109 (26), 93 (12), 81 (27), 69 (100), 55 (28).
6a ,7,8,9,10,10a -Hexa h yd r o-6,6,9-tr im eth yl-3,4-bis(1-m e-
th yleth oxy)-[6aS-(6a b,9b,10a a )]-6H-d iben zo[b,d ]p yr a n -2-
ol (38). Using the standard thermolysis conditions employed
for the synthesis of 33, the above allenylcyclobutenone (60.3
mg, 0.166 mmol) gave 60 mg (95%) of 38 as a yellow oil: [R]D
) 38.8° (c ) 1, CHCl3), T ) 23 °C; 1H NMR (500 MHz, CDCl3)
δ 6.55 (s, 1H), 5.30 (s, 1H), 4.73 (septet, J ) 6.0 Hz, 1H), 4.35
(septet, J ) 6.0 Hz, 1H), 2.25-2.40 (m, 2H), 1.75-1.85 (m,
2H), 1.50-1.55 (m, 1H), 1.40 (s, 3H), 1.20-1.35 (m, 13H), 1.10
(s, 3H), 1.00-1.10 (m, 2H), 0.95 (d, J ) 6.6 Hz, 3H), 0.85 (q, J
) 11.9 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 142.6, 140.7,
139.2, 136.7, 121.2, 105.3, 75.3, 75.0, 47.0, 39.7, 35.7, 34.8, 32.4,
28.0, 27.5, 22.7, 22.6, 22.5, 22.3, 19.8; IR (CDCl3) 3538, 2973,
2927, 2866, 1590 cm-1; HRMS (EI) calcd for C22H34O4 362.2457,
found 362.2442; m/ z 364 (3), 363 (23), 362 (88), 320 (13), 280
(2), 279 (18), 278 (100), 277 (11), 235 (28), 193 (10), 155 (36),
123 (10), 55 (12).

340 J . Org. Chem., Vol. 61, No. 1, 1996
Taing and Moore
chromatography (SiO2, Hexanes:EtOAc, 5:1) to afford 50 (67.8
mg, 26%) as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.45-
7.50 (m, 4H), 7.36-7.41 (m, 1H), 6.82 (s, 1H), 5.49 (s, 1H), 5.31
(s, 1H), 5.27 (s, 1H), 5.19 (s, 1H), 3.62 (septet, J ) 6.2 Hz,
1H), 2.14 (s, 3H), 0.99 (d, J ) 6.2 Hz, 6H); 13C NMR (125 MHz,
CDCl3) δ 142.8, 142.7, 142.6, 141.4, 133.5, 130.5, 128.6, 127.8,
124.9, 121.9, 115.5, 113.2, 75.8, 23.9, 22.1; IR (neat) 3516, 2974,
2930, 1465, 1431, 952, 896 cm-1; HRMS (EI) calcd for C18H20O3
284.1412, found 284.1410.
3-Isop r op oxy-6-(1-m eth yleth en yl-d 1)-2-p h en yl-1,4-ben -
zen ed iol (53). A solution of 50 (16 mg, 0.056 mmoL) in
freshly distilled benzene and ethanol-d1 (0.07 mL) was main-
tained at 30 °C for 12 h. Purification of the crude product
was achieved by chromatography (SiO2, Hexanes:EtOAc, 5:1)
to afford a mixture of the starting material 50 and the
monodeuterio analog 53. Mass spectral analysis of the mixture
revealed a 10% enhancement of the m/ z 285 peak correspond-
ing to the monodeuteriophenol 53.
Ack n ow led gm en t. The authors thank the National
Institutes of Health (GM-36312) for financial support
of this work. We are also grateful to Catherine A. Moore
for technical assistance in obtaining high-resolution
mass spectral data.
4-Isop r op oxy-2-(1-m eth yl-1-eth oxyeth yl)-6-p h en yl-1,4-
ben zen ed iol (52). A solution of 50 in anhyd ethanol was
refluxed for 24 h. Removal of solvent gave a mixture of
starting material 50 and product 52 as a colorless oil. 1H NMR
analysis of the product mixture showed a 3:1 ratio of 52 to 50.
Compound 52: 1H NMR (500 MHz, CDCl3) δ 8.61 (s, 1H),
7.45-7.51 (m, 2H), 7.43 (t, J ) 7.3 Hz, 2H), 7.32 (t, J ) 7.3
Hz, 1H), 6.72 (s, 1H), 5.43 (s, 1H), 3.59 (septet, J ) 6.2 Hz,
1H), 3.42 (q, J ) 7 Hz, 2H), 1.62 (s, 6H), 1.19 (t, J ) 7.0 Hz,
3H), 0.98 (d, J ) 5.9 Hz, 6H); HRMS (CI) calcd for C20H26O4
330.1831, found 330.1820; m/z 331 (8), 330 (55), 286 (16), 285
(72), 284 (86), 243 (40), 242 (100).
Su p p or tin g In for m a tion Ava ila ble: NMR spectra (37
pages). This material is contained in libraries on microfiche,
immediately 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.
J O951445M