Reversible charge-accelerated oxy-cope rearrangements

Article abstract of DOI:10.1021/jo982002w

An asymmetric synthesis of the oxetane-containing norbornanone 23 and its coupling to trans-1-propenyllithium to give 24 are reported, in tandem with the preparation of the related alcohols 28 and 30. All three divinyl carbinols undergo anionic oxy-Cope rearrangement very rapidly at low temperature. Quenching of 24^-K⁺ and 28^-K⁺ under these conditions with water or various aqueous salt solutions results in protonation of the alkoxides. If these reaction mixtures are poured instead onto cold (O °C) silica gel, their sigmatropically related ketones are isolated in very good yield. Whereas the 24^-K⁺?25^-K⁺ equilibrium pair is not reactive to molecular oxygen, 30^-K⁺ is directly converted into an α-hydroperoxy ketone under comparable conditions. These and additional observations are rationalized in the context of atropisomerism involving conversion of oxygen- up enolates, formed reversibly under kinetically controlled conditions, into their thermodynamically favored, more reactive oxygen-down conformers.

Full text of DOI:10.1021/jo982002w

9968
J . Org. Chem. 1998, 63, 9968-9977
Rever sible Ch a r ge-Acceler a ted Oxy-Cop e Rea r r a n gem en ts
Hon-Chung Tsui and Leo A. Paquette*
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210
Received October 5, 1998
An asymmetric synthesis of the oxetane-containing norbornanone 23 and its coupling to trans-1-
propenyllithium to give 24 are reported, in tandem with the preparation of the related alcohols 28
and 30. All three divinyl carbinols undergo anionic oxy-Cope rearrangement very rapidly at low
temperature. Quenching of 24-K+ and 28-K+ under these conditions with water or various aqueous
salt solutions results in protonation of the alkoxides. If these reaction mixtures are poured instead
onto cold (0 °C) silica gel, their sigmatropically related ketones are isolated in very good yield.
Whereas the 24-K+ a 25-K+ equilibrium pair is not reactive to molecular oxygen, 30-K+ is directly
converted into an R-hydroperoxy ketone under comparable conditions. These and additional
observations are rationalized in the context of atropisomerism involving conversion of oxygen-up
enolates, formed reversibly under kinetically controlled conditions, into their thermodynamically
favored, more reactive oxygen-down conformers.
[3,3]-Sigmatropic rearrangements have evolved into
powerful tools for stereocontrolled chirality transfer.1,2 As
a consequence of the adoption of highly ordered transition
states, stereochemical outcomes are often highly predict-
able, with the result that complex molecular scaffolding
can be reliably achieved in rapid fashion.3 From among
the several processes in this category, the oxy-Cope
rearrangement holds a special position as a consequence
of its capacity for significant anionic acceleration.4-6
Because its neutral [1 (R ) H) f 2] and charged variants
[1 (R ) K) f 2-] are so heavily favored thermodynami-
cally, either process has come to be generally viewed as
irreversible.1
vided the forum for discovery of the first remarkable
examples of reversibility under anionic oxy-Cope condi-
tions. These observations are notable because, as denoted
in 1 a 2-, the need now exists to overcome the resonance
stabilization associated with enolate anion 2- which is
not present in the potassium alkoxide, 1. Consequently,
although a driving force to proceed in the forward
direction is present in the great majority of examples
based on the 1 f 2- paradigm, this phenomenon should
no longer be viewed as all-inclusive.
Resu lts a n d Discu ssion
The first system to come under scrutiny was exo-
norbornanol 24 featuring a completely assembled oxetane
ring. The starting material selected for the synthesis of
this segment of 24 was D-glucose, which was converted
into diacetonide 510 and subsequently transformed into
the derived acetate (Scheme 1). Regioselective acid-
catalyzed hydrolysis of the C5,C6-acetonide moiety pro-
duced diol 6a , submission of which to a deoxygenation
protocol11,12 gave the vinyl derivative 7.13 During this
procedure, partial deacetylation was observed and the
mixture was therefore directly saponified to hydrolyze
In 1991, we reported the first example of a thermally
induced retro-oxy-Cope rearrangement, viz. 3 a 4.7
Continued investigation of systems related to 3 and 4
as part of our taxusin/taxol synthesis effort8,9 has pro-
(1) Review: Hill, R. K. In Asymmetric Synthesis; Morrison, J . D.,
Ed.; Academic Press: New York, 1984; Vol. 3, p 503.
(2) Review: Ziegler, F. E. Chem. Ber. 1988, 88, 1423.
(3) Review: Paquette, L. A. Synlett 1990, 67.
(4) Review: Paquette, L. A. Angew. Chem., Int. Ed. Engl. 1990, 29,
609.
(9) Paquette, L. A.; Zhao, M.; Montgomery, F.; Zeng, Q.; Wang, T.
Z.; Elmore, S.; Combrink, K.; Wang, H.-L.; Bailey, S.; Su, Z.; submitted
for publication.
(5) Review: Wilson, S. R. Org. React. 1993, 43, 93.
(6) Review: Paquette, L. A. Tetrahedron 1997, 53, 13971.
(7) Elmore, S. W.; Paquette, L. A. Tetrahedron Lett. 1991, 32, 319.
(8) (a) Paquette, L. A.; Zhao, M. J . Am. Chem. Soc. 1998, 120, 5203.
(b) Paquette, L. A.; Wang, H.-L.; Su, Z.; Zhao, M. J . Am. Chem. Soc.
1998, 120, 5213.
(10) Stevens, J . D. In Methods in Carbohydrate Chemistry; Whistler,
R. L., BeMiller, J . N., Eds.; Academic Press: 1972; Vol. 6, pp 1230-
1282.
(11) J ones, J . K. N.; Thompson, J . L. Can. J . Chem. 1957, 35, 955.
(12) Pietraszkiewicz, M.; Sinay¨, P. Tetrahedron Lett. 1979, 49, 4741.
(13) Garegg, P. J .; Samuelsson, B. Synthesis 1979, 469.
10.1021/jo982002w CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/05/1998

Reversible Oxy-Cope Rearrangements
J . Org. Chem., Vol. 63, No. 26, 1998 9969
Sch em e 1
Direct resilylation gave rise to 15 in >90% yield. This
diol was subsequently oxidized to norbornanone 16 under
Dess-Martin conditions prior to benzylation of the
tertiary hydroxyl substituent.
The time had now arrived for crafting the oxetane
subunit. To this end, it was first necessary to remove the
acetonide functionality. This hydrolysis proved to not be
trivial. However, success did materialize when 17 was
briefly subjected to the action of titanium tetrachloride
in CH2Cl2 at -78 °C.21 Under these unoptimized condi-
tions, a mixture of 18 (28%) and 19 (43%) resulted.
Following the selective reprotection of 18, the hemiacetal
sector of 19 was cleaved to the aldehydo formate with
the Dess-Martin periodinane and subjected in sequence
to reduction with sodium borohydride at -40 °C and
saponification with sodium hydroxide. The resultant diol
20 proved to be a colorless crystalline solid. Its con-
version to oxetane 21 was achieved directly by treatment
with potassium hexamethyldisilazide followed by N-(5-
chloro-2-pyridyl)triflimide.22 The absolute and relative
configurations of 21 follow rigorously from the method
of synthesis and from unambiguous spectroscopic fea-
tures.
The final stages of the route to 24 are depicted in
Scheme 3. Ketone 21 was transformed into its silyl enol
ether in advance of oxidation with dimethyldioxirane.23
The exo stereodisposition of the newly introduced hy-
droxyl group in 22 was based on a similar selectivity
observed in related systems24 and the absence of a vicinal
coupling constant to the bridgehead proton.25 Protection
of the hydroxyl group in 22 as the methoxymethyl ether
was readily effected, thereby making possible the 1,2-
addition of trans-1-propenyllithium from the endo direc-
tion and arrival at 24.
the remaining 7 and facilitate the purification of 8. This
vinyl tetrahydrofuran could also be prepared by sodium
periodate cleavage of triol 6b followed by Wittig olefina-
tion. Hydroboration of 8 with disiamylborane afforded
predominantly 9 (86%), the primary hydroxyl group in
which was chemoselectively protected as the tert-bu-
tyldimethylsilyl ether 10. Oxidation of 10 was accom-
plished with the Dess-Martin periodinane,14 providing
11 in 92% yield.
The anionic oxy-Cope rearrangement of 24 was induced
with potassium hydride and 18-crown-6 in THF solution
at 0 °C. After 15 min, the conversion of 24-K+ to 25-K+
was judged to be complete on the basis of the complete
disappearance on silica gel thin-layer chromatography
(TLC) plates of the spot due to 24 (Rf ) 0.42, elution with
4:1 hexanes-ethyl acetate) in favor of a single spot
arising from a more polar product (Rf ) 0.20) subse-
quently identified as 25. However, all attempts to isolate
ketone 25 by quenching of these reaction mixtures in
conventional ways (e.g., with saturated NH4Cl solution)
returned 24 quantitatively. Faced with these observa-
tions, we reasoned that silica gel might be somehow
mediating a selective protonation of 25-K+ under condi-
tions that did not promote the concomitant formation of
24. This line of conjecture served to suggest a solution
to the preparative isolation of 25. Indeed, when the cold,
basic reaction mixture was poured directly into a beaker
of silica gel cooled to 0 °C, and the product was eluted
from the adsorbent with ether, 25 was now isolated as
the only product. In a typical run, the yield of this bicyclic
ketone was 77%. This result removed all impediment to
At this juncture, the previously described 1215 was
transformed into the alkynyl anion by reaction with
n-butyllithium and added to 11 (Scheme 2). As expected,
this 1,2-addition proceeded with excellent π-facial selec-
tivity to provide 13 as the only detectable diastereomer.
The stereochemistry at the newly generated stereogenic
center is assigned as R on the basis of extensive anal-
ogy.16,17
To guarantee the proper stereodisposition of ring C in
our targeted taxane precursors,18 it was mandatory that
the acetylenic linkage in 13 be chemically modified into
a trans alkene. When Red-Al19 was discovered to be
ineffective for performing this interconversion, recourse
was made instead to lithium aluminum hydride.20 In the
event, refluxing THF was required, these conditions also
cleaving the tert-butyldimethylsilyl protecting group.
(14) (a) Dess, D. B.; Martin, J . C. J . Org. Chem. 1983, 48, 4155. (b)
Ireland, R. E.; Liu, L. B. J . Org. Chem. 1993, 58, 2899.
(15) Paquette, L. A.; Zeng, Q.; Tsui, H.-C.; J ohnston, J . N. J . Org.
Chem. 1998, 63, 8491.
(16) Iversen, T.; Bundle, D. R. J . Chem. Soc., Chem. Commun. 1981,
1240.
(17) Schmeichel, M.; Redlich, H. Synthesis 1996, 1002.
(18) Consult, for example: Paquette, L. A.; Huber, S. K.; Thompson,
R. C. J . Org. Chem. 1993, 58, 6874.
(21) Bulman-Page, P. C.; Roberts, R. A.; Paquette, L. A. Tetrahedron
Lett. 1983, 24, 3555.
(22) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299.
(23) (a) Adam, W.; Chan, Y. Y.; Cremer, D.; Gauss, J .; Scheutzow,
D.; Schindler, M. J . Org. Chem. 1987, 52, 2800. (b) Adam, W.; Prechtl,
F. Chem. Ber. 1991, 124, 2369.
(19) Gugelchuk, M. In Encyclopedia of Reagents for Organic Syn-
thesis; Paquette, L. A., Ed.; J ohn Wiley and Sons: Chichester, 1995;
Vol. 7, pp 4518-4521.
(24) Elmore, S. W.; Paquette, L. A. J . Org. Chem. 1995, 60, 889.
(25) Marchand, A. P. Stereochemical Applications of NMR Studies
in Rigid Bicyclic Systems; Verlag Chemie International: Deerfield
Beach, FL, 1982.
(20) Grant, B.; Djerassi, C. J . Org. Chem. 1974, 39, 968.

9970 J . Org. Chem., Vol. 63, No. 26, 1998
Tsui and Paquette
Sch em e 2
the flow of synthetic material while providing convincing
indication of the reversibility of the 24-K+/25-K+ equi-
librium.
C is not yet annealed onto the framework. However, a
distinction as to whether realignment would materialize
at the enolate anion stage27a or only after protonation was
not yet apparent. 1H NMR analysis of 25 clearly revealed
that its apical syn-methyl substituent is not subject to
electronic perturbation by a proximal carbonyl group.
Also, reduction of this ketone with lithium aluminum
hydride resulted in exclusive formation of the R-carbinol,
whose configuration was deduced by NOE analysis of its
p-methoxybenzyl derivative. Further, should the car-
bonyl-down conformation of 25 be thermodynamically
favored, its regiocontrolled deprotonation should not
result in reconversion to 24-K+ via 25-K+. At the
experimental level, a tr op -25-K+ proved to be indefinitely
stable at -78 °C; above this limit, decomposition sets in.
What role does silica gel play in all of this? We propose
that the rapidity with which 24 undergoes anionic oxy-
Cope rearrangement does not provide adequate op-
portunity for 25-K+ to undergo slower atropisomeriza-
tion. The dominant course of protonation at low tempera-
ture occurs on the alkoxide 24-K+. Admixing of the
reaction mixture with silica gel is accomplished at or
above 0 °C, such that resultant binding to the adsorbent
in combination with a more elevated temperature greatly
facilitates irreversible conversion to a tr op -25-K+.
As a direct consequence of the necessary adoption by
24-K+ of the so-called endo-chair transition-state topol-
ogy26 for effective sigmatropic realignment, the newly
developed carbonyl oxygen in 25 must be initially pro-
jected in an upward direction such that it resides in close
proximity to the apical syn-methyl substituent. However,
this conformation does not persist due to prevailing
nonbonded steric interactions, and σ bond rotations occur
so as to allow the carbonyl group to be preferably endo-
oriented.26,27 This interconversion was expected to occur
with a relatively low energy barrier in 25 because ring
The outcome of two companion experiments allows the
relative relationship of 25-K+ and a t r op -25-K+ to be
established. Treatment of 24 with KHMDS and 18-
crown-6 in THF at -78 °C in the presence of oxygen28
did not result in the formation of R-hydroxy ketone 26
despite TLC evidence for complete isomerization to
25-K+. As before, quenching of the reaction mixture with
(27) (a) Paquette, L. A.; Combrink, K. D.; Elmore, S. W.; Rogers, R.
D. J . Am. Chem. Soc. 1991, 113, 1335. (b) Paquette, L. A.; Elmore, S.
W.; Combrink, K. D.; Hickey, E. R.; Rogers, R. D. Helv. Chim. Acta
1992, 75, 1755. (c) Paquette, L. A.; Combrink, K. D.; Elmore, S. W.;
Zhao, M. Helv. Chim. Acta 1992, 75, 1772.
(26) Paquette, L. A.; Pegg, N. A.; Toops, D.; Maynard, G. D.; Rogers,
R. D. J . Am. Chem. Soc. 1990, 112, 277.
(28) Paquette, L. A.; DeRussy, D. T.; Pegg, N. A.; Taylor, R. T.;
Zydowsky, T. M. J . Org. Chem. 1989, 54, 4576.

Reversible Oxy-Cope Rearrangements
J . Org. Chem., Vol. 63, No. 26, 1998 9971
Sch em e 3
saturated NaHCO3 solution returned only 24. In contrast,
submission of 25 to the identical conditions afforded 26
in 81% yield.29
Interestingly, the previously reported 1,3-dioxanyl
alcohol 28 responds under anionic conditions in a manner
closely paralleling 24 (Scheme 4). Thus, 28-K+ generated
at -78 °C is rapidly transformed into 29-K+ (TLC
analysis), but this enolate anion is unreactive to oxygen.
Only when silica gel becomes involved is R-hydroxylation
observed (81% of 29), presumably because conversion to
a tr op -29-K+ has now materialized. Under these circum-
stances, it is likely that the substantially increased
surface area provided by the adsorbent facilitates enolate
oxygenation.
Con clu sion s
The weight of experimental evidence suggests that the
anionically accelerated [3,3] sigmatropic rearrangements
of 24 and 28 proceed in a reversible manner at -78 °C.
The return to alkoxide can materialize only as long as
the enolate anion has its oxygen atom oriented up toward
the methano bridge. The geometric demands of the oxy-
Cope transition state necessarily generate these enolates
in precisely this conformation. However, these structures
are thermodynamically unstable relative to their oxygen-
down forms. When a methyl group is positioned adjacent
to the bulky oxygenated side chain as it is in 25-K+ and
29-K+, the atropisomeric conversion does not operate
spontaneously but requires silica gel at more elevated
temperatures for its operation. Removal of this steric
interference as in 31-K+ lessens the energy barrier
significantly. In methylation and oxygenation reactions,
the oxygen-down enolates give evidence of being the more
reactive of the atropisomeric pair. The greatly diminished
nucleophilicity of 25-K+ and 29-K+ could well be matched
by a similar decrease in basicity as a consequence of
effective steric shielding on both π surfaces. These factors
would serve to explain why the alkoxides are preferen-
tially protonated at low temperature. Comparable obser-
vations have not previously been reported in any sigma-
tropic context. It is hoped that the principles delineated
It will be recognized that the atropisomerization
processes involving 25-K+ and 29-K+ require that the
bulky oxygenated side chain and adjacent methyl sub-
stituent experience unfavorable A1,3 interaction. On this
basis, the expectation would be that a desmethyl con-
gener might not be destabilized in this manner and would
find it energetically more feasible to undergo irreversible
conformational flexing at significantly lower tempera-
tures. To probe this issue, 27 was reacted with the
vinylcerate reagent to furnish 32 (Scheme 5). This
compound was treated in turn with potassium hexa-
methyldisilazide and 18-crown-6 in the presence of
oxygen at -78 °C. In contrast to 27, which failed to react
until silica gel was introduced, 32 was very efficiently
transformed into R-hydroperoxy ketone 33 within 5 min
at this temperature. Brief exposure of this product to
triphenylphosphine gave 34 in 81% isolated yield as a
single epimer.29
(29) Although 26 and 33 were isolated as single diastereomers, the
stereochemistry of their hydroxyl group was not determined because
of pending oxidation to the R-diketone. (Tsui, H.-C. Ph.D. Thesis, The
Ohio State University, 1998).

9972 J . Org. Chem., Vol. 63, No. 26, 1998
Tsui and Paquette
NMR. The high-resolution and fast-atom-bombardment spec-
tra were recorded at The Ohio State University Campus
Chemical Instrument Center. Elemental analyses were per-
formed at Atlantic Microlab, Inc., Norcross, GA.
Sch em e 4
3-O-Acetyl-1,2,5,6-d iisop r op ylid en e-D-glu cose. To a so-
lution of 5 (251 mg, 0.964 mmol) in CH2Cl2 (5 mL) at 20 °C
were added triethylamine (0.40 mL, 2.9 mmol), acetic anhy-
dride (0.14 mL, 1.5 mmol), and a catalytic amount of DMAP.
The mixture was stirred for 3 h, quenched with saturated
NH4Cl solution, and diluted with water and ether. The
separated aqueous layer was extracted twice with ether. The
combined organic extracts were dried, filtered, and evaporated.
Ensuing chromatographic purification of the residue on silica
gel (elution with 4:1 hexanes-ethyl acetate) gave the acetate
of 5 (258 mg, 89%) as a white solid: mp 62-62.5 °C; IR (film,
cm-1) 1751; 1H NMR (300 MHz, CDCl3) δ 5.86 (d, J ) 3.7 Hz,
1 H), 5.24 (d, J ) 2.2 Hz, 1 H), 4.48 (d, J ) 3.7 Hz, 1 H), 4.24-
4.17 (m, 2 H), 4.09-3.98 (m, 2 H), 2.08 (s, 3 H), 1.50 (s, 3 H),
1.39 (s, 3 H), 1.31 (s, 3 H), 1.29 (s, 3 H); 13C NMR (75 MHz,
CDCl3) ppm 169.5, 112.2, 109.3, 105.0, 83.3, 79.7, 76.1, 72.4,
67.1, 26.8, 26.7, 26.2, 25.2, 20.8; MS m/z (M+) calcd 302.1365,
obsd 302.1327; [R]22 -27.9 (c 1.63, CHCl3).
D
(1R)-1-[(3a R,5R,6S,6a R)-Tetr a h yd r o-6-h yd r oxy-2,2-d i-
m eth ylfu r o[2,3-d ]-1,3-d ioxol-5-yl]-1,2-eth a n ed iol 6-Ace-
ta te (6a ). The acetate of 5 (150 mg, 0.496 mmol) was dissolved
in 50% aqueous acetic acid (2 mL) at 20 °C and stirred for 1
day. Solvents were removed in vacuo. Chromatography of the
residue on silica gel (elution with 4:1 hexanes-ethyl acetate)
gave 6a (114 mg, 87%) as white crystals: mp 126-126.5 °C
(from hexanes-ether); IR (film, cm-1) 3442, 1746; 1H NMR
(300 MHz, CDCl3) δ 5.89 (d, J ) 3.7 Hz, 1 H), 5.26 (d, J ) 2.6
Hz, 1 H), 4.55 (d, J ) 3.7 Hz, 1 H), 4.17 (dd, J ) 8.8, 2.6 Hz,
1 H), 3.85-3.74 (m, 1 H), 3.72-3.62 (m, 2 H), 3.12 (br s, 1 H),
2.42 (br s, 1 H), 2.14 (s, 3 H), 1.51 (s, 3 H), 1.30 (s, 3 H); 13C
NMR (75 MHz, CDCl3) ppm 171.2, 112.4, 104.8, 83.0, 79.4,
76.7, 68.2, 64.1, 26.6, 26.2, 20.8; MS m/z (M+) calcd 263.1131,
Sch em e 5
obsd 263.1110; [R]22 +18 (c 0.93, CHCl3).
D
(3a R,5R,6S,6a R)-Tetr a h yd r o-2,2-d im eth yl-5-vin ylfu r o-
[2,3-d ]-1,3-d ioxol-6-ol (8). A. F r om 6a . To a solution of 6a
(5.00 g, 19.1 mmol) in toluene (200 mL) was added tri-
phenylphosphine (20.0 g, 76.3 mmol) and imidazole (5.19 g,
76.3 mmol). The mixture was heated to 80 °C for 30 min and
cooled to room temperature. Iodine (14.6 g, 57.3 mmol) was
slowly added in small portions, and the mixture was heated
to 80 °C for another 3 h, cooled to room temperature, and
treated with zinc dust (2.0 g) until decolorization was complete.
The mixture was diluted with ether, and the solid was removed
by filtration through a pad of Celite. The filtrate was washed
with saturated NaHCO3 solution, dried, and filtered. Removal
of solvents left a residue which was dissolved in methanol (100
mL). Sodium hydroxide (5 mL, 2 N in water) was introduced,
and the solution was stirred at room temperature for 30 min
and diluted with water and ether. The separated aqueous layer
was extracted with ether (×2). The combined organic extracts
were dried, filtered, and concentrated. Subsequent chroma-
tography on silica gel (elution with 3:1 hexanes-ethyl acetate)
gave 8 (2.6 g, 71%) as a white solid: mp 64-65 °C; IR (film,
1
cm-1) 3452, 1647; H NMR (300 MHz, CDCl3) δ 5.92 (d, J )
3.5 Hz, 1 H), 5.87 (ddd, J ) 17.2, 10.7, 5.1 Hz, 1 H), 5.51 (dt,
J ) 17.4, 1.4 Hz, 1 H), 5.39 (dd, J ) 10.7, 1.3 Hz, 1 H), 4.71
(br s, 1 H), 4.55 (d, J ) 3.6 Hz, 1 H), 4.07 (br s, 1 H), 1.97 (br
s, 1 H), 1.49 (s, 3 H), 1.30 (s, 3 H); 13C NMR (75 MHz, CDCl3)
ppm 131.1, 119.5, 111.6, 104.5, 84.8, 80.8, 75.6, 26.6, 26.1; MS
m/z (M+) calcd 187.0970, obsd 187.0970; [R]22 -52.1 (c 2.27,
D
CHCl3).
here will translate into a sufficiently large number of
systems to justify their broad extrapolation.
B. Via a Wittig Olefin a tion Sequ en ce. To a mixture of
6b (2.00 g, 9.08 mmol) in a mixture of methanol (25 mL) and
water (25 mL) was added sodium periodate (2.91 g, 13.6 mmol)
in small portions. The white suspension was stirred for a
additional 30 min, filtered through a pad of Celite, and freed
of solvents in vacuo. The white residue was extracted with
tetrahydrofuran (×5), and the combined organic extracts were
dried, filtered, and evaporated to give a crude aldehyde which
was used in the next step without further purification.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. The
column chromatographic separations were performed with
Woelm silica gel (230-400 mesh). Solvents were reagent grade
and in most cases dried prior to use. The purity of all
compounds was shown to be >95% by TLC and high field 1H

Reversible Oxy-Cope Rearrangements
J . Org. Chem., Vol. 63, No. 26, 1998 9973
To a solution of methyltriphenylphosphonium iodide (8.00
g, 18.0 mmol) in THF (10 mL) at 0 °C was added a solution of
potassium hexamethyldisilazide (39.5 mL of 0.5 M in toluene,
18.0 mmol). The yellow suspension was stirred at 0 °C for 1
h, and a solution of the aldehyde from above in THF (5 mL)
was added. The resultant brown suspension was allowed to
warm to room temperature, stirred for 3 h, and quenched with
saturated NH4Cl solution. Ether was added, and the white
solid was removed by filtration through a pad of Celite. The
separated aqueous layer was extracted with ether (×2). The
combined organic extracts were dried, filtered, and concen-
trated. Chromatography of the residue on silica gel (elution
with 3:1 hexanes-ethyl acetate) gave 8 (831 mg, 67% for 2
steps) as a white solid spectroscopically identical to the original
sample.
(3a R,5R,6R,6a R)-5-[2-(ter t-Bu tyld im eth ylsiloxy)eth yl]-
tetr ah ydr o-6-[[(1R,2R,4R)-2-h ydr oxy-7,7-dim eth ylbicyclo-
[2.2.1]h ept-1-yl]eth yn yl]-2,2-dim eth ylfu r o[2,3-d]-1,3-dioxol-
6-ol (13). To a solution of 1215
(5.07 g, 15.6 mmol) in THF (30
mL) at -78 °C was added n-butyllithium (29.3 mL of 1.6 M in
hexanes, 46.8 mmol). After 1 h of stirring at -78 °C, a solution
of 11 (2.75 g, 86.9 mmol) in THF (20 mL) was introduced, and
the mixture was stirred at -78 °C for 2 h, quenched with
saturated NaHCO3 solution, warmed to room temperature, and
diluted with water and ether. The separated aqueous layer
was extracted with ether (×2). The combined organic extracts
were dried and filtered. Removal of solvents from the filtrate
in vacuo followed by chromatography on silica gel (elution with
2:1 hexanes-ethyl acetate) furnished 13 (2.1 g, 50%) as a
colorless oil: IR (film, cm-1) 3428; 1H NMR (300 MHz, CDCl3)
δ 5.77 (d, J ) 3.5 Hz, 1 H), 4.57 (d, J ) 3.5 Hz, 1 H), 4.30 (br
s, 1 H), 4.03 (t, J ) 6.7 Hz, 1 H), 3.89-3.82 (m, 1 H), 3.78-
3.70 (m, 2 H), 2.35 (br s, 1 H), 2.16-2.06 (m, 1 H), 1.97-1.68
(m, 6 H), 1.57 (s, 3 H), 1.35 (s, 3 H), 1.31-1.22 (m, 1 H), 1.13
(s, 3 H), 1.11-1.04 (m, 1 H), 0.94 (s, 3 H), 0.89 (s, 9 H), 0.083
(s, 3 H), 0.077 (s, 3 H); 13C NMR (75 MHz, CDCl3) ppm 113.2,
103.9, 88.0, 84.6, 83.8. 80.1, 78.2, 76.2, 60.5, 50.8, 49.7, 44.0,
39.4, 32.6, 32.4, 27.2, 26.6, 26.5, 25.9 (3 C), 21.1, 20.4, 18.3,
-5.4, -5.5; FAB MS m/z (M+ + H) calcd 481.30, obsd 481.36;
(3a R,5R,6S,6a R)-Tetr a h yd r o-6-h yd r oxy-2,2-d im eth yl-
fu r o[2,3-d]-1,3-dioxole-5-eth an ol (9). To a solution of 2-meth-
yl-2-butene (39 mL of 2.0 M in THF, 0.078 mol) at 0 °C was
added borane-tetrahydrofuran complex (39 mL of 1.0 M in
THF, 0.078 mol). The mixture was stirred at 0 °C for 1 h,
treated with a solution of 8 (2.47 g, 13.1 mmol) in THF (10
mL), and stirred at 0 °C for another hour. Sodium hydroxide
solution (2 N, 30 mL) was introduced, followed by 30%
hydrogen peroxide (30 mL), and the contents were warmed to
room temperature and stirred overnight. Solvents were re-
moved in vacuo, and the solid residue was extracted with
tetrahydrofuran (×5). The combined organic solutions were
dried and evaporated. The residue was chromatographed on
silica gel (elution with 1:5 hexanes-ethyl acetate) to afford 9
[R]24 +9.62 (c 1.83, CHCl3). Anal. Calcd for C26H44O6Si: C,
D
64.96; H, 9.23. Found: C, 64.82; H, 9.18.
(3a R ,5R ,6R ,6a R )-T e t r a h y d r o -6-h y d r o x y -6-[(E )-2-
[(1S,2R,4R)-2-h yd r oxy-7,7-d im eth ylbicyclo[2.2.1]h ep t-1-
yl]vin yl]-2,2-dim eth ylfu r o[2,3-d]-1,3-dioxole-5-eth an ol (14).
A solution of 13 (0.85 g, 1.8 mmol) in THF (20 mL) at 0 °C
was treated with lithium aluminum hydride (336 mg, 8.84
mmol), heated to reflux for 3 h, cooled to 0 °C, carefully
quenched with saturated NH4Cl solution, and diluted with
saturated sodium potassium tartrate solution and ether. The
separated aqueous layer was extracted with ether (×4). The
combined organic extracts were dried and filtered. Solvent
evaporation followed by chromatography on silica gel (elution
with 1:5 hexanes-ethyl acetate) gave 14 (638 mg, 98%) as a
white foam: IR (film, cm-1) 3408; 1H NMR (300 MHz, CDCl3)
δ 6.08 (d, J ) 16.3 Hz, 1 H), 5.79 (d, J ) 3.8 Hz, 1 H), 5.36 (d,
J ) 16.3 Hz, 1 H), 4.25 (d, J ) 3.8 Hz, 1 H), 3.99 (t, J ) 6.6
Hz, 1 H), 3.78-3.63 (m, 3 H), 3.18 (br s, 3 H), 1.84-1.63 (m,
7 H), 1.59 (s, 3 H), 1.33 (s, 3 H), 1.14 (s, 3 H), 1.10-0.98 (m, 2
H), 0.77 (s, 3 H); 13C NMR (75 MHz, CDCl3) ppm 130.5, 127.6,
112.6, 103.5, 83.4, 80.4, 80.3, 80.2, 60.1, 54.9, 47.7, 45.6, 40.3,
31.4, 29.9, 26.8, 26.43, 26.39, 20.8, 20.4; MS m/z (M+) calcd
(2.3 g, 86%) as a white solid: mp 94-95 °C; IR (film, cm-1
)
3354, 3199; 1H NMR (300 MHz, CDCl3) δ 5.89 (d, J ) 3.7 Hz,
1 H), 4.51 (d, J ) 3.7 Hz, 1 H), 4.23 (dt, J ) 6.9, 2.4 Hz, 1 H),
4.09 (d, J ) 2.4 Hz, 1 H), 3.87-3.80 (m, 1 H), 3.73-3.66 (m, 1
H), 3.24 (s, 1 H), 3.25-2.95 (br s, 1 H), 2.02-1.89 (m, 2 H),
1.47 (s, 3 H), 1.29 (s, 3 H); 13C NMR (75 MHz, CDCl3) ppm
111.3, 104.3, 85.2, 79.6, 75.7, 59.2, 30.3, 26.6, 26.1; MS m/z
(M+ - CH3) calcd 189.0763, obsd 189.0752; [R]23D -11.9 (c 1.70,
CHCl3).
(3a R,5R,6S,6a R)-5-[2-(ter t-Bu tyld im eth ylsiloxy)eth yl]-
tetr a h yd r o-2,2-d im eth ylfu r o[2,3-d ]-1,3-d ioxol-6-ol (10).
To a solution of 9 (1.25 g, 6.12 mmol) in CH2Cl2 (25 mL) at 0
°C were added imidazole (625 mg, 9.18 mmol) and tert-
butyldimethylsilyl chloride (1.01 g, 6.73 mmol). The mixture
was stirred at 0 °C for 1 h and quenched with saturated
NaHCO3 solution. The separated aqueous layer was extracted
with CH2Cl2 (×2), the combined organic layers were dried, and
the filtrate was evaporated. Chromatography of the residue
on silica gel (elution with 4:1 hexanes-ethyl acetate) gave 10
(1.75 g, 90%) as a colorless oil: IR (film, cm-1) 3456; 1H NMR
(300 MHz, CDCl3) δ 5.79 (d, J ) 3.8 Hz, 1 H), 4.45 (d, J ) 3.8
Hz, 1 H), 4.14 (m, 1 H), 3.98 (d, J ) 2.5 Hz, 1 H), 3.76-3.70
(m, 1 H), 3.61-3.54 (m, 1 H), 3.44 (br s, 1 H), 1.95-1.80 (m, 2
H), 1.39 (s, 3 H), 1.21 (s, 3 H), 0.81 (s, 9 H), 0.00 (s, 6 H); 13C
NMR (75 MHz, CDCl3) ppm 110.8, 104.2, 85.0, 79.5, 75.3, 59.5,
30.7, 26.5, 25.9, 25.6 (3 C), 17.9, -5.8, -5.9; FAB MS m/z (M+
369.2276, obsd 369.2241; [R]24 -11.1 (c 3.00, CH2Cl2). Anal.
D
Calcd for C20H32O6: C, 65.19; H, 8.75. Found: C, 64.99; H,
8.68.
(3a R,5R,6R,6a R)-5-[2-(ter t-Bu tyld im eth ylsiloxy)eth yl]-
tetr a h yd r o-6-[(E)-2-[(1S,2R,4R)-2-h yd r oxy-7,7-d im eth yl-
bicyclo[2.2.1]h ep t-1yl]vin yl]-2,2-d im eth ylfu r o[2,3-d ]-1,3-
d ioxol-6-ol (15). To a solution of 14 (638 mg, 1.73 mmol) in
CH2Cl2 (10 mL) at 0 °C were added imidazole (181 mg, 2.65
mmol) and tert-butyldimethylsilyl chloride (320 mg, 2.12
mmol). The mixture was stirred at 0 °C for 1 h and quenched
with saturated NaHCO3 solution. The separated aqueous layer
was extracted with CH2Cl2 (×2), and the combined organic
layers were dried and concentrated. The residue was chro-
matographed on silica gel (elution with 2:1 hexanes-ethyl
acetate) to give 15 (768 mg, 92%) as a colorless oil: IR (film,
cm-1) 3442; 1H NMR (300 MHz, CDCl3) δ 6.13 (d, J ) 16.3
Hz, 1 H), 5.79 (d, J ) 3.8 Hz, 1 H), 5.38 (d, J ) 16.2 Hz, 1 H),
4.25 (d, J ) 3.8 Hz, 1 H), 3.99 (dd, J ) 8.0, 4.8 Hz, 1 H), 3.78-
3.63 (m, 3 H), 1.87-1.61 (m, 7 H), 1.58 (s, 3 H), 1.34 (s, 3 H),
1.15 (s, 3 H), 1.10-0.98 (m, 2 H), 0.87 (s, 9 H), 0.77 (s, 3 H),
0.04 (s, 6 H); 13C NMR (75 MHz, CDCl3) ppm 130.0, 128.3,
112.4, 103.5, 83.6, 80.4, 80.1, 78.8, 60.1, 55.0, 47.9, 45.5, 40.3,
32.1, 29.9, 27.0, 26.50, 26.45, 25.9 (3 C), 20.7, 20.4, 18.2, -5.4
+ H) calcd 319.19, obsd 319.20; [R]20 +8.09 (c 10.8, CHCl3).
D
Anal. Calcd for C15H30O5Si: C, 56.57; H, 9.49. Found: C, 56.61;
H, 9.53.
(3aR,5R,6aR)-5-[2-(ter t-Bu tyldim eth ylsiloxy)eth yl]dih y-
d r o-2,2-d im eth ylfu r o[2,3-d ]-1,3-d ioxol-6(5H)-on e (11). A
solution of 10 (3.00 g, 9.42 mmol) in CH2Cl2 (20 mL) was
treated with the Dess-Martin periodinane (7.99 g, 18.8 mmol),
stirred for 2 h, diluted with ether, and washed with NaOH
solution (2 N) and brine. The organic phase was dried, freed
of solvents, and subjected to chromatography on silica gel
(elution with 2:1 hexanes-ether) to furnish 11 (2.8 g, 92%) as
a colorless oil: IR (film, cm-1) 1775; 1H NMR (300 MHz, CDCl3)
δ 6.03 (d, J ) 4.4 Hz, 1 H), 4.46 (t, J ) 4.9 Hz, 1 H), 4.41 (dd,
J ) 4.4, 1.0 Hz, 1 H), 3.82 (ddd, J ) 13.8, 8.0, 5.6 Hz, 1 H),
3.69-3.62 (m, 1 H), 2.00-1.94 (m, 2 H), 1.47 (s, 3 H), 1.40 (s,
3 H), 0.85 (s, 9 H), 0.02 (s, 6 H); 13C NMR (75 MHz, CDCl3)
ppm 210.6, 113.7, 103.1, 76.4, 75.8, 58.0, 34.4, 27.4, 27.2, 25.9
(3 C), 18.4, -5.5, -5.7; FAB MS m/z (M+ + H) calcd 317.18,
(2 C); FAB MS m/z (M+ + H) calcd 483.31, obsd 483.40; [R]24
D
-5.90 (c 2.93, CH2Cl2). Anal. Calcd for C26H46O6Si: C, 64.69;
H, 9.60. Found: C, 64.47; H, 9.52.
(1S,4R)-1-[(E)-2-[(3a R,5R,6R,6a R)-5-[2-(ter t-Bu t yld i-
m eth ylsiloxy)-eth yl]tetr a h yd r o-6-h yd r oxy-2,2-d im eth yl-
fu r o[2,3-d]-1,3-dioxol-6-yl]vin yl]-7,7-dim eth ylbicyclo[2.2.1]-
obsd 317.11; [R]20 +91.6 (c 1.36, CHCl3).
D

9974 J . Org. Chem., Vol. 63, No. 26, 1998
Tsui and Paquette
h ep ta n -2-on e (16). A solution of 15 (768 mg, 1.59 mmol) in
CH2Cl2 (20 mL) was treated with the Dess-Martin periodi-
nane (1.13 g, 2.65 mmol), stirred for 30 min, diluted with ether,
filtered, and washed with aqueous NaOH solution (2 N) and
brine. The separated organic layer was dried and freed of
solvent in advance of chromatography (silica gel, elution with
3:1 hexanes-ethyl acetate). There was obtained 749 mg (98%)
35.2, 27.5, 27.1 25.9 (3 C), 20.3, 19.7, 18.3, -5.3 (2 C); FAB
MS m/z (M+) calcd 531.31, obsd 531.38; [R]24 +52.6 (c 1.14,
D
CHCl3).
Continued elution (ethyl acetate) gave 18 (220 mg, 28%),
also as a colorless oil: IR (film, cm-1) 3409, 1736; 1H NMR
(300 MHz, CDCl3) δ 7.39-7.27 (m, 5 H), 5.84 (d, J ) 16.7 Hz,
1 H), 5.72 (d, J ) 16.7 Hz, 1 H), 5.33 (d, J ) 4.2 Hz, 1 H), 4.70
(d, J ) 11.1 Hz, 1 H), 4.57 (d, J ) 11.1 Hz, 1 H), 4.38 (dd, J )
9.7, 3.7 Hz, 1 H), 4.22 (d J ) 4.2 Hz, 1H), 3.80-3.76 (m, 2 H),
2.75-2.25 (br s, 3 H), 2.51-2.43 (m, 1 H), 2.18-2.15 (m, 1 H),
2.09-1.98 (m, 2 H), 1.93 (d, J ) 18.3 Hz, 1 H), 1.85-1.71 (m,
1 H), 1.69-1.54 (m, 2 H), 1.49-1.42 (m, 1 H), 0.97 (s, 3 H),
0.93 (s, 3 H); 13C NMR (75 MHz, CDCl3) ppm 216.0, 137.5,
130.1, 128.5 (2 C), 128.3, 128.0, 127.7 (2 C), 96.3, 85.6, 80.7,
73.0, 67.2, 63.4, 60.6, 49.0, 43.6, 43.3, 33.7, 27.5, 27.1, 20.3,
1
of 16 as a colorless oil: IR (film, cm-1) 3466, 1743; H NMR
(300 MHz, CDCl3) δ 5.91 (d, J ) 16.2 Hz, 1 H), 5.74 (d, J )
3.6 Hz, 1 H), 5.53 (d, J ) 16.1 Hz, 1 H), 4.24 (d, J ) 3.5 Hz, 1
H), 3.96 (dd, J ) 7.6, 5.3 Hz, 1 H), 3.75-3.60 (m, 2 H), 3.01
(br s, 1 H), 2.40 (dd, J ) 18.2, 3.8 Hz, 1 H), 2.10 (t, J ) 3.7 Hz,
1 H), 1.98-1.91 (m, 2 H), 1.85 (d, J ) 18.2 Hz, 1 H), 1.75-
1.58 (m, 2 H), 1.54 (s, 3 H), 1.48-1.35 (m, 2 H), 1.30 (s, 3 H),
0.90 (s, 6 H), 0.84 (s, 9 H), 0.01 (s, 6 H); 13C NMR (75 MHz,
CDCl3) ppm 216.4, 130.9, 125.5, 112.3, 103.4, 83.8, 79.9, 78.8,
63.1, 60.0, 48.6, 43.6 43.2, 31.9, 27.0, 26.9, 26.4, 26.3, 25.8 (3
C), 20.1, 19.4, 18.2, -5.46, -5.49; FAB MS m/z (M+ + H) calcd
481.30, obsd 481.39; [R]24D +16.0 (c 5.44, CH2Cl2). Anal. Calcd
for C26H44O6Si: C, 64.96; H, 9.23. Found: C, 64.87; H, 9.22.
19.7; FAB MS m/z (M+) calcd 417.23, obsd 417.26; [R]22 +3.3
D
(c 0.27, CHCl3).
(1S ,4R )-1-[(1E ,3S ,4R )-3-(Be n zyloxy)-6-(t er t -b u t yld i-
m eth ylsiloxy)-4-h yd r oxy-3-(h yd r oxym eth yl)-1-h exen yl]-
7,7-d im eth ylbicyclo[2.2.1]h ep ta n -2-on e (20). To a solution
of 19 (1.22 g, 2.30 mmol) in CH2Cl2 (20 mL) at 0 °C was added
the Dess-Martin periodinane (1.96 g, 4.60 mmol). The white
suspension was stirred at 0 °C for 30 min, diluted with ether,
filtered through a pad of Celite, and concentrated. Column
chromatography of the residue (silica gel, elution with 6:1
hexanes-ethyl acetate) furnished the formyl ester as a color-
less oil. This oil was dissolved in methanol (10 mL) and cooled
to -40 °C. Sodium borohydride (104 mg, 2.76 mmol) was
added, and the white mixture was stirred at -40 °C for 1 h.
Aqueous NaOH solution (2 N, 10 mL) was introduced, and the
mixture was warmed to room temperature, diluted with
saturated NH4Cl solution and ether, and extracted with ether
(×2). The combined organic phases were dried, freed of solvent,
and chromatographed on silica gel (elution with 2:1 hexanes-
ethyl acetate). There was obtained 752 mg (65%) of 20 as a
white solid: mp 77-78 °C; IR (film, cm-1) 3440, 1742; 1H NMR
(300 MHz, CDCl3) δ 7.42-7.23 (m, 5 H), 5.74 (d, J ) 16.7 Hz,
1 H), 5.49 (d, J ) 16.7 Hz, 1 H), 4.62 and 4.58 (ABq, J ) 10.9
Hz, 2 H), 4.06-4.01 (m, 2 H), 3.95-3.77 (m, 3 H), 3.58 (d, J )
2.5 Hz, 1 H), 3.15 (t, J ) 6.0 Hz, 1 H), 2.44 (ddd, J ) 18.3, 4.8,
2.2 Hz, 1 H), 2.14 (t, J ) 4.3 Hz, 1 H), 2.06-1.84 (m, 3 H),
1.90 (d, J ) 18.3 Hz, 1 H), 1.74-1.62 (m, 1 H), 1.59-1.39 (m,
(1S,4R)-1-[(E)-2-[(3a R,5R,6R,6a R)-6-(Ben zyloxy)-5-[2-
(ter t-bu tyld im eth ylsiloxy)eth yl]tetr a h yd r o-2,2-d im eth -
ylfu r o[2,3-d ]-1,3-d ioxol-6-yl]vin yl]-7,7-d im et h ylb icyclo-
[2.2.1]h ep ta n -2-on e (17). A solution of 16 (704 mg, 1.56
mmol) in DMF (20 mL) at 0 °C was treated with sodium
hydride (75 mg, 0.031 mol), stirred at 0 °C for 15 min before
benzyl bromide (0.37 mL, 0.031 mol) and a catalytic amount
of tetra-n-butylammonium iodide were introduced, warmed to
room temperature, stirred for another 4 h, cooled to 0 °C, and
quenched with saturated NH4Cl solution. Water and ether
were added, and the separated aqueous layer was extracted
with ether (×2). The combined organic extracts were dried and
filtered. Removal of solvents from the filtrate in vacuo followed
by chromatography (silica gel, elution with 5:1 hexanes-ether)
afforded 17 (793 mg, 89%) as a white solid: mp 95-96 °C; IR
(film, cm-1) 1743; 1H NMR (300 MHz, CDCl3) δ 7.42-7.22 (m,
5 H), 5.83 (d, J ) 3.7 Hz, 1 H), 5.73 (d, J ) 16.6 Hz, 1 H), 5.42
(d, J ) 16.6 Hz, 1 H), 4.70 (s, 2 H), 4.61 (d, J ) 3.7 Hz, 1 H),
4.26 (dd, J ) 9.3, 3.4 Hz, 1 H), 3.79-3.65 (m, 2 H), 2.45 (ddd,
J ) 18.3, 4.7, 2.0 Hz, 1 H), 2.14 (m, 1 H), 2.08-1.96 (m, 2 H),
1.91 (d, J ) 18.3 Hz, 1 H), 1.83-1.72 (m, 1 H), 1.61 (s, 3 H),
1.59-1.40 (m, 3 H), 1.38 (s, 3 H), 0.93 (s, 3 H), 0.90 (s, 3 H),
0.87 (s, 9 H), 0.03 (s, 3 H), 0.02 (s, 3 H); 13C NMR (75 MHz,
CDCl3) ppm 216.3, 138.8, 129.5, 128.1 (2 C), 128.0, 127.5 (2
C), 127.2, 112.5, 104.2, 85.5, 81.6, 78.2, 66.9, 63.4, 60.2, 48.7,
43.6, 44.4, 33.0, 27.0, 26.9, 26.7, 26.6, 25.9 (3 C), 20.2, 19.6,
18.2, -5.4 (2 C); FAB MS m/z (M+) calcd 571.35, obsd 571.18;
2 H), 0.92 (s, 3 H), 0.91 (s, 3 H), 0.88 (s, 9 H), 0.52 (s, 6 H); 13
C
NMR (75 MHz, CDCl3) ppm 216.5, 138.9, 131.1, 128.3 (2 C),
128.1, 127.8 (2 C), 127.4, 80.9, 75.6, 64.7, 63.6, 62.9, 61.9, 48.6,
43.6, 43.3, 33.6, 27.0, 26.7, 25.9 (3 C), 20.2, 19.6, 18.2, -5.49,
-5.54; FAB MS m/z (M+ + H) calcd 503.32, obsd 503.40; [R]23
D
[R]24 +37.7 (c 2.87, CH2Cl2). Anal. Calcd for C33H50O6Si: C,
+13.4 (c 2.21, CHCl3). Anal. Calcd for C29H46O5Si: C, 69.28;
D
69.44; H, 8.83. Found: C, 69.48; H, 8.84.
H, 9.22. Found: C, 69.33; H, 9.28.
(1S,4R)-1-[(E)-2-[(2R,3S,4R)-3-(Ben zyloxy)-2-[2-(ter t-
bu tyld im eth ylsiloxy)eth yl]tetr a h yd r o-4,5-d ih yd r oxy-3-
fu r yl]vin yl]-7,7-d im eth ylbicyclo[2.2.1]h ep ta n -2-on e (19).
Titanium tetrachloride (7.6 mL of 1.0 M in CH2Cl2, 7.6 mmol)
in CH2Cl2 (20 mL) at -78 °C was treated with a solution of
17 (1.08 g, 1.89 mmol) in CH2Cl2 (2 mL) in one portion. The
red solution was immediately poured into a mixture of
saturated NaHCO3 solution (100 mL) and ether (100 mL) at 0
°C. The mixture was stirred at room temperature overnight,
and the separated aqueous layer was extracted with ether
(×3). The combined organic extracts were dried and evapo-
rated, and the residue was purified chromatographically (silica
gel, elution with 2:1 hexanes-ethyl acetate) to give the less
polar 19 (430 mg, 43%) as a colorless oil: IR (film, cm-1) 3424,
(1S ,4R )-1-[(E )-2-[(2R ,3S )-3-(B e n zy lo x y )-2-[2-(t er t -
b u t y ld i m e t h y l-s i lo x y )e t h y l]-3-o x e t a n y l]v i n y l]-7,7-
d im eth ylbicyclo[2.2.1]h ep ta n -2-on e (21). A cold (-78 °C)
solution of 20 (96 mg, 0.19 mmol) in THF was treated with
potassium hexamethyldisilazide (0.76 mL of 0.5 M in toluene,
0.38 mmol) and stirred at -78 °C for 15 min before a solution
of N-(5-chloro-2-pyridyl)triflimide (138 mg, 0.383 mmol) in
THF (0.5 mL) was introduced dropwise. The mixture was
stirred at -78 °C for another 10 min before being quenched
with saturated NaHCO3 solution, diluted with ether, and
extracted with ether (×2). The combined organic layers were
dried and evaporated prior to purification of the residue by
chromatography on silica gel (elution with 6:1 hexanes-ethyl
acetate). There was obtained 58 mg (63%) of 21 as a colorless
oil: IR (film, cm-1) 1743; 1H NMR (300 MHz, CDCl3) δ 7.41-
7.27 (m, 5 H), 5.84 (s, 2 H), 4.96 (dd, J ) 8.7, 5.0 Hz, 1 H),
4.67 (d, J ) 6.8 Hz, 1 H), 4.54 (d, J ) 7.0 Hz, 1 H), 4.51 (d, J
) 11.3 Hz, 1 H), 4.35 (d, J ) 11.3 Hz, 1 H), 3.69-3.58 (m, 2
H), 2.48 (ddd, J ) 18.3, 4.8, 1.8 Hz, 1 H), 2.19-2.16 (m, 1 H),
2.11-2.00 (m, 2 H), 1.94 (d, J ) 18.3 Hz, 1 H), 1.89-1.73 (m,
2 H), 1.60 (t, J ) 9.2 Hz, 1 H), 1.46 (t, J ) 9.2 Hz, 1 H), 0.98
(s, 3 H), 0.95 (s, 3 H), 0.87 (s, 9 H), 0.03 (s, 6 H); 13C NMR (75
MHz, CDCl3) ppm 216.2, 138.1, 130.4, 128.5, 128.4 (2 C), 127.7
(2 C), 127.6, 87.7, 81.7, 75.9, 66.4, 63.3, 58.5, 48.7, 43.6, 43.4,
1
1741; H NMR (300 MHz, CDCl3) δ 7.39-7.27 (m, 5 H), 5.87
(d, J ) 16.6 Hz, 1 H), 5.73 (d, J ) 16.6 Hz, 1 H), 5.28 (br s, 1
H), 4.69 (d, J ) 11.2 Hz, 1 H), 4.57 (d, J ) 11.2 Hz, 1 H), 4.39
(dd, J ) 10.3, 2.8 Hz, 1 H), 4.17 (d, J ) 4.2 Hz, 1 H), 3.81-
3.72 (m, 2 H), 2.47 (ddd, J ) 18.3, 4.6, 2.4 Hz, 1 H), 2.17 (m,
1 H), 2.06-2.00 (m, 2 H), 1.93 (d, J ) 18.3 Hz, 1 H), 1.84-
1.74 (m, 2 H), 1.61-1.42 (m, 4 H), 0.97 (s, 3 H), 0.93 (s, 3 H),
0.89 (s, 9 H), 0.063 (s, 3 H), 0.056 (s, 3 H); 13C NMR (75 MHz,
CDCl3) ppm 215.9, 137.3, 129.8, 128.5 (2 C), 128.3, 127.9, 127.6
(2 C), 96.4, 85.5, 78.2, 73.7, 67.0, 63.3, 60.1, 49.0, 43.7, 43.3,

Reversible Oxy-Cope Rearrangements
J . Org. Chem., Vol. 63, No. 26, 1998 9975
36.0, 27.3, 27.1, 25.9 (3 C), 20.3, 19.6, 18.3, -5.4 (2 C); FAB
MS m/z (M+ + H) calcd 485.31, obsd 485.41; [R]23D +42 (c 0.86,
CHCl3).
was introduced, and the solution was stirred at -78 °C for
another 15 min, quenched with saturated NaHCO3 solution,
and diluted with ether. The separated aqueous phase was
extracted with ether (×2), the combined organic extracts were
dried and concentrated, and the residue was chromatographed
on silica gel (elution with 4:1 hexanes-ethyl acetate) to furnish
(1S,3R,4S)-1-[(E)-2-[(2R,3S)-3-(Ben zyloxy)-2-[2-(ter t-
b u t y ld im e t h y ls ilo x y )e t h y l]-3-o x e t a n y l]v in y l]-3-h y -
d r oxy-7,7-d im eth ylbicyclo[2.2.1]h ep ta n -2-on e (22). A so-
lution of 21 (677 mg, 1.40 mmol) in THF (10 mL) at -78 °C
was treated with potassium hexamethyldisilazide (5.6 mL of
0.5 M in toluene, 2.8 mmol) and allowed to stir at -78 °C for
1 h. Trimethylsilyl chloride (0.35 mL, 0.028 mol) was added
at -78 °C followed by triethylamine (0.52 mL). The mixture
was allowed to warm to room temperature and diluted with
ether and saturated NaHCO3 solution. The separated aqueous
layer was extracted with ether (×2), the combined organic
extracts were dried, and the filtrate was concentrated to give
the silyl enol ether, which was dissolved in a mixture of water
(10 mL), acetone (10 mL), and CH2Cl2 (10 mL). A catalytic
amount of 18-crown-6 and NaHCO3 (3.50 g) were added
followed by oxone (3.50 g) in small portions. The mixture was
allowed to stir for another hour, diluted with water and ether,
and extracted with ether (×2). The combined organic layers
were dried and filtered. Removal of solvents under reduced
pressure gave a residue which was dissolved in THF (5 mL)
and cooled to 0 °C. Tetra-n-butylammonium fluoride (1.40 mL
of 1.0 M in THF, 1.40 mmol) was added and the reaction
mixture was stirred at 0 °C for 30 min, diluted with ether and
water, and extracted with ether (×2). The combined organic
extracts were dried, filtered, and freed of solvents in vacuo.
Column chromatography of the residue (silica gel, elution with
2:1 hexanes-ethyl acetate) gave 22 (525 mg, 75%) as a
1
24 (420 mg, 82%) as a colorless oil: IR (film, cm-1) 3529; H
NMR (300 MHz, CDCl3) δ 7.40-7.25 (m, 5 H), 6.21 (d, J )
16.6 Hz, 1 H), 5.74 (dq, J ) 15.3, 6.2 Hz, 1 H), 5.59 (dd, J )
15.3, 1.1 Hz, 1 H), 5.49 (d, J ) 16.6 Hz, 1 H), 4.92 (dd, J )
8.6, 5.0 Hz, 1 H), 4.71 (s, 2 H), 4.63 (s, 2 H), 4.46 (d, J ) 11.2
Hz, 1 H), 4.30 (d, J ) 11.2 Hz, 1 H), 3.69 (s, 1 H), 3.67-3.59
(m, 2 H), 3.39 (s, 3 H), 3.00 (s, 1 H), 1.97 (d, J ) 5.0 Hz, 1 H),
1.90-1.74 (m, 3 H), 1.70 (d, J ) 6.3 Hz, 3 H), 1.63 (dd, J )
12.0, 4.7 Hz, 1 H), 1.51-1.42 (m, 1 H), 1.34 (s, 3 H), 1.15-
1.03 (m, 1 H), 0.88 (s, 9 H), 0.82 (s, 3 H), 0.03 (s, 6 H); 13C
NMR (75 MHz, CDCl3) ppm 138.4, 135.6, 132.6, 128.3 (2 C),
128.0, 127.8 (2 C), 127.5, 124.4, 97.1, 88.3, 87.8, 82.4, 82.0,
75.7, 66.1, 59.0, 58.7, 55.6, 50.7, 50.6, 36.1, 26.5, 25.9 (3 C),
24.2, 22.6, 22.3, 18.3, 17.9, -5.4 (2 C); FAB MS m/z (M+) calcd
587.38, obsd 587.20; [R]24 +14 (c 0.69, CHCl3).
D
(1S,2R,5S,6R,7R)-6-[(2R,3S)-3-(Ben zyloxy)-2-[2-(ter t-bu -
tyldim eth ylsiloxy)eth yl]-3-oxetan yl]-2-(m eth oxym eth oxy)-
5,11,11-tr im eth ylbicyclo[6.2.1]u n d ec-7-en -3-on e (25). To
a mixture of potassium hydride (18 mg, 0.87 mmol) and 18-
crown-6 (46 mg, 0.17 mmol) in THF (5 mL) at 0 °C was added
a solution of 24 (98 mg, 0.17 mmol) in THF (1 mL). After being
stirred at 0 °C for 15 min, the mixture was quenched by slow
transfer to a beaker of silica gel cooled to 0 °C. The silica was
separated by filtration and washed extensively with ether.
Solvent evaporation followed by chromatography (silica gel,
elution with 3:1 hexanes-ethyl acetate) afforded 25 (79 mg,
77%) as a colorless oil: IR (film, cm-1) 1704; 1H NMR (300
MHz, CDCl3) δ 7.45-7.24 (m, 5 H), 5.15 (d, J ) 9.7 Hz, 1 H),
5.05 and 5.02 (ABq, J ) 12.7 Hz, 2 H), 4.95 (dd, J ) 10.3, 3.3
Hz, 1 H), 4.76 and 4.68 (ABq, J ) 8.0 Hz, 2 H), 4.61 (d, J )
6.9 Hz, 1 H), 4.43 (d, J ) 6.9 Hz, 1 H), 3.89 (d, J ) 2.0 Hz, 1
H), 3.73-3.57 (m, 2 H), 3.34 (s, 3 H), 3.13-3.04 (m, 1 H), 2.75
(t, J ) 10.6 Hz, 1 H), 2.66-2.57 (m, 1 H), 2.51-2.36 (m, 1 H),
2.32-2.21 (m, 2 H), 2.18 (dd, J ) 8.6, 1.5 Hz, 1 H), 2.01-1.83
(m, 2 H), 1.78-1.71 (m, 1 H), 1.67 (dd, J ) 15.5, 1.2 Hz, 1 H),
1.15 (s, 3 H), 1.06 (s, 3 H), 0.90 (d, J ) 7.0 Hz, 3 H), 0.85 (s, 9
H), 0.01 (s, 6 H); 13C NMR (75 MHz, CDCl3) ppm 207.6, 146.2,
139.6, 128.4 (2 C), 127.1, 126.5 (2 C), 124.2, 95.1, 87.5, 86.7,
82.6, 78.1, 65.2, 58.9, 55.7, 54.0, 50.4, 48.0, 45.4, 35.2, 34.8,
26.1, 26.0, 25.9 (3 C), 24.4, 20.1, 20.0, 18.2, -5.28, -5.31; FAB
MS m/z (M+ + H) calcd 587.38, obsd 587.38; [R]23D -68 (c 0.95,
CHCl3).
1
colorless oil: IR (film, cm-1) 3415, 1749; H NMR (300 MHz,
CDCl3) δ 7.40-7.26 (m, 5 H), 5.90 and 5.86 (ABq, J ) 16.6
Hz, 2 H), 4.97 (dd, J ) 8.5, 5.1 Hz, 1 H), 4.67 (d, J ) 6.8 Hz,
1 H), 4.54 (d, J ) 6.7 Hz, 1 H), 4.50 (d, J ) 11.2 Hz, 1 H), 4.34
(d, J ) 11.2 Hz, 1 H), 3.80 (s, 1 H), 3.67-3.62 (m, 2 H), 3.05
(br s, 1 H), 2.18-1.89 (m, 3 H), 1.86-1.75 (m, 2 H), 1.65-1.58
(m, 1 H), 1.50-1.43 (m, 1 H), 1.11 (s, 3 H), 0.96 (s, 3 H), 0.87
(s, 9 H), 0.03 (s, 6 H); 13C NMR (75 MHz, CDCl3) ppm 217.0,
138.0, 130.6, 128.4 (2 C), 127.8, 127.7 (2 C), 127.6, 87.7, 81.6,
77.6, 75.8, 66.4, 62.5, 58.5, 49.5, 48.9, 36.0, 26.0, 25.9 (3 C),
25.0, 21.5, 20.6, 18.2, -5.4 (2 C); FAB MS m/z (M+) calcd
501.30, obsd 501.33; [R]24 +46.6 (c 3.29, CHCl3).
D
(1S,3R,4S)-1-[(E)-2-[(2R,3S)-3-(Ben zyloxy)-2-[2-(ter t-
b u t yld im et h ylsiloxy)et h yl]-3-oxet a n yl]vin yl]-3-(m et h -
oxym eth oxy)-7,7-dim eth ylbicyclo[2.2.1]h eptan -2-on e (23).
A cold (0 °C) solution of 22 (525 mg, 1.05 mmol) in CH2Cl2 (10
mL) at 0 °C was treated with diisopropylethylamine (0.91 mL,
0.052 mol) and methoxymethyl chloride (0.24 mL, 0.031 mmol).
The cooling bath was removed, and the mixture was allowed
to stir at room temperature for 5 h, quenched with saturated
NaHCO3 solution, and diluted with ether. The separated
aqueous layer was extracted with ether (×2), and the combined
organic layers were dried and evaporated. Chromatography
of the residue on silica gel (elution with 4:1 hexanes-ethyl
acetate) afforded 23 (474 mg, 83%) as a colorless oil: IR (film,
cm-1) 1755; 1H NMR (300 MHz, CDCl3) δ 7.41-7.25 (m, 5 H),
5.86 (s, 2 H), 4.96 (dd, J ) 8.6, 5.1 Hz, 1 H), 4.84 (d, J ) 6.6
Hz, 1 H), 4.73 (d, J ) 6.6 Hz, 1 H), 4.66 (d, J ) 6.8 Hz, 1 H),
4.53 (d, J ) 6.6 Hz, 1 H), 4.51 (d, J ) 11.2 Hz, 1 H), 4.34 (d,
J ) 11.2 Hz, 1 H), 3.74 (s, 1 H), 3.66-3.62 (m, 2 H), 3.42 (s, 3
H), 2.19 (d, J ) 4.3 Hz, 1 H), 2.15-1.96 (m, 2 H), 1.89-1.75
(m, 2 H), 1.64-1.56 (m, 1 H), 1.51-1.44 (m, 1 H), 1.10 (s, 3
H), 0.96 (s, 3 H), 0.87 (s, 9 H), 0.03 (s, 6 H); 13C NMR (75 MHz,
CDCl3) ppm 214.6, 138.1, 130.7, 128.4 (2 C), 127.9, 127.7 (2
C), 127.6, 96.7, 87.6, 81.6, 81.3, 75.9, 66.4, 62.4, 58.5, 55.5,
48.7, 48.6, 36.0, 26.2, 25.9 (3 C), 25.0, 21.4, 20.4, 18.3, -5.4 (2
Hyd r id e Red u ction of 25. To a solution of 25 (61 mg, 0.10
mmol) in ether (0.5 mL) at 0 °C was added lithium aluminum
hydride (12 mg, 0.32 mmol). The cooling bath was removed,
and the mixture was allowed to stir at room temperature for
3 h, cooled to 0 °C, and quenched with saturated NH4Cl
solution. Water and ether were added, and the separated
aqueous layer was extracted with ether (×2). The combined
organic extracts were dried, freed of solvents, and chromato-
graphed on silica gel (elution with 2:1 hexanes-ethyl acetate)
to provide the R-carbinol as a single diastereomer (53 mg, 86%)
as a colorless oil: IR (film, cm-1) 3480; 1H NMR (300 MHz,
CDCl3) δ 7.41-7.28 (m, 5 H), 5.16 (d, J ) 11.3 Hz, 1 H), 5.05-
4.96 (m, 3 H), 4.81 and 4.77 (ABq, J ) 7.8 Hz, 2 H), 4.64 and
4.61 (ABq, J ) 6.7 Hz, 2 H), 3.77-3.60 (m, 2 H), 3.47 (d, J )
4.9 Hz, 1 H), 3.39 (s, 3H), 3.33-3.29 (m, 1 H), 2.93 (d, J ) 9.8
Hz, 1 H), 2.80 (dd, J ) 11.6, 7.7 Hz, 1 H), 2.49-2.41 (m, 1 H),
2.36-2.23 (m, 2 H), 2.22-1.95 (m, 5 H), 1.38-1.30 (m, 1 H),
1.28 (s, 3 H), 1.12 (d, J ) 7.0 Hz, 3 H), 1.05 (s, 3 H), 1.03-0.90
(m, 1 H), 0.86 (s, 9 H), 0.02 (s, 6 H); 13C NMR (75 MHz, CDCl3)
ppm 143.4, 139.7, 128.3 (2 C), 127.1, 126.6 (2 C), 121.8, 98.3,
95.0, 86.6, 83.8, 76.8, 68.3, 65.4, 59.0, 55.7, 52.8, 47.7, 46.0,
41.2, 35.2, 30.9, 27.3, 25.9 (3 C), 25.8, 23.0, 22.9, 21.4, 18.3,
-5.32, -5.35; FAB MS m/z (M+ + H) calcd 589.39, obsd 589.18;
C); FAB MS m/z (M+ + H) calcd 545.35, obsd 545.11; [R]22
+59.5 (c 1.91, CHCl3).
D
(1S,2S,3R,4S)-1-[(E)-2-[(2R,3S)-3-(Ben zyloxy)-2-[2-(ter t-
b u t yld im et h ylsiloxy)et h yl]-3-oxet a n yl]vin yl]-3-(m et h -
oxym eth oxy)-7,7-dim eth yl-2-[(E)-1-pr open yl]bicyclo[2.2.1]-
h ep ta n -2-ol (24). To a solution of trans-1-bromo-1-propene
(0.37 mL, 0.044 mol) in THF (10 mL) at -78 °C was added
tert-butyllithium (5.1 mL of 1.7 M in pentane, 8.7 mmol). After
15 min, a solution of 23 (474 mg, 0.870 mmol) in THF (2 mL)
[R]22 -121 (c 1.29, CHCl3).
D
To a suspension of sodium hydride (4.0 mg, 0.16 mmol) in
THF (1 mL) at 0 °C was added a solution of the R-carbinol (48
mg, 0.082 mmol) in DMF (0.5 mL). The mixture was stirred

9976 J . Org. Chem., Vol. 63, No. 26, 1998
Tsui and Paquette
at 0 °C for 15 min, and p-methoxybenzyl chloride (26 mg, 0.16
mmol) together with a catalytic amount of tetra-n-butyl-
ammonium iodide in DMF (0.5 mL) was introduced. The
mixture was warmed to room temperature, stirred for another
2 h, cooled to 0 °C, and quenched with saturated NH4Cl
solution. Water and ether were added, and the separated
aqueous layer was extracted with ether (×2). The combined
organic extracts were dried, filtered, and evaporated. Chro-
matography of the residue on silica gel (elution with 5:1
hexanes-ether) gave the p-methoxybenzyl ether (46 mg, 79%)
as a colorless oil: IR (film, cm-1) 1613; 1H NMR (300 MHz,
CDCl3) δ 7.41-7.22 (m, 7 H), 6.88-6.83 (m, 2 H), 5.20 (d, J )
11.6 Hz, 1 H), 5.05-4.95 (m, 3 H), 4.78 (s, 2 H), 4.68 and 4.66
(ABq, J ) 6.5 Hz, 2 H), 4.49 (d, J ) 10.2 Hz, 1 H), 4.19 (d, J
) 10.1 Hz, 1 H), 3.91 (d, J ) 4.4 Hz, 1 H), 3.79 (s, 3 H), 3.78-
3.61 (m, 2 H), 3.35 (s, 3 H), 3.08 (d, J ) 3.6 Hz, 1 H), 2.76 (dd,
J ) 11.6, 8.0 Hz, 1 H), 2.55-2.12 (m, 6 H), 2.03-1.97 (m, 2
H), 1.34 (s, 3 H), 1.34-1.24 (m, 2 H), 1.08 (s, 3 H), 1.02 (d, J
) 7.0 Hz, 3 H), 0.87 (s, 9 H), 0.03 (s, 6 H); 13C NMR (75 MHz,
CDCl3) ppm 159.1, 143.3, 139.6, 130.6, 129.5 (2 C), 128.3 (2
C), 127.1, 126.6 (2 C), 122.0, 113.7 (2 C), 95.7, 86.6, 83.7, 82.0,
77.7, 76.9, 69.8, 65.3, 59.0, 55.3, 55.2, 51.3, 48.0, 46.1, 37.6,
35.2, 31.0, 27.4, 26.0, 25.9 (3 C), 23.1, 22.7, 21.5, 18.3, -5.3,
1.49-1.35 (m, 1 H), 1.32 (m, 3 H), 1.12-1.03 (m, 1 H), 0.89 (s,
9 H), 0.79 (s, 3 H), 0.03 (s, 3 H), 0.02 (s, 3 H); 13C NMR (75
MHz, CDCl3) ppm 139.7, 138.6, 135.6, 131.4, 129.4, 128.7,
128.1 (2 C), 128.0 (2 C), 127.5 (2 C), 127.0, 126.3 (2 C), 124.4,
101.5, 97.1, 88.2, 82.3, 80.3, 74.6, 70.6, 65.4, 59.1, 58.8, 55.6,
50.6, 50.5, 31.1, 26.3, 26.0 (3 C), 24.2, 22.6, 22.2, 18.3, 18.0,
-5.3, -5.4; FAB MS m/z (M+ + H) calcd 693.42, obsd 693.44
[R]24 -11.7 (c 1.54, CHCl3).
D
An ion ic Oxy-Cop e Rea r r a n gem en t of 28. A solution of
28 (48 mg, 0.069 mmol) and 18-crown-6 (38 mg, 0.14 mmol)
in THF (5 mL) was cooled to -78 °C under O2, treated with a
solution of potassium hexamethyldisilazide (0.28 mL, 0.14
mmol, 0.5 M in toluene), and stirred at -78 °C for 1 h prior to
the addition of a solution of triphenylphosphine (18 mg, 0.069
mmol) in THF (0.2 mL). The reaction mixture was transferred
to a beaker of cold (-78 °C) silica. The silica was filtered and
washed with ether, the filtrate was concentrated in vacuo, and
the residue was subjected to column chromatography on silica
gel (elution with 5:1 hexanes-ether). There was recovered 8
mg (17%) of 28, followed by the more polar 29 (2:1 hexanes-
ether) (35 mg, 81%) as a colorless oil: IR (film, cm-1) 3406,
1706; 1H NMR (300 MHz, CDCl3) δ 7.53-7.20 (m, 10 H), 5.59
(s, 1 H), 5.14 (d, J ) 11.7 Hz, 1 H), 5.07 (d, J ) 7.1 Hz, 1 H),
5.06 (d, J ) 11.7 Hz, 1 H), 4.64 (d, J ) 6.7 Hz, 1 H), 4.48 (d,
J ) 13.1 Hz, 1 H), 4.43 (d, J ) 6.7 Hz, 1 H), 4.36 (dd, J )
10.2, 1.6 Hz, 1 H), 4.26 (d, J ) 13.1 Hz, 1 H), 4.18 (d, J ) 2.0
Hz, 1 H), 3.88 (dt, J ) 10.0, 4.1 Hz, 1 H), 3.79-3.73 (m, 1 H),
3.43 (t, J ) 10.3 Hz, 1 H), 3.37 (s, 3 H), 2.62 (q, J ) 10.2 Hz,
1 H), 2.57-2.26 (m, 4 H), 2.22 (dd, J ) 8.2, 1.8 Hz, 1 H), 2.15-
2.11 (m, 1 H), 2.06-1.96 (m, 1 H), 1.77-1.68 (m, 1 H), 1.52 (d,
J ) 11.3 Hz, 1 H), 1.38 (d, J ) 6.3 Hz, 3 H), 1.21 (s, 3 H), 1.09
(s, 3 H), 0.90 (s, 9 H), 0.05 (s, 3 H), 0.04 (s, 3 H); 13C NMR (75
MHz, CDCl3) ppm 208.5, 145.3, 140.0, 138.4, 128.8, 128.2 (2
C), 128.0 (2 C), 127.1 (2 C), 126.9, 126.2, 125.7 (2 C), 101.0,
95.3, 86.2, 79.2, 76.8, 74.3, 70.9, 67.9, 58.8, 5.57, 53.2, 47.5,
45.6, 39.1, 32.1, 26.0 (3 C), 25.9, 25.6, 23.7, 20.3, 19.4, 18.4,
-5.3, -5.4; FAB MS m/z (M+ + H) calcd 709.41, obsd 709.60;
-5.4; FAB MS m/z (M+ + H) calcd 709.45, obsd 709.15; [R]23
D
-110 (c 1.09, CHCl3).
(1S,2R,4R,5R,6S,7E)-6-[(2R,3S)-3-(Ben zyloxy)-2-[2-(ter t-
b u t yld im e t h ylsiloxy)e t h yl]-3-oxe t a n yl]-4-h yd r oxy-2-
(m eth oxym eth oxy)-5,11,11-tr im eth ylbicyclo[6.2.1]u n d ec-
7-en -3-on e (26). To a solution of 25 (70 mg, 0.12 mmol) and
18-crown-6 (63 mg, 0.24 mmol) in THF (5 mL) at -78 °C was
added potassium hexamethyldisilazide (0.48 mL of 0.5 M in
toluene, 0.24 mmol). The mixture was stirred at -78 °C for
15 min, and oxygen was bubbled through for another 15 min.
A solution of triphenylphosphine (63 mg, 0.24 mmol) in THF
(1 mL) was added. After being quenched with saturated
NaHCO3 solution, the mixture was warmed to room temper-
ature and diluted with ether. The separated aqueous layer was
extracted with ether (×2). The combined organic layers were
dried and evaporated, followed by chromatography on silica
gel (elution with 2:1 hexanes-ethyl acetate) to give 26 (60 mg,
[R]23 -89.7 (c 1.38, CHCl3).
D
(1S,2S,3R,4S)-1-[(E)-[2R,4S,5S)-5-(Ben zyloxy)-4-[2-(ter t-
bu tyldim eth ylsiloxy)eth yl]-2-ph en yl-m-dioxan -5-yl]vin yl]-
3-(m eth oxym eth oxy)-7,7-d im eth yl-2-vin ylbicyclo[2.2.1]-
h ep ta n -2-ol (32). A solution of 2715 (112 mg, 0.172 mmol) was
stirred with a suspension of anhydrous cerium trichloride
[prepared from cerium trichloride heptahydrate (242 mg, 0.650
mmol)] in THF at room temperature for 5 h. The suspension
was cooled in an ice-water bath, and a solution of vinyl-
magnesium bromide (0.83 mL of 0.78 M in THF, 0.65 mmol)
was added. After being stirred at 0 °C for 10 min, the reaction
mixture was quenched with saturated NH4Cl solution and
diluted with ether. The separated layer was extracted with
ether (×2). The combined organic extracts were dried, filtered,
and concentrated in vacuo. Chromatography of the residue on
silica gel (elution with hexanes-ether 3:1) gave 32 (107 mg,
92%) as a colorless oil: IR (film, cm-1) 3528; 1H NMR (300
MHz, CDCl3) δ 7.60-7.27 (m, 10 H), 6.17 (d, J ) 16.7 H, 1 H),
5.95 (dd, J ) 17.1, 10.7 Hz, 1 H), 5.66 (s, 1 H), 5.32 (d, J )
17.1 Hz, 1 H), 5.23 (d, J ) 16.7 Hz, 1 H), 5.13 (dd, J ) 10.7,
0.7 Hz, 1 H), 4.82 (d, J ) 11.3 Hz, 1 H), 4.73 (s, 2 H), 4.68 (d,
J ) 11.2 Hz, 1 H), 4.51 (d, J ) 12.8 Hz, 1 H), 4.05-3.99 (m, 2
H), 3.85-3.72 (m, 3 H), 3.40 (s, 3 H), 3.05 (s, 1 H), 2.12-1.92
(m, 3 H), 1.74-1.87 (m, 1 H), 1.60 (dt, J ) 13.0, 4.8 Hz, 1 H),
1.44-1.37 (m, 1 H), 1.37 (s, 3 H), 1.17-1.08 (m, 1 H), 0.93 (s,
9 H), 0.84 (s, 3 H), 0.07 (s, 3 H), 0.06 (s, 3 H); 13C NMR (75
MHz, CDCl3) ppm 142.4, 139.6, 138.6, 131.1, 129.3, 128.7,
128.1 (2 C), 128.0 (2 C), 127.4 (2 C), 126.9, 126.3 (2 C), 113.5,
101.5, 97.1, 87.7, 82.6, 80.2, 74.5, 70.5, 65.3, 59.1, 58.6, 55.6,
50.8, 50.5, 31.1, 26.1, 25.9 (3 C), 24.1, 22.4, 22.2, 18.3, -5.3,
1
84%) as a colorless oil: IR (film, cm-1) 3377, 1705; H NMR
(300 MHz, CDCl3) δ 7.45-7.24 (m, 5 H), 5.10 (d, J ) 8.7 Hz,
1 H), 5.06 and 5.02 (ABq, J ) 12.6 Hz, 2 H), 4.93 (dd, J ) 8.0,
5.7 Hz, 1 H), 4.77 (s, 2 H), 4.63 (d, J ) 6.8 Hz, 1 H), 4.23 (d,
J ) 6.8 Hz, 1 H), 4.18 (d, J ) 1.8 Hz, 1 H), 3.72-3.56 (m, 2
H), 3.48 (t, J ) 10.5 Hz, 1 H), 3.35 (s, 3 H), 3.00-2.85 (m, 2
H), 2.56-2.36 (m, 2 H), 2.30-2.20 (m, 2 H), 1.93-1.84 (m, 2
H), 1.80-1.69 (m, 1 H), 1.60 (d, J ) 11.5 Hz, 1 H), 1.16 (s, 3
H), 1.05 (s, 3 H), 0.92 (d, J ) 6.3 Hz, 3 H), 0.84 (s, 9 H), 0.00
(s, 6 H); 13C NMR (75 MHz, CDCl3) ppm 208.2, 146.5, 139.5,
128.4 (2 C), 127.1, 126.4 (2 C), 124.1, 95.2, 86.5, 86.3, 82.7,
78.0, 75.5, 65.1, 58.8, 55.7, 53.8, 48.3, 45.5, 36.9, 34.9, 25.8 (3
C), 25.6 (2 C), 24.1, 19.9, 18.2, 15.3, -5.29, -5.33; FAB MS
m/z (M+ + H) calcd 603.37, obsd 603.28; [R]23 -67 (c 0.54,
D
CHCl3).
Alcoh ol 28. To a solution of trans-1-bromo-1-propene (0.20
mL, 0.024 mol) in dry THF (5 mL) at -78 °C under N2 was
added tert-butyllithium (2.70 mL, 4.72 mmol). The mixture was
stirred at -78 °C for 15 min, a solution of 2715 (428 mg, 0.658
mmol) in THF (5 mL) was introduced, and the reaction mixture
was stirred at -78 °C for another 30 min prior to being
quenched with saturated NaHCO3 solution and diluted with
ether. The separated aqueous layer was extracted with ether
(×2). The combined organic layers were dried, filtered, and
concentrated. Column chromatography of the residue on silica
gel (elution with 5:1 hexanes-ether) gave 28 (393 mg, 86%)
as a colorless oil: IR (film, cm-1) 3533; 1H NMR (300 MHz,
CDCl3) δ 7.57-7.22 (m, 10 H), 6.12 (d, J ) 16.8 Hz, 1 H), 5.71
(dq, J ) 15.3, 6.4 Hz, 1 H), 5.63 (s, 1 H), 5.54 (dd, J ) 15.4,
1.2 Hz, 1 H), 5.20 (d, J ) 16.7 Hz, 1 H), 4.79 (d, J ) 11.3 Hz,
1 H), 4.71 (s, 2 H), 4.65 (d, J ) 11.2 Hz, 1 H), 4.48 (d, J ) 12.8
Hz, 1 H), 4.00 (d, J ) 12.8 Hz, 1 H), 3.98 (dd, J ) 9.9, 9.2 Hz,
1 H), 3.82-3.71 (m, 2 H), 3.69 (s, 1 H), 3.39 (s, 3 H), 2.94 (s, 1
H), 2.09-1.91 (m, 2 H), 1.95 (d, J ) 5.1 Hz, 1 H), 1.89-1.74
(m, 1 H), 1.71 (dd, J ) 6.3, 1.0 Hz, 3 H), 1.60-1.49 (m, 1 H),
-5.4; FAB MS m/z (M+ + H) calcd 679.40, obsd 679.32; [R]16
-24.1 (c 5.06, CHCl3).
D
(1S,2R,4R,6R,7E)-6-[(2R,4S,5S)-5-(Ben zyloxy)-4-[2-(ter t-
b u t yld im et h ylsiloxy)et h yl]-2-p h en yl-m -d ioxa n -5-yl]-4-
h ydr oxy-2-(m eth oxym eth oxy)-11,11-dim eth ylbicyclo[6.2.1]-
u n d ec-7-en -3-on e (34). To a solution of 32 (85 mg, 0.13 mmol)
and 18-crown-6 (66 mg, 0.25 mmol) in THF (8 mL) at -78 °C
under oxygen was added a solution of potassium hexameth-

Reversible Oxy-Cope Rearrangements
J . Org. Chem., Vol. 63, No. 26, 1998 9977
yldisilazide (0.50 mL of 0.50 M in toluene, 0.25 mmol). The
mixture was stirred at -78 °C for 5 min, and a solution of
triphenylphosphine (33 mg, 0.13 mmol) in THF (0.5 mL) was
added. The reaction mixture was quenched with saturated
NH4Cl solution and diluted with ether. The separated aqueous
layer was extracted with ether (×2), the combined organic
layers were dried, and solvents were removed under reduced
pressure. Chromatography of the residue on silica gel (elution
with 2:1 hexanes-ethyl acetate) gave 34 (78 mg, 90%) as a
126.8, 126.6 (2 C), 126.2 (2 C), 123.8, 101.1, 95.2, 86.5, 80.0,
72.4, 72.0, 71.2, 67.7, 58.7, 55.7, 53.1, 45.4, 42.2, 34.6, 32.3,
26.1, 26.0 (3 C), 25.8, 23.7, 20.0, 18.3, -5.3, -5.4; FAB MS
m/z (MH+ - C7H6) calcd 605.35, obsd 605.47; [R]20D -74 (c 0.99,
CHCl3).
Ack n ow led gm en t. We thank the National Cancer
Institute of the Public Health Service for research
support and Dr. Kurt Lorning for assistance with
nomenclature.
1
colorless oil: IR (film, cm-1) 3417, 1713; H NMR (300 MHz,
CDCl3) δ 7.54-7.21 (m, 10 H), 5.57 (s, 1 H), 5.15 (d, J ) 10.4
Hz, 1 H), 5.14 (d, J ) 12.2 Hz, 1 H), 5.05 (d, J ) 12.2 Hz, 1 H),
4.65 (d, J ) 6.8 Hz, 1 H), 4.51 (d, J ) 12.9 Hz, 1 H), 4.44 (d,
J ) 6.8 Hz, 1 H), 4.18-4.12 (m, 3 H), 3.83-3.76 (m, 2 H), 3.73-
3.67 (m, 1 H), 3.36 (s, 3 H), 2.87 (dt, J ) 11.5, 5.7 Hz, 1 H),
2.65-2.37 (m, 3 H), 2.28-2.20 (m, 2 H), 2.15-2.05 (m, 1 H),
1.96-1.85 (m, 3 H), 1.77-1.68 (m, 1 H), 1.18 (s, 3 H), 1.08 (s,
3 H), 0.91 (s, 9 H), 0.04 (s, 6 H); 13C NMR (75 MHz, CDCl3)
ppm 208.4, 145.5, 140.2, 138.4, 128.9, 128.3 (2 C), 128.1 (2 C),
1
Su p p or tin g In for m a tion Ava ila ble: High-field H NMR
spectra of those compounds lacking elemental analysis (16
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 O982002W