Intercalation of multiple carbon atoms between the carbonyls of α-diketones

Article abstract of DOI:10.1021/jo010494y

The reaction of open-chain or cyclic α-diketones with specific ω-alkenyl organometallics leads readily under the proper conditions to 1,2-diols bonded to terminal olefinic chains. With 1-phenyl-1,2-propanedione, biacetyl, and cyclohexane-1,2-dione, allylindation in aqueous THF proceeds readily at both adjacent carbonyls. For cyclododecane-1,2-dione, recourse must be made to allylmagnesium bromide for completing the second-stage condensation. Grignard reagents have also served well as reactants for biacetyl monoadducts. In contrast, monoallylated camphorquinone is reluctant to couple to Grignard reagents and reacts only when Barbier-type alkyllithium reactions are applied. The ring closing metatheses of these products have been examined. Where six-membered ring formation operates, cyclization can be performed directly on diols. When larger rings are involved, the diols will react only if structural preorganization capable of facilitating mutual approach of the two double bonds is at play. For this purpose, the prior conversion to a cyclic carbonate holds considerable utility. In the latter setting, saponification must precede the diol cleavage step which has been performed with lead tetraacetate. The latter reagent also exhibits the very beneficial effect of facilitating removal of ruthenium and phosphorus byproducts generated during the metathesis step. This chemistry conveniently lends itself to the controlled intercalation of multiple methylene groups between the carbonyl carbons of readily available α-diketones to deliver linear or cyclic products.

Full text of DOI:10.1021/jo010494y

J . Org. Chem. 2001, 66, 6695-6704
6695
In ter ca la tion of Mu ltip le Ca r bon Atom s betw een th e Ca r bon yls of
r-Dik eton es
Emily P. Balskus, J ose´ Me´ndez-Andino, Ruslan M. Arbit, and Leo A. Paquette*
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210
paquette.1@osu.edu
Received May 14, 2001
The reaction of open-chain or cyclic R-diketones with specific ω-alkenyl organometallics leads readily
under the proper conditions to 1,2-diols bonded to terminal olefinic chains. With 1-phenyl-1,2-
propanedione, biacetyl, and cyclohexane-1,2-dione, allylindation in aqueous THF proceeds readily
at both adjacent carbonyls. For cyclododecane-1,2-dione, recourse must be made to allylmagnesium
bromide for completing the second-stage condensation. Grignard reagents have also served well as
reactants for biacetyl monoadducts. In contrast, monoallylated camphorquinone is reluctant to couple
to Grignard reagents and reacts only when Barbier-type alkyllithium reactions are applied. The
ring closing metatheses of these products have been examined. Where six-membered ring formation
operates, cyclization can be performed directly on diols. When larger rings are involved, the diols
will react only if structural preorganization capable of facilitating mutual approach of the two double
bonds is at play. For this purpose, the prior conversion to a cyclic carbonate holds considerable
utility. In the latter setting, saponification must precede the diol cleavage step which has been
performed with lead tetraacetate. The latter reagent also exhibits the very beneficial effect of
facilitating removal of ruthenium and phosphorus byproducts generated during the metathesis
step. This chemistry conveniently lends itself to the controlled intercalation of multiple methylene
groups between the carbonyl carbons of readily available R-diketones to deliver linear or cyclic
products.
The carbonyl functionality has played a pivotal role in
the evolution of synthetic organic chemistry. The fact that
some attention has been paid to the development of
methods for the controlled placement of two such groups
at differing distances is therefore not surprising. Indeed,
the numerous routes to 1,4- and 1,5-diketones, both
symmetrical and unsymmetrical, are generally con-
venient and often adaptable to new structural settings.1
In contrast, 1,6-diketones are recognized to be accessed
less readiy,2 and pathways leading to higher homologues
are sparse,3-5 despite notable advances in chain-exten-
sion methodology.6 In recent years, the coupling of
aldehydes and ketones to allylic indium reagents gener-
ated in water as the reaction medium,7 and ring-closing
metatheses promoted by ruthenium-based catalysts such
as 18 have emerged as useful new preparative tools.
These remarkably versatile reactions have been success-
fully applied to the acquisition of various targets of
interest. We have presently examined the merging of
these two processes in both cyclic and acyclic contexts,
with 1,2-dicarbonyl compounds serving as the starting
materials.9 In addition to the convergency associated with
this protocol and the range of possibilities that it offers
for the controlled insertion of carbon chains or loops of
different length, the reaction sequences are short and
practical. Limitations have surfaced only when entropic,
ring strain, and steric effects kinetically deter the ease
of large-ring formation.10
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Solladie´, G. Ibid., Vol. 6, p 159.
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1974, 687. (b) Ryu, I.; Ando, M.; Ogawa, A.; Murai, S.; Sonoda, N. J .
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2000, 41, 9589.
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Lett. 1985, 851. (c) Zhu, S.; Cohen, T. Tetrahedron 1997, 53, 17607.
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Organomet. Chem. 1993, 447, 311. (b) Ozturk, T. Tetrahedron Lett.
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Chem. Soc. 1969, 46, 743.
(6) Ho, T.-L. Polarity Control for Synthesis; J ohn Wiley and Sons:
New York, 1991.
(9) Preliminary results have appeared in communication form:
Me´ndez-Andino, J .; Paquette, L. A. Org. Lett. 2000, 2, 1263.
(10) Galli, C.; Mandolini, L. Eur. J . Org. Chem. 2000, 3117.
10.1021/jo010494y CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/12/2001

6696 J . Org. Chem., Vol. 66, No. 20, 2001
Balskus et al.
Sch em e 1
Sch em e 2
Resu lts
regard to diastereomer formation was again recognized,
although the level of π-facial discrimination had dropped
somewhat to 7:1 as a consequence of the steric bulk of
the added methyl group. After the ring closure of 3b
under the influence of 1, lead tetraacetate (1.1 equiv) was
added directly to the reaction mixture. After overnight
stirring, cleavage to give 5b was encountered. We were
also pleased to see that the darkly colored ruthenium and
phosphine impurities could now be removed simply by
filtration through a pad of silica gel rather than by
laborious chromatographic methods. These observations
were the bases of our convenient methodology for the
improved workup of such ring closures.18 Its effectiveness
was early recognized and used throughout this investiga-
tion. The catalytic hydrogenation of 4b to 6b19 made
possible the analogous conversion to 7b.20
Bia cetyl. Our attempt to effect comparable four-
carbon homologation of biacetyl (8) again proceeded
efficiently (Scheme 2). This R-diketone proved to be
extraordinarily electrophilic, giving rise to 9 in 87% yield
and a diastereomeric ratio of 3:2.11a,21 The ring-closing
metathesis of 9 to produce the previously unknown diol
10 was followed by hydrogenation to the widely described
saturated congener 12.22 Cleavage of both 10 and 12 as
before led with consistently good efficiency to 1123a and
13,23b respectively. The latter 1,4-diketone has often been
utilized in synthesis.
P h en ylglyoxa l a n d 1-P h en yl-1,2-p r op a n ed ion e.
When commercially available 2a was stirred vigorously
with an excess of powdered indium metal and allyl
bromide in 4:1 THF/H2O, the reaction mixture gradually
took on a milky white appearance during 3 h and afforded
the bisallylated diols 3a 11 efficiently and in a diastereo-
meric ratio of 10:1 (Scheme 1). We attribute this kinetic
bias to the likely intervention of a chelated transition
state as the intermediate R-ketol is brought into the
second carbon-carbon bond-forming step.12 Heating 3a
with 1 in CH2Cl2 at 50 °C for 3 h led readily to 4a (87%).
Despite the recognized preference of neighboring trans-
related C-O alkyl bonds on cyclohexane rings for
adoption of a diequatorial arrangement,13 we regard
the low energy conformation of 4a to be as illustrated
based on decoupling experiments.14 Following the cata-
lytic hydrogenation of 4a to generate 6a ,15 the stage was
set for diol cleavage with lead tetraacetate. While both
5a and 7a 16 were conveniently obtained, the ready
polymerizability of the unsaturated keto aldehyde pre-
cluded its complete spectral characterization.17
The allylindation of 2b likewise proceeded smoothly
and gave 3b.11a On this occasion, a kinetic imbalance with
(11) (a) Gewald, R.; Kira, M.; Sakurai, H. Synthesis 1996, 111. (b)
Hachiya, I.; Kobayashi, S. J . Org. Chem. 1993, 58, 6958.
(12) Paquette, L. A.; Mitzel, T. M. J . Am. Chem. Soc. 1996, 118,
1931.
(13) (a) Paquette, L. A.; Stepanian, M.; Branan, B. M.; Edmondson,
S. D.; Bauer, C. B.; Rogers, R. D. J . Am. Chem. Soc. 1996, 118, 4504.
(b) Paquette, L. A.; Tae, J .; Hickey, E. R.; Trego, W. E.; Rogers, R. D.
J . Org. Chem. 2000, 65, 9160. (c) Paquette, L. A.; Tae, J .; Branan, B.
M.; Bolin, D. G.; Eisenberg, S. W. E. J . Org. Chem. 2000, 65, 9172. (d)
Rablen, P. R.; Paquette, L. A.; Borden, W. T. J . Org. Chem. 2000, 65,
9180.
(14) Me´ndez-Andino, J . Ph.D. Dissertation, The Ohio State Univer-
sity, 2000.
(15) (a) Berti, G.; Bottari, F.; Macchia, B.; Macchia, F. Tetrahedron
1965, 21, 3277. (b) Delgado, A.; Granados, R.; Mauleon, D.; Soucheiron,
I.; Feliz, M. Can. J . Chem. 1985, 63, 3186.
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55, 1490. (b) Kabalka, G. W.; Yu, S.; Li, N.-S. Can. J . Chem. 1998, 76,
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M.; Williams, H. L.; Walshe, N. D. A. Tetrahedron Lett. 1997, 38, 8561.
(b) Dinon, F.; Richards, E.; Murphy, P. J .; Hibbs, D. E.; Hursthouse,
M. B.; Abdul Malik, K. M. Tetrahedron Lett. 1999, 40, 3279.
(18) Paquette, L. A.; Schloss, J . D.; Efremov, I.; Fabris, F.; Gallou,
F.; Me´ndez-Andino, J .; Yang, J . Org. Lett. 2000, 2, 1259.
(19) Fujiwara, T.; Tsuruta, Y.; Arizono, K.; Takeda, T. Synlett 1997,
962.
(20) Nishinaga, A.; Rindo, K.; Matsuura, T. Synthesis 1986, 1038.
(21) (a) Marton, D.; Stivanello, D.; Tagliavini, G. J . Organomet.
Chem. 1997, 540, 77. (b) Masuyama, Y.; Tsunoda, T.; Kurusu, Y. Chem.
Lett. 1989, 1647. (c) Wold, S. Acta Chem. Scand. 1969, 23, 1266.
(22) For example: (a) Kagayama, A.; Igarashi, K.; Mukaiyama, T.
Can. J . Chem. 2000, 78, 657. (b) Dobashi, Y.; Nakamura, K.; Saeki,
T.; Matsuo, M.; Hara, S.; Dobashi, A. J . Org. Chem. 1991, 56, 3299.
(c) Ruholl, H.; Schaefer, H. J . Synthesis 1988, 54. (d) de Petris, G.;
Giacomello, P.; Pizzabiocca, A.; Renzi, G.; Speranza, M. J . Am. Chem.
Soc. 1988, 110, 1098. (e) Gunji, T.; Hirano, M.; Morimoto, T. J . Chem.
Soc., Perkin Trans. 2 1985, 1827. (f) Slemon, C. E.; Yates, P. Can. J .
Chem. 1979, 57, 304. (g) Murayama, E.; Sato, T. Tetrahedron Lett.
1977, 47, 4079. (h) McMurry, J . E.; Choy, W. J . Org. Chem. 1978, 43,
1800.

Intercalation between the Carbonyls of R-Diketones
J . Org. Chem., Vol. 66, No. 20, 2001 6697
Sch em e 3
The successful application of this methodology to four-
carbon intercalation prompted attempts to introduce
larger numbers of methylene units in systematic fashion.
The most direct approach consisted of the controlled
stepwise addition of ω-unsaturated Grignard reagents of
differing chain lengths to 8 (Scheme 3). The commercial
availability of 11-bromo-1-undecene was sufficient cause
for its generic use in the formation of 14 from which
15a -c was subsequently produced. The adoption of this
route would ultimately provide the opportunity to inves-
tigate the ring-closing metathesis of large-ring systems
with unprotected diol functionality and cyclic carbonate
derivatives thereof. Such systems are largely absent in
the literature.
The feasibility and practicality of monoallylating 14
with allyl bromide and indium powder in aqueous THF
soon became apparent as a utilitarian route to 15a . Since
the halogen atom in 6-bromo-1-hexene and 8-bromo-1-
octene is not comparably activated, their incorporation
into 14 rests on their reactivity as Grignard reagents.
Competitive enolization proved not to be a problem, and
diols 15b and 15c were obtained in 38% and 40% yield,
respectively.
unreacted diol was largely recovered. On occasion, partial
conversion to polymerization products was noted. When
the more reactive 1,3-dimesityl-4,5-dihydroimidazol-2-
ylidene-substituted ruthenium complex24 was utilized in
benzene at the higher reflux temperature, the results
were closely comparable. These observations hold interest
in that they appear to contraindicate hypotheses formu-
lated in the context of previous findings involving un-
functionalized dienes.25,26 Coordination to some type of
functionality is generally believed to be required in order
to realize efficient ring closure.27
The failure to obtain cyclized products from 15a -c,
which contain hydroxyl groups capable of coordination
to the ruthenium center, could be suggestive that entropic
factors arising from the nonrigid nature of these sub-
strates may play an important role. Metathesis reactions
are driven by an increase in entropy (e.g., the evolution
of ethylene). Molecules such as the diols in question,
which enjoy high levels of entropy prior to cyclization,
would consequently incur a smaller gain in entropy
during ring formation, the level of which may be too small
to drive the reaction to completion. At this point, it was
(24) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953. (b) Fu¨rstner, A.; Thiel, O. R.; Ackermann, L.; Schanz,
H.-J .; Nolan, S. P. J . Org. Chem. 2000, 65, 2204.
(25) (a) Fu¨rstner, A.; Langemann, K. J . Org. Chem. 1996, 61, 3942.
(b) Fu¨rstner, A.; Langemann, K. Synthesis 1997, 792.
(26) See also: (a) Paquette, L. A.; Me´ndez-Andino, J . Tetrahedron
Lett. 2001, 42, 967. (b) Paquette, L. A.; Fabris, F.; Tae, J .; Gallucci, J .
C.; Hofferberth, J . E. J . Am. Chem. Soc. 2000, 122, 3391.
(27) Alkene Metathesis in Organic Synthesis; Fu¨rstner, A., Ed.;
Springer: Berlin, 1998.
All attempts to engage 15a -c to undergo productive
ring-closing metathesis in the presence of 1 at the reflux
temperature of CH2Cl2 were to no avail. In some runs,
(23) (a) The reported trans isomer exhibits a very different 1H NMR
spectrum: Yasuda, H.; Okamoto, T.; Mashima, K.; Nakamura, A. J .
Organomet. Chem. 1989, 363, 61. (b) J iang, J .-L.; Shi, Z. Synth.
Commun. 1998, 28, 4137.

6698 J . Org. Chem., Vol. 66, No. 20, 2001
Balskus et al.
Sch em e 4
Sch em e 5
with excess reagent under the predescribed aqueous
conditions, rapid reaction ensued to deliver 2111a,21b,28 in
92% yield (Scheme 4). The subsequent metathesis step,
performed with 1 in the usual manner gave rise to 2229
as a 3:1 diastereomeric mixture in near-quantitative
yield. Once again, the introduction of lead tetraacetate
immediately following the ring closure gave optimal
results. Sequential catalytic hydrogenation of 22 provided
2530 from which 1,6-cyclodecanedione (26)31 was derived.
Entirely comparable application of this chemistry directly
onto 22 gave a separable 3:2 mixture of 23 and 24. In 23
where no double bond migration occurs, the olefinic
linkage must necessarily be cis. When conjugation does
materialize as in 24, the favored double bond geometry
is trans (J 2,3 ) 11.9 Hz).
Cyclod od eca n e-1,2-d ion e. If one examines a broad
range of R-diketones in terms of their behavior under the
conditions of exhaustive allylindation, one feature is
made immediately obvious. Successful introduction of the
second allyl group is strongly dependent on steric factors.
In the case of the large-ring example 27,32 nonbonded
transannular interactions are sufficient to impede forma-
tion of the second carbon-carbon bond. This is not
problematic in this instance since the more reactive allyl
Grignard reagent transforms the monoadduct cleanly
into 28 (Scheme 5). In fact, a single diol diastereomer is
formed (83%).
clear that the availability of cyclic carbonates 16 and 17
could shed added light on this relevant issue. Formation
of the heterocyclic ring greatly limits the degrees of
freedom available to diols 15.
When the diols were reacted with phosgene in the
presence of pyridine, the resulting diastereomercic prod-
ucts could be separated chromatographically. No effort
was made to distinguish the stereochemical features of
the carbonates. The less polar isomers were arbitrarily
labeled cis as 16a -c; the more polar diastereomers carry
the trans designation 17a -c. The ring closing metathesis
of these cyclic carbonates were carried out at high
dilution (e5 mM) with a catalyst loading of 20% for a
total reaction time of 40 h in CH2Cl2 at 40-50 °C. Every
run returned starting material (total accounting of
materials approximately 80%), with the series when n
) 1 advancing to the lowest extent. The formation of
small amounts of more polar, unidentified materials
(polymers?) was also noted. The cis and trans isomers
were found to react equally well. The process therefore
shows little, if any, stereochemical dependency. Our
observations of limited reactivity in the a series suggests
that it is probably best to have both double bonds as
distal as possible from the quaternary centers. This is
particularly true if the ring double bond is destined to
be saturated as in the present instance.
With 28 in hand, the discovery was soon made that
the conversion to 29 via ring-closing metathesis was
In the hydrogenations of 18 and 19 ultimately to
generate 20, the reaction mixtures were not freed of
catalysts, but treated directly with aqueous NaOH to
liberate the diols. Exposure of these intermediates to lead
tetraacetate as before furnished the extended diketones.
In examples where sensitivity to base may surface,
cleavage of the carbonate by hydride reduction remains
an attractive alternative.
(28) Marvell, E. N.; Cheng, J . C.-P. J . Org. Chem. 1980, 45, 4511.
(29) The trans isomer of 22 has been reported: Hu¨ckel, W.; Wo¨rffel,
U. Chem. Ber. 1956, 89, 2098.
(30) (a) Dev, S. J . Ind. Chem. Soc. 1954, 31, 1. (b) Betzemeier, B.;
Lhermitte, F.; Knochel, P. Synlett 1999, 489.
(31) House, H. O.; Lee, J . H. C.; VanDerveer, D.; Wissinger, J . E. J .
Org. Chem. 1983, 48, 5285.
Cycloh exa n e-1,2-d ion e. When the allylindation of
cyclohexane-1,2-dione was performed at the 0.08 M level
(32) Kawada, K.; Gross, R. S.; Watt, D. S. Synth. Commun. 1989,
19, 777.

Intercalation between the Carbonyls of R-Diketones
J . Org. Chem., Vol. 66, No. 20, 2001 6699
Sch em e 6
Sch em e 7
instead on the surface of the metal.36 Semiempirical MO
calculations37 are likewise consistent with initial single
electron transfer from elemental lithium to the halide
with formation of the transient radical anion.38 The
presence of the latter species may account for the
increased reactivity and heightened efficiency observed
under these circumstances.35
This tactic provided a useful route from 34 to 36 (60%
isolated). However, a careful study of the ability of this
diol and its cyclic carbonate 37 to enter into ring-closing
metathesis clearly denoted their inertness to these condi-
tions. The Weiler group had previously disclosed that a
structurally unrelated substrate was equally reluctant
to form a 14-membered ring.39 Several factors were
considered to be potentially contributive to inhibition of
the desired cyclization. Of these, the sterically shielded
nature of the allylic double bond featured prominently.
As a consequence, the further use of monoallylated
R-ketols was abandoned.
As outlined in Schemes 7 and 8, a variant of the
Barbier alkyllithium reaction found application in pro-
ducing two useful metathesis substrates. In the new
approach, two identical ω-alkenyl groups were added
concurrently to both carbonyl of camphorquinone to
provide 38 and 39, respectively. Once again, only single
diastereomeric products were generated and these are
formulated as the exo,exo-diols because of sterically
enforced endo attack at both carbonyl reaction sites.
The Grubbs catalyst 1 was found to be effective for
transforming 38 and 39 into the 20- and 22-membered
cyclic diols 40 and 43, respectively. These large-ring
systems were expectedly generated as E/Z mixtures;
these were not differentiated. Instead, cleavage with lead
tetraacetate was subsequently carried out with and
without prior hydrogenation of the intracyclic double
bond to provide the saturated (42 and 45) and unsatu-
rated intercalation products (41 and 44). In all four
examples, the overall yield of these two- or three-step
conversions was in the 45-50% range. The straight-
forward nature of all the transformations delineated in
Scheme 8 is noteworthy.
again notably efficient. Obviously, there is no problem
associated with activation of the double bonds in this
example. As well, minimal difficulty was associated with
the ensuing production of 3233 on one hand, and an easily
separable mixture of 30 and 31 on the other.
(1R)-(-)-Ca m p h or qu in on e. As expected from earlier
developments,34 Barbier allylation of 33 was met with
exclusive monoallylation at its less sterically congested
carbonyl from the endo π-surface (Scheme 6). When
attempts were subsequently made to add Grignard
reagents to 34, the substantive steric shielding about the
resident ketone carbonyl was made apparent. For ex-
ample, the exposure of 34 to 10-decenyl-1-magnesium
bromide resulted in reduction to diol 35. This problematic
behavior was reflected as well in the attempted coupling
of 34 to 10-decenyl-1-lithium. Only unreacted starting
material was returned. This complication was resolved
and second-stage addition successfully achieved when 34
was subjected to Barbier-type alkyllithium reactions. The
Barbier approach differs from a typical alkyllithium
reaction in that the lithium reagent is not preformed.35
Rather, the ketone, halide, and lithium metal are intro-
duced simultaneously to the reaction vessel. The consen-
sus view is that a mechanistic crossover also materializes.
In short, the evidence suggests that an alkyllithium
intermediate is not involved and that reaction occurs
A direct comparison of the reactivity differences noted
for the biacetyl and camphorquinone adducts is difficult
(36) Molle, G.; Bauer, P. J . Am. Chem. Soc. 1982, 104, 3481.
(37) Moyano, A.; Perica`s, M. A.; Riera, A.; Luche, J .-L. Tetrahedron
Lett. 1990, 31, 7619.
(38) When aromatic aldehydes and ketones are involved, ketyl
radical anions may form competitively.
(39) Goldring, W. P. D.; Hodder, A. S.; Weiler, L. Tetrahedron Lett.
1998, 39, 4955.
(33) Leriverend, P.; Conia, J . M. Bull. Soc. Chim. Fr. 1970, 1040.
(34) Ancillary studies have made clear that 1,2-cyclooctanedione,
5-cycloctene-1,2-dione, and dimethyl squarate also share in this
reluctance to enter into 2-fold allylation in an aqueous environment.
(35) Pearce, P. J .; Richards, D. H.; Scilly, N. F. J . Chem. Soc., Perkin
Trans. 1 1972, 1655.

6700 J . Org. Chem., Vol. 66, No. 20, 2001
Balskus et al.
graphed on silica gel (elution with 25% ether in petroleum
ether) to give 977 mg (90%) of 3a as a white solid, mp 42-46
°C, consisting of a 10:1 mixture of diastereomers.11 For the
major diastereomer: 1H NMR (300 MHz, CDCl3) δ 7.41-7.32
(m, 4 H), 7.30-7.22 (m, 1 H), 5.88-5.69 (m, 1 H), 5.59-5.46
(m, 1 H), 5.20-4.99 (m, 4 H), 3.80 (dd, J ) 9.7, 3.1 Hz, 1 H),
2.86 (dd, J ) 14.0, 8.5 Hz, 1 H), 2.77 (dd, J ) 14.0, 6.0 Hz, 1
H), 2.22 (br s, 2 H), 2.09-1.93 (m, 2 H); 13C NMR (75 MHz,
CDCl3) δ 142.8, 135.5, 133.4, 128.2 (2C), 126.8, 125.5 (2C),
119.3, 117.7, 77.6, 76.1, 43.9, 36.1.
Sch em e 8
4-Meth yl-5-p h en yl-1,7-octa d ien e-4,5-d iol (3b).11a Color-
less oil; 90% yield; 7:1 mixture of diastereomers. For the major
diastereomer: 1H NMR (300 MHz, CDCl3) δ 7.50 (d, J ) 7.1
Hz, 2 H), 7.38-7.23 (m, 3 H), 5.90-5.76 (m, 1 H), 5.54-5.40
(m, 1 H), 5.20-4.93 (series of m, 4 H), 3.07 (dd, J ) 13.9, 5.2
Hz, 1 H), 2.78 (dd, J ) 13.9, 9.3 Hz, 1 H), 2.61 (br s, 1 H), 2.47
(dd, J ) 14.0, 6.8 Hz, 1 H), 2.38 (br s, 1 H), 1.73 (dd, J ) 14.0,
7.8 Hz, 1 H), 1.21 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 142.1,
134.5, 134.0, 127.7 (2C), 127.1 (2C), 126.8, 119.9, 118.1, 79.7,
76.1, 41.2, 39.8, 21.0. For minor diastereomer: 13C NMR (75
MHz, CDCl3) δ 142.2, 134.1, 132.1, 127.6 (2C), 127.3 (2C),
125.8, 119.8, 119.4, 76.2, 76.0, 41.4, 40.7, 21.9.
Gen er a l Rin g Closin g Meta th esis P r oced u r e. Diene diol
3a (500 mg, 2.29 mmol) was placed in a septum-capped
recovery flask under argon and diluted with CH2Cl2 (30 mL).
A solution of 1 in CH2Cl2 (55 mg/30 mL) was transferred via
cannula into the reaction mixture. A second septum was placed
atop the existing one and secured with Parafilm. The reaction
mixture was stirred at 50 °C for 3 h, allowed to cool, and
opened to the atmosphere for 2 h. After solvent evaporation,
the residue was chromatographed on silica gel (elution with
40% ethyl acetate in petroleum ether) to furnish 4a as a white
solid, mp 108-109 °C (380 mg, 87%); IR (CHCl3, cm-1) 3588,
1
3440, 1654, 1602; H NMR (300 MHz, C6D6) δ 7.55-7.51 (m,
1 H), 7.22-7.11 (m, 4 H), 5.52-5.46 (m, 1 H), 5.44-5.38 (m, 1
H), 3.80-3.74 (m, 1 H), 2.75-2.67 (m, 1 H), 2.34-2.26 (m, 1
H), 2.18-2.10 (m, 1 H), 1.86 (s, 1 H), 1.76-1.67 (m, 1 H), 1.32
(d, J ) 5.0 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 145.9, 128.4
(2C), 127.5, 126.1 (2C), 74.5, 73.2, 31.4, 28.4, 21.0, 19.2; EI
MS m/z (M+) calcd 190.0944, obsd 190.1005. Anal. Calcd for
C
12H14O2: C, 75.76; H, 7.42. Found: C 75.56; H, 7.60.
2-Met h yl-1-p h en yl-4-cycloh exen e-1,2-d iol (4b ). White
and may be unwarranted. The structural features and
applicable conformational criteria vary significantly.
When entropic factors are weighed, the camphor-derived
diols 38 and 39 can reliably be regarded as topologically
more restricted than 15a -c. The bicyclo[2.2.1]heptane
part structure resident in 38 and 39 probably serves to
ensure that the terminal double bonds of both long chains
are constrained to a more or less proximal relationship
than otherwise.
crystals, mp 104-106 °C (79% yield); IR (CHCl3, cm-1) 3591,
1654, 1601; 1H NMR (300 MHz, CDCl3) δ 7.66 (d, J ) 7.0 Hz,
2 H), 7.38-7.27 (m, 3 H), 5.83-5.74 (m, 2 H), 3.12-3.04 (m, 1
H), 2.53-2.46 (m, 1 H), 2.33 (br s, 1 H), 2.24-2.03 (series of
m, 2 H), 1.78 (br s, 1 H), 1.05 (s, 3 H); 13C NMR (75 MHz,
CDCl3) δ 143.4, 127.6 (2C), 126.9, 126.5 (2C), 125.4, 125.1, 76.0,
72.9, 38.5, 38.1, 23.6; EI MS m/z (M+) calcd 204.1150, obsd
204.1147. Anal. Calcd for C13H16O2: C, 76.44; H, 7.90. Found:
C, 76.59; H, 7.97.
Gen er a l P r oced u r e for Ca ta lytic Hyd r ogen a tion . A
mixture of 4a (200 mg, 1.05 mmol) and 10% palladium on
charcoal (10 mg) in absolute ethanol (2 mL) was stirred
overnight under 1 atm of hydrogen. The reaction mixture was
filtered through a pad of silica gel, and the pad was rinsed
with ether. The solvent was removed under reduced pressure
to yield 205 mg (quant) of 6a ; white solid, mp 98-99 °C;41 1H
NMR (300 MHz, C6D6) δ 7.45 (d, J ) 7.2 Hz, 2 H), 7.19-7.05
(series of m, 3 H), 3.59 (m, 1 H), 2.32 (td, J ) 12.6, 4.2 Hz, 1
H), 1.81-1.57 (series of m, 4 H), 1.54-1.33 (series of m, 4 H),
1.07 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 145.9, 128.5 (2C),
127.6, 126.1 (2C), 74.6, 73.3, 31.5, 28.5, 21.1, 19.2.
Exp er im en ta l Section
Gen er a l Con sid er a tion s. Melting points are uncorrected.
The column chromatographic separations were performed on
silica gel (230-400 or 200-325 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
NMR spectroscopy. The high-resolution mass spectra were
recorded at The Ohio State University Campus Chemical
Instrumentation Center. Elemental analyses were performed
at Atlantic Microlab, Inc., Norcross, GA.
Gen er a l P r oced u r e for In d iu m -P r om oted Allyla tion .
Phenyl glyoxal monohydrate (670 mg, 5.0 mmol) dissolved in
65 mL of 4:1 THF/H2O was vigorously stirred while indium
powder (1.53 g, 2.7 equiv) and then allyl bromide (1.73 mL,
4.0 equiv) were introduced. The reaction mixture was stirred
for 3 h during which time a milky appearance developed and
the metal separated as pellets. At this point, 5 mL of 2 N
potassium hydrogen sulfate solution and 75 mL of CHCl3 were
introduced. The separated aqueous phase was extracted with
CHCl3 (2 × 75 mL), and the combined organic layers were
dried and concentrated to leave a residue that was chromato-
2-Meth yl-1-p h en yl cycloh exa n e-1,2-d iol (6b).19 Quanti-
1
tative yield; H NMR (300 MHz, CDCl3) δ 7.59 (dt, J ) 7.1,
1.5 Hz, 2 H), 7.38-7.24 (series of m, 3 H), 2.62 (td, J ) 12.4,
4.6 Hz, 1 H), 1.99-1.89 (m, 1 H), 1.84-1.33 (series of m, 8 H),
0.97 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 144.6, 127.6 (2C),
126.9, 126.8 (2C), 77.1, 72.5, 35.3, 34.5, 25.4, 21.0, 20.8.
Gen er a l P r oced u r e for On e-P ot Rin g-Closin g Meta th -
esis/Oxid a tive Clea va ge. The first stage of the process was
carried out exactly as described above. The cooled reaction
mixture was treated portionwise with lead tetraacetate (892
mg, 2.0 mmol), stirred for 20 min at room temperature, and
concentrated in vacuo. The residue was taken up in ether (50

Intercalation between the Carbonyls of R-Diketones
J . Org. Chem., Vol. 66, No. 20, 2001 6701
mL) and the solids were removed by filtration through a short
pad of silica gel. The pad was rinsed with ether (20 mL) and
the filtrate was washed with dilute NaHCO3 solution and
water, dried, and concentrated. The residue was chromato-
graphed on silica gel (elution with 40% ethyl acetate in
petroleum ether).
(s, 3 H); 13C NMR (75 MHz, CDCl3) δ 212.3, 139.1, 114.1, 78.7,
39.4, 33.7, 29.7 (2C), 29.4 (2C), 29.0, 28.8, 25.4, 23.6, 23.3, ES
MS m/z (M + Na)+ calcd 263.1987, obsd 263.1985.
Diol 15a . Colorless oil (83% yield); IR (neat, cm-1) 3451;
1H NMR (300 MHz, CDCl3) δ 6.03-5.89 (m, 1 H), 5.88-5.74
(m, 1 H), 5.20-5.08 (m, 2 H), 5.02-4.89 (m, 2 H), 2.45 (dd, J
) 13.7, 7.3 Hz, 1 H), 2.25-2.15 (m, 1 H), 2.10-2.00 (m, 2 H),
1.96 (br s, 2 H), 1.67-1.20 (series of m, 16 H), 1.15 (s, 6 H);
13C NMR (75 MHz, CDCl3) δ 139.2, 134.65, 134.58, 118.9,
118.8, 114.1, 76.7, 76.4, 41.1, 40.8, 36.2, 36.0, 33.8, 30.4, 29.7,
29.6, 29.5, 29.1, 28.9, 23.7, 23.6, 22.0, 21.6, 21.0, 20.7; ES MS
m/z (M + Na)+ 305.2457, obsd 305.2451. Anal. Calcd for
C18H34O2: C, 76.54; H, 12.13. Found: C, 76.18; H, 11.86.
Diol 15b. Magnesium metal (0.608 g, 25.0 mmol) was
ground and added to 3 mL of anhydrous ether. To this mixture
was added dropwise a solution of 6-bromo-1-hexene (2.04 g,
12.5 mmol) with vigorous stirring at 0 °C under argon. After
the addition was complete, the mixture was warmed to room
temperature and stirred for the additional 3 h. The resulting
Grignard reagent was added to the solution of 600.0 mg (2.50
mmol) of 14 during a period of 1 h at 0 °C under argon. The
mixture was warmed to room temperature, stirred for an
additional 24 h, quenched with 10% HCl solution, and ex-
tracted with 3 × 50 mL of ether. The combined organic phases
were washed with brine, dried, and evaporated. The residue
was chromatographed on silica gel (elution with hexanes:ethyl
acetate 4:1) to give 0.312 g (38%) of 15b as well as unreacted
14; colorless oil; IR (neat, cm-1) 3446; 1H NMR (300 MHz,
CDCl3) δ 5.88-5.73 (m, 2 H), 5.03-4.91 (m, 4 H), 2.12-1.97
(m, 4 H), 1.80 (br s, 2 H), 1.60-1.20 (series of m, 22 H), 1.14
(s, 6 H); 13C NMR (75 MHz, CDCl3) δ 139.2, 138.9, 114.3, 114.1,
77.1, 36.3, 36.1, 36.0, 35.7, 33.8, 31.4, 29.7, 29.64, 29.59, 29.53,
29.48, 29.4, 29.1, 28.9, 23.8, 23.5, 23.3, 21.2, 20.9 (2C); ES MS
m/z (M + Na)+ calcd 347.2926, obsd 347.2919.
For (Z)-1-P h en yl-3-h ep ten e-1,6-d ion e (5b): 65% yield;
1
colorless oil; H NMR (300 MHz, CDCl3) δ 7.93 (dd, J ) 7.2,
1.5 Hz, 2 H), 7.57-7.52 (m, 1 H), 7.44 (t, J ) 7.2 Hz, 2 H),
5.97-5.76 (series of m, 2 H), 3.71 (d, J ) 6.8 Hz, 2 H), 3.22 (d,
J ) 6.9 Hz, 2 H), 2.15 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ
205.7, 197.1, 136.4, 133.1, 128.5 (2C), 128.1 (2C), 125.1, 124.5,
42.5, 37.4, 29.5.
6-Oxo-6-p h en ylh exa n a l (7a ).16 White solid, mp 32-33
1
°C;15a (91% yield); IR (neat, cm-1) 1720, 1688; H NMR (300
MHz, CDCl3) δ 9.78 (t, J ) 1.6 Hz, 1 H), 7.94 (d, J ) 7.1 Hz,
2 H), 7.58-7.52 (m, 1 H), 7.48-7.42 (m, 2 H), 2.99 (t, J ) 6.9
Hz, 2 H), 2.49 (td, J ) 7.1, 1.6 Hz, 2 H), 1.84-1.67 (m, 4 H);
13C NMR (100 MHz, CDCl3) δ 202.1, 199.6, 136.8, 132.9, 128.5
(2C), 127.9 (2C), 43.6, 38.0, 23.5, 21.6.
1-P h en ylh ep ta n e-1,6-d ion e (7b).20 White solid, mp 42-
43 °C;20 (80% yield); 1H NMR (300 MHz, CDCl3) δ 7.90 (dd, J
) 7.1, 1.2 Hz, 2 H), 7.54-7.48 (m, 1 H), 7.44-7.39 (m, 2 H),
2.95 (t, J ) 7.1 Hz, 2 H), 2.45 (t, J ) 7.1 Hz, 2 H), 2.10 (s, 3
H), 1.75-1.57 (m, 4 H); 13C NMR (75 MHz, CDCl3) δ 208.5,
199.7, 136.8, 132.8, 128.5 (2C), 127.9 (2C), 43.4, 38.1, 29.7, 23.5,
23.3.
4,5-Dim eth yl-1,7-octa d ien e-4,5-d iol (9).11a,21 Colorless oil
1
(87% yield, dr 3:2); H NMR (300 MHz, CDCl3) δ 6.04-5.89
(m, 2 H), 5.19-5.09 (m, 4 H), 2.54-2.42 (m, 2 H), 2.24-2.17
(m, 2 H), 2.06 (br s, 2 H), 1.19 (s, 0.40 × 6 H), 1.16 (s, 0.60 ×
6 H). For the major diastereomer: 13C NMR (75 MHz, CDCl3)
δ 134.5 (2C), 118.7 (2C), 76.1 (2C), 41.1 (2C), 21.5 (2C). For
the minor diastereomer: 13C NMR (75 MHz, CDCl3) δ 134.4
(2C), 118.5 (2C), 76.2 (2C), 40.9 (2C), 21.8 (2C).
Diol 15c. Colorless oil (40% yield); IR (neat, cm-1) 3418;
1H NMR (300 MHz, CDCl3) δ 5.90-5.73 (m, 2 H), 5.04-4.90
(m, 4 H), 2.10-2.00 (m, 4 H), 1.79 (br s, 2 H), 1.63-1.19 (series
of m, 26 H), 1.15 (s, 3 H), 1.14 (s, 3 H); 13C NMR (75 MHz,
CDCl3) δ 139.2, 139.1, 114.15, 114.07, 77.1, 36.3, 35.9, 33.8,
33.7, 30.4, 30.3, 29.7, 29.6, 29.5, 29.2, 29.1, 28.9, 23.74, 23.71,
21.1, 20.7 (3C not observed); ES MS m/z (M + Na)+ calcd
375.3239, obsd 375.3255. Anal. Calcd for C23H44O2: C, 78.35;
H, 12.58. Found: C, 78.13; H, 12.56.
Gen er a l P r oced u r e for Cyclic Ca r bon a te F or m a tion .
A solution of the diol (0.60 mmol) in dry CH2Cl2 (20 mL) was
cooled to 0 °C, treated with pyridine (290 µL) and then a 1.9
M solution of phosgene in toluene (0.60 mmol), and allowed
to warm to 20 °C over 1 h. The volatiles were evaporated, and
the residue was chromatographed on silica gel (elution with
5% ether in petroleum ether) to achieve separation of the less
polar from the more polar isomer.
1,2-Dim eth yl-4-cycloh exen e-1,2-d iol (10). Colorless oil
1
(71%); H NMR (500 MHz, CDCl3) δ 5.58 (s, 2 H), 2.32-2.26
(m, 2 H), 2.19-2.10 (m, 2 H), 1.93 (br s, 2 H), 1.24 (s, 0.76 ×
6 H), 1.21 (s, 0.24 × 6 H). For the major diastereomer: 13C
NMR (125 MHz, CDCl3) δ 125.6 (2C), 73.6 (2C), 39.2 (2C), 22.8
(2C). For the minor diastereomer: 13C NMR (75 MHz, CDCl3)
δ 125.2 (2C), 73.8 (2C), 39.3 (2C), 23.1 (2C).
(Z)-4-Octen e-2,7-d ion e (11).23a Colorless oil (66% from 9);
1
IR (neat, cm-1) 1714; H NMR (300 MHz, CDCl3) δ 5.77 (t, J
) 5.5 Hz, 2 H), 3.15 (d, J ) 5.5 Hz, 4 H), 2.13 (s, 6 H); 13C
NMR (75 MHz, CDCl3) δ 205.4 (2C), 124.3 (2C), 42.0 (2C), 29.3
(2C); EI MS m/z (M+) calcd 140.0837, found 140.0836.
1,2-Dim eth ylcycloh exa n e-1,2-d iol (12).22 Colorless oil
1
(quant yield); H NMR (300 MHz, CDCl3) δ 2.06 (br s, 2 H),
1.70-1.25 (series of m, 8 H), 1.22 (s, 0.8 × 6 H), 1.15 (s, 0.2 ×
6 H); For the major diastereomer: 13C NMR (75 MHz, CDCl3)
δ 74.3 (2C), 36.4 (2C), 23.2 (2C), 22.1 (2C). For the minor
diastereomer: 13C NMR (75 MHz, CDCl3) δ 73.9 (2C), 36.6
(2C), 23.4 (2C), 22.2 (2C).
For 16a and 17a : (combined 87% yield; 4:1 ratio); less polar
isomer: colorless oil; IR (neat, cm-1) 1801, 1641; 1H NMR (300
MHz, CDCl3) δ 5.84-5.69 (m, 2 H), 5.22-5.09 (m, 2 H), 4.99-
4.85 (m, 2 H), 2.58 (dd, J ) 14.2, 5.9 Hz, 1 H), 2.27 (dd, J )
14.2, 8.8 Hz, 1 H), 2.06-1.93 (m, 2 H), 1.85-1.15 (series of m,
16 H), 1.36 (s, 3 H), 1.32 (s, 3 H); 13C NMR (75 MHz, CDCl3)
δ 153.7, 139.0, 131.2, 120.0, 114.0, 88.2, 87.4, 39.7, 35.0, 33.6,
29.8, 29.3 (2C), 29.2, 28.9, 28.8, 23.7, 19.1, 18.6; ES MS m/z
(M + Na)+ calcd 331.2249, obsd 331.2231. Anal. Calcd for
Octa n e-2,8-d ion e (13). White solid, mp 42-44 °C;23b (80%
yield); 1H NMR (300 MHz, CDCl3) δ 2.45-2.40 (m, 4 H), 2.11
(s, 6 H), 1.57-1.52 (m, 4 H); 13C NMR (75 MHz, CDCl3) δ 208.6
(2C), 43.4 (2C), 29.9 (2C), 23.1 (2C).
r-Ketol 14: Magnesium metal (4.63 g, 190.6 mmol) was
ground and added to 10 mL of anhydrous ether. To this
mixture was added dropwise a solution of 8.00 g (34.3 mmol)
of 11-bromo-1-undecene with vigorous stirring at 0 °C under
argon. After the addition was complete, the mixture was
warmed to room temperature and stirred for an additional 3
h. The resulting Grignard reagent was added to a solution of
3.30 g (38.1 mmol) of 2,3-butanedione during 12 h at room
temperature under argon. The reaction mixture was stirred
for 10 h, quenched with 10% HCl solution, and extracted with
3 × 200 mL of ether. The combined organic phases were
washed with brine, dried, and evaporated. Chromatography
of the residue on silica gel (elution with hexanes:ethyl ace-
tate: 6:1) gave 6.58 g (72%) of 14 as a colorless oil; IR (neat,
C
19H32O3: C, 73.98; H, 10.46. Found: C, 74.16; H, 10.28.
More polar isomer: colorless oil; IR (neat, cm-1) 1800, 1641;
1H NMR (300 MHz, CDCl3) δ 5.87-5.74 (m, 2 H), 5.24-5.14
(m, 2 H), 5.04-4.90 (m, 2 H), 2.62 (dd, J ) 14.6, 5.9 Hz, 1 H),
2.29 (dd, J ) 14.6, 8.9 Hz, 1 H), 2.09-2.00 (m, 2 H), 1.87-
1.22 (series of m, 16 H), 1.35 (s, 6 H); 13C NMR (75 MHz,
CDCl3) δ 153.8, 139.1, 131.3, 120.2, 114.1, 88.3, 87.5, 39.3, 34.3,
33.7, 29.9, 29.40, 29.36, 29.3, 29.0, 28.9, 23.7, 19.7, 19.5; ES
MS m/z (M + Na)+ calcd 331.2249, obsd 331.2234.
For 16b and 17b: (combined 93% yield; 3:1 ratio); less polar
isomer: colorless oil; IR (neat, cm-1) 1799, 1640; 1H NMR (300
MHz, CDCl3) δ 5.87-5.72 (m, 2 H), 5.05-4.91 (m, 4 H), 2.15-
1
cm-1) 3474, 1711, 1641; H NMR (300 MHz, CDCl3) δ 5.86-
2.00 (m, 4 H), 1.85-1.28 (series of m, 22 H), 1.35 (s, 6 H); 13
C
5.72 (m, 1 H), 5.01-4.89 (m, 2 H), 2.19 (s, 3 H), 2.06-1.97 (m,
2 H), 1.72-1.62 (m, 2 H), 1.49-1.17 (series of m, 15 H), 1.34
NMR (75 MHz, CDCl3) δ 154.1, 139.2, 138.3, 114.8, 114.1, 88.5,
88.4, 35.0, 34.8, 33.8, 33.4, 29.9, 29.43 (2C), 29.39 (2C), 29.1,

6702 J . Org. Chem., Vol. 66, No. 20, 2001
Balskus et al.
28.9, 23.9, 23.3, 18.9 (2C); ES MS m/z (M + Na)+ calcd
373.2719, obsd 373.2723.
Com p ou n d s 18c a n d 19c. Ring closing metathesis of 16c
(less polar) afforded 18c in 50% yield as a colorless oil; IR (neat,
cm-1) 1800; 1H NMR (300 MHz, CDCl3) δ 5.35-5.29 (m, 2 H),
2.05-1.95 (m, 4 H), 1.76-1.59 (m, 4 H), 1.53-1.17 (series of
m, 22 H), 1.39 (s, 6 H); 13C NMR (75 MHz, CDCl3) δ 154.0,
130.9, 130.5, 130.3, 129.7, 88.63, 88.57, 34.9, 34.3, 32.6, 32.1,
29.5, 29.0, 28.8, 28.72, 28.67, 28.4, 28.3, 28.0, 27.8, 27.7, 27.6,
27.1, 24.2, 22.9, 22.8, 20.1, 19.9; ES MS m/z (M+) calcd
373.2719, obsd 373.2723. Anal. Calcd for C22H38O3: C, 75.38;
H, 10.93. Found: C, 75.26; H, 11.04.
More polar isomer: colorless oil; IR (neat, cm-1) 1799, 1640;
1H NMR (300 MHz, CDCl3) δ 5.86-5.72 (m, 2 H), 5.05-4.90
(m, 4 H), 2.13-2.01 (m, 4 H), 1.85-1.29 (series of m, 22 H),
1.36 (s, 6 H); 13C NMR (75 MHz, CDCl3) δ 154.1, 139.2, 138.3,
114.8, 114.1, 88.4, 88.3, 34.4, 34.2, 33.8, 33.4, 30.0, 29.44 (2C),
29.40 (2C), 29.1, 28.9, 23.7, 23.1, 19.42, 19.39; EI MS m/z (M
+ H)+ calcd 351.2899, obsd 351.2904.
For 16c and 17c: (combined 75% yield; 3:1 ratio); less polar
isomer: colorless oil; IR (neat, cm-1) 1802, 1640; 1H NMR (300
MHz, CDCl3) δ 5.88-5.73 (m, 2 H), 5.03-4.91 (m, 4 H), 2.07-
2.00 (m, 4 H), 1.81-1.73 (m, 2 H), 1.63-1.20 (series of m, 24
H), 1.35 (s, 6 H); 13C NMR (75 MHz, CDCl3) δ 154.1, 139.2,
138.9, 114.3, 114.1, 88.4 (2C), 35.0, 33.8, 33.6, 29.9, 29.8, 29.43
(2C), 29.39 (2C), 29.1, 28.9, 28.8, 28.7, 23.90, 23.87, 18.9 (2C);
ES MS m/z (M + Na)+ calcd 401.3032, obsd 401.3034. Anal.
Calcd for C24H42O3: C, 76.14, H, 11.18. Found: C, 76.32; H,
11.33.
Comparable treatment of 17c (more polar) furnished 19c
1
in 46% yield as a colorless oil; IR (neat, cm-1) 1799, 1641; H
NMR (300 MHz, CDCl3) δ 5.39-5.27 (m, 2 H), 2.09-2.00 (m,
4 H), 1.80-1.63 (m, 4 H), 1.58-1.24 (series of m, 22 H), 1.36
(s, 6 H); 13C NMR (75 MHz, CDCl3) δ 154.2, 130.7, 130.6, 130.3,
130.0, 88.5, 88.3, 35.0, 34.8, 34.3, 33.5, 32.1, 32.0, 29.7, 29.3,
28.9, 28.83, 28.76, 28.7, 28.5, 27.7, 27.4, 26.8, 26.6, 23.6, 23.4,
22.9, 22.5, 20.3, 20.2, 20.1, 20.0; ES MS m/z (M + Na)+ calcd
373.2719, obsd 373.2714.
More polar isomer: colorless oil; IR (neat, cm-1) 1799, 1641;
1H NMR (300 MHz, CDCl3) δ 5.88-5.73 (m, 2 H), 5.02-4.91
(m, 4 H), 2.07-2.01 (m, 4 H), 1.80-1.70 (m, 2 H), 1.59-1.28
(series of m, 24 H), 1.35 (s, 6 H); 13C NMR (75 MHz, CDCl3) δ
154.2, 139.2, 138.9, 114.3, 114.1, 88.5, 88.4, 34.4, 33.8, 33.7,
29.9, 29.8, 29.42 (2C), 29.40 (2C), 29.1, 28.9 (2C), 28.7, 23.72,
23.68, 19.4 (2C); ES MS m/z (M + Na)+ calcd 401.3032, obsd
401.3036.
Gen er a l P r oced u r e for th e Gen er a tion of Keton es 20.
A solution of 19b (22 mg, 0.068 mmol) in absolute ethanol (3
mL) containing 4 mg of 10% palladium on charcoal was
vigorously stirred overnight under 1 atm of H2, treated with
2 mL of 2 M sodium hydroxide solution, and stirred for an
additional 2 h. The mixture was filtered through a small pad
of Celite, and the filtrate was partitioned between water (100
mL) and CH2Cl2 (100 mL). The separated aqueous layer was
extracted with CH2Cl2 (3 × 50 mL), and the combined organic
layers were dried and evaporated. The residue was taken up
in CH2Cl2 (5 mL), treated with lead tetraacetate (60 mg, 0.14
mmol), stirred for 30 min, and freed of solvent. The diketone
was purified by flash chromatography on silica gel.
Rin g Closin g Meta th esis of Cyclic Ca r bon a tes. To a
solution of 16 or 17 (0.10 mmol) in CH2Cl2 (25 mL) was added
17 mg (0.02 mmol) of Grubbs’s catalyst at 20 °C under argon.
The reaction mixture was stirred at 40 °C for 36 h, cooled,
treated with 15 mg of lead tetraacetate, and stirred overnight.
Following solvent evaporation under reduced pressure, the
residue was taken up in hexanes and filtered through a short
pad of silica gel. The filtrate was evaporated and final
purification was achieved by flash chromatography on silica
gel (elution with hexanes to 3% ethyl acetate in hexanes).
Unreacted 16 or 17 was invariably recovered (25-40%).
Com p ou n d s 18a a n d 19a . Ring closing metathesis of 16a
(less polar) gave rise to 18a in 37% yield; colorless oil; IR (neat,
cm-1) 1800; 1H NMR (300 MHz, CDCl3) δ 5.41-5.19 (m, 2 H),
2.42-2.32 (m, 2 H), 2.27-1.08 (m, 18 H), 1.39 (s, 3 H), 1.36 (s,
3 H); 13C NMR (75 MHz, CDCl3) δ 153.9, 130.8, 129.9, 126.4,
125.6, 88.7, 87.9, 40.3, 39.3, 34.4, 34.2, 33.5, 33.2, 29.9, 29.7,
29.43, 29.37, 29.2, 29.0, 27.3, 23.2, 23.0, 20.5, 20.4, 19.7, 19.5;
ES MS m/z (M + Na)+ calcd 303.1931, obsd 303.1941. Anal.
Calcd for C17H28O3: C, 72.82; H, 10.06. Found: C, 72.60; H,
10.14.
Ring closure of 17a (more polar) afforded 19a (30%) as a
colorless oil; IR (neat, cm-1) 1801; 1H NMR (300 MHz, CDCl3)
δ 5.30-5.18 (m, 2 H), 2.43-2.30 (m, 2 H), 2.25-1.07 (m, 18
H), 1.38 (s, 3 H), 1.36 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ
154.0, 130.7, 129.7, 126.2, 125.7, 88.6, 87.7, 41.2, 39.2, 34.2,
34.1, 33.4, 33.2, 29.8, 29.6, 29.2, 29.1, 29.0, 28.9, 23.2, 22.9,
20.6, 20.4, 19.8, 19.7; ES MS m/z (M + Na)+ calcd 303.1931,
obsd 303.1904.
Com p ou n d s 18b a n d 19b. Ring closing metathesis of 16b
(less polar) furnished 18b in 47% yield as a colorless oil; IR
(neat, cm-1) 1799; 1H NMR (300 MHz, CDCl3) δ 5.46-5.17 (m,
2 H), 2.26-1.07 (series of m, 26 H), 1.39 (s, 3 H), 1.38 (s, 3 H);
13C NMR (75 MHz, CDCl3) δ 154.0, 131.8, 131.1, 129.8, 129.6,
88.7, 88.3, 35.4, 34.0, 33.9, 32.6, 32.0, 29.4, 29.01, 28.96, 28.9,
28.04, 27.97, 27.62, 27.57, 27.42, 27.36, 26.6, 26.3, 25.6, 25.3,
23.1, 23.0, 21.9, 21.5, 20.5, 20.4, 19.4; ES MS m/z (M + Na)+
calcd 345.2400, obsd 345.2398.
2,15-Hexa d eca n ed ion e (20a ).40 Obtained from 19a in 79%
1
overall yield; white solid, mp 82-83 °C; H NMR (300 MHz,
CDCl3) δ 2.40 (t, J ) 7.0 Hz, 4 H), 2.12 (s, 6 H), 1.59-1.53 (m,
4 H), 1.27-1.24 (m, 16 H); 13C NMR (75 MHz, CDCl3) δ 208.1
(2C), 43.6 (2C), 29.8 (2C), 29.6 (2C), 29.5 (2C), 29.4 (2C), 29.2
(2C), 23.8 (2C).
2,18-Non a d eca n ed ion e (20b).41a Obtained from 19b in
84% overall yield; white solid, mp 89.5-90.5 °C; 1H NMR (300
MHz, CDCl3) δ 2.40 (t, J ) 7.4 Hz, 4 H), 2.12 (s, 6 H), 1.58-
1.53 (m, 4 H), 1.26-1.24 (m, 22 H); 13C NMR (75 MHz, CDCl3)
δ 209.3 (2C), 43.8 (2C), 29.8 (2C), 29.59 (3C), 29.56 (2C), 29.43
(2C), 29.36 (2C), 29.2 (2C), 23.9 (2C).
2,20-Hen eicosa n ed ion e (20c).41b Obtained from 19c in
80% overall yield; colorless solid, mp 91-92 °C; 1H NMR (300
MHz, CDCl3) δ 2.41 (t, J ) 7.4 Hz, 4 H), 2.13 (s, 6 H), 1.61-
1.52 (m, 4 H), 1.27-1.25 (m, 26 H); 13C NMR (75 MHz, CDCl3)
δ 205.7 (2C), 43.8 (2C), 29.8 (2C), 29.7 (3C), 29.65 (2C), 29.61
(2C), 29.5 (2C), 29.4 (2C), 29.2 (2C), 23.9 (2C).
1,2-Dia llylcycloh exa n e-1,2-d iol (21).11a,21b,28 Isolated as
a colorless oil in 92% yield; 1H NMR (500 MHz, CDCl3) δ 5.95-
5.87 (m, 2 H), 5.14-5.08 (m, 4 H), 2.47-2.20 (m, 4 H), 2.15 (s,
2 H), 1.70-1.65 (m, 2 H), 1.58-1.47 (series of m, 4 H), 1.37-
1.30 (m, 2 H); 13C NMR (125 MHz, CDCl3) δ 134.0 (2C), 118.4
(2C), 75.2 (2C), 39.1 (2C), 32.9 (2C), 21.5 (2C).
1,2,3,4,5,8-Hexah ydr on aph th alen e-4a,8a-diol (22).29 Col-
1
orless oil; 96% yield; H NMR (500 MHz, CDCl3) δ 5.75-5.72
(m, 0.18 × 2 H), 5.57-5.52 (m, 0.82 × 2 H), 2.31-2.05 (series
of m, 6 H), 1.83-1.56 (series of m, 4 H), 1.53-1.21 (series of
m, 4 H); For the major diastereomer 13C NMR (75 MHz, CDCl3)
δ 124.2 (2C), 72.0 (2C), 37.1 (2C), 34.5 (2C), 22.4 (2C). For the
(40) (a) Chen, W.; J iao, Z.; Xie, Y.; J iao, K. Huaxue Tongbao 1998,
42. (b) Chen, H. S.; Liu, X. F.; Xu, H. S. Chin. Chem. Lett. 1997, 8, 17.
(c) Griesbaum, K.; Ball, V.; Beck, J .; McCullough, K. Liebigs Ann. 1995,
1993. (d) Barbry, D.; Faven, C.; Ajana, A. Synth. Commun. 1993, 23,
2647. (e) Babudri, F.; D’Ettole, A.; Fiandanese, V.; Marchese, G.; Naso,
F. J . Organomet. Chem. 1991, 405, 53. (f) Yamashita, M.; Matsumiya,
K.; Morimoto, H.; Suemitsu, R. Bull. Chem. Soc. J pn. 1989, 62, 1668.
(g) McMurry, J . E.; Lectka, T.; Rico, J . G. J . Org. Chem. 1989, 54, 3748.
(41) (a) Canonica, L.; Bacchetti, T. Atti Acad. Nazl. Lincei, Rend.,
Classe sci. fis., mat. e mat. 1953, 15, 278; Chem. Abstr. 1955, 49, 8121h.
(b) Cope, A. C.; Axen, U.; Burrows, E. P.; Weinlich, J . J . Am. Chem.
Soc. 1966, 88, 4228.
Comparable treatment of 17b (more polar) gave rise to 19b
1
(45%) as a colorless oil; IR (neat, cm-1) 1798; H NMR (300
MHz, CDCl3) δ 5.39-5.29 (m, 2 H), 2.12-1.95 (m, 4 H), 1.87-
1.66 (m, 4 H), 1.61-1.22 (series of m, 18 H), 1.40 (s, 3 H), 1.36
(s, 3 H); 13C NMR (75 MHz, CDCl3) δ 154.1, 131.2, 130.3, 130.1,
129.4, 88.6, 88.2, 36.3, 34.54, 34.49, 33.1, 31.8, 31.6, 30.4, 29.9,
28.4, 28.0, 27.9, 27.72, 27.69, 27.5, 27.4, 26.8, 26.6, 26.5, 26.2,
25.9, 22.9, 22.8, 22.1, 21.8, 21.1, 20.6, 20.3, 19.7; ES MS m/z
calcd 345.2400, obsd 345.2411.

Intercalation between the Carbonyls of R-Diketones
J . Org. Chem., Vol. 66, No. 20, 2001 6703
minor diastereomer 13C NMR (75 MHz, CDCl3) δ 133.3 (2C),
71.7 (2C), 36.1 (2C), 31.7 (2C), 24.4 (2C).
H), 1.77-1.24 (series of m, 16 H); 13C NMR (75 MHZ, CDCl3)
δ 211.2, 202.5, 145.7, 128.0, 43.3, 42.5, 41.0, 27.5, 27.4, 26.9,
26.8, 26.5, 26.2, 24.4, 23.4, 22.7; EI MS m/z (M+) calcd
250.1933, obsd 250.1933.
(Z)-3-Cyclod ecen e-1,4-d ion e (23). White solid, mp 78-
79 °C; 46% yield; IR (neat, cm-1) 1705; 1H NMR (300 MHz,
CDCl3) δ 5.81 (t, J ) 4.9 Hz, 2 H), 3.12 (d, J ) 6.1 Hz, 4 H),
2.43-2.40 (m, 4 H), 1.84-1.79 (m, 4 H); 13C NMR (75 MHz,
CDCl3) δ 211.2 (2C), 126.1 (2C), 41.7 (2C), 40.4 (2C), 23.3 (2C);
EI MS m/ z (M+) calcd 166.0944, obsd 166.0993. Anal. Calcd
for C10H14O2: C, 72.26; H, 8.49. Found: C, 72.42; H, 8.68.
(E)-2-Cyclod ecen e-1,6-d ion e (24). White solid, mp 85-
Cycloh exa d eca n e-1,6-d ion e (32).33 White solid, mp 83-
1
84 °C; 86% yield; IR (CHCl3, cm-1) 1706; H NMR (300 MHz,
CDCl3) δ 2.36 (t, J ) 6.7 Hz, 8 H), 1.61-1.54 (m, 8 H), 1.33-
1.16 (m, 12 H); 13C NMR (75 MHz, CDCl3) δ 211.8 (2C), 42.2
(2C), 41.4 (2C), 27.4 (2C), 26.9 (2C), 26.6 (2C), 23.6 (2C), 23.0
(2C); HRMS m/z (M+) calcd 252.2089, obsd 252.2083. Anal.
Calcd for C16H28O2: C, 76.14; H, 11.18. Found C, 76.96; H,
11.23.
1
87 °C; 23% yield; IR (neat, cm-1) 1709, 1634, 1460; H NMR
(300 MHz, CDCl3) δ 6.14 (d, J ) 11.9 Hz, 1 H), 5.80 (dt, J )
11.9, 8.4 Hz, 1 H), 2.82-2.75 (m, 2 H), 2.45-2.34 (m, 6 H),
1.84-1.72 (m, 4 H); 13C NMR (75 MHz, CDCl3) δ 211.0, 208.2,
136.8, 132.0, 44.0, 42.0, 36.0, 23.7, 23.2, 23.0; EI MS m/z (M+)
calcd 166.0944, obsd 166.0984. Anal. Calcd C10H14O2: C, 72.26;
H, 8.49. Found: C, 72.31; H, 8.61.
3-Allyl-3-h yd r oxy-1,7,7-tr im eth ylbicyclo[2.2.1]h ep ta n -
2-on e (34). Colorless oil; 90% yield: 1H NMR (300 MHz,
CDCl3) δ 5.91-5.80 (m, 1 H), 5.14-5.08 (m, 2 H), 2.69 (br s, 1
H), 2.27 (dd, J ) 14.8, 6.6 Hz, 1 H), 2.18 (dd, J ) 14.8, 7.7 Hz,
1 H), 1.92 (d, J ) 4.2 Hz, 1 H), 1.85-1.75 (m, 1 H), 1.64-1.48
(m, 2 H), 1.42-1.35 (m, 1 H), 0.98 (s, 3 H), 0.91 (s, 3 H), 0.85
(s, 3 H); 13C NMR (75 MHz, CDCl3) δ 220.4, 132.3, 119.3, 77.6,
58.2, 51.4, 46.1, 40.7, 29.7, 22.3, 22.1, 20.3, 9.4.
Octa h yd r on a p h th a len e-4a ,8a -d iol (25).30 Colorless oil
1
obtained in quantitative yield; H NMR (300 MHz, CDCl3) δ
2.03 (br s, 2 H), 1.79-1.56 (m, 8 H), 1.54-1.19 (m, 8 H); 13C
NMR (75 MH, CDCl3) δ 73.0 (2C), 36.7 (4C), 33.2 (4C), 23.4
(4C), 20.9 (4C).
Com p ou n d 36. Colorless oil; 60% yield; IR (neat, cm-1
)
3440, 1640; 1H NMR (300 MHz, CDCl3) δ 5.99-5.82 (m, 1 H),
5.80-5.74 (m, 1 H), 5.19-5.12 (m, 2 H), 5.02-4.90 (m, 2 H),
2.82 (br s, 2 H), 2.70 (dd, J ) 14.0, 6.7 Hz, 1 H), 2.22, (dd, J
) 14.0, 7.7 Hz, 1 H), 2.03 (m, 2 H), 1.75-1.17 (series of m, 22
H), 0.91 (s, 3 H), 0.83 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ
139.0, 135.0, 118.1, 114.0, 83.1, 82.2, 53.8, 53.4, 48.4, 40.8, 35.4,
33.7, 30.8, 29.7, 29.5, 29.4, 29.0, 28.8, 24.8, 23.2, 23.1, 22.5,
11.6; ES MS m/z (M + Na)+ calcd 371.2926, obsd 371.2935;
Cyclod eca n e-1,6-d ion e (26).31 White solid, mp 99-100
°C;32 79% yield; 1H NMR (300 MHz, CDCl3) δ 2.45-2.33 (m, 8
H), 1.86-1.79 (m, 8 H); 13C NMR (75 MHz, CDCl3) δ 214.1
(2C), 42.2 (4C), 23.4 (4C).
2-Allyl-2-h yd r oxycyclod od eca n on e. This R-ketol was
prepared in the manner described above in 95% yield: colorless
solid; mp 55-56 °C; IR (CHCl3, cm-1) 3478, 1704, 1640; 1H
NMR (300 MHz, CDCl3) δ 5.79-5.65 (m, 1 H), 5.10-5.04 (m,
2 H), 3.97 (m, 1 H), 3.08-2.97 (m, 1 H), 2.49-2.39 (m, 2 H),
2.20-2.07 (m, 2 H), 1.89-1.66 (series of m, 2 H), 1.55-1.17
(series of m, 14 H), 0.83-0.71 (m, 1 H); 13C NMR (75 MHz,
CDCl3) δ 213.9, 132.5, 118.3, 82.2, 43.2, 36.5, 32.7, 26.4, 26.2,
23.9, 22.7, 22.5, 22.4, 21.6, 19.6; EI MS m/z (M+) calcd
238.1933, obsd 238.1939. Anal. Calcd for C15H26O2: C, 75.58;
H, 10.99. Found: C, 75.29; H, 11.01.
1,2-Dia llylcyclod od eca n e-1,2-d iol (28). The preceding
R-ketol (500 mg, 3.1 mmol) was dissolved in anhydrous ether
(30 mL) and treated with 1 M allylmagnesium bromide in
ether (9.0 mL, 9.0 mmol) at -20 °C. After 30 min, the reaction
mixture was poured into saturated NH4Cl solution, the layers
were separated, and the aqueous layer was extracted with
ether (2 × 35 mL). The combined organic fractions were dried,
filtered, and concentrated under reduced pressure. The residue
was chromatographed on silica gel (elution with 10% ether in
ligroin) to give 755 mg (87%) of 28 as a single diastereomer:
colorless oil; IR (CHCl3, cm-1) 3540, 1637; 1H NMR (300 MHz,
CDCl3) δ 6.04-5.89 (m, 2 H), 5.14-5.08 (m, 4 H), 2.43-2.25
(m, 4 H), 2.36 (br s, 2 H), 1.83-1.24 (series of m, 20 H); 13C
NMR (75 MHz, CDCl3) δ 134.9 (2C), 118.3 (2C), 78.5 (2C), 40.9
(2C), 34.6 (2C), 26.7 (2C), 24.7 (2C), 23.2 (2C), 21.5 (2C); EI
MS m/z (M+) 280.2402, obsd 280.2403. Anal. Calcd for
[R]22 +4.7 (c 1.0, CHCl3).
D
Com p ou n d 37. Colorless oil; 80% yield; IR (neat, cm-1
)
1789, 1641; 1H NMR (300 MHz, CDCl3) δ 5.90-5.71 (m, 2 H),
5.17-5.12 (m, 2 H), 4.99-4.87 (m, 2 H), 2.65 (dd, J ) 14.6,
8.6 Hz, 1 H), 2.46 (dd, J ) 14.6, 5.5 Hz, 1 H), 2.05-1.97 (m, 3
H), 1.93-1.83 (m, 1 H), 1.73-1.58 (m, 2 H), 1.53-1.20 (series
of m, 15 H), 1.13 (s, 3 H), 0.98 (s, 3 H), 0.92 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 154.8, 139.0, 131.9, 118.9, 114.1, 94.6, 94.2,
53.2, 50.3, 47.3, 37.7, 33.7, 31.9, 30.2, 29.3 (2C), 29.0, 28.9,
28.7, 24.4, 24.3, 21.7, 20.5, 10.7; ES MS m/z (M + Na)+ calcd
397.2719, obsd 397.2725; [R]22 -11.5 (c 0.98, CHCl3). Anal.
D
Calcd for C24H38O3: C, 76.96; H, 10.23. Found: C, 76.97; H,
10.36.
Gen er a l P r oced u r e for Tw ofold Alk yllith iu m Ad d i-
tion . (1R)-(-)-Camphorquinone (100 mg, 0.60 mmol) was
dissolved in dry THF (2 mL), treated with lithium wire (74
mg, 10.6 mmol), placed under argon, and cooled to 0 °C. A
solution of 10-bromo-1-decene (1.05 g, 4.8 mmol) in dry THF
(3 mL) was introduced dropwise into the stirred reaction
mixture, which was allowed to warm to room temperature
after the addition was complete. After 12 h, the solvent was
evaporated, and the residue was taken up in ether (10 mL)
and added to a separatory funnel containing water (10 mL)
and 1 M NH4Cl solution (1 mL). Extraction of the aqueous
layer with ether (3 × 10 mL) following by drying, concentra-
tion, and flash chromatographic purification (silica gel, elution
with 9:1 petroleum ether/ether) afforded diol 38 as a colorless
oil (75 mg, 28%); IR (neat, cm-1) 3440, 1462; 1H NMR (300
MHz, CDCl3) δ 5.88-5.74 (m, 2 H), 5.02-4.91 (m, 4 H), 2.07-
2.00 (m, 4 H), 1.70-1.15 (series of m, 35 H), 1.25 (s, 3 H), 0.90
(s, 3 H), 0.83 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 139.2 (2C),
114.1 (2C), 83.6, 83.5, 53.3, 48.4, 36.5, 35.1, 33.8 (2C), 30.8,
30.4, 29.9, 29.7, 29.64, 29.57, 29.5 (2C), 29.1 (2C), 28.9 (2C),
24.9, 24.6, 23.32, 23.27, 22.8, 11.7; ES MS (M + Na)+ calcd
469.4022, obsd 469.4038; [R]22D +0.7 (c 2.4, CHCl3). Anal. Calcd
for C30H54O2: C, 80.65; H, 12.18. Found: C, 80.32; H. 12.16.
C
18H32O2: C, 77.09; H, 11.50. Found: C, 77.13; H, 11.51.
1,4,5,6,7,8,9,10,11,12,13,14-Dod eca h yd r ob en zocyclo-
d od ecen e-4a ,14a -d iol (29). White solid, mp 73-75 °C; 96%
yield; IR (CHCl3, cm-1) 3567, 1470; 1H NMR (300 MHz, CDCl3)
δ 5.51 (s, 2 H), 2.23-2.09 (series of m, 6 H), 1.75-1.59 (series
of m, 4 H), 1.53-1.25 (series of m, 16 H); 13C NMR (75 MHz,
CDCl3) δ 124.3 (2C), 75.5 (2C), 37.4 (2C), 33.2 (2C), 26.0 (2C),
24.1 (2C), 22.8 (2C), 20.8 (2C); EI MS m/z (M+) calcd 252.2089,
obsd 252.2084. Anal. Calcd for C16H28O2: C, 76.14; H, 11.18.
Found: C, 76.24; H, 11.24.
(Z)-3-Cycloh exa d ecen e-1,6-d ion e (30). White solid, mp
92-93 °C; 42% yield; IR (neat, cm-1) 1703, 1438; 1H NMR (300
MHz, CDCl3) δ 5.77 (t, J ) 4.8 Hz, 2 H), 3.18 (d, J ) 5.9 Hz,
4 H), 2.43 (t, J ) 6.8 Hz, 4 H), 1.68-1.42 (m, 4 H), 1.26-1.15
(m, 12 H); 13C NMR (75 MHz, CDCl3) δ 208.4 (2C), 124.1 (2C),
42.1 (2C), 41.3 (2C), 27.1 (2C), 26.3 (2C), 26.1 (2C), 22.7 (2C);
EI MS m/z (M+) calcd 250.1933, obsd 250.1936. Anal. Calcd
for C16H26O2: C, 76.75; H, 10.47. Found: C, 76.75; H, 10.39.
(E)-2-Cycloh exa d ecen e-1,6-d ion e (31). Colorless oil; 23%
Com p ou n d 39. Colorless oil; 24% yield; IR (neat, cm-1
)
3442, 1463; 1H NMR (300 MHz, CDCl3) δ 5.87-5.73 (m, 2 H),
5.01-4.90 (m, 4 H), 2.58 (br s, 2 H), 2.06-2.00 (m, 4 H), 1.81-
1.03 (m, 40 H), 0.89 (s, 3 H), 0.83 (s, 3 H); 13C NMR (75 MHz,
CDCl3) δ 139.2 (2C), 114.1, (2C), 83.6, 83.5, 53.4, 53.3, 48.3,
36.5, 35.1, 33.8 (2C), 30.8, 30.4, 29.8, 29.7, 29.60, 29.58 (2C),
29.5 (2C), 29.1 (2C), 28.9 (2C), 24.9, 24.6, 23.30, 23.25, 22.8,
11.6; ES MS m/z (M + Na)+ calcd 497.4335, obsd 497.4318;
[R]22D +2.7 (c 1.73, CHCl3). Anal. Calcd for C32H58O2: C, 80.95;
H, 12.31. Found: C, 80.88; H. 12.46.
1
yield; IR (neat, cm-1) 1710, 1640, 1463; H NMR (300 MHz,
CDCl3) δ 6.21-6.10 (m, 2 H), 2.92-2.85 (m, 2 H), 2.56 (t, J )
6.7 Hz, 2 H), 2.44 (t, J ) 6.3 Hz, 2 H), 2.37 (t, J ) 7.1 Hz, 2

6704 J . Org. Chem., Vol. 66, No. 20, 2001
Balskus et al.
Com p ou n d 41. Submission of 38 (70 mg, 0.16 mmol) to one-
pot ring-closing metathesis/oxidative cleavage according to the
general protocol furnished 29.4 mg (45% overall) of diketone
41 as a colorless oil; IR (neat, cm-1) 1696; 1H NMR (300 MHz,
CDCl3) δ 5.33-5.32 (m, 2 H), 2.93 (dd, J ) 9.6, 8.4 Hz, 1 H),
2.66-2.35 (m, 5 H), 2.27-2.15 (m, 1 H), 1.93-1.89 (m, 4 H),
1.78-1.37 (m, 6 H), 1.33-1.14 (m, 23 H), 1.16 (s, 3 H), 0.70 (s,
3 H); 13C NMR (75 MHz, CDCl3) δ 214.2, 214.0, 212.2, 212.0,
130.3, 130.2, 129.8, 61.4, 61.3, 60.0, 59.8, 47.6, 47.3, 43.3, 39.3,
32.8, 32.5, 32.4, 29.6, 29.2, 29.0, 28.9, 28.72, 28.67, 28.6, 28.5,
28.3, 28.2, 28.13, 28.06, 27.9, 27.8, 27.7, 27.5, 27.2, 27.1, 24.7,
24.4, 22.9, 22.7, 22.2, 21.9, 21.6, 21.2, 21.0; EI MS m/z (M+)
m/z (M+) calcd 418.3811, obsd 418.3790; [R]20 +46.3 (c 0.45,
D
CHCl3).
Com p ou n d 44. Colorless oil; 49% yield over two steps; IR
1
(neat, cm-1) 1704, 1462; H NMR (300 MHz, CDCl3) δ 5.36-
5.33 (m, 2 H), 2.95-2.89 (m, 1 H), 2.57-2.36 (m, 5 H), 2.19
(m, 1 H), 1.98-1.94 (m, 4 H), 1.75-1.40 (m, 6 H), 1.33 (s, 3
H), 1.33-1.14 (m, 24 H), 1.14 (s, 3 H), 0.69 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 214.3, 214.0, 212.3, 212.1, 130.4, 130.3,
129.82, 129.77, 61.3, 61.2, 59.9, 59.8, 47.5, 47.4, 43.7, 43.5, 39.8,
39.6, 32.7, 32.6, 32.3, 29.8, 29.4, 29.33, 29.26, 29.2, 29.1, 28.9,
28.8, 28.7, 28.6, 28.54, 28.51, 28.4, 28.3, 28.25, 28.20, 28.15,
28.1, 28.06, 27.9, 27.13, 27.10, 24.6, 24.5, 22.9, 22.8, 22.54,
22.47, 22.3, 21.6, 21.2, 21.1; EI MS m/z (M+) calcd 444.3967,
calcd 416.3654, obsd 416.3649; [R]22 +30.9 (c 0.22, CHCl3).
D
obsd 444.4017; [R]22 +42.4 (c 0.50, CHCl3).
D
Anal. Calcd for C28H48O2: C, 80.71; H, 11.61. Found: C, 80.72;
H, 11.65.
Com p ou n d 45. Colorless oil; 45% yield over three steps;
IR (neat, cm-1) 1701; 1H NMR (300 MHz, CDCl3) δ 2.95 (dd, J
) 8.3, 9.6 Hz, 1 H), 2.61-2.32 (m, 5 H), 2.30-2.14 (m, 1 H),
1.78-1.41 (m, 6 H), 1.33 (s, 3 H), 1.33-1.15 (m, 32 H), 1.15 (s,
3 H), 0.70 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 214.2, 212.2,
61.2, 59.7, 47.3, 43.8, 39.8, 32.5, 29.25, 29.15, 29.0 (2C), 28.8,
28.7, 28.42, 28.38, 28.33, 28.26, 28.2, 28.1, 28.0 (2C), 27.9 (2C),
24.3, 22.73, 22.65, 22.5, 21.4, 21.3; ES MS m/z (M + Na)+ calcd
Com p ou n d 42. Sequential ring closing metathesis/hydro-
genation/oxidative cleavage of 37 (47 mg, 0.11 mmol) gave 19.5
mg (45% over three steps) of 42 as a colorless oil; IR (neat,
1
cm-1) 1727; H NMR (300 MHz, CDCl3) δ 2.95 (dd, J ) 8.2,
9.7 Hz, 1 H), 2.65-2.30 (m, 5 H), 2.26-2.16 (m, 1 H), 1.78-
1.16 (series of m, 37 H), 1.16 (s, 3 H), 0.70 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 214.2, 212.1, 61.4, 59.8, 47.4, 43.6, 39.5,
32.5, 29.1 (2C), 29.0 (2C), 28.8, 28.7, 28.44, 28.36, 28.2, 28.1,
27.8 (2C), 27.6 (2C), 24.4, 22.8, 22.2 (2C), 21.6, 21.2; EI MS
469.4022, obsd 469.4059; [R]22 +51.3 (c 2.71, CHCl3).
D
J O010494Y