Double-Tandem [4π+2π]·[2 π+2π]·[4π+2π] ·[2π+2π] Synthetic Sequence with Photoprotolytic Oxametathesis and Photoepoxidation in the Chromone Series

Article abstract of DOI:10.1021/jo102221q

Chromones are introduced into a double-tandem [4_π+2 _π]·[2_π+2_π]·[4 _π+2_π]·[2_π+2_π] synthetic sequence, culminating in photoprotolytic oxametathesis, which leads to an expeditious growth of molecular complexity over a few experimentally simple steps. The overall reaction can potentially be utilized in diversity-oriented synthesis, as it allows for three or more diversity inputs furnishing novel unique polycyclic scaffolds decorated with a variety of functionalities and aromatic/heterocyclic pendants. The polycyclic alkenes, resulting from the oxametathesis step, were found to undergo efficient and clean photoinduced epoxidation when irradiated in the presence of molecular oxygen.(Figure Presented)

Full text of DOI:10.1021/jo102221q

pubs.acs.org/joc
Double-Tandem [4πþ2π] [2πþ2π] [4πþ2π] [2πþ2π] Synthetic Sequence
3
3
3
with Photoprotolytic Oxametathesis and Photoepoxidation in the
Chromone Series
Roman A. Valiulin, Teresa M. Arisco, and Andrei G. Kutateladze*
Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado 80208, United States
akutatel@du.edu
Received November 9, 2010
Chromones are introduced into a double-tandem [4πþ2π] [2πþ2π] [4πþ2π] [2πþ2π] synthetic se-
3
3
3
quence, culminating in photoprotolytic oxametathesis, which leads to an expeditious growth of
molecular complexity over a few experimentally simple steps. The overall reaction can potentially be
utilized in diversity-oriented synthesis, as it allows for three or more diversity inputs furnishing novel
unique polycyclic scaffolds decorated with a variety of functionalities and aromatic/heterocyclic
pendants. The polycyclic alkenes, resulting from the oxametathesis step, were found to undergo
efficient and clean photoinduced epoxidation when irradiated in the presence of molecular oxygen.
Introduction
Also, several accounts of various acid- and base-catalyzed
rearrangements involving either diene B or its Diels-Alder
adducts have been published.4 A related series of [2þ2]
intramolecular photocycloadditions in alkene-arene pairs
or between two aromatic moieties were utilized by Prinzbach
to produce a diverse array of polycyclic hydrocarbons, pag-
odanes.5
Filipescu1 and Kushner2 independently showed that the
Diels-Alder adducts of 1,4-naphthoquinone with cyclic
dienes undergo intramolecular alkene-arene [2þ2]
photocycloaddition, yielding a facially stereodifferen-
tiated cyclohexadiene (Scheme 1). Coxon, Marchand,
and others systematically studied facial selectivity of
Diels-Alder additions to B, concluding that the attack
of alkenic dienophiles, such as maleic anhydride, occurs
preferentially at the face of the two carbonyl groups,3
while hetero-Diels-Alder reactions of singlet oxygen or
1,2,4-triazoline-3,5-dione occur mostly from the cyclobu-
tyl face.3f
With this abundance of synthetic results, the ready access
to the starting materials, and the palpable promise of syn-
thetic developments around the basic [4þ2] [2 þ 2] [4 þ 2]
3
3
sequence shown in Scheme 1, it was surprising for us to
realize that 1,4-naphthoquinone is the only aromatic ketone
that is known to form polycyclic dienes of type B in intra-
molecular [2þ2] alkene-arene photocycloadditions. Con-
ceivably this limited variety is explained by the fact that very
few aromatic ketones have been reported as good dieno-
philes for the first, i.e., Diels-Alder, step (f A). For
example, Diels-Alder reactions of benzo-fused heterocyclic
aromatic ketones were not known until about a decade ago,
when Hsung reported the first such reaction of 3-cyanochro-
mone derivatives.6
(1) Filipescu, N.; Menter, J. M. J. Chem. Soc. B 1969, 616–620.
(2) Kushner, A. S. Tetrahedron Lett. 1971, 35, 3275–3278.
(3) (a) Marchand, A. P.; Zope, U. R.; Burritt, A.; Bott, S. G.; Coxon,
J. M. Tetrahedron 1995, 51, 9319–9326. (b) Coxon, J. M.; Fong, S. T.;
Lundie, K.; McDonald, D. Q.; Steel, P. J.; Marchand, A. P.; Zaragoza, F.;
Zope, U. R.; Rajagopal, D. Tetrahedron 1994, 50, 13037–13048. (c) Coxon,
J. M.; Maclagan, R. G. A. R.; McDonald, D. Q.; Steel, P. J. J. Org. Chem.
1991, 56, 2542–2549. (d) Coxon, J. M.; O’Connell, M. J.; Steel, P. J. J. Org.
Chem. 1987, 52, 4726–4732. (e) Mehta, G.; Uma, R. Tetrahedron Lett. 1995,
36, 4873–4876. (f) Mehta, G.; Uma, R. J. Org. Chem. 2000, 65, 1685–1696.
(g) See also: Mehta, G.; Uma, R. Acc. Chem. Res. 2000, 33, 278-286, and
references therein.
(5) (a) Wollenweber, M.; Etzkorn, M.; Reinbold, J.; Wahl, F.; Voss, T.;
€
Melder, J.-P.; Grund, C.; Pinkos, R.; Hunkler, D.; Keller, M.; Worth, J.;
(4) (a) Marchand, A. P.; Chong, H.-S.; Shukla, R.; Sharma, G. V. M.;
Kumar, K. A.; Zope, U. R.; Bott, S. G. Tetrahedron 1996, 52, 13531–
13538. (b) Mehta, G.; Rao, K. S. J. Chem. Soc., Chem. Commun. 1981, 755–
756.
Knothe, L.; Prinzbach, H. Eur. J. Org. Chem. 2000, 3855–3886. (b) Fessner,
W. D.; Scheumann, K.; Prinzbach, H. Tetrahedron Lett. 1991, 32, 5939–
5942.
(6) Hsung, R. P. J. Org. Chem. 1997, 62, 7904–7905.
DOI: 10.1021/jo102221q
r
Published on Web 01/26/2011
J. Org. Chem. 2011, 76, 1319–1332 1319
2011 American Chemical Society

Valiulin et al.
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SCHEME 1
SCHEME 3
undergo facile thermal decarboxylation into 1b or 1c
(Scheme 3).
SCHEME 2
Intramolecular [2þ2] Arene-Alkene Photocyclization.
Upon irradiation in a Rayonet photoreactor with RPR-
3500 lamps (a broadband UV source with λ = 350 ( 50
nm) or with 365 nm UV LEDs, the Diels-Alder adducts
1a-c cyclize into dienes 2a-c. To our knowledge, this is the
first tandem Diels-Alder reaction followed by a photoin-
duced aryl-alkene [2πþ2π] cyclization, which involves an
aromatic ketone other than a 1,4-naphthoquinone (1d and 2d
in Scheme 3).
The [2πþ2π] cage formation in the chromone series carries
a 10-15 kcal/mol lesser penalty than the photocyclization in
the naphthoquinone series. According to our density func-
tional theory (DFT) calculations at the B3LYP/6-311þG(d,
p) level, the transformation of naphthoquinone-derived 1d
to 2d is 40.1 kcal/mol endergonic, whereas the cyclization of
1c to 2c is only 25.3 kcal/mol.
Diels-Alder Reactions of 2. Dienes 2 react with dieno-
philes such as in situ-generated vinyl phenyl ketone to yield
Diels-Alder adducts 3 (Scheme 4). We found that the facial
selectivity of this second Diels-Alder step was the same as
for naphthoquinone cages; that is, the incoming dienophile
was approaching from the functionalized “keto” face. The
regiochemistry of this step was as shown, where the position
of the endobenzoyl group is proximal to the keto, not the
ether, group of the chromone moiety.
Other dienophiles produce similar results. Scheme 4 also
shows the formation of Diels-Alder adducts 3e,f derived
from dibenzoyl ethylene and 3-cyanochromone or naphtho-
quinone.
We, on the other hand, have recently developed a high-
yielding tandem ground state-excited state [4πþ2π] [2πþ2π]
3
ꢀ
€
modular approach, where the photochemical Paterno-Bu-
chi step in a strained polycycle is accompanied by an acid-
catalyzed fragmentation of the oxetane E into an alternative
carbonyl-alkene pair, Scheme 2.7
This synthetic sequence amounts to photoprotolytic ox-
ametathesis because the intermediate, an oxetane formed at
ꢀ
€
the Paterno-Buchi step, undergoes acid-catalyzed cyclore-
version, producing an alternative pair of the alkene and the
carbonyl compound, similar to pyrolytic olefin-carbonyl
metathesis first reported by Jones.8 This synthetic method
allows for a ready incorporation of three diversity inputs and
provides expeditious growth of molecular complexity over
very few simple synthetic steps. As the polycyclic dienes of
type B represent an appealing diversity input for such
oxametathetic transformations, our aim in this study was
(i) to evaluate the feasibility of the intramolecular [2πþ2π]
photoinduced cycloaddition in the Diels-Alder adducts of
chromone derivatives and (ii) to ascertain whether secondary
Diels-Alder addition and the subsequent one-pot photo-
protolytic oxametathesis is possible in the strained poly-
cycles derived from such photocyclized Diels-Alder
adducts of chromones.9
Photoprotolytic Oxametathesis of 3. endo-Benzoyl poly-
cycles 3 were then introduced into our photoprotolytic
sequence. Irradiation with a broadband 300-400 nm UV
Results and Discussion
ꢀ
€
source in benzene triggered an intramolecular Paterno-Bu-
chi reaction to give oxetanes 4. As we sought to develop high-
yielding photoassisted transformations, we noticed that the
presence of the second benzoyl group in compounds 3e,f
complicated photochemistry. Contrary to that, the mono-
benzoylated polycycles 3a-d possessing a single chromo-
phore gave clean and high-yielding conversions into
oxetanes 4a-d. These oxetanes were then treated with HCl
to initiate the acid-catalyzed oxetane cycloreversion to an
alternative alkene-carbonyl pair, which amounts to alkene-
carbonyl (oxa)metathesis. Scheme 5 shows the protolytic
oxametathesis in the chromone series (oxetanes 4a-c).
The excess acid determines the outcome of the rearrange-
ment. With small amounts, 2 molar equiv, the main products
of oxametathesis are aldehydes 5a-c. However, with excess
HCl a secondary electrophilic addition of Hþ to the styrene
moiety in 5 takes place, plausibly generating a benzylic
Diels-Alder Reaction of Substituted Chromones. As de-
scribed by Hsung, 3-cyanochromone reacts with cyclic
dienes to furnish bicyclic Diels-Alder adducts. Contrary
to that, the unsubstituted chromone in our hands proved
unreactive. Clearly the cyano group makes it a much more
reactive dienophile. However, we found that the formal
Diels-Alder adduct of the unsubstituted chromone still
can be obtained in moderate to good yields of 55-70% by
reacting chromone-3-carboxylic acid instead. This is achieved
simply because the initial products of its Diels-Alder reaction
(7) Valiulin, R. A.; Kutateladze, A. G. Org. Lett. 2009, 11, 3886–3889.
(8) Jones, G.; Schwartz, S. B.; Marton, M. T. J. Chem. Soc., Chem.
Commun. 1973, 374–375. (b) Jones, G.; Acquadro, M. A.; Carmody, M. A.
J. Chem. Soc., Chem. Commun. 1975, 206–207.
(9) For the initial communication see: Valiulin, R. A.; Kutateladze, A. G.
Tetrahedron Lett. 2010, 51, 3803–3806.
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SCHEME 4
SCHEME 5
SCHEME 6
which we never observed in the case of nonfused bicyclo-
[3.2.1]octanes or bicyclo[2.2.1]heptanes. However, the en-
ergy bias is not significant, and the cyclopropyl ring is
dissipated in favor of the styrene moiety when the formyl
group in 6 is converted into an acetal, as shown in Scheme 5.
Acetals 7 are also obtained directly by running the acid-
catalyzed oxametathetic transformation of oxetanes 4 in the
presence of ethylene glycol. One plausible explanation for
this is that the formyl-cyclopropane conjugation makes the
ring-closed form 6 slightly more stable than 5. However,
acetal formation abolishes such stabilizing conjugation, thus
changing the delicate balance in favor of alkenes 7.
Seeking a computational support for this hypothesis, we
have compared pairwise the relative energies of the uncon-
jugated formyl-alkene F-ene and formyl-cyclopropane F-
cp (Figure 1 and Table 1) and their acetals A-ene and A-cp.
To evaluate the mitigating effect of the phenyl group con-
jugation to the double bond, we also compared the relative
energies of species FH-ene and FH-cp where the phenyl
was replaced by hydrogen (and their corresponding acetals
AH-ene and AH-cp).
cation, which is intercepted by an internal nucleophile, the
enol, formed from the formyl group, as shown in Scheme 6.
We have reported a similar cyclopropanation in the past in
a polycyclic substrate derived from cyclooctatetraene and
also possessing a fused cyclobutyl moiety.7 It appears that
the additional rigidity of a bicyclo[3.2.1] system fused to a
cyclobutane favors the formation of formyl cyclopropanes 6,
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FIGURE 1. Schematic topology of the structures involved in the ene-cyclopropane equilibria (see also Table 1).
The bicyclo[2.2.1], [2.2.2], [3.2.1] and tricyclo[4.2.1.02,4],
[5.2.1.02,5] cores were also included because we have experi-
mental data for these systems as well.7
strain. Of entries 1-5 it is the tricyclo[5.2.1.02.5] moiety
(i.e., entry 5) that is most distressed and has the lowest IP
of 9.02 eV. It is precisely this tricyclic core that showed
experimental propensity to form the cyclopropyl ring as we
previously reported.7
Furthermore, it is easy to see that in the chromone series
(entry 6) the calculated ionization potential of the double
bond is even lower (8.94 eV), providing additional rationale
for the experimentally observed formation of cyclopropanes
6. The least strained cyclohexenyl moiety (entry 7 in the FH-
ene column) has the highest IP in the series, 9.33 eV, exceed-
ing the IP of the FH-ene chromone (entry 6) by almost 0.4 eV.
A related partial formation of nortricyclenes as a side
reaction in electrophilic reactions of norbornenes has been
long known.12 However, the relative stability shift via acetal
formation allows for the quantitative control of the F-ene a
F-cp equilibrium in the polycyclic structures and can be a
useful technique in the synthetic chemistry toolbox.
Stereochemical Relay. We note that in the synthetic se-
quence 1 f 2 f 3 f 4 f 5-7 the stereochemical outcome is
not decided at the photochemical steps. Rather, the stereo-
chemistry inherited in 3 is simply passed onto the rearranged
5-7. The stereo- and regiochemistry of 3 in turn are effec-
tively defined at the first Diels-Alder step, which yields
adducts 1. This fact is notable because a number of ap-
proaches have already been developed to control the stere-
ochemistry of the Diels-Alder reactions. According to
Hsung6 and our own observations, in the particular case of
3-cyanochromone, the endo/exo ratio of the initial [4þ2]
cycloaddition is high (>95:5). One would argue that enan-
tioselective formation of 1 can also be readily achieved, as a
number of suitable chiral catalysts, such as Corey’s oxaza-
borolidines, etc.,13 have been developed for this task. It is all
the more important since the overall sequence chromone f
6a produces a decorated polycycle possessing 12 stereogenic
centers, five of which are quaternary.
The DFT computations were performed with the Zhao-
Truhlar M06-2X functional10 and 6-311þG(d,p) basis set as
implemented in the Gaussian 2009 package. For the pairs
F-ene and F-cp, computations strongly, by 3-8 kcal/mol,
favor the cyclopropyl-containing isomer F-cp. Even stronger
bias is observed for the FH-ene and FH-cp pair, where the
mitigating conjugation in the vinyl-benzene moiety is re-
moved. The removal of the Ph group produces an additional
3-4 kcal/mol bias favoring the cyclopropyl system FH-cp.
However, this bias is diminished or even slightly reversed
when the formyl group is deconjugated from the cyclopro-
pane ring by conversion into a cyclic acetal (A-cp vs A-ene).
While the actual reversal in relative stability was calculated
only for the entries 2 and 3, the dioxolane derivatives A-ene
and A-cp in the chromone series (entry 6) are predicted to be
nearly degenerate within 0.3 kcal/mol, whereas the free
aldehyde equilibrium F-ene vs F-cp in the same entry 6 favors
the cyclopropane by 5.6 kcal/mol, which is in keeping with
the observed experimental trend.
Granted, this peculiar behavior cannot be fully accounted
for by the stabilizing effect of the formyl-cyclopropyl con-
jugation. As expected, in the less strained monocyclic system
such as 3-phenylcyclohex-3-ene-1-carboxaldehyde (entry 7)
the cyclopropyl form is disfavored by 3.3 kcal/mol in the
conjugated formyl cyclopropane form F-cp and even more
disfavored in a deconjugated acetal A-cp (by 5.2 kcal/mol).
The unprecedented delicate balance between the alkene and
the cyclopropyl forms in polycyclic aldehydes is a reflection
of the destabilization exerted by the polycyclic scaffold on
the endocyclic double bond (the C-CdC angle in
norbornene11 is 108.6° instead of an idealized sp2 angle of
120°), which makes the “saturated” cyclopropyl form rela-
tively less disfavorable. One readily computed criterion for
estimating the extent of such destabilization in the double
bond is its ionization potential (IP), shown in the FH-ene
column of Table 1 in addition to the relative energies. Figure
2 graphically illustrates the decrease in the calculated ioniza-
tion potential values as the polycyclic core accumulates
Photoprotolytic Oxametathesis in the Naphthoquinone Series.
A similar double-tandem [4πþ2π] [2πþ2π] [4πþ2π] [2πþ2π]
3
3
3
(12) Roberts, J. D.; Trumbull, E. R., Jr.; Bennett, W.; Armstrong, R.
J. Am. Chem. Soc. 1950, 72, 3116–3124.
(13) (a) Corey, E. J. Angew. Chem., Int. Ed. 2009, 48, 2100–2117.
(b) Reetz, M. T.; Jiao, N. Angew. Chem., Int. Ed. 2006, 45, 2416–2419.
(c) Roelfes, G.; Feringa, B. L. Angew. Chem., Int. Ed. 2005, 44, 3230–3232.
(d) Boersma, A. J.; Feringa, B. L.; Roelfes, G. Org. Lett. 2007, 9, 3647–3650.
(e) Barroso, S.; Blay, G.; Pedro, J. R. Org. Lett. 2007, 9, 1983–1986.
(10) Zhao, Y.; Truhlar, D. G. Acc. Chem. Res. 2008, 41, 157–167.
(11) Chiang, J. F.; Chiang, R.; Lu, K. C.; Sung, E.-M.; Harmony, M. D.
J. Mol. Struct. 1977, 41, 67–77.
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TABLE 1. Ene-Cyclopropyl Pairwise Comparison of the DFT Relative Stabilities Calculated at the M06-2X/6-311þG(d,p) Level of Theorya,b
aUnits: relative kcal/mol. bIonization potentials in column FH-ene are also calculated at the M062X/6-311þG(d,p) level of theory.
sequence was implemented starting from 1,4-naphthoqui-
none and cyclopentadiene. As noted above, the alkene-
arene intramolecular [2πþ2π] photocycloadditions are
known only for the Diels-Alder adducts derived from
cyclopentadienes and 1,4-naphthoquinones. Our attempt
to photocyclize 1g derived from cyclohexadiene did not
produce cage 2g but rather led to the photoinduced endo
to exo isomerization yielding 1g0. Such endo/exo conver-
sion under electron-transfer conditions is precedented.14
However, the known Diels-Alder adduct of cyclopenta-
diene and naphthoquinone 1d was expectedly photocy-
clized into known 2d, then reacted with in situ-generated
ꢀ
€
vinyl phenyl ketone and subjected to Paterno-Buchi
conditions to yield oxetane 4d (Scheme 7).
Under acidic conditions, oxetane 4d underwent similar
cycloreversion to 4a-c: with a small amount of HCl/dioxane
it produced epimerized aldehyde 5d (Scheme 8). Carrying out
the reaction in excess HCl or BF3 Et2O yielded formylcy-
3
clopropane 6d, whereas in the presence of acidic ethyl-
ene glycol the acetal formation shifted the equilibrium to
alkene 7d. The two keto- groups exhibited very different
(14) Pandey, B.; Dalvi, P. V.; Athawale, A. A.; Pant, B. G.; Kewale, P. P.
J. Chem. Soc., Chem. Commun. 1990, 1505–1506.
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SCHEME 8
SCHEME 9
FIGURE 2. Calculated vertical ionization potentials, eV, as a
function of the ring strain in FH-ene, M062X/6-311þG(2d,2p).
SCHEME 7
SCHEME 10
excited chromophore with ethylene glycol, presumably yield-
ing oxetane 4d, which undergoes acid-catalyzed oxameta-
thetic conversion with in situ trapping of the diketo aldehyde
5d in the form of bis-dioxolane 7d. Provided that an appro-
priate pregenerated aryl vinyl ketone is used as a dienophile
at the 2 f 3 step, the entire double-tandem [4πþ2π] [2πþ2π]
reactivity: the carbonyl proximal to the formyl group survived,
while the distal carbonyl was converted into a spiro-acetal.
Diels-Alder reaction of 1,2-naphthoquinone with cyclo-
hexadiene produced cyclohexene 1i (X-ray structure is avail-
able in the SI) as a result of a fragmentation on silica gel during
purification (Scheme 9). Cyclopentadiene furnished the known
1h,15 which did not exhibit any promising photochemistry.
One-Pot Implementation of the 3 f 7 Transformation.
With optimization of conditions the photoprotolytic oxa-
metathesis can be implemented as a one-pot procedure
(Scheme 10). We found that when irradiation of 3d is carried
out in dichloromethane with a 5-fold molar excess of ethy-
lene glycol and 5 molar equiv of HCl/dioxane, 7d is the only
product in the reaction mixture (by NMR).
3
3
[4πþ2π] [2πþ2π] sequence could potentially be carried out as
3
a one-pot procedure.
Photoepoxidation. We further found that upon extended
irradiation, the styrene moiety in aldehydes 5 or acetals 7 is
epoxidized by molecular oxygen present in oxygenated solu-
tions (oxygen’s concentration in DCM under 1 atm of O2 gas
is 10.7 mM, and similar concentrations are achieved in other
common solvents16) (Scheme 11). While photoepoxidations
of olefins in the presence of organic sensitizers or transition
metal complexes are well-known,17 the direct, i.e., nonsensi-
tized, photoreactions between vinyl arenes and molecular
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€
Clearly the intramolecular Paterno-Buchi step occurs
much faster than the potential bimolecular reduction of the
(16) Battino, R. Oxygen and Ozone; Solubility Data Series: Vol. 7;
Pergamon: Oxford, England, 1981; p 519.
(17) (a) Koo, J.-Y.; Schuster, G. B. J. Org. Chem. 1979, 44, 847–851.
(b) Sawaki, Y.; Foote, C. S. J. Org. Chem. 1983, 48, 4934–4940. (c) Murata,
C.; Yoshida, H.; Hattori, T. J. Chem. Soc., Chem. Commun. 2001, 2412–2413.
(d) Inoue, H.; Okamoto, T.; Komiyama, M.; Hida, M. J. Photochem.
Photobiol. A, Chem. 1992, 65, 221–227.
(15) (a) Friedrichsen, W.; Kallweit, I.; Schmidt, R. Liebigs Ann. Chem.
1977, 116–144. (b) Gelman, D. M.; Forsyth, C. M.; Perlmutter, P. Org. Lett.
2009, 11, 4958–4960.
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SCHEME 11
level (the endo products were left out of consideration
because the steric clash of the two polycyclic pendants in
the syn structures is too severe). As the structures of two
dimers, 9a and 9c, were confirmed by X-ray crystallography,
the crystal structure of 9a was superimposed onto its com-
puted structure, which gave an excellent rmsd of 0.046 for all
heavy atoms, indicating that this large molecular system is
adequately handled by the B3LYP/6-311þG(d,p) level of
theory.
Table 2 lists computational results grouped by the facial
selectivity of Diels-Alder reaction and sorted by the (global)
relative energy, kcal/mol. The observed dimer indeed has the
lowest relative energy.
In the syndiene-syndienophile and antidiene-syndienophile
cases, the most pronounced steric clash is observed when
A2 is the carbonyl group, i.e., the carbonyl in immediate
proximity to the double bond in the bicyclo[2.2.2] moiety.
The relative positions of the A1 and B1 groups in the “diene”
component expectedly have much lesser differentiating ef-
fect, because the double bond in a more symmetric bicyclo-
[2.2.2] moiety is equidistantly removed from either A1 or B1
(which is not the case for A2 and B2 in the dienophilic moiety,
where such distances differ by more than an angstrom).
The steric clash of the carbonyl group in position A2 can
possibly explain the reluctance to dimerize of the 1,4-
naphthoquinone-based caged diene 2d, for which this clash
is unavoidable. Another factor is that, unlike 2d, the diene
moiety in the chromone-based 2a-c is polarized. Figure 3
shows that atoms in the butadiene moiety of 2d are depleted
of electronic density to a much greater extent; the cumulative
positive charge of the moiety is 1.16 vs 0.40 in 2a, i.e., almost
a 3-fold difference. The electronic density in the chromone-
derived 2a is much less depleted, and it is also appropriately
polarized with the “dienophile” double bond being more
electrophilic, Figure 3. Experimentally we did not observe
any evidence for the Diels-Alder dimerization of 2d.
We believe that it is this lack of symmetry and the resulting
polarization in the cyclohexadienyl moiety of the chromone-
derived 2 that is likely responsible for high regio- and
stereoselectivity of Diels-Alder additions of nonsymmetric
dienophiles, such as vinyl ketones, to 2a-c.
SCHEME 12
oxygen are very rare. In fact we found only one study in the
literature proposing a contact charge-transfer pair mechan-
ism of such photoepoxidation of 1-arylcyclohexenes,18
where the yields of photoepoxides were poor due to several
side reactions, including the ene reaction, i.e., allylic oxida-
tion, and the sensitized isomerization of the substrate into
trans-cycloalkene followed by solvent capture. Our findings
demonstrate that the rigid polycyclic scaffolds improve
photoepoxidation yields dramatically. Obviously, allylic
alcohols or R,β-unsaturated ketones cannot form in these
structures, as there are no easily abstracted allylic hydrogens,
and the photoinduced cis-trans isomerization of the double
bond is not possible either.
The initial light-absorbing chromophore in this system is
undoubtedly the styrene moiety. It is conceivable that the
additional rigidity of the polycyclic network in 5 and 7
prevents the alkene from dissipating its excitation via twist-
ing, thus further improving the overall efficiency of photo-
epoxidation. The ionization potential of 8.94 eV calculated
for the double bond in the chromone series (Figure 2) is
0.27 eV lower than that in the bicyclo[2.2.1] series, indicating
that the double-bond reactivity in 7 toward oxygen can be
exceptionally high.
Conclusions
We have demonstrated that the Diels-Alder adducts of
chromones are capable of photoinduced alkene-arene
[2πþ2π] cycloaddition, furnishing a versatile diene, which
can dimerize or can be introduced into a double-tandem
[4πþ2π] [2πþ2π] [4πþ2π] [2πþ2π] synthetic sequence, fol-
3
3
3
Thermal Dimerization of Dienes 2. One arresting difference
between the chromone-based dienes 2a-c and naphthoqui-
none-based dienes B is that asymmetric 2a-c undergo a
Diels-Alder dimerization when heated at 200-210 °C, yield-
ing a single diastereomer as shown in Scheme 12. The struc-
ture of 9 was proved unambiguously by X-ray analysis.
The diasteroselectivity of Diels-Alder dimerization is
correlated with the computed relative DFT energies of the
Diels-Alder product. The geometries of 16 possible exo
dimers of 2b were optimized at the B3LYP/6-311þG(d,p)
lowed by an acid-catalyzed ring-opening-ring-closure, lead-
ing to expeditious growth of molecular complexity over a few
experimentally simple steps. Additionally, the oxametathesis
products containing a vinyl arene moiety (i.e., acetals 7)
undergo clean and stereoselective photoepoxidation when
irradiated in oxygenated solutions, further enhancing the
value of this method, which contains three high-yielding key
photochemical steps and could conceivably be implemented
in a one-pot fashion. From the stereochemical standpoint,
the appealing feature of this synthetic sequence is that the
initial Diels-Alder step controls the stereochemical outcome
of the entire sequence. As a number of suitable methods have
been developed to achieve enantioselective Diels-Alder
(18) Kojima, M.; Sakuragi, H.; Tokumaru, K. Bull. Chem. Soc. Jpn. 1987,
60, 3331–3336.
J. Org. Chem. Vol. 76, No. 5, 2011 1325

Valiulin et al.
JOCArticle
TABLE 2. Relative Energies of 16 Possible Diastereomers of the exo Dimers
aRelative energy, kcal/mol. bFacial selectivity of cycloaddition: syn (or anti) to the carbonyl/ether functionality for both the diene (first) and
dienophile (second).
1H), 7.55 (ddd, J=8.5, 7.2, 1.8 Hz, 1H), 7.03 (ddd, J=8.0, 7.2, 1.0
Hz, 1H), 6.95 (dd, J=8.5, 1.1 Hz, 1H), 6.58 (m, J=8.5, 5.9 Hz, 1H),
6.48 (ddd, J=8.0, 6.9, 1.4 Hz, 1H), 4.77 (dd, J=3.6, 1.7 Hz, 1H),
3.47 (m, 1H), 3.12 (m, 1H), 1.71-1.65 (m, J=12.8, 9.7, 4.1, 2.5 Hz,
1H), 1.46-1.40 (m, 1H), 1.28-1.22 (m, 1H), 1.20-1.13 (m, 1H).
endo-4,5-Benzo-3-oxatricyclo[6.2.2.02,7]dodeca-4,5-dien-6-
one (1b): from 2.00 g of chromone-3-carboxylic acid (10.5
mmol) and 5.0 mL of 1,3-cyclohexadiene (52.5 mmol) at
FIGURE 3. Calculated Mulliken charges in the butadiene moiety
200 °C (hexane/EtOAc gradient 30:1 f 10:1): 1.67 g (70%).
1H NMR (500 MHz, CDCl3): δ 7.68 (dd, J=7.9, 1.8 Hz, 1H),
of 2a and 2d (with hydrogen charges summed into heavy atoms) at
B3LYP/6-311þG(2d,2p).
7.36 (ddd, J=8.4, 7.1, 1.8 Hz, 1H), 6.95 (ddd, J=8.0, 7.1, 1.0
Hz, 1H), 6.91 (dd, J=8.4, 1.0 Hz, 1H), 6.28 (ddd, J=8.0, 6.5,
cycloadditions, one envisions a straightforward access to
enantiopure structures 6-9.
1.3 Hz, 1H), 6.20 (t, J=7.2 Hz, 1H), 4.95 (dd, J=9.4, 3.3 Hz,
1H), 3.27 (m, 1H), 3.12 (m, 1H), 2.86 (dd, J=9.4, 2.1 Hz, 1H),
1.62 (dddd, J=12.3, 9.5, 3.0, 3.0 Hz, 1H), 1.54 (dddd, J=
12.5, 9.8, 4.6, 1.8 Hz, 1H), 1.37 (dddd, J=12.1, 12.1, 3.6, 3.6
Hz, 1H), 1.27 (dddd, J = 11.8, 11.8, 4.4, 2.8 Hz, 1H). 13C
NMR (125 MHz, CDCl3): δ 192.9, 160.9, 136.3, 134.3, 132.3,
126.8, 120.9, 119.7, 117.8, 79.6, 50.7, 36.9, 34.5, 25.5, 20.5.
exo-4,5-Benzo-3-oxatricyclo[6.2.2.02,7]dodeca-4,9-diene-6-one:
0.67 g (28%). 1H NMR (500 MHz, CDCl3): δ 7.81 (dd,
J=7.8, 1.8 Hz, 1H), 7.46 (ddd, J=8.3, 7.1, 1.8 Hz, 1H), 6.95
(ddd, J=8.0, 7.1, 1.0 Hz, 1H), 6.91 (dd, J=8.4, 1.0 Hz, 1H), 6.49
(m, J=8.4, 6.2 Hz, 1H), 6.28 (m, J=8.1, 6.8, 1.2 Hz, 1H), 4.64 (ddd,
J=11.0, 3.7, 1.1 Hz, 1H), 3.23 (m, 1H), 3.02 (m, 1H), 2.59 (ddd, J=
11.0, 2.8, 1.8 Hz, 1H), 1.92 (m, 1H), 1.48 (m, 1H), 1.17 (m, 2H).
endo-4,5-Benzo-3-oxatricyclo[6.2.1.02,7]undeca-4,9-dien-6one
(1c): from 2.00 g of chromone-3-carboxylic acid (10.5 mmol)
and 3.0 mL of 1,3-cyclopentadiene (36.8 mmol) at 135 °C
(hexane/EtOAc gradient 60:1 f 30:1): 1.23 g (55%). 1H NMR
(500 MHz, CDCl3): δ 7.69 (dd, J=7.9, 1.7 Hz, 1H), 7.36 (ddd,
J=8.4, 7.1, 1.8 Hz, 1H), 6.85 (ddd, J=8.0, 7.2, 1.0 Hz, 1H), 6.74
(dd, J=8.4, 1.0 Hz, 1H), 6.11 (m, 2H), 5.25 (dd, J=9.3, 4.0 Hz,
1H), 3.49 (m, 2H), 3.14 (dd, J=9.2, 3.9 Hz, 1H), 1.46 (ddd, J=
9.2, 1.9, 1.9 Hz, 1H), 1.36 (d, J=9.2 Hz, 1H). 13C NMR (100
MHz, CDCl3): δ 193.4, 160.9, 137.2, 136.5, 134.5, 126.6, 120.6,
119.5, 117.7, 80.0, 49.9, 49.3, 49.0, 45.18. exo-4,5-Benzo-3-
oxatricyclo[6.2.1.02,7]undeca-4,9-dien-6-one: 0.56 g (25%). 1H
Experimental Section
Diels-Alder Adducts (1a-c). General Procedure. A solution
of chromone (1.0 equiv) and 1,3-cyclohexadiene or freshly
distilled 1,3-cyclopentadiene (5.0 equiv) in 15 mL of 1,2-dichloro-
benzene was heated in a screw-cap pressure flask at 200-210 °C
(for 1,3-cyclohexadiene) and 130-140 °C (for 1,3-cyclopenta-
diene) overnight. After the reaction was cooled to room tempera-
ture, the solvent was removed under vacuum. The crude reaction
mixture was purified on a silica gel column using hexane/EtOAc as
the eluent.
endo-4,5-Benzo-7-cyano-3-oxatricyclo[6.2.2.02,7]dodeca-4,5
dien-6-one (1a): from 2.50 g of 3-cyanochromone (14.6 mmol)
and 7.0 mL of 1,3-cyclohexadiene (73.0 mmol) at 200 °C
(hexane/EtOAc gradient 20:1 f 5:1): 2.19 g (60%). 1H NMR
(500 MHz, CDCl3): δ 7.69 (dd, J=7.9, 1.8 Hz, 1H), 7.45 (ddd,
J=8.5, 7.2, 1.8 Hz, 1H), 6.94 (t, J=7.5 Hz, 1H), 6.80 (ddd, J=
8.0, 7.1, 1.1 Hz, 1H), 6.26 (dd, J=8.3, 1.1 Hz, 1H), 6.14 (t, J=
7.3 Hz, 1H), 5.06 (ddd, J=7.9, 6.4, 1.2 Hz, 1H), 3.50 (d, J=
2.8 Hz, 1H), 3.12 (m, 1H), 2.15 (m, 1H), 1.75 (m, 1H), 1.38 (m,
2H). 13C NMR (100 MHz, CDCl3): δ 184.4, 159.8, 137.7,
133.6, 132.1, 127.6, 121.9, 120.1, 118.3, 118.1, 82.9, 50.4,
39.7, 37.1, 21.3, 21.1. exo-4,5-Benzo-7-cyano-3-oxatricyclo-
[6.2.2.02,7]dodeca-4,5-dien-6-one: δ 7.85 (dd, J=8.0, 1.7 Hz,
1326 J. Org. Chem. Vol. 76, No. 5, 2011

Valiulin et al.
JOCArticle
NMR (500 MHz, CDCl3): δ 7.78 (dd, J=7.9, 1.7 Hz, 1H), 7.42
(ddd, J=8.6, 7.1, 1.7 Hz, 1H), 6.92 (ddd, J=8.0, 7.1, 1.0 Hz, 1H),
6.88 (dd, J=8.4, 1.0 Hz, 1H), 6.44 (dd, J=5.7, 3.0 Hz, 1H), 6.10
(dd, J=5.7, 3.2 Hz, 1H), 4.61 (ddd, J=8.0, 1.3, 1.3 Hz, 1H), 3.36
(m, 1H), 3.27 (m, 1H), 2.58 (dd, J=8.0, 1.8 Hz, 1H), 1.67 (d, J=
9.4 Hz, 1H), 1.55 (m, J=9.4, 1.6 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 192.9, 160.9, 141.8, 136.6, 133.8, 127.1, 121.0, 120.1,
118.1, 80.1, 51.7, 48.4, 48.4, 45.3.
2.1 Hz, 1H), 3.13 (ddd, J=6.4, 1.8, 1.8 Hz, 1H), 2.83 (m, 1H),
2.68 (ddd, J=7.4, 5.8, 1.5 Hz, 1H), 2.3 (m, 1H), 2.16 (m, 1H),
2.11 (dd, J=7.6, 5.0 Hz, 1H), 2.04-1.94 (m, 1H), 1.93-1.85
(m, 4H), 1.54-1.46 (m, 1H). 13C NMR (100 MHz, CDCl3): δ
203.2, 200.5, 147.5, 136.1, 133.4, 133.2, 131.4, 129.99,
128.94, 117.3, 91.3, 83.4, 57.8, 52.6, 40.2, 36.6, 35.4, 35.1,
33.8, 33.8, 21.9, 16.2, 14.3. HRMS (ESI): calcd for
C
25H21NNaO3þ (MNaþ) 406.1414, found 406.1425.
General Procedure for Photoinduced [2πþ2π] Intramolecular
Cyclization. An approximately 10 mM solution of an endo
precursor 1 in benzene (unless otherwise noted) was irradiated
in Pyrex reaction vessels in a Rayonet reactor equipped with
RPR-3500 UV lamps (broadband 300-400 nm UV source with
peak emission at 350 nm) for 24-48 h. Irradiation resulted in a
quantitative conversion to 2, which can be used without further
purification.
1R(S),2S(R),11S(R),12R(S),16R(S)-16-Benzoyl-3-oxahepta-
cyclo[10.2.2.12,5.18,11.02,11.04,9.017,18]octadec-13-en-10-one (3b):
from 2.24 g of 2b (9.9 mmol) and 2.16 g of 3-chloropropiophe-
none (12.8 mmol) at 140 °C (hexane/EtOAc gradient 20:1 f
1
10:1): 1.24 g (35%). H NMR (500 MHz, CDCl3): δ 8.11 (m,
2H), 7.51 (t, J=7.3 Hz, 1H), 7.44 (m, 2H), 6.37 (ddd, J=8.3, 7.2,
1.2 Hz, 1H), 6.17 (dd, J=8.5, 6.1 Hz, 1H), 4.65 (ddd, J=7.7, 4.2,
1.5 Hz, 1H), 4.50 (ddd, J=9.7, 4.8, 2.1 Hz, 1H), 3.05 (ddd, J=
6.4, 1.7, 1.7 Hz, 1H), 2.78 (m, 1H), 2.62-2.57 (m, 2H), 2.02 (m,
1H), 2.01-1.96 (m, 2H), 1.93 (m, 1H), 1.87 (ddd, J=12.9, 4.8,
3.2 Hz, 1H), 1.84-1.79 (m, 1H), 1.77-1.70 (m, 1H), 1.69-1.63
(m, 1H), 1.44-1.38 (m, 1H). 13C NMR (100 MHz, CDCl3): δ
213.8, 201.3, 136.4, 133.2, 132.9, 131.5, 129.1, 128.8, 90.2, 79.9,
58.1, 52.1, 41.3, 40.4, 35.8, 35.3, 35.1þ, 34.0, 31.2, 22.2, 18.1, 15.3.
HRMS (ESI): calcd for C24H23O3 (MHþ) 359.1642, found
359.1657.
15-Cyano-13-oxahexacyclo[6.4.4.0.02,7.03,14.06,15]hexadec-9,-
11-dien-16-one (2a): from 2.23 g of 1a (8.9 mmol) in 1.0 L of
benzene, irradiation for 24 h (hexane/EtOAc gradient 15:1 f
5:1): 1.23 g (55%). 1H NMR (400 MHz, CDCl3): δ 6.00 (dd, J=
9.6, 5.8 Hz, 1H), 5.95 (ddd, J=9.8, 5.8, 1.0 Hz, 1H), 5.54 (d, J=
9.6 Hz, 1H), 5.45 (d, J=9.8 Hz, 1H), 4.75 (d, J=4.2 Hz, 1H), 3.43
(ddd, J=8.0, 5.6, 1.4 Hz, 1H), 2.86 (dd, J=8.3, 5.0 Hz, 1H), 2.30
(m, 1H), 2.24 (m, 1H), 2.00-1.91 (m, 3H), 1.60-1.54 (m, 1H).
13C NMR (100 MHz, CDCl3): δ 199.5, 126.3, 125.7, 121.7,
120.5, 117.3, 84.0, 82.0, 56.4, 53.3, 50.7, 43.0, 36.5, 36.0,
1R(S),2S(R),10S(R),11R(S),15R(S)-15-Benzoyl-3-oxahepta-
cyclo[9.2.2.12,5.17,10.02,10.04,8.016,17]heptadec-12-en-9-one (3c):
from 0.92 g of 2c (4.3 mmol) and 0.95 g of 3-chloropropiophe-
none (5.6 mmol) at 140 °C (hexane/EtOAc gradient 20:1 f
15.8, 14.2. HRMS (ESI): calcd for C16H13NNaO2 (MNaþ)
þ
274.0838, found 274.0835.
13-Oxahexacyclo[6.4.4.0.02,7.03,14.06,15]hexadec-9,11-dien-
16-one (2b): from 1.50 g of 1b (6.6 mmol) in 1.0 L of benzene,
irradiation for 24 h (hexane/EtOAc gradient 20:1 f 10:1):
1.05 g (70%). 1H NMR (500 MHz, CDCl3): δ 5.95-5.88 (m,
2H), 5.53 (d, J=9.4 Hz, 1H), 5.42 (d, J=9.7 Hz, 1H), 4.60 (dd,
J=8.0, 4.2 Hz, 1H), 3.38 (ddd, J=7.8, 5.6, 1.5 Hz, 1H), 2.78
(ddd, J=8.1, 4.8, 2.2 Hz, 1H), 2.73 (ddd, J=8.1, 3.4, 2.4 Hz,
1H), 2.09 (m, 1H), 1.94 (m, 1H), 1.92-1.86 (m, 1H),
1.82-1.75 (m, 1H), 1.73-1.66 (m, 1H), 1.52-1.45 (dddd, J=
14.0, 11.8, 5.7, 2.5 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 210.1,
125.8, 124.8, 122.6, 122.3, 83.3, 78.7, 57.4, 52.7, 52.3, 45.1, 36.1,
31.3, 17.7, 15.2.
1
10:1): 0.54 g (36%). H NMR (500 MHz, CDCl3): δ 8.12 (m,
2H), 7.52 (t, J=7.4 Hz, 1H), 7.44 (m, 2H), 6.37 (ddd, J=8.3, 7.2,
1.3 Hz, 1H), 6.16 (dd, J=8.5, 6.1 Hz, 1H), 5.10 (ddd, J=8.0, 3.7,
1.6 Hz, 1H), 4.46 (ddd, J=9.6, 4.9, 2.2 Hz, 1H), 3.10 (ddd, J=
6.4, 1.8, 1.8 Hz, 1H), 2.81 (m, 1H), 2.79-2.74 (m, 2H), 2.63 (m,
1H), 2.50 (ddd, J=8.0, 4.3, 1.9 Hz, 1H), 2.13 (m, 1H), 1.96 (ddd,
J=12.7, 9.7, 2.4 Hz, 1H), 1.88 (ddd, J=12.8, 4.9, 3.2 Hz, 1H),
1.79 (d, J=11.4 Hz, 1H), 1.56 (d, J=11. 4 Hz, 1H). 13C NMR
(125 MHz, CDCl3): δ 214.6, 201.3, 136.4, 133.4, 133.0, 131.6,
129.1, 128.8, 90.6, 88.1, 57.2, 54.3, 47.9, 47.2, 42.1, 40.3, 38.2,
36.3, 35.9, 34.2, 22.5. HRMS (ESI): calcd for C23H21O3þ (MHþ)
345.1485, found 345.1479.
12-Oxahexacyclo[5.4.4.0.02,6.03,13.05,14]pentadeca-8,10-
dien-15-one (2c): from 0.89 g of 1c (4.2 mmol) in 1.0 L of
benzene, irradiation for 24 h: 0.88 g (90%). H NMR (500
General Procedure for Preparation of the Paterno-Buchi
Adducts 4a-c. An approximately 1-3 mM solution of a pre-
cursor 3 in benzene was irradiated in Pyrex reaction vessels in a
Rayonet reactor equipped with RPR-3500 UV lamps
(broadband 300-400 nm UV source with peak emission at
350 nm) for 48-72 h. Irradiation resulted in a quantitative
conversion to 4, which were used without further purification.
NOTE: strained polycyclic oxetanes 4 are not stable on silica gel,
which induces oxametathesis.
ꢀ
€
1
MHz, CDCl3): δ 6.00 (dd, J=9.5, 5.7 Hz, 1H), 5.95 (ddd, J=
9.9, 5.7, 1.0 Hz, 1H), 5.63 (d, J=9.5 Hz, 1H), 5.49 (d, J=9.9
Hz, 1H), 5.02 (dd, J=8.4, 4.0 Hz, 1H), 3.42 (ddd, J=7.8, 6.0,
1.3 Hz, 1H), 2.91 (m, 1H), 2.82 (ddd, J=8.0, 5.4, 1.9 Hz, 1H),
2.75 (m, 1H), 2.61 (ddd, J=8.4, 4.3, 1.9 Hz, 1H), 1.80 (d, J=
11.3 Hz, 1H), 1.51 (d, J=11.5 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ 211.5, 125.4, 124.6, 122.3, 122.3, 87.1, 83.1, 56.9,
56.3, 55.0, 48.4, 46.3, 42.6, 33.8.
General Procedure for Preparation of the Diels-Alder Adducts
3a-c. A solution of 2 (1.0 equiv) and 3-chloropropiophenone
(1.3 equiv) in 10 mL of pyridine was heated in a screw-cap
pressure flask at 130-140 °C overnight. After the reaction was
cooled to room temperature, the solvent was removed on a high-
vacuum pump. The crude reaction mixture was purified on a
silica gel flash column using hexane/EtOAc (or EtOH) as an
eluent. NOTE: To avoid epimerization of the benzoyl group, the
column was pretreated with 2 mL of pyridine.
9-Cyano-15-phenyl-3,14-dioxanonacyclo[10.4.2.12,5.18,11.02,11
.
04,9.013,16.015,18.019,20]icosan-10-one (4a): from 1.50 g of 3a
(3.9 mmol) in 1.5 L of benzene, irradiation for 72 h: >85%.
1H NMR (500 MHz, CDCl3): δ 7.38-7.36 (m, 4H), overlaps
7.36-7.32 (m, 1H), 4.80 (m, 1H), 4.72 (d, J=4.0 Hz, 1H), 3.50
(dddd, J=5.5, 3.5, 1.7, 1.7 Hz, 1H), 2.95-2.91 (m, 2H), 2.74
(ddd, J=6.5, 1.8, 1.8 Hz, 1H), 2.54 (dd, J=7.6, 5.2 Hz, 1H), 2.36
(m, 1H), 2.26 (m, 1H), 2.12 (ddd, J = 6.2, 6.2, 1.3 Hz, 1H),
2.01-1.90 (m, 4H), 1.81 (ddd, J = 13.2, 6.7, 1.9 Hz, 1H),
1.63-1.56 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 202.0,
136.3, 129.1, 128.8, 127.2, 117.5, 101.1, 90.4, 81.5, 81.4, 56.8,
54.6, 53.2, 44.2, 39.6, 38.6, 37.0, 36.1,þ35.4, 32.3, 31.9, 15.9, 14.1.
HRMS (ESI): calcd for C25H22NO3 (MHþ) 384.1594, found
384.1586.
1R(S),2S(R),11S(R),12R(S),16R(S)-16-Benzoyl-9-cyano-3-
oxaheptacyclo[10.2.2.12,5.18,11.02,11.04,9
.
017,18]octadec-13-
en-10-one (3a): from 1.13 g of 2a (4.5 mmol) and 1.00 g of
3-chloropropiophenone (5.9 mmol) at 140 °C (hexane/
EtOAc gradient 20:1 f 1:1): 0.86 g (50%). 1H NMR (400
MHz, CDCl3): δ 8.06 (m, 2H), 7.54 (t, J=7.3 Hz, 1H), 7.45
(m, 2H), 6.39 (ddd, J=8.3, 7.2, 1.3 Hz, 1H), 6.19 (dd, J=8.3,
6.3 Hz, 1H), 4.80 (d, J=4.0 Hz, 1H), 4.43 (ddd, J=9.6, 4.8,
15-Phenyl-3,14-dioxanonacyclo[10.4.2.12,5.18,11.02,11.04,9
.
013,16.015,18.019,20]icosan-10-one (4b): from 1.20 g of 3b (3.3
mmol) in 1.5 L of benzene, irradiation for 72 h: >85%. H
1
NMR (500 MHz, CDCl3): δ 7.40-7.35 (m, 4H), overlaps
7.35-7.31 (m, 1H), 4.82 (m, 1H), 4.57 (dd, J=8.0, 4.1 Hz,
J. Org. Chem. Vol. 76, No. 5, 2011 1327

Valiulin et al.
JOCArticle
1H), 3.49 (dddd, J=5.5, 3.6, 1.8, 1.8 Hz, 1H), 2.91 (d, J=6.4
Hz, 1H), 2.86 (m, J=7.6, 5.6, 1.2 Hz, 1H), 2.69 (ddd, J=6.5,
1.8, 1.8 Hz, 1H), 2.63 (ddd, J = 8.0, 3.3, 2.4 Hz, 1H), 2.42
(ddd, J=7.5, 5.1, 2.3 Hz, 1H), 2.12 (m, 1H), 2.08 (m, J=6.2,
1.3 Hz, 1H), 2.03-2.00 (m, 1H), 1.99 (m, 1H), 1.86-1.68 (m,
4H), 1.51 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 213.3,
136.7, 128.9, 128.7, 127.2, 101.2, 89.5, 82.1, 77.9, 57.6, 54.8,
52.5, 44.4, 40.6, 38.7, 37.2, 35.7, 33.5, 32.1, 31.0, 17.8, 15.1.
HRMS (ESI): calcd for C24H23O3þ (MHþ) 359.1642, found
359.1629.
rule, this method produces a mixture of the alkene 5 and the
cyclopropane 6.
B. (B1) BF3- or (B2) HCl-Catalyzed Formation of Aldehydes 6.
BF3 Et2O (small molar excess per heteroatom in 4) or a >10-
3
fold excess of HCl (4.0 M solution in dioxane) was added to a
solution of oxetane 4 in dichloromethane (DCM), stirred over-
night at room temperature, and washed twice with a 5%
solution of NaOH and water. The crude aldehyde 6 was purified
on a silica gel column using hexane/ethyl acetate as an eluent.
For cyano-containing aldehydes a hexane/ethanol was used as the
eluent.
14-Phenyl-3,13-dioxanonacyclo[9.4.2.12,5.17,10.02,10.04,8.012,15
.
014,17.018,19]nonadecan-9-one (4c): from 0.55 g of 3c (1.6 mmol)
in 1.5 L of benzene, irradiation for 48 h: >90%. 1H NMR (500
MHz, CDCl3): δ 7.40-7.35 (m, 4H), overlaps 7.35-7.31 (m, 1H),
5.04 (dd, J=8.2, 4.1 Hz, 1H), 4.80 (ddd, J=3.6, 1.8, 0.8 Hz, 1H),
3.48 (dddd, J=5.5, 3.6, 1.8, 1.8 Hz, 1H), 3.03 (t, J=6.7 Hz, 1H),
2.89 (m, 2H), 2.74 (ddd, J=6.6, 1.8, 1.8 Hz, 1H), overlaps
2.72 (m, 1H), 2.61-2.57 (m, 1H), overlaps 2.57-2.54 (ddd,
J=8.2, 4.2, 1.9 Hz, 1H), 2.10 (ddd, J=6.2, 6.2, 1.4 Hz, 1H),
1.91 (dd, J=12.8, 1.8 Hz, 1H), 1.87 (d, J=11.3 Hz, 1H), 1.79
(ddd, J=12.9, 6.7, 1.9 Hz, 1H), 1.65 (d, J=11.3 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 214.0, 136.9, 128.9, 128.7, 127.2, 101.0, 90.1,
86.8, 81.9, 56.5, 54.8, 54.7, 49.3, 47.0, 44.0, 42.3, 38.9, 37.2,
C. Oxametathesis in Alcohols Yielding Acetals 7. Oxetane 4
was dissolved in a 5% HCl solution in methanol, 4-bromobenzyl
alcohol/DCM, or ethylene glycol/THF and stirred for 24 h. The
resulting mixture was evaporated, dissolved in DCM, and
washed twice with a 5% solution of NaOH and water. The
crude acetals 7 were purified on a silica gel column using hexane/
ethyl acetate as an eluent. For cyano-containing acetals hexane/
ethanol was used as the eluent. To avoid the hydrolysis of the
cyano-containing acetals, 2 mL of pyridine was passed through
the column before purification.
1S(R),8S(R),9R(S),12R(S),13R(S)-15-Cyano-14-oxo-11-phe-
nyl-17-oxaheptacyclo[6.5.4.19,12.01,8.02,7.03,15.06,16]octadec-
10-ene-13-carboxaldehyde (5a): (method A) from 217 mg
(0.56 mmol) of 4a and 0.28 mL of HCl (4.0 M, 1.13 mmol)
in DCM: forms a mixture of 5a and 6a (56% and 18% by
NMR). 1H NMR (500 MHz, CDCl3): δ 9.90 (s, 1H), 7.47 (d,
J=7.4 Hz, 2H), 7.34 (t, J=7.2 Hz, 2H), 7.29 (t, J=7.3 Hz,
1H), 6.30 (d, J=3.4 Hz, 1H), 4.70 (d, J=4.1 Hz, 1H), 3.82 (dd,
J=5.8, 4.7 Hz, 1H), 3.39 (d, J=4.5 Hz, 1H), 2.86 (ddd, J=8.5,
5.7, 1.5 Hz, 1H), 2.82 (dd, J=4.8, 3.6 Hz, 1H), 2.64 (dd, J=
8.6, 4.8 Hz, 1H), 2.43-2.38 (m, 2H), 2.19 (m, 1H), 2.00-1.85
(m, 3H), 1.77 (d, J=11.2 Hz, 1H), 1.57-1.50 (m, 1H). 13C
NMR (125 MHz, CDCl3): δ 202.6, 200.1, 148.3, 134.5, 129.1,
129.0, 128.2, 126.6, 117.4, 87.8, 82.4, 56.6, 51.7, 47.0, 43.6,
40.5, 39.4, 37.5, 36.1, 35.0, 33.5, 16.0, 14.3. HRMS (ESI):
calcd for C25H22NO3þ (MHþ) 384.1594, found 384.1590.
1S(R),8S(R),9R(S),12R(S),13R(S)-14-Oxo-11-phenyl-17-ox-
aheptacyclo[6.5.4.19,12.01,8.02,7.03,15.06,16]octadec-10-ene-13-
carboxaldehyde (5b): (method A) from 30 mg (0.08 mmol) of
4b and 43 μL of HCl (4.0 M, 0.17 mmol) in DCM: forms an
inseparable mixture of 5b, 5b0 (epimer), and 6b (39%, 4%,
and 24% by NMR).
1S(R),2R(S),5R(S),6R(S),7S(R)-16-Oxo-4-phenyl-13-oxahe-
ptacyclo[5.5.4.12,5.01,7.08,12.09,15.011,14]heptadec-3-ene-6-ca-
rboxaldehyde (5c): (method A) from 140 mg (0.41 mmol) of 4c
and 0.20 mL of HCl (4.0 M, 0.81 mmol) in DCM: forms an
inseparable mixture of 5c and 6c. 1H NMR (500 MHz,
CDCl3): δ 9.45 (d, J=1.1 Hz, 1H), 7.44 (d, J=7.2 Hz, 2H), 7.31
(t, J=7.5 Hz, 2H), 7.25 (m, 1H) overlaps with CDCl3, 6.44 (d,
J=3.3 Hz, 1H), 4.96 (dd, J=8.2, 4.1 Hz, 1H), 3.73 (dd, J=5.7,
4.3 Hz, 1H), 3.20 (dd, J=8.1, 5.9 Hz, 1H), 2.93 (dd, J=5.0,
3.4 Hz, 1H), 2.85 (m, 1H), 2.81 (dd, J = 4.2, 1.0 Hz, 1H),
2.63-2.57 (m, 2H), 2.44 (ddd, J=8.4, 5.3, 2.3 Hz, 1H), 2.38
(ddd, J=11.0, 5.7, 5.0 Hz, 1H), 1.88 (d, J=11.6 Hz, 1H), 1.85
(d, J=11.4 Hz, 1H), 1.67 (d, J=11.4 Hz, 1H).
36.2, 35.7, 32.6. HRMS (ESI): calcd for C23H21O3 (MHþ)
þ
345.1485, found 345.1472.
1S(R),2R(S),11S(R),12R(S),15S(R),16S(R)-15,16-Dibenzo-
yl-9-cyano-3-oxaheptacyclo[10.2.2.12,5.18,11.02,11.04,9.017,18
]
octadec-13-en-10-one (3e): from 0.10 g of 2a (0.4 mmol) and
0.19 g of trans-1,2-dibenzoylethylene (0.8 mmol) at 200 °C
(hexane/EtOAc gradient 10:1 f 1:1): <10%. 1H NMR (400
MHz, CDCl3): δ 8.31 (m, 2H), 7.84 (m, 2H), 7.57 (t, J=7.3
Hz, 1H), 7.53-7.47 (m, 3H), 7.42 (m, 2H), 6.60 (ddd, J=8.4,
7.3, 1.4 Hz, 1H), 6.17 (dd, J=8.0, 6.4 Hz, 1H), 5.48 (dd, J=
5.6, 1.8 Hz, 1H), 4.67 (d, J=4.0 Hz, 1H), 4.20 (dd, J=5.6, 2.5
Hz, 1H), 3.39 (ddd, J=7.2, 2.4, 0.7 Hz, 1H), 3.22 (ddd, J=
6.3, 1.5, 1.5 Hz, 1H), 2.57 (ddd, J=7.4, 5.8, 1.5 Hz, 1H), 2.25
(m, 1H), 2.07 (dd, J=7.7, 4.9 Hz, 1H), 1.97-1.86 (m, 2H),
1.79 (dd, J=8.8, 3.5 Hz, 1H), overlaps 1.78-1.75 (m, 1H),
1.48-1.39 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 201.28,
199.94, 176.9, 137.4, 135.8, 133.8, 133.5, 132.4, 131.7, 129.4,
129.0, 128.7, 128.6, 117.2, 90.1, 83.8, 57.5, 52.4, 45.2, 41.0,
40.4, 39.7, 36.6, 34.5, 34.3, 33.7, 16.1, 14.1. HRMS (ESI):
calcd for C32H26NO4þ (MHþ) 488.1856, found 488.1855.
1R(S),2S(R),10R(S),11S(R),14S(R),15S(R)-14,15-Dibenzo-
ylheptacyclo[9.2.2.12,5.17,10.02,10.04,8.016,17]heptadec-12-ene-
3,9-dione (3f): from 0.16 g of 2d (0.7 mmol) and 0.26 g of
trans-1,2-dibenzoylethylene (1.1 mmol) at 200 °C (recrys-
tallization from DCM/hexane): 0.08 g, < 25%. 1H NMR
(400 MHz, CDCl3): δ 8.36 (d, J=7.6 Hz, 2H), 8.02 (d, J=7.6
Hz, 2H), 7.56-7.43 (m, 6H), 6.76 (t, J=7.5 Hz, 1H), 6.20 (t,
J=7.3 Hz, 1H), 5.12 (dd, J=6.8, 1.5 Hz, 1H), 4.17 (dd, J=6.8,
2.1 Hz, 1H), 3.3 (d, J=6.8 Hz, 1H), 3.14 (d, J=6.3 Hz, 1H),
2.83 (m, 1H), 2.72 (m, 1H), 2.64 (m, 2H), 2.61-2.52 (m, 2H),
1.88 (d, J=11.5 Hz, 1H), 1.69 (d, J=11.5 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 211.8, 209.4, 200.4, 197.9, 137.8, 135.9,
135.6, 133.4, 132.4, 131.0, 129.6, 128.9, overlaps 128.9,
128.5, 55.3, 55.0, 53.6, 52.9, 46.2, 43.6, 43.2, 42.5, 41.9,
1S(R),8S(R),9R(S),10S(R),13R(S)-16-Cyano-17-oxo-11-phe-
.
nyl-14-oxaoctacyclo[6.5.4.110,13.01,8
decane-9-carboxaldehyde (6a): (method B1) from 390 mg (1.02
02,7.09,11.03,15.06,16]octa-
þ
40.8, 40.0, 35.7, 35.0. HRMS (ESI): calcd for C31H25O4
(MHþ) 461.1747, found 461.1739.
mmol) of 4a and 2.00 mL of BF3 Et2O (48%, 15.86 mmol) in
3
DCM (hexane/EtOH 10:1, then DCM/MeOH 2:1): 223 mg
(57%); (method B2) from 200 mg (0.52 mmol) of 4a and 2.61
mL of HCl (4.0 M, 10.43 mmol) in DCM (hexane/EtOH 10:1,
General Procedures for Oxametathesis in the Chromone (a-c)
Series. A. HCl-Catalyzed Formation of Aldehydes 5. To a solu-
tion of oxetane 4 in DCM was added a catalytic amount of
HCl (4.0 M solution in dioxane). The resulting reaction mixt-
ure was stirred at room temperature for 24 h, washed twice
with a 5% solution of NaOH and water, concentrated, and
purified on a silica gel column using hexane/ethyl acetate (or
hexane/ethanol for the cyano-containing products a). As a
1
then DCM/MeOH 2:1): 278 mg (71%). H NMR (500 MHz,
CDCl3): δ 8.41 (s, 1H), 7.38-7.30 (m, 5H), 4.74 (d, J=4.1 Hz,
1H), 3.16 (ddd, J=7.8, 5.9, 1.3 Hz, 1H), 2.89 (d, J=2.9 Hz, 1H),
2.82 (m, 1H), 2.69 (dd, J=7.9, 5.0 Hz, 1H), 2.52 (m, 1H), 2.27-2.18
(m, 5H), 2.11-2.04 (m, 1H), 2.02-1.96 (m, 2H), 1.72-1.65
1328 J. Org. Chem. Vol. 76, No. 5, 2011

Valiulin et al.
JOCArticle
þ
(m, 1H). 13C NMR (125 MHz, CDCl3): δ 200.4, 198.8, 137.6,
129.3, 129.0, 128.0, 117.4, 89.4, 82.7, 54.4, 52.4, 42.5, 40.1,
39.9, 37.7, 35.8, 35.7, 35.6, 34.6, 29.4, 28.2, 15.9, 14.3. HRMS
(ESI): calcd for C25H22NO3þ (MHþ) 384.1594, found 384.1592.
1S(R),8S(R),9R(S),10S(R),13R(S)-17-Oxo-11-phenyl-14-ox-
aoctacyclo[6.5.4.110,13.01,8.02,7.09,11.03,15.06,16]octadecane-9-
carboxaldehyde (6b): (method B1) from 40 mg (0.11 mmol) of
34.3, 30.6, 18.0, 15.5. HRMS (ESI): calcd for C26H28NaO4
(MNaþ) 427.1880, found 427.1898.
1S(R),8S(R),9R(S),12R(S),13R(S)-15-Cyano-13-(1,3-dioxo-
lan-2-yl)-11-phenyl-17-oxaheptacyclo[6.5.4.19,12.01,8.02,7.03,15
.
06,16]octadec-10-en-14-one (7a0): (method C) from 190 mg
(0.50 mmol) of 4a and 1.24 mL of HCl (4.0 M, 4.95 mmol)
in ethylene glycol/THF mixture (10/3) (hexane/EtOH 20:1 f
10:1): 148 mg (70%). 1H NMR (500 MHz, CDCl3): δ 7.63 (d,
J=7.3 Hz, 2H), 7.33 (t, J=7.5 Hz, 2H), 7.25 (t, J=7.4 Hz, 1H)
overlaps with CDCl3, 6.44 (d, J=3.6 Hz, 1H), 4.67 (d, J=4.1
Hz, 1H), 4.46 (d, J=9.1 Hz, 1H), 3.92-3.88 (m, 1H), 3.65 (m,
2H), 3.55-3.51 (m, 1H), 3.34 (dd, J=5.7, 4.8 Hz, 1H), 2.82
(ddd, J=8.4, 5.7, 1.4 Hz, 1H), 2.75 (dd, J=4.7, 3.8 Hz, 1H),
2.70 (dd, J=9.1, 4.6 Hz, 1H), 2.39 (dd, J=8.4, 4.8 Hz, 1H),
2.27 (m, 2H), 2.17 (m, 1H), 1.97-1.86 (m, 3H), 1.65 (d, J=11.1
Hz, 1H), 1.52-1.45 (m, 1H) overlaps with HOD. 13C NMR
(125 MHz, CDCl3): δ 203.1, 148.4, 135.4, 128.6, 128.2, 128.0,
126.4, 117.9, 103.6, 87.6, 82.3, 65.0, 64.5, 57.2, 52.0, 43.4,
40.5, 38.7, 38.3, 38.2, 35.6, 35.þ2, 33.0, 16.1, 14.5. HRMS
(ESI): calcd for C27H25NNaO4 (MNaþ) 450.1676, found
450.1678.
4b and 0.20 mL of BF3 Et2O (48%, 1.59 mmol) in DCM
3
(hexane/EtOH 10:1, then DCM/MeOH 2:1): 18 mg (45%).
1H NMR (500 MHz, CDCl3): δ 8.39 (s, 1H), 7.30 (m, 4H),
7.24 (m, 1H) overlaps with CDCl3, 4.56 (dd, J=8.1, 4.3 Hz,
1H), 3.05 (ddd, J=7.8, 5.8, 1.3 Hz, 1H), 2.81 (d, J=2.9 Hz,
1H), 2.66 (ddd, J = 8.2, 3.4, 2.2 Hz, 1H), 2.56 (ddd, J =
7.4, 4.9, 2.3 Hz, 1H), 2.51 (d, J=12.3 Hz, 1H), 2.43 (m, 1H),
2.19-2.13 (m, 4H), 2.06 (m, 1H), 1.94-1.87 (m, 1H),
1.84-1.72 (m, 2H), 1.57 (m, 1H). 13C NMR (125 MHz,
CDCl3): δ 199.5, 197.4, 138.4, 129.1, 129.1, 127.7, 88.5,
79.4, 55.2, 51.7, 42.4, 41.3, 40.1, 38.1, 36.0, 35.93, 35.91,
30.8, 29.7, 28.3, 17.8, 15.4. HRMS (ESI): calcd for
C
24H23O3þ (MHþ) 359.1642, found 359.1630.
1S(R),2R(S),3S(R),6R(S),7S(R)-13-Oxo-4-phenyl-16-oxao-
ctacyclo[5.5.4.13,6.01,7.02,4.08,12.09,15.011,14]heptadecane-2-car-
boxaldehyde (6c). Method B1 and method B2 failed. Under
these conditions oxetane 4c produced a complicated mixture
of inseparable compounds.
1S(R),8S(R),9R(S),12R(S),13R(S)-13-(1,3-Dioxolan-2-yl)-
11-phenyl-17-oxaheptacyclo[6.5.4.19,12.01,8.02,7.03,15.06,16]oc-
tadec-10-en-14-one (7b0): (method C) from 180 mg (0.50
mmol) of 4b and 0.32 mL of HCl (4.0 M, 1.26 mmol) in an
ethylene glycol/THF mixture (10:3) (hexane/EtOAc 25:1): 158 mg
(78%). 1H NMR (500 MHz, CDCl3): δ 7.64 (d, J=7.3 Hz, 2H),
7.32 (t, J=7.6 Hz, 2H), 7.24 (t, J=7.3 Hz, 1H) overlaps with CDCl3,
6.46 (d, J=3.6 Hz, 1H), 4.53 (ddd, J=8.1, 4.2, 1.4 Hz, 1H), 4.47 (d,
J=9.1 Hz, 1H), 3.92-3.87 (m, 1H), 3.66-3.59 (m, 2H), 3.53-3.49
(m, 1H), 3.32(dd,J=5.7, 4.7 Hz, 1H), 2.76 (ddd, J=8.2, 5.6, 1.5 Hz,
1H), 2.72 (dd, J=4.6, 3.9 Hz, 1H), 2.68 (dd, J=9.1, 4.6 Hz, 1H),
2.63 (ddd, J=8.2, 3.3, 2.1 Hz, 1H), 2.28 (ddd, J=8.3, 4.7, 2.1 Hz,
1H), 2.24 (ddd, J=11.0, 5.5, 5.5 Hz, 1H), 2.04 (m, 1H), 1.91 (m,
1H), 1.88-1.81 (m, 1H), 1.79-1.72 (m, 1H), 1.70-1.63 (m, 1H)
overlaps with 1.66 (d, J=10.8 Hz, 1H), 1.45-1.38 (dddd, J=13.8,
11.8, 5.9, 2.5 Hz, 1H). 13C NMR (125 MHz, CDCl3):δ213.2, 148.1,
135.9, 128.6, 128.5, 127.9, 126.4, 104.0, 86.6, 79.0, 64.8, 64.3, 57.7,
51.1, 43.9, 41.7, 39.0, 38.5, 37.6, 35.4, 34.0, 30.2, 18.0, 15.5. HRMS
(ESI): calcd for C26H27O4þ (MHþ) 403.1904, found 403.1903.
1S(R),8S(R),9R(S),12R(S),13R(S)-15-Cyano-13-bis(4-brom-
1S(R),8S(R),9R(S),12R(S),13R(S)-15-Cyano-13-dimethoxy-
methyl-11-phenyl-17-oxaheptacyclo[6.5.4.19,12.01,8.02,7.03,15
.
06,16]octadec-10-en-14-one (7a): (method C) from 320 mg
(0.83 mmol) of 4a and 3.13 mL of HCl (4.0 M, 12.52 mmol)
in MeOH (hexane/EtOH 10:1, then DCM/MeOH 2:1): 258
mg (59%). 1H NMR (500 MHz, CDCl3): δ 7.51 (d, J=7.4 Hz,
2H), 7.33 (t, J=7.6 Hz, 2H), 7.26 (t, J=7.3 Hz, 1H), 6.28 (d,
J=3.6 Hz, 1H), 4.67 (d, J=4.1 Hz, 1H), 3.84 (d, J=9.7 Hz,
1H), 3.29 (t, J=5.3 Hz, 1H), 2.92 (dd, J=9.7, 4.8 Hz, 1H),
2.87 (s, 3H) overlaps with 2.85 (ddd, J=8.5, 5.8, 1.4 Hz, 1H),
2.79 (s, 3H), 2.72 (dd, J=4.7, 3.8 Hz, 1H), 2.36 (dd, J=8.5,
4.8 Hz, 1H), 2.30 (ddd, J=11.1, 5.9, 5.1 Hz, 1H), 2.18 (m, 1H)
overlaps with 2.15 (m, 1H), 1.96-1.87 (m, 3H), 1.67 (d, J=
11.2 Hz, 1H), 1.54-1.48 (m, 1H). 1H NMR (500 MHz, C6D6):
δ 7.45 (d, J=7.6 Hz, 2H), 7.17 (m, 2H) overlaps with C6D6,
7.08 (t, J=7.4 Hz, 1H), 5.87 (d, J=3.6 Hz, 1H), 4.35 (d, J=4.1
Hz, 1H), 3.82 (d, J=9.3 Hz, 1H), 3.18-3.13 (m, 2H), 2.70
(s, 3H), 2.66 (s, 3H), 2.55 (dd, J=4.7, 3.8 Hz, 1H), 2.19 (ddd,
J=8.5, 5.7, 1.4 Hz, 1H), 2.05 (ddd, J=10.9, 5.4, 5.4 Hz, 1H),
2.01 (m, 1H), 1.92 (dd, J=8.5, 4.8 Hz, 1H), 1.73 (d, J=11.1
Hz, 1H), 1.66-1.59 (m, 1H), 1.53 (m, 1H), 1.31-1.26 (m, 2H),
0.96-0.89 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 203.3,
149.5, 136.1, 128.6, 128.5, 128.2, 126.7, 117.8, 102.0,
88.0, 82.2, 57.9, 53.1, 52.2, 50.1, 43.6, 40.5, 39.3, 38.3,
35.9, 35.2, 34.8, 33.2, 16.1, 14.4. HRMS (ESI): calcd for
obenzyloxymethyl)-11-phenyl-17-oxaheptacyclo[6.5.4.19,12.01,8
.
02,7.03,15.06,16]octadec-10-en-14-one (7b00): (method C) from 200 mg
(0.56 mmol) of 4b, 0.37 g (1.95 mmol) of 4-bromobenzyl alcohol,
and 0.35 mL of HCl (4.0 M, 1.39 mmol) in DCM (hexane/EtOAc
1
20:1 f 10:1): 215 mg (54%). H NMR (500 MHz, CDCl3): δ
7.46-7.43 (m, 4H), 7.28 (d, J=8.4 Hz, 2H), 7.22-7.17 (m, 3H),
7.09 (d, J=8.4 Hz, 2H), 6.87 (d, J=8.4 Hz, 2H), 6.27 (d, J=3.5 Hz,
1H), 4.52 (ddd, J=8.2, 4.3, 1.3 Hz, 1H), 4.29 (d, J=12.0 Hz, 1H)
overlaps with 4.27 (d, J=9.9 Hz, 1H), 4.10 (m, 2H), 3.51 (d, J=12.1
Hz, 1H), 3.34 (dd, J=5.7, 4.8 Hz, 1H), 3.12 (dd, J=9.9, 4.7 Hz, 1H),
2.79 (ddd, J=8.3, 5.7, 1.4 Hz, 1H), 2.72 (dd, J=4.6, 3.7 Hz, 1H),
2.59 (ddd, J=8.1, 2.5, 2.5 Hz, 1H), 2.29 (ddd, J=11.0, 5.5, 5.5 Hz,
1H), 2.18 (ddd, J=8.4, 4.3, 2.0 Hz, 1H), 2.04 (m, 1H), 1.88-1.80
(m, 1H), 1.76-1.69 (m, 1H) overlaps with 1.71 (d, J=11.0 Hz, 1H),
1.58-1.55 (m, 2H), 1.35-1.28 (m, 1H). 13C NMR (125 MHz,
CDCl3): δ 213.5, 149.0, 137.5, 137.0, 136.7, 131.5, 131.5, 129.7,
129.6, 128.5, 128.4, 127.9, 126.7, 121.4, 121.1, 100.5, 87.0, 78.8, 65.4,
63.5, 58.4, 51.1, 43.9, 41.6, 40.0, 38.3, 35.3, 34.8, 34.1, 30.3, 17.8,
15.3. HRMS (ESI): calcd for C38H38Br2NO4þ (MNH4þ) 732.1147,
found 732.1149.
1S(R),2R(S),5R(S),6R(S),7S(R)-6-(1,3-Dioxolan-2-yl)-4-
phenyl-13-oxaheptacyclo[5.5.4.12,5.01,7. 08,12.09,15.011,14]heptadec-3-
en-16-one (7c0): (method C produced a mixture of 7c0 and 7c00 3:1)
from 210 mg (0.61 mmol) of 4c and 0.30 mL of HCl (4.0 M, 1.22
mmol) in an ethylene glycol/THF mixture (10/3) (hexane/EtOAc
20:1 f 10:1, then hexane/EtOH 10:1 to get 7c00): 71 mg (<30%,
major loss is on the column). 1H NMR (500 MHz, CDCl3): δ 7.63
C
27H27NNaO4þ (MNaþ) 452.1832, found 452.1810.
1S(R),8S(R),9R(S),12R(S),13R(S)-13-Dimethoxymethyl-
11-phenyl-17-oxaheptacyclo[6.5.4.19,12.01,8.02,7.03,15.06,16]oc-
tadec-10-en-14-one (7b): (method C) from 91 mg (0.25 mmol)
of 4b and 0.32 mL of HCl (4.0 M, 1.27 mmol) in MeOH
(hexane/EtOH 20:1 f 10:1): 83 mg (81%). 1H NMR (500
MHz, CDCl3): δ 7.53 (d, J=7.4 Hz, 2H), 7.32 (t, J=7.6 Hz,
2H), 7.24 (t, J=7.4 Hz, 1H) overlaps with CDCl3, 6.28 (d, J=
3.5 Hz, 1H), 4.53 (ddd, J=8.2, 4.3, 1.3 Hz, 1H), 3.85 (d, J=9.8
Hz, 1H), 3.27 (t, J=5.3 Hz, 1H), 2.88 (dd, J=9.9, 4.8 Hz, 1H)
overlaps with 2.87 (s, 3H), 2.79 (ddd, J=8.5, 5.8, 1.5 Hz, 1H),
2.76 (s, 3H), 2.70 (dd, J=4.8, 3.7 Hz, 1H), 2.64 (ddd, J=8.3,
3.4, 2.2 Hz, 1H), 2.28-2.23 (ddd, J=11.0, 5.3, 5.3 Hz, 1H)
overlaps with 2.28-2.23 (m, 1H), 2.04 (m, 1H), 1.89-1.74 (m,
3H), 1.71-1.65 (m, 1H) overlaps with 1.67 (d, J=10.9 Hz,
1H), 1.48-1.41 (m, 1H). 13C NMR (125 MHz, CDCl3): δ
213.4, 149.2, 136.6, 129.1, 128.5, 127.9, 126.7, 102.4, 87.1,
78.8, 58.5, 53.2, 51.3, 49.8, 44.0, 41.7, 39.7, 38.4, 35.4, 34.4,
J. Org. Chem. Vol. 76, No. 5, 2011 1329

Valiulin et al.
JOCArticle
(d, J=7.3 Hz, 2H), 7.32 (t, J=7.6 Hz, 2H), 7.23 (t, J=7.3 Hz, 1H)
overlaps with CDCl3, 6.47 (d, J=3.6 Hz, 1H), 4.99 (dd, J=8.2,
4.0 Hz, 1H), 4.49 (d, J=9.1 Hz, 1H), 3.91-3.88 (m, 1H), 3.68-3.61
(m, 2H), 3.55-3.51 (m, 1H), 3.33 (dd, J=5.6, 4.8 Hz, 1H), 2.90
(ddd, J=7.9, 6.2, 1.4 Hz, 1H), 2.75 (m, 2H), 2.67 (dd, J=9.1, 4.6 Hz,
1H), 2.62-2.58 (ddd, J=8.2, 4.3, 1.8 Hz, 1H) overlaps with 2.57 (m,
1H), 2.51 (ddd, J=8.4, 5.2, 1.7 Hz, 1H), 2.25 (ddd, J=10.9, 5.5, 5.5
Hz, 1H), 1.84 (d, J=11.3 Hz, 1H), 1.65 (d, J=10.8 Hz, 1H) overlaps
with 1.62 (d, J=11.3 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ
214.8, 148.1, 135.9, 128.8, 128.5, 127.9, 126.4, 103.9, 87.2, 86.4,
64.9, 64.3, 56.8, 54.3, 48.2, 47.4, 43.9, 42.1, 39.0, 38.8, 38.3, 37.7,
36.3. HRMS (ESI): calcd for C25H25O4þ (MHþ) 389.1747, found
389.1761.
[6.5.4.12,6.01,8.03,5.09,13.010,16.012,15]octadecane-14,17-dione
(8d): 180 mg (0.40 mmol) dissolved in 100 mL of benzene
(4 mM) irradiated for 48 h, solvent was evaporated, and the
crude product was purified by column chromatography on
silica gel (gradient hexane [0f100% EtOAc]): 150 mg (82%). 1H
NMR (500 MHz, CDCl3): δ 7.55 (d, J=6.8 Hz, 2H), 7.40-7.32
(m, 3H), 4.12 (s, 1H), 4.09 (d, J=9.2 Hz, 1H), 3.99-3.84 (m, 5H),
3.96-3.88 (m, 5H), 3.62 (ddd, J=12.0, 6.3, 6.3 Hz, 1H), 3.48-3.39
(m, 2H), 3.18 (ddd, J=9.2, 5.6, 1.6 Hz, 1H), 3.05 (dd, J=5.3, 5.3
Hz, 1H), 2.76 (m, 1H), 2.66 (ddd, J = 9.0, 4.7, 2.2 Hz, 1H),
2.61-2.51 (m, 5H), 1.89 (d, J = 10.8 Hz, 1H), 1.81 (ddd, J =
11.2, 5.6, 5.6 Hz, 1H), 1.67 (d, J=10.8 Hz, 1H), 1.08 (d, J=11.2 Hz,
1H). 13C NMR (125 MHz, CDCl3): δ 214.1, 136.3, 128.9, 128.6,
114.5, 102.2, 66.21, 66.17, 65.4, 64.4, 63.9, 59.6, 55.0, 53.5, 50.2,
46.8, 44.8, 42.4, 41.7, 40.3, 39.3, 38.9, 36.1, 32.6, 28.2. HRMS
(ESI): calcd for C28H28NaO6þ (MNaþ) 483.1778, found.
1S(R),2R(S),5R(S),6R(S),7S(R)-6-(Bis(2-hydroxyethoxy)-
methyl)-4-phenyl-13-oxaheptacyclo[5.5.4.12,5.01,7.08,12.09,15
.
011,14]heptadec-3-en-16-one (7c00): (hexane/EtOH 10:1): 23
mg (<10%). 1H NMR (500 MHz, CDCl3): δ 7.48 (d, J =
7.3 Hz, 2H), 7.31 (t, J=7.5 Hz, 2H), 7.24 (t, J=7.3 Hz, 1H)
overlaps with CDCl3, 6.28 (d, J=3.5 Hz, 1H), 5.00 (dd, J=
8.3, 4.0 Hz, 1H), 4.15 (d, J=9.6 Hz, 1H), 3.65 (ddd, J=11.9,
7.6, 2.8 Hz, 1H), 3.56 (ddd, J = 11.9, 4.8, 2.9 Hz, 1H),
3.51-3.43 (m, 2H), 3.40 (ddd, J = 10.2, 7.7, 2.9 Hz, 1H),
3.28 (dd, J=5.8, 4.9 Hz, 1H) overlaps with 3.26 (m, 2H), 2.96
(ddd, J=7.8, 6.3, 1.2 Hz, 1H) overlaps with 2.94 (dd, J=9.7,
4.6 Hz, 1H), 2.78 (m, 1H), 2.74 (dd, J=4.7, 3.7 Hz, 1H), 2.68
(ddd, J=10.0, 4.8, 2.8 Hz, 1H), 2.62 (ddd, J=8.4, 4.3, 1.8 Hz,
1H), 2.58 (m, 1H), 2.55 (ddd, J=8.2, 5.4, 1.7 Hz, 1H), 2.30
(ddd, J=11.0, 5.5, 5.5 Hz, 1H), 1.86 (d, J=11.3 Hz, 1H), 1.67
(d, J=11.2 Hz, 1H) overlaps with 1.66 (d, J=11.0 Hz, 1H).
13C NMR (125 MHz, CDCl3): δ 215.4, 149.2, 136.9, 129.7, 128.6,
128.0, 126.7, 101.0, 87.2, 87.0, 66.1, 64.4, 62.21, 62.18, 57.7, 54.4,
48.2, 47.4, 44.1, 42.3, 39.9, 38.8, 37.8, 36.4, 35.8. HRMS (ESI):
calcd for C27H30NaO6þ (MNaþ) 473.1935, found 473.1938.
Photoinduced Epoxidation. 1S(R),2R(S),11S(R),12R(S),13S
(R),14S(R),16S(R)-9-Cyano-12-dimethoxymethyl-14-phenyl-
endo-4,5-Benzotricyclo[6.2.1.02,7]undec-9-ene-3,6-dione (1d):
from 1.00 g of 1,4-naphthoquinone (6.3 mmol) and 1.0 mL of
1,3-cyclopentadiene (12.3 mmol) at room temperature: 1.35 g
(95%). 1H NMR (500 MHz, CDCl3): δ 8.00 (m, 2H), 7.67 (m,
2H), 5.95 (t, J=1.8 Hz, 2H), 3.64 (m, 2H), 3.43 (dd, J=2.5, 1.5
Hz, 2H), 1.56-1.49 (m, 2H).
Hexacyclo[5.4.4.0.02,6.03,13.05,14]pentadeca-8,10-diene-12,15-
dione (2d): from 1.35 g of 1d (6.0 mmol) in 1.0 L of DCM,
irradiation for 24 h (hexane/EtOAc gradient 20:1 f 10:1): 1.30 g
1
(96%). H NMR (500 MHz, CDCl3): δ 5.99 (m, 2H), 5.40 (m,
2H), 3.36 (m, 2H), 3.01 (m, 2H), 2.82 (m, 2H), 2.01 (d, J=11.4 Hz,
1H), 1.78 (d, J=11.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
210.5, 124.9, 120.0, 54.8, 51.8, 50.4, 44.4, 39.2.
1R(S),2S(R),10S(R),11R(S),14R(S)-14-Benzoylheptacyclo-
[9.2.2.12,5.17,10.02,10.04,8.016,17]heptadec-12-ene-3,9-dione (3d):
from 1.30 g of 2d (5.8 mmol) and 0.98 g of 3-chloropropio-
phenone (5.8 mmol) at 140 °C (hexane/EtOAc gradient 10:1 f
1:1): 1.94 g (94%). 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J=
7.1 Hz, 2H), 7.51 (t, J=7.3 Hz, 1H), 7.44 (t, J=7.5 Hz, 2H),
6.45 (ddd, J=8.2, 6.9, 1.1 Hz, 1H), 6.24 (ddd, J=8.1, 6.7, 1.3
Hz, 1H), 4.10 (ddd, J=10.0, 5.5, 1.9 1H), 3.06 (ddd, J=6.6,
1.9, 1.3 Hz, 1H), 2.86 (m, 2H), 2.81 (dddd, J=6.8, 2.8, 2.8, 1.3 Hz,
1H), 2.74, (d, J=2.1 Hz, 2H), 2.62 (m, 2H), 2.26, (ddd, J=12.8,
10.0, 2.6 Hz, 1H), 1.95 (d, J=11.2 Hz, 1H), 1.78 (d, J=11.3 Hz,
1H), 1.71 (ddd, J=13.0, 5.5, 3.1 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 213.4, 212.8, 201.0, 136.2, 134.5, 133.1, 131.2, 129.1,
128.8, 56.3, 56.2, 54.6, 54.4, 43.9, 43.7, 42.2, 4þ2.0, 41.1, 39.8, 34.3,
31.2, 23.4. HRMS (ESI): calcd for C24H21O3 (MHþ) 357.1485,
found 357.1479.
3,15-dioxaoctacyclo[11.3.1.12,5.18,11.02,11.04,9.014,16.018,19
]
nonadecan-10-one (8a). A 46 mg amount of 7a (0.11 mmol) in
2.0 mL of aerated benzene was irradiated in a Pyrex flask in a
Rayonet reactor equipped with RPR-3500 UV lamps
(broadband 300-400 nm UV source with peak emission at
350 nm) for 24 h, solvent was evaporated, and the crude
product was purified by column chromatography on silica gel
(gradient hexane [0% f 50% EtOH]), 33 mg, 69%. 1H NMR
(500 MHz, CDCl3): δ 7.51 (m, 2H), 7.45-7.38 (m, 3H), 4.70
(d, J=4.2 Hz, 1H), 3.94 (s, 1H), 3.57 (d, J=10.0 Hz, 1H), 3.42
(ddd, J=8.6, 5.9, 1.2 Hz, 1H), 3.01 (t, J=5.5 Hz, 1H), 2.88 (dd,
J=10.0, 5.0 Hz, 1H), 2.81 (s, 3H), 2.69 (s, 3H), 2.51 (dd, J=
4.7, 1.5 Hz, 1H), 2.45 (dd, J=8.6, 4.8 Hz, 1H), 2.30 (m, 1H),
2.18 (m, 1H), 2.06-1.96 (m, 3H), 1.91 (ddd, J=11.9, 5.9, 5.0
Hz, 1H), 1.65-1.59 (m, 1H) overlaps with HOD, 1.08 (d, J=
12.0 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 201.76, 135.56,
129.11, 128.83, 117.23, 100.21, 90.95, 80.88, 65.88, 58.22,
57.22, 53.32, 51.53 (m), 49.45, 48.26 (m), 38.61, 38.51, 36.67,
36.18, 35.33, 35.21, 32.67, 27.67, 15.68, 14.04. 1H NMR (500
MHz, C6D6): δ 7.30 (m, 2H), 7.09-7.03 (m, 3H), 4.26 (d, J=
4.2 Hz, 1H), 3.58 (d, J=10.0 Hz, 1H), 3.47 (s, 1H), 3.05 (dd, J=
10.0, 5.0 Hz, 1H), 2.94 (dd, J=6.0, 5.0 Hz, 1H), 2.64 (s, 3H),
2.58 (ddd, J=8.5, 5.7, 1.2 Hz, 1H), 2.48 (s, 3H), 2.32 (dd, J=
4.6, 1.3 Hz, 1H), 2.12 (dd, J=8.6, 4.8 Hz, 1H), 2.02 (m, 1H),
1.90 (ddd, J=11.5, 6.0, 5.0 Hz, 1H), 1.64-1.57 (m, 1H), 1.44
(m, 1H), 1.30-1.26 (m, 2H), 1.10 (d, J = 11.8 Hz, 1H),
0.91-0.83 (m, 1H). 13C NMR (125 MHz, C6D6): δ 202.2,
137.1, 129.1, 129.1, 127.9, 117.8, 100.6, 91.3, 81.3, 66.1, 58.3,
57.8, 53.2, 52.5, 49.1, 39.4, 38.6, 37.4, 36.6, 35.9, 35.5, þ33.1, 28.4,
16.1, 14.3. HRMS (ESI): calcd for C27H27KNO5 (MKþ)
484.1521, found 484.1530.
14-Phenyl-13-oxanonacyclo[9.4.2.12,5.17,10.02,10.04,8.012,15
.014,17.018,19]nonadecane-3,9-dione (4d): from 0.74 g of 3d (2.1
mmol) in 0.5 L of benzene, irradiation for 72 h: 0.68 g (92%). 1H
NMR (500 MHz, CDCl3): δ 7.37-7.31 (m, 5H), 4.90 (ddd, J=3.7,
1.9, 0.8 Hz, 1H), 3.46 (dddd, J=5.5, 3.5, 1.7, 1.7 Hz, 1H), 3.03 (dd,
J=8.1, 6.3 Hz, 1H), 2.99-2.94 (m, 2H), 2.91 (m, 1H), 2.75 (m, 1H)
overlaps with 2.74 (m, 1H), 2.68 (ddd, J=6.6, 1.8, 1.8 Hz, 1H), 2.13
(ddd, J=7.0, 5.8, 1.3 Hz, 1H), 2.04 (d, J=11.4 Hz, 1H), 1.91 (ddd,
J=13.4, 7.1, 2.0 Hz, 1H) overlaps with 1.87 (d, J=11.5 Hz, 1H),
1.55 (m, 1H) overlaps with HOD, 1.44 (dd, J=13.4, 1.9 Hz, 1H).
1H NMR (500 MHz, C6D6): δ 7.32 (m, 2H), 7.15-7.12 (m, 2H),
7.08 (m, 1H), 4.54 (ddd, J=3.6, 1.9, 0.9 Hz, 1H), 3.14 (m, 1H), 2.74
(d, J=6.7 Hz, 1H), 2.64 (ddd, J=6.6, 1.7, 1.7 Hz, 1H), 2.27 (m,
2H), 2.14-2.04 (m, 4H), 1.95-1.89 (m, 2H), 1.74 (d, J=11.3 Hz,
1H), 1.19 (d, J=11.0 Hz, 1H), 1.08 (d, J=11.0 Hz, 1H).
Oxametathesis in the Naphthoquinone (d) Series. 1S(R),2R-
(S),5R(S),6R(S),7S(R)-13,16-Dioxo-4-phenylheptacyclo[5.5.-
4.12,5.01,7.08,12.09,15.011,14]heptadec-3-ene-6-carboxaldehyde-
(5d): (method B2) from 100 mg (0.28 mmol) of 4d and 0.09 mL of
HCl (4.0 M, 0.34 mmol) in DCM (hexane/EtOH 10:1): gave an
inseparable mixture of 5d and 6d (2:3). 1H NMR (500 MHz,
C6D6): δ 9.17 (s, 1H), 7.20 (d, J = 7.8 Hz, 2H), 7.11 (t, J =
7.4 Hz, 2H), 7.09-7.03 (m, 1H), 5.93 (d, J=3.1 Hz, 1H), 3.12 (d,
13-Ethylene Glycol Monoacetal of 1S(R),2S(R),3S(R),5S(R),-
6R(S),7S(R)-7-(1,3-Sioxolan-2-yl)-5-phenyl-4-oxaoctacyclo-
1330 J. Org. Chem. Vol. 76, No. 5, 2011

Valiulin et al.
JOCArticle
J=4.1 Hz, 1H), 3.09 (dd, J=5.7, 4.4 Hz, 1H), 2.82 (dd, J=9.1, 5.4
Hz, 1H), 2.69 (dd, J=5.0, 3.3 Hz, 1H), 2.52-2.49 (m, 2H), 2.33
(ddd, J=10.3, 4.1, 2.1 Hz, 1H), 2.14 (ddd, J=9.0, 5.8, 1.8 Hz, 1H),
2.11-2.05 (m, 2H), 1.49 (d, J=11.1 Hz, 1H), 1.28-1.23 (m, 2H).
1S(R),2R(S),3S(R),6R(S),7S(R)-13,16-Dioxo-4-phenyloctac-
yclo[5.5.4.13,6.01,7.02,4.08,12.09,15.011,14]heptadecane-2-carbox-
aldehyde (6d): (method B1) from 170 mg (0.48 mmol) of 4d and
160.6, 135.7, 134.8, 132.0, 131.3, 130.72 overlaps with 130.71,
127.0, 126.6, 126.0, 37.2, 29.0, 25.1, 20.2. HRMS (ESI): calcd for
C16H14NaO2þ (MNaþ) 261.0886, found 261.0896.
Dimerization of Caged Dienes 2. A solution of 2 in 5-10 mL of
1,2-dichlorobenzene was heated in a screw-cap pressure flask at
200-210 °C for 24-72 h. After the reaction was cooled to room
temperature, the solvent was removed on a high-vacuum pump.
The crude reaction mixture was purified on a silica gel column
using hexane/EtOAc (hexane/EtOH and DCM/MeOH in the
case of 2a) as an eluent.
0.30 mL of BF3 Et2O (48%, 2.38 mmol) in DCM (hexane/EtOH
3
20:1 f 10:1): 80 mg (47%); (method B2) from 100 mg (0.28 mmol)
of 4d and 0.14 mL of HCl (4.0 M, 0.56 mmol) in DCM (hexane/
EtOH 20:1 then 10:1): 61 mg (61%). 1H NMR (500 MHz, CDCl3):
δ 8.85 (s, 1H), 7.31 (d, J=4.3 Hz, 4H), 7.27-7.23 (m, 1H) overlaps
with CDCl3, 3.27 (m, 1H) overlaps with 3.26-3.22 (ddd, J=8.2,
5.7, 1.7 Hz, 1H), 3.01 (ddd, J=7.8, 6.0, 1.6 Hz, 1H), 2.86 (m, 1H)
overlaps with 2.86-2.83 (ddd, J=10.4, 4.0, 1.8 Hz, 1H), 2.76-2.73
(ddd, J=10.3, 4.1, 1.6 Hz, 1H) overlaps 2.75 (m, 1H), 2.52 (d, J=
13.1 Hz, 1H), 2.22-2.17 (m, 2H), 2.10 (dd, J=13.1, 5.5 Hz, 1H),
2.06 (d, J=11.3 Hz, 1H), 2.00 (d, J=12.5 Hz, 1H), 1.93 (d, J=11.3
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 212.3, 210.7, 199.3,
138.1, 129.2, 129.0, 127.8, 56.5, 55.4, 54.1, 48.5, 44.9, 44.5, 43.9,
42.6, 41.8, 41.0, 38.9, 38.4, 30.5, 29.8, 28.9. HRMS (ESI): calcd for
C24H21O3þ (MHþ) 357.1485, found 357.1477.
1S(R),2R(S),5R(S),14R(S),15S(R),16S(R),17R(S),26R(S-
7,24-Dicyano-13,18-dioxatridecacyclo[14.10.2.15,8.111,14.117,20
.
123,26.02,15.05,14.07,12.017,26.019,24.029,30.031,32]dotriaconta-3,27-
diene-6,25-dione (9a): from 0.46 g of 2a (1.8 mmol) in 10 mL
of 1,2-dichlorobenzene at 210 °C for 72 h (hexane/EtOH
gradient 10:1 f 1:1 and DCM/MeOH 5:1): 0.15 g (33%). 1H
NMR (500 MHz, CDCl3): δ 6.19 (ddd, J=8.0, 6.4, 1.1 Hz,
1H), 6.13 (ddd, J=8.1, 6.9, 1.4 Hz, 1H), 5.75 (dd, J=10.4,
2.8 Hz, 1H), 5.55 (dd, J=10.4, 2.3 Hz, 1H), 4.71 (d, J=4.1
Hz, 1H), 4.64 (d, J=4.1 Hz, 1H), 3.38 (dddd, J=9.1, 2.7, 2.7,
2.7 Hz, 1H), 3.15 (d, J=6.8 Hz, 1H), 2.81 (ddd, J=6.3, 2.7,
1.5 Hz, 1H), 2.74 (ddd, J=8.3, 5.5, 1.2 Hz, 1H), 2.64 (ddd,
J=7.4, 5.8, 1.4 Hz, 1H), 2.50 (dd, J=9.1, 1.5 Hz, 1H), 2.25
(m, 3H), 2.15 (dd, J=8.4, 5.2 Hz, 1H), 2.11 (m, 1H) overlaps
with 2.08 (dd, J = 7.7, 5.0 Hz, 1H), 1.94-1.82 (m, 6H),
1.57-1.45 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 202.8,
201.3, 133.4, 133.3, 131.8, 120.1, 117.4, 117.4, 91.2, 85.4,
83.1, 80.5, 56.9, 55.5, 53.3, 52.6, 43.3, 39.7, 37.1, 37.0, 36.4,
35.9, 35.8, 35.7, 35.2, 35.1, 34.0, 33.8,þ16.1, 15.9, 14.2, 14.1.
HRMS (ESI): calcd for C32H30N3O4 (MNH4þ) 520.2231,
found 520.2232.
13-Ethylene Glycol Monoacetal of 1S(R),2R(S),5R(S),6R(S),-
7S(R)-6-(1,3-dioxolan-2-yl)-4-phenylheptacyclo[5.5.4.12,5.01,7
.
08,12.09,15.011,14]heptadec-3-en-16-one (7d): (method C) from 360
mg (1.01 mmol) of 4f and 1.26 mL of HCl (4.0 M, 5.05 mmol) in an
ethylene glycol/THF mixture (10:3) (hexane/EtOAc 10:1 f 5:1):
229 mg (51%). 1H NMR (500 MHz, CDCl3): δ 7.62 (d, J=7.2 Hz,
2H), 7.30 (t, J=7.6 Hz, 2H), 7.20 (t, J=7.3 Hz, 1H), 6.54 (d, J=3.6
Hz, 1H), 4.53 (d, J=9.0 Hz, 1H), 3.96-3.88 (m, 5H), 3.71-3.62
(m, 2H), 3.53-3.49 (m, 1H), 3.31 (dd, J=5.6, 4.6 Hz, 1H), 2.81 (dd,
J=5.0, 3.6 Hz, 1H), 2.62 (m, 1H), 2.59-2.48 (m, 6H), 2.10 (ddd, J
=10.8, 5.5, 5.5 Hz, 1H), 1.80 (d, J=10.9 Hz, 1H), 1.62 (d, J=10.5
Hz, 1H), 1.54 (d, J=10.9 Hz, 1H). 13C NMR (125 MHz, CDCl3):δ
215.8, 147.3, 136.4, 130.7, 128.5, 127.5, 126.2, 114.6, 104.2, 66.3,
65.5, 64.7, 64.3, 54.3, 51.5, 50.6, 47.5, 44.2, 44.2, 42.7, 40.0, 39.2,
1S(R),2R(S),5R(S),14R(S),15S(R),16S(R),17R(S),26R(S)-
13,18-Dioxatridecacyclo[14.10.2.15,8.111,14.117,20.123,26.02,15
.
05,14.07,12.017,26.019,24.029,30.031,32]dotriaconta-3,27-diene-6,25-
dione (9b): from 170 mg of 2b (0.75 mmol) in 5 mL of 1,2-
dichlorobenzene at 200 °C for 24 h (hexane/EtOAc gradient
20:1 f 4:1): 41 mg (24%). 1H NMR (500 MHz, CDCl3): δ 6.20
(m, J = 7.3 Hz, 1H), 6.12 (m, J = 7.5 Hz, 1H), 5.71
(dd, J=10.5, 2.8 Hz, 1H), 5.54 (dd, J=10.3, 2.2 Hz, 1H), 4.56
(dd, J=7.6, 4.1 Hz, 1H), 4.47 (dd, J=8.0, 4.0 Hz, 1H), 3.39 (dddd,
J=8.6, 2.7, 2.7, 2.7 Hz, 1H), 3.15 (d, J=6.7 Hz, 1H), 2.73 (d, J=6.3
Hz, 1H), 2.66 (dd, J=8.3, 5.6 Hz, 1H), 2.57-2.49 (m, 4H), 2.10 (m,
1H), 2.02 (ddd, J=7.8, 5.1, 2.4 Hz, 1H), 1.98 (m, 1H), 1.94 (m, 1H),
1.90 (m, 2H), 1.85-1.69 (m, 4H), 1.67-1.59(m, 2H), 1.47-1.36(m,
2H). 13C NMR (125 MHz, CDCl3): δ 213.9, 212.8, 133.4, 133.0,
131.8, 121.2, 90.4, 84.8, 79.7, 77.0, 57.5, 56.5, 52.9, 52.2, 44.7, 40.8,
37.7, 37.4, 37.4, 36.5, 35.9, 35.4, 35.1, 34.3, 31.2, 30.1, 18.1, 17.9, 15.4,
15.2. HRMS (ESI): calcd for C30H29O4þ (MHþ) 453.2060, found
453.2077.
þ
39.0, 38.8, 38.1, 37.1. HRMS (ESI): calcd for C28H28NaO5
(MNaþ) 467.1829, found 467.1822.
13-Ethylene Glycol Monoacetal of 1S(R),2R(S),5R(S),6R(S),
7S(R)-6-(1,3-Dioxolan-2-yl)-4-phenylheptacyclo[5.5.4.12,5.01,7
.08,12.09,15.011,14]heptadec-3-en-16-one (7d) from 3d (NMR
experiment). To 5 mg (14 μmol) of 3d dissolved in 0.6 mL of
CD2Cl2 in a Pyrex NMR tube were added 4 μL (71 μmol) of
ethylene glycol and 17 μL of 4 M HCl/dioxane. The solution was
irradiated with RPR-3500 lamps (λmax=350 nm) until the starting
material was consumed (ca. 3-4 h). At the end of the experiment
NMR of the reaction mixture contained only peaks of 7d, de-
scribed in the preceding experiment.
endo-5,6-Benzotricyclo[6.2.1.02,7]undec-9-ene-3,4-dione (1h)
(ref 15): from 1.0 g of 1,2-naphthoquinone (6.3 mmol) and 1.0
g of 1,3-cyclopentadiene (15.1 mmol) in 20 mL of DCM at room
1S(R),2R(S),5R(S),14R(S),15S(R),16S(R),17R(S),26R(S)-
13,18-Dioxatridecacyclo[14.10.2.18,11.120,23.02,15.05,9.05,14.07,12.010,14
.
1
017,21.017,26.019.24.022,26]triaconta-3,27-diene-6,25-dione (9c). from
0.56 g of 2c (2.6 mmol) in 10 mL of 1,2-dichlorobenzene at 210 °C
for 48 h (hexane/EtOAc gradient 20:1 f 10:1): 0.45 g (80%). H
temperature: 0.85 g (>60% by NMR). H NMR (400 MHz,
CDCl3): δ 7.92 (d, J=7.9 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.47
(d, J=7.8 Hz, 1H), 7.33 (t, J=7.6 Hz, 1H), 6.14 (dd, J=5.7, 2.8
Hz, 1H), 5.62 (dd, J=5.7, 2.9 Hz, 1H), 3.96 (dd, J=7.9, 3.7 Hz,
1H), 3.48 (m, 1H), 3.36 (dd, J=8.0, 4.2 Hz, 1H) overlaps with
3.32 (m, 1H), 1.69-1.62 (m, 2H). Irradiation of 1h produced a
complex mixture of products.
4-(Cyclohex-2-enyl)-1,2-naphthoquinone (1g): from 1.0 g of
1,2-naphthoquinone (6.3 mmol) and 0.81 g of 1,3-cyclohexa-
diene (10.1 mmol) in 20 mL of 1,2-dichlorobenzene at 150 °C
(hexane/EtOAc 25:1 f 10:1). The initial Diels-Alder adduct
(1g0) rearranges into 1g on standing or on a silica gel column:
0.75 g (50%). 1H NMR (400 MHz, CDCl3): δ 8.15 (dd, J=7.6,
1.5 Hz, 1H), 7.69-7.61 (m, 2H), 7.50 (ddd, J=7.4, 7.4, 1.4 Hz,
1H), 6.43 (s, 1H), 6.04 (dddd, J=9.9, 3.8, 3.8, 2.1 Hz, 1H), 5.60
(dddd, J=10.1, 3.1, 2.3, 2.3 Hz, 1H), 3.72 (m, 1H), 2.10 (m, 3H),
1.67 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 181.1, 180.1,
1
NMR (500 MHz, CDCl3):δ6.20(ddd, J=7.9, 6.5, 1.1 Hz, 1H), 6.11
(ddd, J=8.2, 7.0, 1.3 Hz, 1H), 5.71 (dd, J=10.4, 2.8 Hz, 1H), 5.54
(dd, J=10.4, 2.3 Hz, 1H), 5.02 (ddd, J=8.0, 3.1, 2.2 Hz, 1H), 4.94
(dd, J=8.4, 3.8 Hz, 1H), 3.35 (dddd, J=9.1, 2.7, 2.7, 2.7 Hz, 1H),
3.18 (d, J=6.9 Hz, 1H), 2.85-2.79 (m, 2H), 2.76 (ddd, J=6.4, 2.7,
1.4 Hz, 1H), 2.73-2.69 (m, 2H), 2.59 (m, 2H), 2.51 (dd, J=9.3, 1.5
Hz, 1H), 2.47 (ddd, J=8.4, 4.2, 2.0 Hz, 1H), 2.42 (ddd, J=8.0, 4.2,
1.9 Hz, 1H), 2.20 (ddd, J=7.8, 5.6, 2.0 Hz, 1H), 2.09 (m, 1H), 1.81
(d, J=11.3 Hz, 1H), 1.75 (d, J=11.3 Hz, 1H), 1.61 (d, J=11.3 Hz,
1H), 1.52 (d, J=11.3 Hz, 1H). 1H NMR (500 MHz, C6D6): δ 6.21
(ddd, J=8.2, 7.0, 1.3 Hz, 1H), 6.04 (ddd, J=7.8, 6.5, 1.2 Hz, 1H),
5.75-5.68 (m, 2H), 4.59 (dd, J=8.0, 4.0 Hz, 1H), 4.53 (ddd, J=8.5,
2.6, 2.6 Hz, 1H), 3.80 (dddd, J=9.3, 2.5, 2.5, 2.5 Hz, 1H), 3.50 (d, J=
7.0 Hz, 1H), 2.84 (dd, J=9.3, 1.6 Hz, 1H), 2.64 (ddd, J=6.3, 2.8,
J. Org. Chem. Vol. 76, No. 5, 2011 1331

Valiulin et al.
JOCArticle
1.4 Hz, 1H), 2.27 (ddd, J=7.4, 6.2, 1.2 Hz, 1H), 2.23-2.18 (m, 3H),
2.17-2.13 (m, 2H), 2.05 (m, 1H), 1.99 (m, 1H), 1.78 (m, J=5.5, 2.5
Hz, 1H), 1.62 (ddd, J=7.4, 5.5, 1.9 Hz, 1H), 1.14-1.10 (m, 2H), 0.97
(m, 2H). 13C NMR (125 MHz, CDCl3): δ 214.7, 214.1, 133.7, 132.9,
131.7, 121.3, 90.7, 87.8, 85.4, 84.9, 56.4, 55.3, 55.0, 54.3, 51.3,
48.2, 47.3, 47.2, 42.0, 41.2, 40.8, 38.3, 37.9, 37.3, 37.2, 36.6, 36.2,
Acknowledgment. Support of this research by the Na-
tional Institutes of Health (GM093930) is gratefully ac-
knowledged.
Supporting Information Available: 1H and 13C NMR spec-
tra, X-ray data, and computational details. This material is
available free of charge via the Internet at http://pubs.acs.org.
þ
34.0. HRMS (ESI): calcd for C28H25O4 (MHþ) 425.1747, found
425.1748.
1332 J. Org. Chem. Vol. 76, No. 5, 2011