Enantio- and diastereomerically pure decalins by deslongchamps-type annulation of dienolates containing a chiral lactone substituent

Article abstract of DOI:10.1002/ejoc.200601047

A conceptionally novel 1,3-asymmetric induction has been established. It controls the relative and absolute configuration of up to 5 stereocenters. They emerge from the anionic Diels-Alder reactions ("Deslongchamps ambulations") between oxocyclohexenecarb

Full text of DOI:10.1002/ejoc.200601047

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200601047
Enantio- and Diastereomerically Pure Decalins by Deslongchamps-Type
Annulation of Dienolates Containing a Chiral Lactone Substituent
Thomas Tricotet[a] and Reinhard Brückner*[a]
Keywords: 1,3-Asymmetric induction / Bicyclo[4.4.0]decane / De(alkoxycarbonylation) / Homoallyl anion equivalent /
γ-Lactone fragmentation / Stereoselective synthesis / Tandem reaction
A conceptionally novel 1,3-asymmetric induction has been
established. It controls the relative and absolute configura-
tion of up to 5 stereocenters. They emerge from the anionic
Diels–Alder reactions (“Deslongchamps annulations”) be-
tween oxocyclohexenecarboxylates 25, 29 and dienolates 26,
30. The latter contain a γ-lactone. A Ph3Si–CH2 substituent
therein controls the asymmetry of C–C bond formation with
ds ≈ 10:1. Strangely, the preferred sense of attack of the dien-
ophile is contrasteric. Cycloadduct 31 was processed by an
unprecedented fluoride-induced ambient-temperature tan-
dem fragmentation. It turned the lactone moiety into an allyl
group and the β-oxo (trimethylsilyl)ethyl ester into a ketone.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
The stereocontrolled construction of decalins is required
in many contexts. The dominating accesses are by Diels–
Alder reactions – both inter- and intramolecular –, Robin-
son annulation – the most conspicuous variant of the latter
being the Hajos–Parrish–Eder–Sauer–Wiechert reaction –,
and cation- or radical-induced polyene cyclizations. Argu-
ably, a runner-up strategy for establishing decalin scaffolds
is the “anionic Diels–Alder reaction” developed by
Deslongchamps et al. It is a cyclohexenone annulation
highlighted in steroid synthesis repeatedly, the most recently
accomplished target being ouabagenin.[1] Usually, such
“Deslongchamps annulations” consist of the addition of an
ester-substituted dienolate 2 – generated from Cs2CO3 and
a
γ,δ-unsaturated β-oxo ester
3
or so-called
Nazarov reagent[2] – to an oxocyclohexenecarboxylate 1
(Scheme 1).[3–6] These entities combine with the indicated
simple diastereoselectivity[7] and in pairs of properly de-
signed reactants with good induced diastereoselectivities as
well.[8,9] Deslongchamps et al. obtained dioxodecalindicar-
boxylates 5 by such annulations and dioxodecalinmonocar-
boxylates 6 by the subsequent removal of the CO2R3 group.
Such annulations 1 + 3 Ǟ 6 created up to four new
stereocenters which matches the “stereogenecity” of Diels–
Alder reactions.
Scheme 1. Deslongchamps annulations past (Ǟ 5, 6) and present
(Ǟ 7, 8; ref.[10] and this work). Polycyclic structures 9 and 10 to be
derived from 8. Rx stands for substituents introduced in the annu-
lation step and RЈx for potentially modified substituents generated
thereafter.
[a] Institut für Organische Chemie und Biochemie, Albert-Lud-
wigs-Universität,
Albertstr. 21, 79104 Freiburg, Germany
Fax: +49-761-2036100
E-mail: reinhard.brueckner@organik.chemie.uni-freiburg.de
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T. Tricotet, R. Brückner
SHORT COMMUNICATION
Recently, we showed that dioxodecalindicarboxylates 5
(with CO2R3 = CO2allyl) give dioxodecalinmonocarboxyl-
ates 7[10] by Tsuji’s Pd-catalyzed decarboxylation/al-
lylation.[11] They and the readily derived decalindiones 8[10]
display five new stereocenters. By this token their syntheses
surpass the “stereogenecity” of a Diels–Alder reaction – a
rare attribute in synthetic methodology! In the present
study we were able to increase the hitherto unsatisfactory
yields of 7 and thereby 8 two- to threefold. This was pos-
sible by incorporating lactone- rather than ester-substituted
dienolates. At the same time a stereocenter in the lactone
moiety allowed to control the absolute configuration of the
annulation products. Both features are important steps
towards developing type-8 decalindiones into precursors of
tricyclic or tetracyclic structures 9 and 10.[12]
Results and Discussion
Our concept is shown in Scheme 2. It emerged from the
finding[13] that in Deslongchamps annulations γ-lactone-
substituted dienolates tolerate a non-hydrogen substituent
at one of the positions where ester-substituted dienolates 2
do not.[10] Accordingly, we expected that dienolates 11 with
a γ-chiral γ-lactone moiety would undergo Deslongchamps
annulations, too. We hoped that the latter would proceed
with considerable induced diastereoselectivity because of
the ample precedence for such a selectivity in many other
functionalizations of γ-chiral γ-lactone enolates.[14] Finally,
the partial sequence 12 Ǟ 13 Ǟ 7 of our strategy illustrates
a previously unrecognized synthetic equivalence between
appropriately substituted γ-lactones and a homoallyl group.
This sequence was conceived of a nucleophilic (for E =
R3Si) or a reductive (for E = ArS, Hal) elimination (12 Ǟ
13) followed by protonation and in-situ decarboxylation (13
Ǟ 7). We were particularly attracted by the possibility of a
fluoride-mediated elimination 12 Ǟ 13.[29] This was because
of the prospect of cleaving simultaneously the acyclic ester
moiety of intermediate 12 – provided the latter would be
CO2–CH2–CH2–SiR3 and not, as shown in Scheme 2,
CO2Me.
Scheme 2. Novel strategy for the asymmetric synthesis of type-8
decalins and challenges faced in its realization.
Lactone-containing Nazarov reagents 19 and 20 were
prepared starting from the readily available triphenyl-
silylated ethyl acetate 14[15] (Scheme 3). Hydroxylaminolysis
gave Weinreb amide 15.[16] Then, allylmagnesium bromide
was added, affording the unsaturated ketone 16 (83% over-
all yield for the 2 steps). We hydroborated its C=C bond
intermolecularly and its C=O bond intramolecularly[17]
with Brown’s (+)-Ipc2BH.[18] After treatment with NaOOH,
this furnished 1,4-diol 17 in 75% yield and with an ee,[19]
which varied somewhat (90–95%) from experiment to ex-
periment. 1,3-Diols in which the 1-OH group is primary
can be selectively oxidized with TEMPO (cat.)/PhI(OAc)2
(stoichiom.) affording hydroxy aldehydes.[20] Under iden-
tical conditions, 1,5-diols in which the 1-OH group is pri-
mary are oxidized via lactol intermediates giving δ-lac-
tones.[21] Analogously, we oxidized the primary OH group
Scheme 3. Synthesis of Nazarov reagents 19 and 20. a) HNMe-
(OMe)·HCl (1.5 equiv.), iPrMgCl (3.0 equiv.), THF, –20 °C,
15 min, 14, –10 °C, 10 min, 92%; b) AllylMgBr (1.5 equiv.), THF,
–20 °C, 15 min, –10 °C, 15 min, 90%; c) (+)-Ipc2BH (1.05 equiv.),
THF, 0 °C, 40 min, 4 °C, 36 h, 0 °C, NaOH (3 ), H2O2 (30%),
room temp., 10 min, 73%; d) 17 (90% ee), PhI(OAc)2 (2.2 equiv.),
TEMPO (10 mol-%), CH2Cl2, room temp., 3 h, 84%; e) LDA
(1.1 equiv.), THF, –78 °C, 1 h, 23 (1.1 equiv.), 20 min, 77%; f) same
as (e) but with 24, 88%; g) PDC (2.5 equiv.), CH2Cl2, room temp.,
18 h, 60%; h) same as (g) but 3 d, 74%. PMB = p-methoxybenzyl;
of a 90% ee specimen of 1,4-diol 17 selectively. This made TEMPO = 2,2,6,6-tetramethylpiperidinoxyl.
1070 Eur. J. Org. Chem. 2007, 1069–1074
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Decalins by Deslongchamps-Type Annulation of Dienolates
SHORT COMMUNICATION
γ-lactone 18 accessible in 84% yield and with unchanged
The major part of spirolactone 27 was separated from
ee.[22] Since compound 18 crystallized nicely, we were able the minor isomer epi-27 by flash chromatography on silica
to determine its absolute configuration crystallographi- gel.[28] Treatment of pure 27 with a solution of Bu4NF in
cally.[23] Our result was in accordance with the prediction THF led to Ͼ63% of a separable (vide infra) 75:25 mixture
from the literature.[17] The lithium enolate of lactone 18 was of decalindione isomers 28 and epi-28. This transformation
1,2-added to crotonaldehyde (23) as well as to the more shows that a γ-[(triphenylsilyl)methyl]-γ-butyrolactone may
highly substituted α,β-unsaturated aldehyde 24.[24] This led be used as synthetic equivalent of a homoallyl group. The
to hydroxyalkylated lactones 21 and 22. Oxidation with first step is analogous to the fluoride-induced β-elimination
PDC took the material on to Nazarov reagents 19 and 20, of γ-[(trimethylsilyl)methyl]-γ-butyrolactones delivering γ,δ-
respectively. Each of them consisted of two ketone epimers unsaturated carboxylic acids.[29] Here, however, the reaction
and the enol tautomer.[25]
continues. This is because here the γ,δ-unsaturated carbox-
A 90% ee sample of Nazarov reagent 19 was annulated ylic acid intermediate is a β-oxo acid, which decarboxylates
to oxocyclohexenecarboxylate 25[26] under standard Des- and renders the ketone. The configuration of the newly
longchamps conditions,[3,4] i.e., by exposure to a suspen- formed, i.e., homoallylic stereocenter in decalindiones 28
sion of Cs2CO3 (0.5 equiv.) in dichloromethane at room and epi-28 was deduced from the H,H coupling constants
temp. (Scheme 4). After 10 h and complete consumption – compiled in Figure 2. We observed one trans-diaxial H,H
as judged by TLC – of both reactants, we obtained a 91:9 coupling per cyclohexanone ring, which means that each of
mixture of two spirolactones. The major product possesses them is a chair conformer and in that regard conformation-
4
stereostructure 27 as revealed by X-ray structural analysis ally distinct from predecessor 27. The occurrence of J7eq,5
(Figure 1). If the minor spirolactone is epi-27 as we be- = 1.2 Hz in 28 and its absence (4J7eq,5 ≈ 0 Hz) in epi-28
lieve,[27] 27 and epi-27 would be derived from the same di- imply a W-conformation for substructure H–C5–C6–C7–Heq
enolate stereoisomer 26 [with a (Z)-configured Cα=C1Ј in 28 and a different array of the same substructure in epi-
bond]. In addition, both 27 and epi-27 would be formed 28. This means that the C5–H bond of 28 is equatorial and
with the usual simple diastereoselectivity (ketone exo, ester the C5–allyl bond accordingly axial, while the opposite is
endo[3,4]). The difference between annulation products 27 true for epi-28.
and epi-27 would be the opposite orientation of the newly
The Deslongchamps annulation of the cesium enolate of
formed stereogenic bonds relative to the Cγ–CH2SiPh3 Nazarov reagent 20 to oxocyclohexenecarboxylate 29[31]
bond at the inducing stereocenter of the lactone. Unequivo- proceeded similarly (Scheme 5) as the annulation of
cally, the major annulation product 27 stems from an ap- Scheme 4. The spirolactones 31 and epi-31 resulted as a
proach of cyclohexenecarboxylate 25 to dienolate 26 from 94:6 mixture (76% yield). Again, the underlying stereocon-
the hindered β-face. This direction of the asymmetric induc- trol is due to a hitherto unprecedented 1,3-asymmetric in-
tion is unprecedented in the chemistry of γ-chiral γ-lactone duction[14] by the chiral γ-lactone substituent of dienolate
enolates.[14] The expected combination of the reactants intermediate 30; as in the example of Scheme 4, the favored
should have occurred on the unhindered α-face of dienolate sense of attack is contrasteric and presently inexplicable.
26 (Ǟ epi-27). At present, we have no clue as to what the
Isomers 31 and epi-31 were chromatographically[28] in-
reason for this behavior is.
separable. Thus, their mixture was subjected to the Bu4NF-
Figure 1. ORTEP plots of the crystal structure of decalindione 27.[23] Projection (a) shows relative configuration at C-4a vs. C-8a and a
front-view of a twist-boat conformation of cyclohexanone C-1/C-2/C-3/C-4/C-4a/C-8a (the oxygen atom attached to C-6 is hardly visible).
Projection (b) shows relative configurations at C-5 vs. C-4a vs. C-8a vs. C-8 vs. C-γ and represents a view upon a chair conformation of
cyclohexanone C-4a/C-5/C-6/C-7/C-8/C-8a (the oxygen atom attached to C-1 and the α-oriented oxygen atom of the dioxolane ring are
hardly visible).
Eur. J. Org. Chem. 2007, 1069–1074
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T. Tricotet, R. Brückner
SHORT COMMUNICATION
Scheme 4. Deslongchamps annulation of lactone 19 to oxocy-
clohexenecarboxylate 25. a) Cs2CO3 (0.5 equiv.), CH2Cl2, room
temp., 3 h (crude product: 27/epi-27 = 91:9), 27 (36%) + 75:25 mix-
ture of 27/epi-27 (23%); b) Bu4NF (2.2 equiv.), THF, room temp.,
10 h (crude product: 28/epi-28 = 75:25), 28 (37%) + 28/epi-28 mix-
ture (50:50; 20%) + epi-28 (6%).
Scheme 5. Deslongchamps annulation of lactone 20 to oxocy-
clohexenecarboxylate 29. a) Cs2CO3 (0.5 equiv.), CH2Cl2, room
temp., 10 h, 76% of an inseparable mixture of 31 and epi-31; b)
Bu4NF (3.0 equiv.), THF, room temp., 10 h, 64% (80% ee); c)
pTsOH·H2O (0.5 equiv.), acetone/H2O (2:1), room temp., 2 h, 88%.
companying tandem process, namely the cleavage/decarbox-
ylation of the β-oxo (trimethylsilyl)ethyl ester unit. This re-
action appears to be novel, too. It may become a room-
temp. alternative and orthogonal supplement to the Pd-cat-
alyzed cleavage/decarboxylation of β-oxo allyl esters.[32] The
result of this twin-tandem defunctionalization was a 64%
yield of decalindione 32.[33] This compound possessed 80%
ee.[29] This value means – considering that the precursor
Nazarov reagent 20 had 90% ee – that decalindione 32 was
generated from both precursors 31 and epi-31 in their mix-
ing ratio of 94:6.
1
Figure 2. H NMR coupling constants (500 MHz in CDCl3) prov-
ing the relative configurations of decalindiones 28 and epi-28.
The acid-catalyzed cleavage of the dimethyl ketal moiety
of decalindione 32 in wet acetone led to decalintrione 33 in
induced tandem elimination/decarboxylation reaction first the terminating step of Scheme 5. According to our analy-
described in the context of Scheme 4. The lactone moieties ses of the magnitudes of Jring-H,vicinal ring-H values and
gave allyl groups thereby. Remarkably, there was an ac- ROESY cross-peaks in the 500 MHz NMR spectra of deca-
1072
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Eur. J. Org. Chem. 2007, 1069–1074

Decalins by Deslongchamps-Type Annulation of Dienolates
SHORT COMMUNICATION
[8]
Diastereoselectivity in Deslongchamps annulations induced by
chiral oxocyclohexenecarboxylates: a) ref.[3c]; b) ref.[3e]; c)
ref.[3f]; d) ref.[4f]; e) ref.[1]
lindione 32 and decalintrione 33, the latter compounds con-
serve the cis junction of the underlying rings already present
in spirolactones 31 and epi-31.
[9]
Diastereoselectivity in Deslongchamps annulations induced by
chiral dienolates: a) ref.[4a]; b) ref.[4c]; c) ref.[4d]
[10]
[11]
T. Tricotet, R. Brückner, Tetrahedron Lett. 2006, 47, 8499–
8502.
Conclusions
a) I. Shimizu, T. Yamada, J. Tsuji, Tetrahedron Lett. 1980, 21,
3199–3202; b) J. Tsuji, T. Yamada, I. Minami, M. Yuhara, M.
Nisar, I. Shimizu, J. Org. Chem. 1987, 52, 2988–2995.
In order to attain tetracycles 9 or 10 from 7 via 8, substituent
R1 must be functionalized in anticipation of the second ring-
closure. Implementing such an option we chose R1 = CH2–
CH2–OPMB in our study (PMB = p-methoxybenzyl).
T. Tricotet, Dissertation, University of Freiburg, 2006.
Representative examples for the selective functionalization of
lithium enolates of γ-chiral γ-lactones by electrophiles (“Eᮍ”)
from the unhindered side: a) Eᮍ = proton source: S. Takano,
W. Uchida, S. Hatakeyama, K. Ogasawara, Chem. Lett. 1982,
733–736; b) Eᮍ = RX: K. Tomioka, H. Mizuguchi, K. Koga,
Chem. Pharm. Bull. 1982, 30, 4304–4313 and references cited
therein; c) Eᮍ = RX, RCHO: C. Anceau, G. Dauphin, G. Co-
udert, G. Guillaumet, Bull. Soc. Chim. Fr. 1994, 131, 291–303;
d) Eᮍ = MoO5·pyridine·HMPA: S. Hanessian, S. P. Sahoo, P. J.
The present investigation establishes a conceptually novel
1,3-asymmetric induction as an efficient means for achiev-
ing stereocontrol in Deslongchamps annulations. The latter
provided substituted decalindiones and -triones with up to
five contiguous stereocenters. Functionalized side-chains
were incorporated, which should allow further elaboration
into tricyclic or tetracyclic ring systems like 9 and 10. Last
but not least, there are two worthwhile spin-off results,
namely (1) the use of a silylated lactone enolate as a homo-
allyl anion equivalent and (2) the first observation of the
dealkoxycarbonylation of a β-oxo (trimethylsilyl)ethyl ester
by treatment with Bu4NF at room temp.
[12]
[13]
[14]
Murray, Tetrahedron Lett. 1985, 26, 5631–5634; e) Eᮍ
=
Ph2S2:L. J. Wilson, D. C. Liotta, J. Org. Chem. 1992, 57, 1948–
1950; f) Eᮍ = Ts2NF: J. J. McAtee, R. F. Schinazi, D. C. Liotta,
J. Org. Chem. 1998, 63, 2161–2167.The same asymmetric in-
duction is encountered in the hydrogenation of α-(arylmethy-
lene)-γ-valerolactones (ref.[14b]).
Acknowledgments
This work was generously supported by the Fonds der Chemischen
Industrie through a Kekulé fellowship for T. T. We are indebted to
Dr. Manfred Keller for contributing the X-ray structural analyses
and detailed NMR studies.
[15]
[16]
We prepared ester 14 from ethyl diazoacetate, Ph3SiH, and
either Rh2(OAc)4 as described by V. Bagheri, M. P. Doyle, J.
Taunton, E. E. Claxton, J. Org. Chem. 1988, 53, 6158–6160 or
Cu(OTf)2 as described by O. Audrey, Y. Landais, D. Planch-
enault, V. Weber, Tetrahedron 1995, 51, 12083–12096.
[1] a) L. Chen, P. Deslongchamps, Can. J. Chem. 2005, 83, 728–
740; b) Erratum: L. Chen, P. Deslongchamps, Can. J. Chem.
2005, 83, 2144.
[2] a) I. N. Nazarov, S. I. Zavyalov, Zh. Obshch. Khim. 1953, 23,
1703; b) I. N. Nazarov, S. I. Zavyalov, Chem. Abstr. 1954, 48,
13667h.
1
All new compounds gave satisfactory H and 13C NMR spectra
and either correct combustion analyses (except oxo ester 29,
which was used without purification, and β-hydroxylactones 21
and 22, which were oxidized without characterization) or cor-
rect HRMS data (19, 20).
[3] Deslongchamps annulations with CO2tBu-containing Nazarov
reagents: a) J.-F. Lavallée, P. Deslongchamps, Tetrahedron Lett.
1988, 29, 5117–5118; b) J.-F. Lavallée, P. Deslongchamps, Tet-
rahedron Lett. 1988, 29, 6033–6036; c) R. Ruel, P. Deslongch-
amps, Tetrahedron Lett. 1990, 31, 3961–3964; d) R. Ruel, K. T.
Hogan, P. Deslongchamps, Synlett 1990, 516–518; e) J.-F. Lav-
allée, C. Spino, R. Ruel, K. T. Hogan, P. Deslongchamps, Can.
J. Chem. 1992, 70, 1406–1426; f) R. Ruel, P. Deslongchamps,
Can. J. Chem. 1992, 70, 1939–1949; g) D. Chapdelaine, J.
Belzile, P. Deslongchamps, J. Org. Chem. 2002, 67, 5669–5672;
h) B. Guay, P. Deslongchamps, J. Org. Chem. 2003, 68, 6140–
6148.
[4] Deslongchamps annulations with CO2Allyl-containing Naza-
rov reagents: a) O. Lepage, C. Stone, P. Deslongchamps, Org.
Lett. 2002, 4, 1091–1094; b) Z. Yang, D. Shannon, V. Truong,
P. Deslongchamps, Org. Lett. 2002, 4, 4693–4696; c) O. Lepage,
P. Deslongchamps, J. Org. Chem. 2003, 68, 2183–2186; d) A.
Rouillard, M.-A. Bonin, P. Deslongchamps, Helv. Chim. Acta
2003, 86, 3730–3739; e) ref.[3h]; f) S. Trudeau, P. Deslong-
champs, J. Org. Chem. 2004, 69, 832–838; g) ref.[1]
[5] Deslongchamps annulation with an SO2Ph-containing Naza-
rov reagent: ref.[3e]
[17]
[18]
[19]
Method: G. A. Molander, K. L. Bobitt, J. Org. Chem. 1994, 59,
2676–2678.
Prepared from (–)-α-pinene as described by H. C. Brown, N. N.
Joshi, J. Org. Chem. 1988, 53, 4059–4062.
The ee of diol 17 was determined by HPLC {Chiralpak AD
column, n-heptane/iPrOH 90:10, 0.8 mL/min, 23 °C, UV detec-
tion 223 nm; tR[(S) enantiomer] = 14.9 min, tR[(R) enantiomer]
= 19.7 min}, the result varying (90–95%) with the (+)-(IPC)2-
BH sample used.
[20]
[21]
[22]
A. De Mico, R. Margarita, L. Parlanti, A. Vescovi, G. Piancat-
elli, J. Org. Chem. 1997, 62, 6974–6977.
T. M. Hansen, G. J. Florence, P. Lugo-Mas, J. Chen, J. N. Ab-
rams, C. J. Forsyth, Tetrahedron Lett. 2003, 44, 57–59.
The ee of lactone 18 was determined by HPLC {Chiralpak AD
column, n-heptane/iPrOH 97:3, 0.8 mL/min, 23 °C, UV detec-
tion 223 nm; tR[(S) enantiomer] = 13.1 min, tR[(R) enantiomer]
= 14.4 min}.
[23]
[24]
CCDC-627185 (for 18) and -627186 (for 27) contain the sup-
plementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
α,β-Unsaturated aldehyde 24 was prepared from p-anisal-
dehyde and propane-1,3-diol in 3 known steps (F. M. Cordero,
F. Pisaneschi, M. Gensini, A. Goti, A. Branchi, Eur. J. Org.
Chem. 2002, 1941–1951) followed by a Wittig reaction with
Ph3P=C(Me)–CH=O (prepared by the procedure of R. H.
Schlessinger, M. A. Poss, S. Richardson, P. Lin, Tetrahedron
Lett. 1985, 26, 2391–2394).
[6] Deslongchamps annulations with SOPh-containing Nazarov
reagents: a) ref.[3e]; b) ref.[3h]
[7] exo with respect to the oxo group and endo with respect to the
ester group of dienophiles 1. This equals the simple diastereo-
selectivity of SnCl4-catalyzed Diels–Alder reactions between
neutral dienes and oxocyclohexenecarboxylates: a) H.-J. Liu,
T. K. Ngooi, Can. J. Chem. 1984, 62, 2676–2681; b) H.-J. Liu,
T. K. Ngooi, E. N. C. Browne, Can. J. Chem. 1988, 66, 3143–
3152.
1
[25]
The H NMR spectrum (500 MHz, CDCl3) of Nazarov reagent
19 showed a 33:30:37 mixture of 2 diastereomeric ketones and
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T. Tricotet, R. Brückner
SHORT COMMUNICATION
an enol, respectively, the spectrum of Nazarov reagent 20 a
quite differently composed 52:45:3 mixture.
[26] Oxocyclohexenecarboxylate 25 was prepared from 4,4-(ethyl-
enedioxy)cyclohexanone in 3 steps as described by D. Liotta,
C. Barnum, G. Zima, C. Bayer, H. S. Kezar III, J. Org. Chem.
1981, 46, 2920–2923.
[33] (4aS,5S,7R,8S,8aR)-5-Allyl-4,4-dimethoxy-3,4,4a,7,8,8a-
hexahydro-8-{2-[(4-methoxybenzyl)oxy]ethyl}-7-methylnaph-
thalene-1,6(2H,5H)-dione (32): At 0 °C Cs2CO3 (180 mg,
0.55 mmol, 0.5 equiv.) was added to a stirred solution of Naza-
rov reagent 19 (656 mg, 1.11 mmol) in CH2Cl2 (10 mL). After
5 min, a solution of oxocyclohexenecarboxylate 29 (333 mg,
1.11 mmol, 1.0 equiv.) in CH2Cl2 (5 mL) was added dropwise
over a period of 1 min. A yellow heterogeneous mixture re-
sulted, which was stirred at 0 °C for 1 h and at room temp. for
2 h and then filtered through a pad of silica gel. The pad was
eluted first with CH2Cl2, then with EtOAc. The late fractions
were collected and the solvent was evaporated under reduced
pressure. This provided a mixture of annulation products 31
and epi-31 (750 mg, 76%). Without further purification, a por-
tion of this mixture (154 mg, 173 µmol) was dissolved in THF
(4 mL). Bu4NF (1.0  in THF, 518 µL, 518 µmol, 3.0 equiv.)
was added dropwise while stirring at 0 °C during 2 min. The
mixture was warmed to room temp. slowly (3 h), stirred for
another 7 h, and poured into a mixture of water (20 mL) and
brine (10 mL). Extraction with Et2O (4ϫ30 mL), drying of the
combined extracts with Na2SO4, evaporation of the solvent un-
der reduced pressure, and flash chromatography on silica gel[28]
(cyclohexane/EtOAc, 5:1) furnished the title compound
(49.0 mg, 64%) as a colorless oil. 1H NMR (500.0 MHz,
CDCl3): δ = 0.97 (d, J7-CH3,7 = 6.6 Hz, 7-CH3), 1.03 (mc,
[27] This assignment accomodates the following observations: a)
the 1H NMR subspectra of the A-ring/B-ring moieties of com-
pounds epi-27 and 27 are nearly identical; b) the proton at Cγ
of the lactone moiety is deshielded in the major (δ27
=
4.91 ppm) compared to the minor isomer (δepi-27 = 4.57 ppm);
this appears to reflect the proximity between the γ-H and the
B-ring carbonyl group in isomer 27.
[28] W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923–
2925.
[29] a) G. Schmid, W. Hofheinz, J. Am. Chem. Soc. 1983, 105, 624–
625; b) T. Mori, K. Suzuki, Chem. Lett. 1989, 2165–2168.
[30] The ee of decalindione 32 was determined by HPLC [Chiralpak
AD column, n-heptane/iPrOH 95:5, 0.8 mL/min, 23 °C, UV
detection 226 nm; tR(minor enantiomer) = 17.4 min, tR(major
enantiomer) = 20.8 min].
[31] Oxocyclohexenecarboxylate 29 was prepared in 5 steps: (1) ad-
dition (!) of 2 equiv. of MeOH to 3-(furan-2-yl)acrylic acid giv-
ing dimethyl 4-oxopimelate, yet not employing HCl gas as in
the original report (W. Markwald, Ber. Dtsch. Chem. Ges. 1887,
2811–2817) but solvolyzing SOCl2 as published for the other-
wise analogous preparation of diethyl 4-oxopimelate (A. L.
Gutman, K. Zuobi, T. Bravdo, J. Org. Chem. 1990, 55, 3546–
3552); (2) ketal formation with HC(OMe)3/pTsOH; (3) Dieck-
mann condensation as reported by J. A. Marshall, R. A.
Ruden, J. Org. Chem. 1971, 36, 594–596; (4) transesterification
with 2-(trimethylsilyl)ethanol catalyzed by ClBu2SnOSnBu2OH
(method: J. Otera, T. Yano, A. Kawabata, H. Nozaki, Tetrahe-
dron Lett. 1986, 27, 2383–2386); (5) successive treatments with
PhSeCl/pyridine and H2O2 as described in ref.[4f] Because of the
instability of oxocyclohexenecarboxylate 29 its phenyl selenide
precursor was oxidized directly before use. This afforded 29 in
100% yield sufficiently pure.
1ЈЈ-HA), 1.72 (dddd, Jgem
= 14.3 Hz, J1ЈЈ-H(B),2ЈЈ-H(A) =
J1ЈЈ-H(B),2ЈЈ-H(B) = 7.1 Hz, J1ЈЈ-H(B),8 = 4.0 Hz, 1ЈЈ-HB), 1.93 (mc,
3-Hax), 2.16 (mc, 5-H), 2.22 (mc, 3-Heq), 2.44–2.54 (m, 4a-H,
2-H2, 1Ј-HA), 2.66 (mc, 1Ј-HB), 2.76 (mc, 8-H), 2.87 (dq,
J7,7-CH3 = J7,8 = 6.4 Hz, 7-H), 2.98 (dd, J8a,8 = 4.7 Hz, J8a,4a
=
1.9 Hz, 8a-H), 3.15 (s, 4-OMe), 3.17 (s, 4-OMe), AB signal (δA
= 2.88, δB = 2.88, JAB = 6.5 Hz, 2ЈЈ-H2), 3.80 (s, OMe, PMB),
AB signal (δA = 4.34, δB = 4.42, JAB = 11.7 Hz, OCH2Ar), 4.91
(mc, 3Ј-HE), 4.96 (mc, 3Ј-HZ), 5.72 (dddd, Jtrans = 17.1 Hz, Jcis
= 10.2, J2Ј,1Ј-H(A) ≈ J2Ј,1Ј-H(B) = 6.8 Hz, 2Ј-H), 6.85 (mc,
2ϫHmeta), 7.20 (mc, 2ϫHortho).
Received: December 1, 2006
Published Online: January 25, 2007
[32] T. Tricotet, R. Kramer, R. Brückner, unpublished results.
1074
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Eur. J. Org. Chem. 2007, 1069–1074