Enantiopure polycycles by sequential cycloadditions

Article abstract of DOI:10.1002/1099-0690(200111)2001:21<4051::AID-EJOC4051>3.0.CO;2-5

The enolsilyl ether 2, generated from butynone adduct 3, which is easily available from the enantiomerically pure cyclopentadiene 1, proved to be a general building block for polycyclic anellation products to cyclohexenone. After proper adjustment of functional groups in the cycloadducts by means of high pressure Diels-Alder cycloadditions, the thermal retro-process provided routes to various enantiopure alicyclic and heterocyclic target compounds in high yields.

Full text of DOI:10.1002/1099-0690(200111)2001:21<4051::AID-EJOC4051>3.0.CO;2-5

FULL PAPER
Enantiopure Polycycles by Sequential Cycloadditions
Martina Wolter,*[a] Claudia Borm,[a] Erik Merten,[a] Rudolf Wartchow,[a] and
Ekkehard Winterfeldt[a]
Keywords: Asymmetric synthesis / Cycloadditions / High-pressure chemistry / Polycycles / Retro reactions
The enolsilyl ether 2, generated from butynone adduct 3,
proper adjustment of functional groups in the cycloadducts
which is easily available from the enantiomerically pure
by means of high pressure Diels−Alder cycloadditions, the
cyclopentadiene 1, proved to be a general building block for thermal retro-process provided routes to various enantiopure
polycyclic anellation products to cyclohexenone. After
alicyclic and heterocyclic target compounds in high yields.
Introduction
step. Once optimized, this reaction should work reliably for
a whole series of compounds, thus generating polycyclic li-
braries with these functional groups in common.
While selectivity studies with the chiral cyclopentadiene
1 had opened up highly efficient options for clearcut kinetic
resolutions[1,2] and for the differentiation of enantiotopic
double bonds in high yield,[3,4] subsequent retro-reactions
producing the enantiopure target compounds proved to be
quite structure-dependent.[5] Individual optimisation stud-
ies for this step were generally called for if high yields of
the retro-product and good recovery of diene 1 were to be
achieved.[6]
For this reason we became interested in an intermediate
4π-system 2 (Scheme 1), which would enable polycyclic
compounds to be ’’grown’’ on the butadiene moiety in sub-
sequent cycloadditions and which would then permit recon-
struction of comparable structural units in the final retro-
Results and Discussion
It was therefore with quite some excitement that we ob-
served highly diastereoselective and regioselective α-exo ad-
ditions (see 5 and 11), kinetic resolutions (see 9) and differ-
entiations of enantiotopic double bonds (see 7) in the
DielsϪAlder chemistry of the electron rich diene 2, which
is easily generated from the butynone adduct 3.
Out of quite a number of cycloadditions performed with
diene 2, we focus here on the DielsϪAlder cycloadditions
of dienophiles 4, 6, 8, and 10, all of which provided high
yields of the corresponding cycloadducts 5, 7, 9, and 11
under high pressure conditions (12Ϫ14 kbar). Additionally,
they all underwent highly selective proton-catalysed enol
ether hydrolysis to yield the parent ketones.
In the case of the kinetic resolution of keto ester 8, it
was possible not only to readily reisolate the pure unreacted
enantiomer 12 from the reaction mixture, with an ee higher
than 98%, but also to generate the enantiopure cyclohex-
enone derivative 13 from cycloadduct 9, by means of a silyl
ether hydrolysis followed by a thermal retro-reaction.
Although the α-exo addition configurations portrayed in
Scheme 2 for all cycloadducts are fully in line with earlier
observations in the field of bicycloheptanes of this type,[7]
they were also explicitly proved by NMR experiments in
all cases.
This was of particular importance for the quinone-mono-
ketal adduct 11, since this compound is clearly set up for
further ring-anellating cycloadditions with electron-rich 4π-
systems, thus highlighting the possibility of making poly-
cyclic systems ‘‘grow’’ on the chiral template in a sterically
highly predictable manner (Scheme 3).
Scheme 1
As a simple example we picked 1-methoxybutadiene, and
were pleased to isolate a quantitative yield of the single di-
astereomer 15.
While the first addition is in all cases reliably directed in
an α-exo fashion by the configuration of diene 2, this se-
[a]
Institut für Organische Chemie der Universität Hannover
Schneiderberg 1B, 30167 Hannover, Germany
Fax: (internat.) ϩ49 511 / 762 3011
E-mail: martina.wolter@gmx.de
Eur. J. Org. Chem. 2001, 4051Ϫ4060
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/1121Ϫ4051 $ 17.50ϩ.50/0
4051

M. Wolter, C. Borm, E. Merten, R. Wartchow, E. Winterfeldt
FULL PAPER
Scheme 3
Scheme 4
Scheme 2
Another typical case of double bond shift was encoun-
cond one Ϫ since it takes place on a cis-decalone system Ϫ tered with the cyclopentenone intermediate 21. Although
is expected to operate in an α-endo mode, which is perfectly this material was obtained easily from the cycloaddition be-
borne out by the NMR data of cycloadduct 15.
tween 4-acetoxycyclopentenone-1 and butadiene 2, followed
This compound, in the same way as already described for by enol ether hydrolysis accompanied by a very high-
9, underwent the retro-DielsϪAlder reaction as predicted, yielding elimination process, the polycyclic systems pro-
under fairly comparable conditions, to provide the cyclo- duced in remarkably high yields from 21 (see Scheme 5),
hexenone-anellation product 16. While this outcome was proved to be hard to handle.
left unoptimized in the case of 13, the nearly quantitative
yield (99%) attainable with the polyfunctionalized tricyclic acetoxybutadiene and providing nice crystals for X-ray-
compound 15 is certainly worth mentioning.
structure determination,[8] thus once more proving the α-
Compound 20, although produced in 99% yield from
Although the outcome of the retro-process is highly satis- endo addition process, created difficulties in the thermal re-
factory with this diketone, other cycloadducts generated tro-process. Similarly, the tetracyclic triketone 23, obtained
from 14 clearly suffered from the fact that their retro-prod- in excellent yield from dienophile 22 by way of enol silyl
ucts represent vinylogous 1,3-dicarbonyl systems, which ether 24, gives rise to a complex mixture of retro-products.
show a high tendency towards double bond shifts and even
Finally, a very similar outcome was obtained by use of
aromatization, owing to enolization processes.
β-indolylacrylate as the 4π-system (Scheme 6). This time, a
Typical examples are the adducts with dimethylbutadiene high-pressure cycloaddition-isomerization sequence re-
(see 17, Scheme 4) and with cyclopentadiene (see 18), which sulted in a 72% yield of the α-endo addition product 25 (X-
both produced partially aromatic compounds (NMR evi- ray data).[9] The retro-process, however, although it took
dence) on heating.
place even at 200 °C, unfortunately provided a mixture of
4052
Eur. J. Org. Chem. 2001, 4051Ϫ4060

Enantiopure Polycycles by Sequential Cycloadditions
FULL PAPER
be a selective reduction of the keto group in cycloadduct 11
to abolish this functional group pattern.
This indeed worked nicely with K-Selectride, which pro-
vided a quantitative yield of allylic alcohol 26, and when
this material was treated with Amberlyst 15[10] at room tem-
perature it gave rise to the sterically well defined unsatur-
ated ketone 27 in quantitative yield (Scheme 7).
Scheme 7
Of particular interest in this case, however, was the obser-
vation of an unusually easy retro-reaction. The stable unsa-
turated ketone 28 was generated as soon as the reaction
temperature of the subsequent silyl ether hydrolysis rose
above 30 °C.
Scheme 5
This was a very encouraging result, which called for the
preparation of a more complicated ring-system starting
from the unsaturated ketone 27. To benefit from the reactiv-
ity of an electron-rich 4π-system additionally offering op-
tions for heterocyclic compounds, we selected butadiene 29,
which had been prepared[11,12] and investigated[11] by
Nicolaou in connection with lactam-derived aminal-phos-
phates.[11]
The cycloaddition of this diene took place at 14 kbar, to
provide adduct 31 as one single enantiopure reaction prod-
uct (Scheme 8). This was quantitatively cleaved into diene 1
and the heterocyclic diketone 30, even at 150 °C, without
any enolization, elimination, or aromatization.
retro-products containing the cyclohexenone only in a
meagre 20% yield. All the rest of the retro-material proved
to be the outcome of ill-defined enolisation and aromatiz-
ation processes.
While these eclectic results certainly prove the high po-
tential of the cycloadditions involved in the preparation of
a wide range of polycyclic systems, they also point to the
retro-reaction as the bottleneck of the project.
As all the information thus far collected left no doubt
that the unsaturated dicarbonyl system (vinylogous 1,3-di-
carbonyl) was the culprit, the simplest solution seemed to
Although this convincingly establishes the advantages of-
fered by Selectride reduction of the dienophile, one should
in this particular case not overlook the ready isomerization
of the enamine double bond from the trisubstituted to the
thermodynamically more stable tetrasubstituted position
under retro-reaction conditions. This shift can in some
cases take place during the cycloaddition process itself, but
was also observed under the conditions of workup or of
purification of cycloaddition products. Traces of hydro-
chloric acid in chloroform or treatment with silica can easily
trigger this reaction and, as it seems to be far more general
with our system than with that documented in Nicolaou’s
seminal paper on these very useful dienes, we refer readers
Scheme 6
Eur. J. Org. Chem. 2001, 4051Ϫ4060
4053

M. Wolter, C. Borm, E. Merten, R. Wartchow, E. Winterfeldt
FULL PAPER
provide the synthetically highly flexible indoloquinolizinone
building block 34, which has a high potential for enantiose-
lective alkaloid synthesis.[15,16]
A close investigation of this cycloaddition proved the
non-protonated imine itself to be a comparatively poor di-
enophile, providing only quite low yields (ഠ 15%) of cyclo-
adduct 33. When salts were employed, however, the yield
rose substantially and by far the best results were obtained
with the corresponding trifluoroacetate 32b in the presence
of 10% α,αЈ-bis-tert-butylpyridine as a proton scavenger.
Subsequent treatment with camphorsulfonic acid provided
the sterically pure α-exo adduct 33 in an overall yield of
98%. In the presence of other, less hindered, bases this ster-
eoisomer was generally accompanied by the corresponding
α-endo product (β HA).
With this simple and high-yielding preparation of the en-
antiopure cycloadduct 33 in hand, the thermal retro-process
was studied. We were very pleased to note the clean (86%)
formation of the versatile indoloquinolizinone 34 even at
150 °C, with an ee value of Ͼ 98%.
Conclusions
In conclusion, we have demonstrated that starting with
the electron-rich and very efficiently directing enantiopure
diene 2 one can make polycyclic systems ‘‘grow’’ quite
easily on this chiral template.
It was also shown that the quinone monoketal adduct 7,
despite being a very attractive dienophile, has to be select-
ively reduced for further anellations if clean and reliable
retro-reactions are to be secured.
Scheme 8
to the dissertation by one of us (M. W.)[9] for a detailed
report on the behaviour of cycloadducts of this type.
Finally, to complete the list of dienophiles in the trans-
formations with diene 2, we chose salts of dihydro-norhar-
mane 32[13,14] as examples of
a
heterodienophile
A very simple synthesis of the enantiopure general alka-
loid building block 34 illustrates the preparative value of
diene 2.
(Scheme 9).
Experimental Section
General Remarks: Melting points were determined on a Gallen-
kamp apparatus and are uncorrected. Ϫ Optical rotations were
measured on a PerkinϪElmer 241 or 341. Ϫ IR spectra were re-
corded in CHCl3 or in KBr with a Bruker IFS 25 spectrometer or
with a Bruker Vector 22 spectrometer using an attenuated total
reflection (ATR) method. Ϫ UV spectra were measured on a
Beckmann 3600 spectrometer. Ϫ NMR spectra were recorded on a
Bruker WP 200 (200 MHz) or AM 400 (400 MHz) spectrometer;
δH values are given relative to TMS ϭ 0; δC values are given relative
to CDCl3 (δ ϭ 77.05); multiplicities of 13C NMR were determined
by DEPT (90°/135°) or by APT. Ϫ MS assays were obtained using
a Finnigan MAT 312 (MS) or a VG Autospec (MS-FAB and
HRMS) with an ionization potential of 70 eV. Ϫ Elemental analysis
were carried out on a Heraeus CHN rapid analyser. Ϫ For flash
chromatography, Baker silica gel (30Ϫ60 µm) was used. TLC analy-
60
sis were carried out on ‘‘DC aluminium foils’’, coated with
F
254
silica gel (E. Merck); the spots were detected by UV (254 nm) and
also with the aid of a dipping bath of cerium(IV) sulfate/phospho-
molybdic acid reagent. Ϫ Organic solvents were purified and dried
by standard procedures. Air- and moisture-sensitive reactions were
Scheme 9
This imine, however, was not picked mainly for mecha-
nistic reasons. We were of course also well aware of the
fact that with this 2π-system our reaction sequence should performed in flame-dried reaction vessels under inert atmospheres
4054 Eur. J. Org. Chem. 2001, 4051Ϫ4060

Enantiopure Polycycles by Sequential Cycloadditions
FULL PAPER
of argon or nitrogen. High-pressure reactions were carried out in °C): m/z (%) ϭ 567 (96) [Mϩ], 552 (77), 510 (15), 484 (17), 472
a Nova Swiss apparatus (max. 6.5 kbar) or in a Hofer apparatus (56), 458 (13), 380 (15), 365 (12), 296 (12), 240 (16), 188 (42), 165
(max. 14 kbar). For retro-DielsϪAlder reactions, a special flash- (23), 121 (50), 95 (51), 83 (57). Ϫ HRMS: C35H41NO4Si (567.3):
vacuum pyrolysis apparatus was used. Cyclopentadiene 1 was pre-
calcd. 567.280488; found 567.278870.
pared according to the procedure described by Winterfeldt et al.[17]
Spirolactone Adduct 7: A solution of siloxydiene 2 (100 mg, 263
µmol) and spirolactone 6 (43 mg, 263 µmol) in dry dichlorome-
thane (1 mL) was introduced into a Teflon vessel and subjected to
6.5 kbar in a high pressure autoclave for 14 days. Purification of
the raw material by flash chromatography (Et2O/PE, 1:1) afforded
7 (90 mg, 63%) as a white solid. [α]2D0 ϭ ϩ28.1 (c ϭ 0.100, CHCl3).
Siloxydiene 2: ZnCl2 (100 mg, 747 µmol) was flame-dried under
vacuum. Afterwards, NEt3 (2 mL) was added under nitrogen atmo-
sphere. After the suspension had been stirred at room temperature
for 30 min, a solution of butynone adduct 3 (235 mg, 760 µmol) in
dry toluene (2 mL) was added. After 10 min, dry TMS-Cl (116 µL,
916 µmol) was added. The solution was stirred for 1 h. Purification
by fast flash chromatography on Alox N (III) afforded siloxydiene
2 (283 mg, 98%) as a bright yellow oil. [α]2D0 ϭ Ϫ12.7 (c ϭ 0.350,
˜
Ϫ IR (KBr): ν ϭ 2928 (m), 2859 (m), 1781 (vs), 1515 (s), 1463 (m),
1
1250 (s), 865 (m), 845 (m) cmϪ1. Ϫ H NMR (200 MHz, CDCl3):
δ ϭ Ϫ0.20 (s, 9 H), 0.41 (dbr, J ϭ 13.0 Hz, 1 H), 0.81 (s, 3 H),
1.04Ϫ1.41 (m, 4 H), 1.55 (m, 1 H), 1.74 (dbr, J ϭ13 Hz, 2 H), 1.90
(ddd, J ϭ 1/5/11 Hz, 2 H), 2.17 (m, 2 H), 2.32Ϫ2.43 (m, 1 H), 2.52
(quin, J ϭ 4.0 Hz, 1 H), 2.72 (m, 2 H), 2.82 (d, J ϭ 10.0 Hz, 1 H),
3.78 (s, 3 H), 5.91 (d, J ϭ 5.5 Hz, 1 H), 6.09 (d, J ϭ 1/10 Hz, 1 H),
6.18 (d, J ϭ 5.5 Hz, 1 H), 6.65 (d, J ϭ 10.0 Hz, 1 H), 6.80 (m, 2
H), 7.12Ϫ7.27 (sbr, 2 H). Ϫ MS (150 °C): m/z (%) ϭ 544 (41) [Mϩ],
529 (4), 379 (7), 240 (100). Ϫ HRMS: C33H40O5Si (544.3): calcd.
544.2645; found 544.2651. Ϫ C33H40O5Si (544.3): calcd. C 72.76,
H 7.41; found C 72.76, H 7.40.
˜
CHCl3). Ϫ IR (film): ν ϭ 3055 (m), 2927 (s), 2857 (s), 1670 (m),
1614 (m), 1515 (s), 1463 (m), 1443 (m), 1250 (s), 1179 (s), 848 (s)
1
cmϪ1. Ϫ H NMR (200 MHz, CDCl3): δ ϭ Ϫ0.19 (m, 9 H), 0.55
(dbr, J ϭ 13.0 Hz, 1 H), 1.05 (s, 3 H), 1.15Ϫ1.36 (m, 3 H),
1.58Ϫ1.76 (m, 2 H), 2.05Ϫ2.24 (m, 2 H), 3.80 (s, 3 H), 3.87 (d, J ϭ
0.5 Hz, 1 H), 4.12 (d, J ϭ 0.5 Hz, 1 H), 6.59 (d, J ϭ 5.0 Hz, 1 H),
6.85 (m, 2 H), 6.97 (d, J ϭ 5.0 Hz, 1 H), 7.17 (m, 2 H). Ϫ 13C
NMR (100 MHz, CDCl3): δ ϭ 0.3 (CH3), 17.5 (CH3), 21.4 (CH2),
23.8 (CH2), 24.2 (CH2), 30.0 (CH2), 55.5 (CH3), 65.9 (C), 74.7 (C),
82.5 (C), 93.8 (CH2), 113.0 (CH), 129.8 (C), 130.1 (CH), 142.2
(CH), 144.7 (CH), 148.0 (CH), 154.2 (C), 157.0 (C), 158.4 (C). Ϫ
MS (60 °C): m/z (%) ϭ 380 (35) [Mϩ], 365 (16), 308 (4), 297 (12),
240 (22), 73 (78). Ϫ HRMS: C24H32O2Si (380.2): calcd. 380.2172;
found 380.2171.
Keto Ester Adduct 9: A solution of siloxydiene 2 (100 mg, 263
µmol) and keto ester 8 (70 mg, 263 µmol) in dry dichloromethane
(1 mL) was introduced into a Teflon vessel and subjected to 6.5
kbar in a high pressure autoclave for 5 days. Purification of the
raw material by flash chromatography (Et2O/PE, 1:30) afforded 9
(85 mg, 50%) as a colourless oil. [α]2D0 ϭ ϩ42.2 (c ϭ 1.250, CHCl3).
Butynone Adduct 3:
A solution of cyclopentadiene 1 (3 g,
12.5 mmol) and butynone (4.2 g, 62 mmol) in dry dichloromethane
(15 mL) was refluxed for 18 h under a nitrogen atmosphere with
exclusion of light. Toluene (15 mL) was then added at room tem-
perature and the mixture was concentrated. Purification of the raw
material by flash chromatography (Et2O/PE, 1:5) afforded 3
(3.85 g, 100%) as a white solid. M.p.: 73 °C. Ϫ [α]2D0 ϭ Ϫ294 (c ϭ
˜
Ϫ IR (CHCl3): ν ϭ 2960 (s), 2864 (m), 1732 (s), 1612 (m), 1512
(s), 1464 (m), 1444 (m), 1252 (s), 1156 (m), 1076 (s), 848 (s) cmϪ1
1H NMR (200 MHz, CD2Cl2): δ ϭ Ϫ0.13 (m, 9 H), 0.39 (dbr,
.
Ϫ
J ϭ 13.0 Hz, 1 H), 0.70 (s, 3 H), 0.79 (s, 3 H), 1.14 (s, 3 H), 1.25
(tr, J ϭ 7.0 Hz, 3 H), 1.10Ϫ1.47 (m, 6 H), 1.66 (m, 1 H), 2.01Ϫ2.35
(m, 3 H), 2.57 (d, J ϭ 6.0 Hz, 2 H), 3.12 (tr, J ϭ 6.0 Hz, 1 H), 2.77
(m, 1 H), 3.29Ϫ3.73 (m, 5 H), 3.78 (s, 3 H), 4.15 (q, J ϭ 7.0 Hz, 2
H), 5.90 (d, J ϭ 5.5 Hz, 1 H), 6.25 (d, J ϭ 5.5 Hz, 1 H), 6.82 (m,
2 H), 7.22 (m, 2 H). Ϫ MS (130 °C): m/z (%) ϭ 648 (100) [Mϩ],
634 (4), 603 (9), 576 (2), 379 (16), 240 (59), 73 (50). Ϫ HRMS:
C38H52O7Si (648.4): calcd. 648.3482; found 648.3479.
˜
1.000, CHCl3). Ϫ IR (CHCl3): ν ϭ 2932 (m), 2856 (w), 1660 (s),
1612 (m), 1512 (m), 1448 (w), 1248 (w), 1180 (m), 832 (m) cmϪ1
.
1
Ϫ UV (MeOH): λmax ϭ 206 (s), 221 (s), 260Ϫ270 (sh) nm. Ϫ H
NMR (200 MHz, CDCl3): δ ϭ 0.70 (dbr, J ϭ 13.0 Hz, 1 H), 1.00
(s, 3 H), 1.22Ϫ1.51 (m, 3 H), 1.61Ϫ1.78 (m, 2 H), 2.03Ϫ2.30 (m,
2 H), 2.22 (s, 3 H), 3.78 (s, 3 H), 6.58 (d, J ϭ 5.5 Hz, 1 H), 6.83
(m, 2 H), 6.97 (d, J ϭ 5.5 Hz, 1 H), 6.98 (m, 2 H), 7.36 (s, 1 H).
Monoketal Adduct 11: A solution of siloxydiene 2 (400 mg,
1.05 mmol) and monoketal 10 (208 mg, 1.37 mmol) in dry dichloro-
methane (1.5 mL) was introduced into a Teflon vessel and sub-
jected to 14 kbar in a high pressure autoclave for 4 days. Purifica-
tion of the raw material by flash chromatography (Et2O/PE, 1:10)
Ϫ
13C NMR (100 MHz, CDCl3): δ ϭ 16.8 (CH3), 20.7 (CH2), 23.2
(CH2), 23.6 (CH2), 27.3 (CH3), 29.3 (CH2), 55.1 (CH3), 67.1 (C),
74.7 (C), 84.0 (C), 113.0 (CH), 128.5 (C), 128.9 (CH), 143.4 (CH),
146.8 (CH), 158.0 (C), 159.1 (CH), 160.2 (C), 196.1 (CϭO). Ϫ MS
(RT): m/z (%) ϭ 308 (9) [Mϩ], 293 (27), 277 (11), 265 (30), 251
(26), 240 (12), 223 (21), 178 (21), 165 (27), 115 (25). Ϫ HRMS:
C21H24O2 (308.2): calcd. 308.1776; found 308.1771. Ϫ C21H24O2
(308.2): calcd. C 81.77, H 7.85; found C 81.66, H 7.77.
yielded 553 mg (1.04 mmol, 99%) of 11 as a white solid. [α]2D0
ϭ
˜
ϩ112.4 (c ϭ 1.250, CHCl3). Ϫ IR (film): ν ϭ 3039 (w), 2919 (s),
2859 (m), 1682 (vs), 1515 (vs), 1439 (m), 1249 (s), 845 (s) cmϪ1. Ϫ
1H NMR (400 MHz, CDCl3): δ ϭ Ϫ0.21 (s, 9 H), 0.37 (dbr, J ϭ
12.5 Hz, 1 H), 0.75 (s, 3 H), 1.01Ϫ1.18 (m, 2 H), 1.20Ϫ1.36 (m, 2
H), 1.50 (dbr, J ϭ 13.0 Hz, 1 H), 1.70Ϫ1.82 (m, 2 H), 1.88 (ddd,
Methyl-N-phenylmaleinimide Adduct 5: A solution of siloxydiene 2
(150 mg, 0.39 mmol) and methyl-N-phenylmaleinimide 4 (74 mg,
0.39 mmol) in dry THF (1 mL) was introduced into a Teflon vessel J ϭ 1/4.4/11 Hz, 1 H), 1.96 (ddd, J ϭ 2/8.5/18 Hz, 1 H), 2.27 (d,
and subjected to 6.5 kbar in a high pressure autoclave for 7 days. J ϭ 18.0 Hz, 1 H), 2.81 (dd, J ϭ 4.5/7.7 Hz, 1 H), 2.85 (d, J ϭ
Purification of the raw material by flash chromatography (Et2O/ 11.0 Hz, 1 H), 3.78 (s, 3 H), 4.00Ϫ4.20 (m, 4 H), 5.90 (d, J ϭ
PE, 3:1) afforded 5 (188 mg, 85%) as a colourless oil. Ϫ IR 6.0 Hz, 1 H), 5.95 (dd, J ϭ 1/10 Hz, 1 H), 6.12 (d, J ϭ 6.0 Hz, 1
˜
(CHCl3): ν ϭ 2932 (w), 1712 (s), 1512 (m), 1384 (m), 1252 (s), 1032 H), 6.56 (d, J ϭ 10.0 Hz, 1 H), 6.78 (dbr, J ϭ 7.5 Hz, 2 H), 7.17
(w), 856 (m) cmϪ1. Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ Ϫ0.09 (m, (mc, 2 H). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ 0.1 (CH3), 16.8
9 H), 0.48 (dbr, J ϭ 13.0 Hz, 1 H), 0.85 (s, 3 H), 1.23 (s, 3 H), (CH3), 21.7 (CH2), 24.0 (CH2), 25.5 (CH2), 29.1 (CH2), 29.7 (CH2),
1.26Ϫ1.57 (m, 4 H), 1.61Ϫ1.90 (m, 2 H), 2.10Ϫ2.20 (m, 2 H), 2.29 42.6 (CH), 46.1 (CH), 51.5 (CH), 55.6 (CH3), 59.0 (C), 61.7 (C),
(dbr, J ϭ 13.0 Hz, 1 H), 2.47Ϫ2.60 (m, 2 H), 3.81 (s, 3 H), 6.01 (d, 64.5 (CH2), 66.3 (CH2), 67.0 (C), 105.7 (C), 121.6 (C), 128.2 (CH),
J ϭ 6.0 Hz, 1 H), 6.33 (d, J ϭ 6.0 Hz, 1 H), 6.84 (d, J ϭ 9.0 Hz, 129.1 (CH), 131.2 (C), 134.8 (CH), 135.0 (CH), 142.7 (C), 143.7
2 H), 7.22 (d, J ϭ 9.0 Hz, 2 H), 7.28Ϫ7.52 (m, 5 H). Ϫ MS (140 (CH), 143.8 (CH), 158.3 (C), 203.5 (CϭO). Ϫ MS (130 °C): m/z
Eur. J. Org. Chem. 2001, 4051Ϫ4060
4055

M. Wolter, C. Borm, E. Merten, R. Wartchow, E. Winterfeldt
(%) ϭ 532 (100) [Mϩ], 517 (5), 379 (6), 308 (7). Ϫ HRMS: J ϭ 9.0 Hz, 1 H), 3.44 (s, 3 H), 3.79 (s, 3 H), 3.80 (d, J ϭ 9.0 Hz,
FULL PAPER
C32H40O5Si (532.3): calcd. 532.2645; found 532.2637.
1 H), 3.89Ϫ4.10 (m, 5 H), 5.58 (mc, 1 H), 5.85 (ddbr, J ϭ 1/10.4 Hz,
1 H), 6.15 (ABq, J ϭ 6.0 Hz, 2 H), 6.87 (d, J ϭ 9.0 Hz, 2 H), 7.26
(d, J ϭ 9.0 Hz, 2 H). Ϫ 13C NMR (100 MHz, CDCl3, DEPT): δ ϭ
15.2 (CH3), 21.2 (CH2), 23.3 (CH2), 24.5 (CH2), 25.5 (CH2), 28.8
(CH2), 38.8 (CH2), 42.3 (CH), 42.8 (CH), 44.1 (CH), 46.6 (CH),
51.9 (CH), 53.1 (CH), 55.2 (CH3), 57.1 (CH3), 61.3 (C), 61.4 (C),
64.9 (CH2), 65.3 (CH2), 68.3 (C), 76.5 (CH), 109.3 (C), 113.0 (CH),
124.3 (CH), 128.0 (CH), 128.7 (CH), 130.1 (C), 137.5 (CH), 139.6
(CH), 158.0 (C), 209.0 (CϭO), 210.4 (CϭO). Ϫ MS-FAB: m/z
(%) ϭ 677 (49), 545 (2) [MHϩ], 544 (6) [Mϩ], 514 (2), 305 (4), 286
(6), 273 (12), 240 (100), 154 (13), 133 (27).
Cyclohexenone 13: Camphorsulfonic acid monohydrate (35 mg, 140
µmol) was added at 0 °C to a solution of keto ester adduct 9
(90 mg, 139 µmol) in dichloromethane (20 mL) for silyl ether hy-
drolysis. After the reaction mixture had been stirred for 90 min, it
was quenched with saturated, aqueous NaHCO3 and extracted
with dichloromethane. The combined organic layers were washed
with brine, dried (MgSO4), and concentrated. Chromatographic
purification (Et2O/PE, 1:3) yielded 78 mg (135 µmol, 97%) of the
hydrolysis product as a white foam. This product was placed in a
flash-vacuum pyrolysis apparatus and sublimed at 170 °C/10Ϫ3
mbar through a pyrolysis tube heated to 350 °C. Within 20 min a
1:1 mixture of 1 and cyclohexenone 13 was collected in a cold trap.
Chromatographic purification (Et2O/PE, 1:10) yielded 44 mg (130
Cyclohexenone 16: Compound 15 (188 mg, 0.37 mmol) was placed
in a flash-vacuum pyrolysis apparatus and sublimed at 250 °C/10Ϫ2
mbar through a pyrolysis tube heated to 350 °C. After 15 min, all
µmol, 96%) of 13 as a bright yellow oil. [α]2D0 ϭ ϩ22 (c ϭ 0.425, of the starting material had sublimed and a 1:1 mixture of cyclo-
˜
CHCl3). Ϫ IR (CHCl3): ν ϭ 3000 (w), 2936 (w), 1732 (s), 1684 (s) pentadiene 1 and cyclohexenone 16 was collected in a cold trap.
1
cmϪ1. Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.80 (s, 3 H), 1.14 (s, Chromatographic purification (Et2O/PE, 1:1) yielded 111 mg
3 H), 1.25 (tr, J ϭ 7.0 Hz, 3 H), 2.51 (d, J ϭ 12.0 Hz, 1 H), 2.63 (0.37 mmol, 99%) of 16 as a yellow oil. [α]2D0 ϭ ϩ152.0 (c ϭ 0.9,
˜
CHCl3). Ϫ IR (CHCl3): ν ϭ 2900 (w), 1724 (w), 1636 (s), 1568 (w),
(dd, J ϭ 6/12 Hz, 1 H), 3.24 (dd, J ϭ 5/6 Hz, 1 H), 3.30Ϫ3.45 (m,
1 H), 3.47 (d, J ϭ 7.0 Hz, 2 H), 3.55Ϫ3.75 (m, 3 H), 3.82 (m, 2 1408 (m), 1228 (s), 1152 (s), 1088 (s) cmϪ1. Ϫ 1H NMR (400 MHz,
H), 4.15 (q, J ϭ 7.0 Hz, 2 H), 6.06 (dd, J ϭ 2/10 Hz, 1 H), 6.92 CDCl3): δ ϭ 1.98Ϫ2.21 (m, 3 H), 2.33Ϫ2.46 (m, 3 H), 3.18Ϫ3.23
(dd, J ϭ 5/10 Hz, 1 H). Ϫ MS (140 °C): m/z (%) ϭ 336 (100) [Mϩ],
(m, 1 H), 3.41Ϫ3.49 (m, 1 H), 3.59 (s, 3 H), 3.88Ϫ3.92 (m, 2 H),
291 (72), 263 (25), 208 (31), 141 (99). Ϫ HRMS: C18H24O6 (336.2): 4.00Ϫ4.08 (m, 2 H), 4.29Ϫ4.32 (m, 1 H), 5.70 (d, J ϭ 10.0 Hz, 1
calcd. 336.1573; found 336.1572.
H), 5.73Ϫ5.81 (m, 2 H), 7.64 (d, J ϭ 10.0 Hz, 1 H). Ϫ 13C NMR
(100 MHz, CDCl3, DEPT): δ ϭ 24.3 (CH2), 35.6 (CH), 36.2 (CH2),
37.5 (CH), 38.2 (CH), 57.5 (CH3), 64.9 (CH2), 65.9 (CH2), 80.3
(CH), 109.4 (C), 113.8 (CH), 121.5 (CH), 125.2 (CH), 128.8 (CH),
141.7 (CH), 155.7 (CϭO), 200.1 (CϭO). Ϫ MS (90 °C): m/z (%) ϭ
304 (3) [Mϩ], 272 (2), 244 (2), 193 (7), 166 (3), 149 (4), 120 (4),
109 (16), 87 (11). Ϫ HRMS: C17H20O5 (304.1): calcd. 304.131074;
found 304.131653.
Monoketal Adduct 14: Camphorsulfonic acid monohydrate (25 mg,
100 µmol) was added at 0 °C to a solution of 11 (43 mg, 81 µmol)
in dichloromethane (10 mL). After the reaction mixture had been
stirred for 10 min, it was quenched with saturated, aqueous
NaHCO3 and extracted with dichloromethane. The combined or-
ganic layers were washed with brine, dried (MgSO4), and concen-
trated. Chromatographic purification (Et2O/PE, 1:1) yielded 36 mg
(78 µmol, 98%) of monoketal adduct 14 as a colourless oil. [α]2D0
ϭ
Dimethylbutadiene Adduct 17: A solution of 14 (155 mg,
Ϫ0.3 (c ϭ 1.75, CHCl3). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 0.47 0.34 mmol) and 2,3-dimethylbutadiene (75 µL, 0.68 mmol) in dry
(dbr, J ϭ 13.0 Hz, 1 H), 0.76 (s, 3 H), 1.08Ϫ1.45 (m, 4 H), dichloromethane (1 mL) was introduced into a Teflon vessel and
1.55Ϫ1.90 (m, 2 H), 2.04 (m, 1 H), 2.06 (dd, J ϭ 6.5/17 Hz, 1 H), subjected to 14 kbar in a high pressure autoclave for 14 days. Puri-
2.29 (dd, J ϭ 5/17 Hz, 1 H), 2.58 (dd, J ϭ 5/9 Hz, 1 H), 2.78 (qbr, fication of the raw material by flash chromatography (Et2O/PE,
J ϭ 5.5 Hz, 1 H), 3.01 (tr, J ϭ 9.0 Hz, 1 H), 3.89 (d, J ϭ 9.0 Hz,
1:1) yielded 37 mg (0.07 mmol, 20%) of 17 as a white foam. [α]2D0
ϭ
˜
1 H), 3.89 (s, 3 H), 3.92Ϫ4.10 (m, 4 H), 6.04 (dd, J ϭ 1/10.5 Hz, 1 Ϫ60.0 (c ϭ 0.68, CHCl3). Ϫ IR (CHCl3): ν ϭ 2924 (m), 1712 (s),
H), 6.13 (d, J ϭ 5.5 Hz, 1 H), 6.19 (d, J ϭ 5.5 Hz, 1 H), 6.54 (d,
1612 (w), 1516 (m), 1444 (w), 1376 (m), 1248 (s), 1124 (m) cmϪ1
.
J ϭ 10.5 Hz, 1 H), 6.86 (m, 2 H), 7.21 (m, 2 H). Ϫ 13C NMR Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.50 (dbr, J ϭ 14.0 Hz, 1 H),
(100 MHz, CDCl3, DEPT): δ ϭ 15.4 (CH3), 21.2 (CH2), 23.5 0.80 (s, 3 H), 0.95Ϫ1.49 (m, 6 H), 1.58 (s, 3 H), 1.68 (s, 3 H),
(CH2), 25.5 (CH2), 28.7 (CH2), 38.8 (CH2), 42.3 (CH), 44.1 (CH), 1.61Ϫ1.75 (m, 1 H), 1.85Ϫ2.09 (m, 4 H), 2.27Ϫ2.52 (m, 4 H), 2.82
47.6 (CH), 53.2 (CH), 55.2 (CH3), 60.6 (C), 61.3 (C), 64.6 (CH2), (d, J ϭ 10.0 Hz, 1 H), 2.87Ϫ2.95 (m, 1 H), 3.54 (tr, J ϭ 8.0 Hz, 1
66.0 (CH2), 67.7 (C), 104.2 (C), 113.0 (CH, 2 ϫ), 128.4 (CH, 2 ϫ), H), 3.79 (d, J ϭ 10.0 Hz, 1 H), 3.80 (s, 3 H), 3.90Ϫ4.10 (m, 4 H),
128.7 (CH), 130.7 (C), 138.2 (CH), 139.1 (CH), 143.0 (CH), 157.9 6.12 (d, J ϭ 8.0 Hz, 1 H), 6.18 (d, J ϭ 8.0 Hz, 1 H), 6.87 (d, J ϭ
1
(C), 201.5 (CϭO), 209.9 (CϭO). Ϫ MS (140 °C): m/z (%) ϭ 460
9.0 Hz, 2 H), 7.25 (d, J ϭ 2.0 Hz, 2 H). Ϫ MS (200 °C): m/z (%) ϭ
(1) [Mϩ], 240 (100), 225 (9), 197 (6), 126 (10), 98 (7). Ϫ HRMS: 543 (1) [Mϩ], 317 (1), 302 (5), 275 (1), 240 (100), 225 (10), 212 (7),
C29H32O5 (460.2): calcd. 460.224974; found 460.223785.
197 (9), 181 (4), 165 (8), 121 (5), 107 (5), 91 (6). Ϫ HRMS:
C32H42O5 (542.3): calcd. 542.303225; found 542.303040.
Methoxybutadiene Adduct 15: A solution of 14 (230 mg, 0.5 mmol)
and 1-methoxybutadiene (100 µL, 1 mmol) in dry dichloromethane
Cyclopentadiene Adduct 18: A solution of 14 (400 mg, 0.87 mmol)
(2 mL) was introduced into a Teflon vessel and subjected to 14 and freshly distilled cyclopentadiene (120 µL, 1.74 mmol) in dry
kbar in a high pressure autoclave for 14 days. Purification of the dichloromethane (1.5 mL) was introduced into a Teflon vessel and
raw material by flash chromatography (Et2O/PE, 1:1) yielded subjected to 14 kbar in a high pressure autoclave for 14 days. Puri-
272 mg (100%) of 15 as a colourless oil. [α]2D0 ϭ Ϫ15.4 (c ϭ 4.10,
fication of the raw material by flash chromatography (Et2O/PE,
˜
CHCl3). Ϫ IR (ATR): ν ϭ 2918 (m), 1714 (s), 1698 (vs), 1614 (m),
1:1) yielded 183 mg (0.35 mmol, 40%) of 18 as a white solid. M.p.:
1518 (vs), 1445 (m), 1387 (m), 1258 (s), 1122 (s), 1102 (s) cmϪ1. Ϫ 206 °C. Ϫ [α]2D0 ϭ ϩ27.3 (c ϭ 0.06, CHCl3). Ϫ IR (CHCl3): ν ϭ
1H NMR (400 MHz, CDCl3): δ ϭ 0.50 (d, J ϭ 13.0 Hz, 1 H), 0.82 2928 (w), 1696 (m), 1516 (m), 1464 (w), 1336 (w), 1248 (m), 1036
(s, 3 H), 1.05Ϫ1.34 (m, 3 H), 1.36Ϫ1.44 (m, 1 H), 1.55Ϫ1.63 (m, (w) cmϪ1. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 0.49 (dbr, J ϭ
2 H), 1.76Ϫ1.88 (m, 2 H), 1.91 (dd, J ϭ 7/16.3 Hz, 1 H), 1.99 (d, 13.0 Hz, 1 H), 0.77 (s, 3 H), 1.09Ϫ1.32 (m, 3 H), 1.34Ϫ1.44 (m, 2
˜
J ϭ 13.0 Hz, 1 H), 2.15 (dbr, J ϭ 19.0 Hz, 1 H), 2.32 (dd, J ϭ 2/
H), 1.55Ϫ1.70 (m, 2 H), 1.82 (dtr, J ϭ 4/13 Hz, 1 H), 1.87Ϫ2.00
16.3 Hz, 1 H), 2.40Ϫ2.48 (m, 2 H), 2.86Ϫ2.94 (m, 1 H), 2.90 (d, (m, 2 H), 2.08Ϫ2.18 (m, 2 H), 2.28 (dd, J ϭ 3/17 Hz, 1 H), 2.86
4056
Eur. J. Org. Chem. 2001, 4051Ϫ4060

Enantiopure Polycycles by Sequential Cycloadditions
(tr, J ϭ 10.0 Hz, 1 H), 2.93 (dd, J ϭ 3/10 Hz, 1 H), 3.03 (sbr, 1 H), (66), 83 (38). Ϫ HRMS: C26H28O3 (388.2): calcd. 388.2038458;
FULL PAPER
3.13 (dd, J ϭ 4/10 Hz, 1 H), 3.42 (sbr, 1 H), 3.79 (s, 3 H), 3.82 (d,
J ϭ 10.0 Hz, 1 H), 3.88Ϫ3.98 (m, 1 H), 4.00Ϫ4.07 (m, 2 H),
4.10Ϫ4.18 (m, 1 H), 6.05 (d, J ϭ 5.0 Hz, 1 H), 6.10 (dd, J ϭ 3/
5 Hz, 1 H), 6.12Ϫ6.15 (m, 2 H), 6.85 (d, J ϭ 9.0 Hz, 2 H), 7.18 (d,
J ϭ 9.0 Hz, 2 H). Ϫ 13C NMR (100 MHz, CDCl3, DEPT): δ ϭ
15.2 (CH3), 21.1 (CH2), 23.3 (CH2), 25.4 (CH2), 26.8 (CH2), 28.6
(CH2), 38.3 (CH2), 40.2 (CH), 45.3 (CH), 46.2 (CH), 46.2 (CH),
48.0 (CH2), 48.9 (CH), 50.5 (CH), 51.1 (CH), 54.0 (CH), 55.1
(CH3), 60.2 (C), 60.9 (C), 64.7 (CH2), 66.5 (C), 109.1 (C), 112.9
(C), 128.1 (CH), 131.0 (C), 135.1 (CH), 137.4 (CH), 138.0 (CH),
138.5 (CH), 157.8 (C), 211.0 (CϭO), 213.6 (CϭO). Ϫ MS (190 °C):
m/z (%) ϭ 526 (5) [Mϩ], 460 (5), 286 (9), 258 (1), 240 (100), 225
(23), 212 (14), 197 (18), 164 (13), 126 (11), 91 (12), 66 (16). Ϫ
HRMS: C34H38O5 (526.3): calcd. 526.271925; found 526.272461.
found 388.2039530.
Cyclohexanone Adduct 23: A solution of 21 (27 mg, 0.07 mmol) and
22 (25 mg, 0.10 mmol) in dry dichloromethane (1.5 mL) was intro-
duced into a Teflon vessel and subjected to 14 kbar in a high pres-
sure autoclave for 2 days. Afterwards, TBAF (1  in THF) was
added at room temperature. The reaction mixture was stirred for
10 min and concentrated. Chromatographic purification (Et2O/PE,
1:1) yielded 30 mg (59 µmol, 84%) of 23 as a colourless oil. [α]2D0
Ϫ58.0 (c ϭ 0.10, CHCl3). Ϫ IR (ATR): ν˜ ϭ 2921 (m), 2856 (m),
1726 (m), 1704 (s, br), 1613 (w), 1515 (s), 1248 (s), 1034 (s) cmϪ1
ϭ
.
Ϫ 1H NMR (400 MHz, CD2Cl2): δ ϭ 0.48 (dbr, J ϭ 13.0 Hz, 1 H),
0.77 (s, 3 H), 1.09Ϫ1.38 (m, 8 H), 1.39Ϫ1.49 (m, 2 H), 1.64Ϫ1.73
(m, 2 H), 1.74Ϫ1.93 (m, 4 H), 1.96Ϫ2.10 (m, 1 H), 2.11Ϫ2.21 (m,
4 H), 2.22Ϫ2.38 (m, 2 H), 2.48Ϫ2.58 (m, 2 H), 3.01 (dd, J ϭ 3/
9.4 Hz, 1 H), 3.67 (d, J ϭ 9.4 Hz, 1 H), 3.79 (s, 3 H), 5.93 (d, J ϭ
6.0 Hz, 1 H), 6.19 (d, J ϭ 6.0 Hz, 1 H), 6.85 (d, J ϭ 9.0 Hz, 2 H),
7.13 (d, J ϭ 9.0 Hz, 2 H). Ϫ 13C NMR (100 MHz, CD2Cl2, DEPT):
δ ϭ 15.3 (CH3), 21.6 (CH2), 23.5 (CH2), 25.3 (CH2), 25.4 (CH2),
26.4 (CH2), 26.5 (CH2), 28.5 (CH2), 29.3 (CH2), 41.56 (CH), 41.62
(CH), 42.3 (CH), 43.4 (CH2), 44.4 (CH2), 45.0 (CH), 47.9 (CH),
48.5 (CH), 50.2 (CH), 55.2 (CH3), 56.1 (CH), 60.7 (C), 60.9 (C),
67.4 (C), 113.1 (CH, 2 ϫ), 128.1 (CH, 2 ϫ), 131.4 (C), 138.0 (CH),
140.4 (CH), 158.2 (C), 209.9 (CϭO), 211.1 (CϭO); 218.4 (CϭO).
Ϫ MS (120 °C): m/z (%) ϭ 513 (1) [MHϩ], 512 (1) [Mϩ], 307 (6),
272 (22), 240 (100), 149 (52). Ϫ HRMS: C34H40O4 (512.3): calcd.
512.292660; found 512.291748.
Acetoxybutadiene Adduct 20: A solution of 21 (60 mg, 0.15 mmol)
and 1-acetoxybutadiene (20 µL, 0.17 mmol) in dry dichlorome-
thane (0.5 mL) was introduced into a Teflon vessel and subjected
to 14 kbar in a high pressure autoclave for 14 days. Purification of
the raw material by flash chromatography (Et2O/PE, 1:1) yielded
74 mg (0.15 mmol, 99%) of 20 as a white solid. M.p.: 180 °C. Ϫ
[α]2D0 ϭ ϩ17.5 (c ϭ 0.40, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 2928 (m),
1740 (s), 1708 (m), 1516 (m), 1444 (w), 1372 (w), 1248 (s), 1180
1
(m), 1036 (m) cmϪ1. Ϫ H NMR (400 MHz, CDCl3): δ ϭ 0.53 (d,
J ϭ 13.0 Hz, 1 H), 0.77 (s, 3 H), 1.15Ϫ1.48 (m, 6 H), 1.59Ϫ1.72
(m, 1 H), 1.76Ϫ1.87 (m, 2 H), 1.94Ϫ2.07 (m, 1 H), 2.08 (s, 3 H),
2.15Ϫ2.25 (m, 1 H), 2.26Ϫ2.39 (m, 3 H), 2.97 (dd, J ϭ 8/8 Hz, 1
H), 3.06 (dd, J ϭ 3/9 Hz, 1 H), 3.63 (d, J ϭ 9.0 Hz, 1 H), 3.79 (s,
3 H), 5.49 (ddd, 1/4/8 Hz, 1 H), 5.94 (d, J ϭ 6.0 Hz, 1 H),
5.90Ϫ5.97 (m, 1 H), 6.02Ϫ6.08 (m, 1 H), 6.23 (d, J ϭ 6.0 Hz, 1
H), 6.85 (d, J ϭ 9.0 Hz, 2 H), 7.14 (d, J ϭ 9.0 Hz, 2 H). Ϫ 13C
NMR (100 MHz, CDCl3, DEPT): δ ϭ 15.4 (CH3), 21.1 (CH3), 21.5
(CH2), 23.4 (CH2), 25.3 (CH2), 26.9 (CH2), 28.4 (CH2), 37.0 (CH),
42.0 (CH), 43.2 (CH), 44.6 (CH2), 45.8 (CH), 48.9 (CH), 55.2
(CH3), 55.3 (CH), 60.6 (C), 61.0 (C), 67.0 (C), 67.9 (CH), 113.2
(CH, 2 ϫ), 127.0 (CH), 128.0 (CH, 2 ϫ), 130.9 (C), 131.4 (CH),
138.1 (CH), 140.2 (CH), 158.0 (C), 170.4 (CϭO), 210.0 (CϭO),
215.7 (CϭO). Ϫ MS (180 °C): m/z (%) ϭ 500 (1) [Mϩ], 441 (1),
359 (1), 306 (1), 293 (1), 251 (2), 240 (100), 225 (24), 197 (21), 165
(10), 153 (8), 115 (10), 95 (21), 79 (14). Ϫ HRMS: C32H36O5
(500.2): calcd. 500.256275; found 500.256287.
Silylenol Adduct 24: A solution of adduct 21 (90 mg, 0.23 mmol)
and diene 22 (83 mg, 0.35 mmol) in dry dichloromethane (2 mL)
was introduced into a Teflon vessel and subjected to 14 kbar in a
high pressure autoclave for 2 days. Purification of the raw material
by flash chromatography (Et2O/PE, 1:4) yielded 130 mg
(0.21 mmol, 91%) of 24 as a colourless oil. [α]2D0 ϭ Ϫ7.6 (c ϭ 1.30,
CHCl3). Ϫ IR (ATR): ν˜ ϭ 2925 (m), 1734 (m), 1708 (m), 1614 (w),
1515 (s), 1249 (vs), 1179 (vs) cmϪ1. Ϫ 1H NMR (400 MHz,
CD2Cl2): δ ϭ 0.09 (s, 2 ϫ, 6 H), 0.48 (dbr, J ϭ 13.0 Hz, 1 H), 0.74
(s, 3 H), 0.92 (s, 2 ϫ, 9 H), 1.10Ϫ1.46 (m, 7 H), 1.48Ϫ1.58 (m, 1
H), 1.68 (dbr, J ϭ 10.5 Hz, 2 H), 1.78Ϫ1.92 (m, 5 H), 1.96Ϫ2.04
(m, 1 H), 2.13Ϫ2.21 (m, 3 H), 2.22Ϫ2.30 (m, 1 H), 2.42Ϫ2.55 (m,
3 H), 2.85 (dbr, J ϭ 15.0 Hz, 1 H), 2.92 (dd, J ϭ 3/9 Hz, 1 H), 3.63
(d, J ϭ 9.0 Hz, 1 H), 3.78 (s, 3 H), 5.94 (d, J ϭ 6.0 Hz, 1 H), 6.20
(d, J ϭ 6.0 Hz, 1 H), 6.84 (d, J ϭ 9.0 Hz, 2 H), 7.14 (d, J ϭ 9.0 Hz,
2 H). Ϫ 13C NMR (100 MHz, CD2Cl2, DEPT): δ ϭ Ϫ4.1 (CH3),
Ϫ3.9 (CH3), 15.2 (CH3), 18.2 (C), 21.7 (CH2), 23.54 (CH2), 25.52
(CH2), 25.7 (CH3, 3 ϫ), 26.1 (CH2), 26.2 (CH2), 26.8 (CH2), 28.6
(CH2), 30.0 (CH2), 32.3 (CH2), 37.4 (CH), 38.5 (CH), 41.4 (CH),
43.9 (CH2), 45.6 (CH), 46.5 (CH), 47.0 (CH), 55.2 (CH3), 56.2
(CH), 60.7 (C), 61.1 (C), 67.3 (C), 113.1 (CH, 2 ϫ), 117.2 (C),
128.1 (CH, 2 ϫ), 131.4 (C), 138.1 (CH), 139.4 (C), 140.1 (CH),
158.1 (C), 210.8 (CϭO), 218.3 (CϭO). Ϫ MS-FAB: C40H54O4Si
(626): m/z (%) ϭ 627 (3) [MHϩ], 626 (4) [Mϩ], 625 (8), 387 (13),
263 (6), 240 (100).
Cyclopentenone Adduct 21: A solution of 2 (405 mg, 1.06 mmol)
and 1-acetoxycyclopentadiene (150 mg, 1.07 mmol) in dry THF (3
mL) was introduced into a Teflon vessel and subjected to 6.5 kbar
in a high pressure autoclave for 5 days. Afterwards, camphorsul-
fonic acid monohydrate (265 mg, 1.06 mmol) was added at room
temperature. After the reaction mixture had been stirred for 15
min, it was quenched with saturated, aqueous NaHCO3 and ex-
tracted with dichloromethane. The combined organic layers were
washed with brine, dried (MgSO4), and concentrated. Chromato-
graphic purification (Et2O/PE, 1:1) yielded 308 mg (0.79 mmol,
75%) of 21 as a white solid. M.p.: 178 °C. Ϫ [α]2D0 ϭ Ϫ140.2 (c ϭ
˜
1.64, CHCl3). Ϫ IR (CHCl3): ν ϭ 2928 (m), 1708 (s), 1516 (m), Methyl Indolylacrylate Adduct 25: A solution of cyclopentenone
1340 (w), 1248 (m), 1104 (w), 908 (m) cmϪ1. Ϫ 1H NMR adduct 21 (135 mg, 0.35 mmol) and methyl indolylacrylate (77 mg,
(200 MHz, CDCl3): δ ϭ 0.59 (dbr, J ϭ 13.0 Hz, 1 H), 0.80 (s, 3 H),
0.38 mmol) in dry dichloromethane (4 mL) was introduced into a
1.16Ϫ1.52 (m, 4 H), 1.53Ϫ1.78 (m, 3 H), 1.79Ϫ1.98 (m, 2 H), 2.24 Teflon vessel and subjected to 14 kbar in a high pressure autoclave
(dd, J ϭ 5/6 Hz, 1 H), 2.50 (dd, J ϭ 5/12 Hz, 1 H), 3.12 (dd, J ϭ for 14 days. Purification by flash chromatography (Et2O/PE, 1:1)
5/10 Hz, 1 H), 3.71 (d, J ϭ 10.0 Hz, 1 H), 3.80 (s, 3 H), 5.96 (d,
yielded 146 mg (0.25 mmol, 72%) of 25 as a white solid. [α]2D0
ϭ
˜
J ϭ 6.0 Hz, 1 H), 6.26 (dd, J ϭ 2/6 Hz, 1 H), 6.34 (d, J ϭ 6.0 Hz, Ϫ34.7 (c ϭ 0.30, CHCl3). Ϫ IR (ATR): ν ϭ 3357 (m), 2929 (m),
1 H), 6.86 (d, J ϭ 9.0 Hz, 2 H), 7.14 (d, J ϭ 9.0 Hz, 2 H), 7.66 1740 (s), 1721 (vs), 1706 (vs), 1612 (m), 1514 (s), 1248 (vs) cmϪ1
.
1
(dd, J ϭ 3/6 Hz, 1 H). Ϫ MS (70 °C): m/z (%) ϭ 388 (2) [Mϩ], 264
Ϫ H NMR (400 MHz, CDCl3): δ ϭ 0.52 (dbr, J ϭ 13.0 Hz, 1 H),
(2), 240 (100), 225 (23), 197 (26), 165 (20), 152 (20), 120 (19), 91 0.78 (s, 3 H), 1.18Ϫ1.68 (m, 5 H), 1.79 (mc, 1 H), 1.90Ϫ1.95 (m, 1
Eur. J. Org. Chem. 2001, 4051Ϫ4060 4057

M. Wolter, C. Borm, E. Merten, R. Wartchow, E. Winterfeldt
FULL PAPER
H), 2.12Ϫ2.19 (m, 1 H), 2.24 (d, J ϭ 5.8 Hz, 1 H), 2.26Ϫ2.32 (m,
Cyclohexenone Adduct 27: Amberlyst 15 was added to a solution
1 H), 2.57Ϫ2.67 (m, 1 H), 2.81 (dd, J ϭ 7/9.4 Hz, 1 H), 2.84Ϫ2.93 of 26 (30 mg, 56 µmol) in acetone (3 mL). The suspension was
(m, 1 H), 3.00Ϫ3.07 (m, 1 H), 3.09Ϫ3.18 (m, 2 H), 3.70 (dbr, J ϭ stirred for 2 h at room temperature (max. 20 °C!). Filtration, con-
9.4 Hz, 1 H), 3.76 (s, 3 H), 3.80 (s, 3 H), 3.92 (dbr, J ϭ 8.3 Hz, 1
centration and chromatographic purification (Et2O) afforded ad-
H), 5.97 (d, J ϭ 6.0 Hz, 1 H), 6.23 (d, J ϭ 6.0 Hz, 1 H), 6.86 (d, duct 27 (23 mg, 100%) as a colourless oil. [α]2D0 ϭ Ϫ113.2 (c ϭ 1.60,
˜
CHCl3). Ϫ IR (ATR): ν ϭ 3392 (w), 2922 (m), 1671 (s), 1613 (m),
J ϭ 9.0 Hz, 2 H), 7.11 (dtr, J ϭ 1/8 Hz, 1 H), 7.19 (mc, 1 H), 7.19
(d, J ϭ 9.0 Hz, 2 H), 7.33 (d, J ϭ 8.0 Hz, 1 H), 7.51 (d, J ϭ 8.0 Hz, 1514 (s), 1247 (vs), 1034 (s) cmϪ1. Ϫ 1H NMR (400 MHz, CDCl3):
1 H), 8.22 (sbr, 1 H). Ϫ 1H NMR (400 MHz, [D5]pyridine): δ ϭ δ ϭ 0.48 (d, J ϭ 13.0 Hz, 1 H), 0.78 (s, 3 H), 1.15Ϫ1.34 (m, 2 H),
0.48 (d, J ϭ 13.0 Hz, 1 H), 0.79 (s, 3 H), 1.02Ϫ1.21 (m, 2 H), 1.42 (dbr, J ϭ 8.0 Hz, 1 H), 1.68 (dbr, J ϭ 5.0 Hz, 1 H), 1.82 (dtr,
1.26Ϫ1.38 (m, 2 H), 1.44 (dbr, J ϭ 10.5 Hz, 1 H), 1.78 (mc, 1 H), J ϭ 4/13 Hz, 1 H), 1.93Ϫ2.07 (m, 3 H), 2.11 (dd, J ϭ 5/16.5 Hz, 1
1.93 (d, J ϭ 13.0 Hz, 1 H), 2.45Ϫ2.53 (m, 3 H), 2.74 (dtr, J ϭ 16/ H), 2.42 (m, 1 H), 2.69Ϫ2.78 (m, 2 H), 2.82Ϫ2.89 (m, 1 H),
8 Hz, 1 H), 3.08Ϫ3.21 (m, 3 H), 3.22Ϫ3.33 (m, 2 H), 3.67 (s, 3 H), 3.62Ϫ3.68 (m, 2 H), 3.79 (s, 3 H), 4.58 (sbr, 1 H), 6.06 (d, J ϭ
3.73 (s, 3 H), 4.03 (d, J ϭ 9.5 Hz, 1 H), 4.11 (d, J ϭ 8.0 Hz, 1 H), 6.0 Hz, 1 H), 6.07 (dd, J ϭ 1/10 Hz, 1 H), 6.17 (d, J ϭ 6.0 Hz, 1
5.96 (d, J ϭ 6.0 Hz, 1 H), 6.34 (d, J ϭ 6.0 Hz, 1 H), 7.04 (d, J ϭ H), 6.85 (d, J ϭ 9.0 Hz, 2 H), 6.95 (dd, J ϭ 4/10 Hz, 1 H), 7.23
1
9.0 Hz, 2 H), 7.27 (dtr, J ϭ 1/7 Hz, 1 H), 7.32 (dtr, J ϭ 1/7 Hz, 1 (d, J ϭ 9.0 Hz, 2 H). Ϫ H NMR (400 MHz, C6D6): δ ϭ 0.47 (d,
H), 7.39 (d, J ϭ 9.0 Hz, 2 H), 7.66 (d, J ϭ 7.0 Hz, 1 H), 7.74 (d,
J ϭ 13.0 Hz, 1 H), 0.62 (s, 3 H), 0.89Ϫ1.40 (m, 4 H), 1.52Ϫ1.58
(m, 1 H), 1.69Ϫ1.92 (m, 4 H), 2.04 (dd, J ϭ 5/17 Hz, 1 H), 2.46
J ϭ 7.0 Hz, 1 H), 12.19 (s, 1 H). Ϫ 13C NMR (100 MHz, [D5]pyrid-
ine, DEPT): δ ϭ 15.3 (CH3), 20.1 (CH2), 21.6 (CH2), 23.7 (CH2), (mc, 1 H), 2.59 (dd, J ϭ 5/9 Hz, 1 H), 2.93 (dd, J ϭ 8/17.4 Hz, 1
26.0 (CH2), 29.2 (CH2), 37.6 (CH), 41.3 (CH), 42.4 (CH), 44.58 H), 3.40 (s, 3 H), 3.60 (d, J ϭ 9.0 Hz, 1 H), 3.90 (sbr, 1 H), 5.58 (d,
(CH), 44.63 (CH2), 46.8 (CH), 47.9 (CH), 51.8 (CH3), 54.9 (CH), J ϭ 6.0 Hz, 1 H), 5.90 (dd, J ϭ 1.5/10 Hz, 1 H), 6.07 (d, J ϭ
55.1 (CH3), 61.1 (C), 61.5 (C), 68.0 (C), 109.4 (C), 111.9 (CH), 6.0 Hz, 1 H), 6.31 (dd, J ϭ 4/10 Hz, 1 H), 6.88 (d, J ϭ 9.0 Hz, 2
113.7 (CH, 2 ϫ), 118.6 (CH), 119.5 (CH), 122.1 (CH), 127.8 (C), H), 7.19 (d, J ϭ 9.0 Hz, 2 H). Ϫ 13C NMR (100 MHz, C6D6,
128.99 (CH, 2 ϫ), 129.02 (C), 131.4 (C), 138.4 (C), 138.8 (CH), DEPT): δ ϭ 15.8 (CH3), 21.7 (CH2), 24.1 (CH2), 29.0 (CH2), 30.2
139.8 (CH), 158.6 (C), 174.7 (CϭO), 209.8 (CϭO), 214.4 (CϭO). (CH2), 30.5 (CH), 41.3 (CH2), 45.0 (CH), 45.4 (CH), 54.0 (CH),
Ϫ MS-FAB: C38H39NO5 (589): m/z (%) ϭ 589 (41) [Mϩ], 391 (65),
350 (48), 327 (48), 307 (100), 281 (86).
54.8 (CH3), 60.9 (C), 61.5 (C), 65.9 (C), 69.6 (CH), 113.5 (CH),
128.3 (CH), 128.4 (CH), 129.2 (CH), 130.9 (C), 138.8 (CH), 139.0
(CH), 158.7 (C), 198.9 (CϭO), 208.8 (CϭO). Ϫ MS (190 °C): m/z
(%) ϭ 418 (0.2) [Mϩ], 240 (100), 225 (16), 197 (11), 178 (6), 84 (18).
Ϫ HRMS: C27H30O4 (418.2): calcd. 418.214410; found 418.214600.
Allylic Alcohol Adduct 26: In a flame-dried, two-necked flask, ad-
duct 11 (300 mg, 564 µmol) was dissolved in dry dichloromethane
(50 mL) under argon atmosphere. The solution was cooled to Ϫ78
°C and K-Selectride (1.69 mL, 1  in THF) was added dropwise.
After the reaction mixture had been stirred for 3 h at Ϫ78 °C, it
was warmed up to Ϫ10 °C over 3.5 h. Afterwards it was quenched
with saturated, aqueous NH4Cl and extracted with EE. The com-
bined organic layers were washed with brine, dried (MgSO4), and
concentrated. Chromatographic purification (Et2O/PE, 1:1) yielded
Cyclohexenone 28: Amberlyst 15 (250 mg) was added to a solution
of 26 (237 mg, 511 µmol) in acetone (30 mL) . The suspension
was stirred for 6 h at around 30 °C. Filtration, concentration and
chromatographic purification (1. Et2O, 2. EE) afforded cyclo-
pentadiene 1 (98%) and retro product 28 (31 mg, 34%) as a bright
yellow oil. [α]2D0 ϭ ϩ112.5 (c ϭ 2.60, CHCl3). Ϫ IR (ATR): ν ϭ
˜
301 mg (564 µmol, 100%) of adduct 26 as a colourless oil. [α]2D0
ϭ
3403 (m, br), 2905 (w), 1714 (m), 1667 (vs, br), 1384 (s), 1226 (s,
1
br) cmϪ1. Ϫ H NMR (400 MHz, CD2Cl2): δ ϭ 2.40 (dd, J ϭ 5/
˜
Ϫ18.0 (c ϭ 0.10, CHCl3). Ϫ IR (ATR): ν ϭ 3495 (w), 2920 (m),
1687 (m), 1613 (m), 1514 (s), 1245 (vs) cmϪ1. Ϫ 1H NMR
(400 MHz, CD2Cl2): δ ϭ Ϫ0.24 (s, 9 H), 0.30 (dbr, J ϭ 13.0 Hz, 1
H), 0.81 (s, 3 H), 1.25Ϫ1.35 (m, 2 H), 1.36Ϫ1.44 (m, 2 H),
1.54Ϫ1.61 (m, 1 H), 1.77 (dtr, J ϭ 4/13 Hz, 1 H), 1.92 (dd, J ϭ 6/
15 Hz, 1 H), 2.23Ϫ2.34 (m, 3 H), 2.36 (ddd, J ϭ 1/7/15 Hz, 1 H),
2.70 (d, J ϭ 11.0 Hz, 1 H), 3.75 (s, 3 H), 3.75 (sbr, 1 H), 3.92Ϫ4.04
(m, 4 H), 4.21Ϫ4.28 (m, 1 H), 5.81 (dd, J ϭ 1/10 Hz, 1 H), 5.82
17 Hz, 1 H), 3.04 (mc, 1 H), 3.14 (ddd, J ϭ 1/3/17 Hz, 1 H), 3.38
(dbr, J ϭ 3.0 Hz, 1 H), 3.45 (mc, 1 H), 5.03 (sbr, 1 H), 5.95 (dd, J ϭ
2.6/10 Hz, 1 H), 6.06 (dd, J ϭ 3/10 Hz, 1 H), 6.83 (ddd, J ϭ 2/2/
10 Hz, 1 H), 7.18 (ddd, J ϭ 2/2/10 Hz, 1 H). Ϫ MS (110 °C): m/z
(%) ϭ 179 (18) [MHϩ], 178 (32) [Mϩ], 160 (4), 149 (14), 95 (90),
84 (100). Ϫ HRMS: C10H10O3 (178.1): calcd. 178.062994; found
178.063034.
(d, J ϭ 6.0 Hz, 1 H), 6.07Ϫ6.12 (m, 1 H), 6.09 (d, J ϭ 6.0 Hz, 1
1
H), 6.77 (d, J ϭ 9.0 Hz, 2 H), 7.19 (dbr, J ϭ 8.0 Hz, 2 H). Ϫ H Enamine Alcohol 30: Adduct 31 (12 mg, 19 µmol) was placed in a
NMR (400 MHz, C6D6): δ ϭ Ϫ0.03 (s, 9 H), 0.62 (dbr, J ϭ13 Hz,
1 H), 1.12 (s, 3 H), 1.28 (trtr, J ϭ 4/14 Hz, 1 H), 1.37 (mc, 1 H),
flash-vacuum pyrolysis apparatus and heated to 150 °C at 10Ϫ2
mbar for 10 min. Cyclopentadiene 1 was collected in a cold trap
1.42Ϫ1.56 (m, 2 H), 1.61 (dtr, J ϭ 3/13 Hz, 1 H), 1.72 (dbr, J ϭ and retro-reaction product 30 was left in the heated flask. Chroma-
13.0 Hz, 1 H), 1.92 (dbr, J ϭ 7.0 Hz, 1 H), 2.04 (dtr, J ϭ 4/13 Hz, tographic purification (1. Et2O/PE, 4:1, 2. Et2O) yielded 8 mg (19
1 H), 2.18 (dd, J ϭ 7/16 Hz, 1 H), 2.51 (dtr, J ϭ 7/7 Hz, 1 H), µmol, 100%) of 30 as a colourless oil. [α]2D0 ϭ Ϫ96.7 (c ϭ 0.30,
˜
CHCl3). Ϫ IR (ATR): ν ϭ 3489 (w, br), 2921 (vs), 1694 (s, br),
2.63Ϫ2.74 (m, 2 H), 3.08 (d, J ϭ 11.0 Hz, 1 H), 3.39Ϫ3.54 (m, 4
H), 3.45 (s, 3 H), 4.16 (sbr, 1 H), 5.71 (dd, J ϭ 1/10 Hz, 1 H), 5.83 1597 (w), 1494 (w), 1458 (m), 1390 (m), 1190 (s) cmϪ1. Ϫ 1H NMR
(d, J ϭ 6.0 Hz, 1 H), 6.05 (ddd, J ϭ 1/4/10 Hz, 1 H), 6.26 (d, J ϭ (400 MHz, CD2Cl2): δ ϭ 1.57Ϫ1.65 (m, 1 H), 1.81 (dbr, J ϭ
6.0 Hz, 1 H), 6.93 (d, J ϭ 9.0 Hz, 2 H), 7.50 (sbr, 2 H). Ϫ 13C NMR
18.0 Hz, 1 H), 1.86Ϫ1.93 (m, 2 H), 1.94Ϫ2.02 (m, 2 H), 2.21 (d,
(100 MHz, C6D6, DEPT): δ ϭ 0.6 (CH3, 3 ϫ), 16.8 (CH3), 21.9 J ϭ 4.0 Hz, 1 H), 2.22Ϫ2.28 (m, 1 H), 2.30 (dd, J ϭ 5/17 Hz, 1
(CH2), 24.6 (CH2), 26.9 (CH2), 29.4 (CH2), 31.2 (CH2), 44.0 (CH), H), 2.41 (dbr, J ϭ 18.0 Hz, 1 H), 2.90 (dd, J ϭ 5.5/17 Hz, 1 H),
44.1 (CH), 44.3 (CH), 54.8 (CH3), 59.5 (C), 62.7 (C), 64.0 (CH2), 2.94Ϫ3.05 (m, 1 H), 3.11 (dtr, J ϭ 5.0 Hz, 1 H), 3.20 (mc, 1 H),
65.7 (CH2), 68.1 (C), 69.1 (CH), 107.3 (C), 123.3 (C), 128.3 (CH),
3.26 (sbr, 1 H), 3.38 (dtr, J ϭ 12/5.5 Hz, 1 H), 3.98 (dtr, J ϭ 13/
129.5 (CH), 131.0 (C), 134.1 (CH, 2 ϫ), 134.5 (CH, 2 ϫ), 136.2 5 Hz, 1 H), 4.43 (dtr, J ϭ 9.4/4.4 Hz, 1 H), 6.05 (dd, J ϭ 2.5/10 Hz,
(CH, 2 ϫ), 142.3 (C), 158.6 (C). Ϫ MS (110 °C): m/z (%) ϭ 534 1 H), 6.98 (dd, J ϭ 3/10 Hz, 1 H), 7.11 (dd, J ϭ 1/8.5 Hz, 2 H),
(100) [Mϩ], 516 (6), 489 (4), 403 (12), 240 (15), 105 (24). Ϫ HRMS:
C32H42O5Si (534.3): calcd. 534.280153; found 534.278137.
7.23 (trtr, J ϭ 1/7.5 Hz, 1 H), 7.39 (trbr, J ϭ 8.0 Hz, 2 H). Ϫ 13C
NMR (100 MHz, CD2Cl2, APT): δ ϭ 23.5 (CH2), 23.6 (CH2), 26.2
4058
Eur. J. Org. Chem. 2001, 4051Ϫ4060

Enantiopure Polycycles by Sequential Cycloadditions
FULL PAPER
(CH2), 29.8 (CH2), 30.1 (CH), 38.1 (CH2), 39.3 (CH), 43.3 (CH), 5.5/12.3 Hz, 1 H), 3.67 (d, J ϭ 8.4 Hz, 1 H), 3.76 (s, 3 H), 3.90 (d,
45.3 (CH2), 46.1 (CH), 67.5 (CH), 117.7 (C), 121.9 (CH, 2 ϫ), J ϭ 8.4 Hz, 1 H), 4.42 (tr, J ϭ 6.5 Hz, 1 H), 6.16 (d, J ϭ 6.0 Hz,
125.5 (CH), 129.3 (CH, 2 ϫ), 131.5 (CH), 134.1 (C), 145.5 (CH), 1 H), 6.18 (d, J ϭ 6.0 Hz, 1 H), 6.83 (d, J ϭ 9.0 Hz, 2 H),
151.3 (CϭO), 182.7 (C), 196.9 (CϭO), 210.1 (CϭO). Ϫ MS-FAB: 7.02Ϫ7.10 (m, 3 H), 7.19 (d, J ϭ 9.0 Hz, 2 H), 7.45 (d, J ϭ 7.0 Hz,
C24H25NO5 (407): m/z (%) ϭ 408 (52) [MHϩ], 407 (93) [Mϩ], 307 1 H), 8.13 (s, 1 H). Ϫ 13C NMR (100 MHz, CD2Cl2, DEPT): δ ϭ
(32), 289 (22), 279 (26), 154 (100), 136 (68).
15.5 (CH3), 21.2 (CH2), 21.5 (CH2), 23.6 (CH2), 26.4 (CH2), 28.5
(CH2), 44.1 (CH2), 50.6 (CH2), 52.2 (CH), 53.6 (CH), 55.2 (CH3),
60.7 (C), 62.5 (C), 68.1 (C), 69.3 (CH), 108.6 (C), 111.1 (CH), 113.1
(CH, 2 ϫ), 117.9 (CH), 119.2 (CH), 121.5 (CH), 127.1 (C), 128.5
(CH, 2 ϫ), 130.8 (C), 134.7 (C), 136.3 (C), 138.1 (CH), 139.9 (CH),
158.3 (C), 209.8 (CϭO). Ϫ MS-FAB: C32H34N2O2 (478): m/z (%) ϭ
479 (11) [MHϩ], 460 (7) [Mϩ], 307 (60), 289 (28), 240 (30), 154
(100), 137 (66).
Enamine Alcohol Adduct 31: A solution of adduct 27 (15 mg, 36
µmol) and diene 29 (10 mg, 43 µmol) in dry toluene (2 mL) was
introduced into a Teflon vessel and subjected to 14 kbar in a high
pressure autoclave for 14 days. Purification by flash chromato-
graphy (Et2O/PE, 3:1) yielded 15 mg (24 µmol, 67%) of 31 as a
colourless oil. [α]2D0 ϭ Ϫ8.0 (c ϭ 0.10, CHCl3). Ϫ IR (ATR): ν ϭ
˜
3449 (w), 2921 (s), 1703 (s, br), 1613 (w), 1515 (m), 1398 (m), 1248
1
(s), 1204 (s), 1033 (s) cmϪ1. Ϫ H NMR (400 MHz, CD2Cl2): δ ϭ Indoloquinolizinone (34): Adduct 33 (66 mg, 138 µmol) was placed
0.43 (d, J ϭ 13.0 Hz, 1 H), 0.79 (s, 3 H), 1.18Ϫ1.38 (m, 3 H), in a flash-vacuum pyrolysis apparatus and heated to 150 °C at 10Ϫ2
1.39Ϫ1.47 (m, 1 H), 1.51Ϫ1.72 (m, 3 H), 1.79Ϫ1.96 (m, 4 H), 2.03 mbar for 5 min. Cyclopentadiene 1 was collected in a cold trap and
(dd, J ϭ 5/15 Hz, 1 H), 2.17Ϫ2.35 (m, 4 H), 2.41 (sbr, 1 H), the crude retro-reaction product 34 was left in the heated flask.
2.49Ϫ2.60 (m, 2 H), 2.72 (d, J ϭ 9.0 Hz, 1 H), 2.98 (dd, J ϭ 13.5/
Chromatographic purification (EE) yielded 28 mg (118 µmol, 86%)
15 Hz, 1 H), 3.05 (d, J ϭ 11.5 Hz, 1 H), 3.63 (tr, J ϭ 4.5 Hz, 1 H), of indoloquinolizinone 34 as a bright yellow oil. [α]2D0 ϭ ϩ137.1
˜
(c ϭ 2.3, CHCl3). Ϫ IR (ATR): ν ϭ 3193 (w, br), 2920 (w), 1713
3.79 (s, 3 H), 3.81 (d, J ϭ 9.0 Hz, 1 H), 3.83 (s, 1 H), 4.31 (d, J ϭ
12.5 Hz, 1 H), 5.64 (mc, 1 H), 6.08 (ABq, J ϭ 6.0 Hz, 2 H), 6.86 (w, br), 1621 (m, br), 1564 (vs, br), 1450 (s), 1376 (s), 1242 (s), 1171
(d, J ϭ 9.0 Hz, 2 H), 7.09 (dd, J ϭ 1/7.4 Hz, 2 H), 7.20 (trtr, J ϭ
(s), 724 (s, br) cmϪ1. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 2.64
1/7.4 Hz, 1 H), 7.24 (d, J ϭ 9.0 Hz, 2 H), 7.36 (mc, 2 H). Ϫ 13C (dd, J ϭ 15.9/15.9 Hz, 1 H), 2.92 (dd, J ϭ 4/15 Hz, 1 H), 2.97Ϫ3.10
NMR (100 MHz, CD2Cl2, APT): δ ϭ 15.6 (CH3), 21.7 (CH2), 23.5 (m, 2 H), 3.54 (ddd, 4/12/12 Hz, 1 H), 3.74 (dd, J ϭ 4/12.5 Hz, 1
(CH2), 25.4 (CH2), 25.7 (CH2), 26.1 (CH2), 28.2 (CH2), 29.8 (CH2), H), 4.89 (dbr, J ϭ 15.0 Hz, 1 H), 5.09 (d, J ϭ 7.4 Hz, 1 H), 7.12
36.8 (CH), 37.0 (CH), 41.4 (CH2), 41.9 (CH), 46.1 (CH), 46.4 (ddd, 1/7.8/7.8 Hz, 1 H), 7.19 (dtr, J ϭ 1/8.2 Hz, 1 H), 7.26 (dbr,
(CH2), 47.4 (CH), 50.4 (CH), 54.8 (CH), 55.2 (CH3), 61.1 (C), 61.8 J ϭ 7.4 Hz, 1 H), 7.41 (d, J ϭ 8.2 Hz, 1 H), 7.51 (d, J ϭ 7.8 Hz,
(C), 69.1 (C), 75.9 (CH), 113.0 (CH, 2 ϫ), 116.8 (CH), 121.9 (CH, 1 H), 9.13 (s, 1 H). Ϫ 13C NMR (100 MHz, CDCl3, DEPT): δ ϭ
2 ϫ), 125.2 (CH), 128.6 (CH, 2 ϫ), 129.2 (CH, 2 ϫ), 131.1 (C),
22.1 (CH2), 41.8 (CH2), 50.8 (CH2), 54.0 (CH), 98.4 (CH), 107.8
135.4 (C), 138.3 (CH), 138.8 (CH), 151.9 (C), 153.5 (C), 158.2 (Cϭ (C), 111.5 (CH), 118.1 (CH), 119.7 (CH), 122.3 (CH), 126.4 (C),
O), 209.8 (CϭO), 210.4 (CϭO). Ϫ MS-FAB: C41H45NO6 (647): m/ 131.5 (C), 136.6 (C), 154.9 (CH), 192.2 (CϭO). Ϫ MS (180 °C): m/
z (%) ϭ 648 (2) [MHϩ], 647 (2) [Mϩ], 460 (15), 427 (20), 391 (39),
307 (100), 289 (53), 240 (33).
z (%) ϭ 238 (100) [Mϩ], 209 (31), 156 (54), 129 (17), 122 (31),
105 (43), 81 (21), 69 (43). Ϫ HRMS: C15H14N2O (238.1): calcd.
238.110613; found 238.110718.
Adduct 33: A solution of siloxydiene 2 (20 mg, 53 µmol), the tri-
fluoroacetate salt of dihydronorharmane 32b (22 mg, 79 µmol) and X-ray Crystallographic Study: Single-crystal X-ray diffraction ex-
10% of α,αЈ-bis-tert-butylpyridine in a dry 1:1 mixture of CH3CN/ periments were carried out with a Stoe IPDS (area detector) dif-
DMF (0.6 mL) was introduced into a Teflon vessel and subjected
to 14 kbar in a high pressure autoclave for 44 h. Afterwards, cam-
phorsulfonic acid monohydrate and Et2O were added. After the
fractometer, using graphite-monochromated Mo-Kα radiation. The
data collection nominally covered a full sphere of reciprocal space
within 2θmax of about 48°. Since the crystal was rotated only about
reaction mixture had been stirred for 30 min at room temperature, one axis, the reflections of a small part of the reciprocal lattice were
it was quenched with saturated, aqueous NaHCO3 and extracted not accessible. A second measurement using another rotation axis
with dichloromethane. The combined organic layers were washed
was thought unnecessary. A few reflections with very low 2θ (Ͻ
with brine, dried (MgSO4), and concentrated. Chromatographic 3.6°) could not be measured, due to collision with the primary
purification (Et2O/PE, 1:1) yielded 25 mg (52 µmol, 98%) of adduct
33 as a bright yellow oil. [α]2D0 ϭ ϩ4.4 (c ϭ 2.30, CHCl3). Ϫ IR
beam stop. In the case of compound 20, three strong reflections
exceeded the intensity range of the imaging plate. Repetition of
(CHCl3): ν˜ ϭ 3466 (vs, br), 2927 (vs), 1699 (s), 1612 (m, br), 1516 the measurement using a shorter exposure time was again thought
(vs), 1463 (m), 1445 (m), 1380 (m), 1290 (m), 1249 (vs), 1181 (m), unnecessary. Intensity integration and data reduction were per-
1
1038 (m) cmϪ1. Ϫ H NMR (400 MHz, [D6]DMSO): δ ϭ 0.28 (d, formed using Stoe IPDS software. The structures were solved by
J ϭ 13.0 Hz, 1 H), 0.73 (s, 3 H), 1.12Ϫ1.39 (m, 3 H), 1.50 (dtr, J ϭ direct methods (SHELXS) and refined by full-matrix, least-squares
3.6/12.4 Hz, 1 H), 1.62 (dbr, J ϭ 13.0 Hz, 1 H), 1.80 (dtr, J ϭ 3.6/ against F2 of all data (SHELXL). Non-hydrogen atoms were re-
13 Hz, 1 H), 2.16 (d, J ϭ 13.0 Hz, 1 H), 2.43Ϫ2.57 (m, 2 H), fined with anisotropic displacement parameters. Hydrogen atom
2.62Ϫ2.71 (m, 1 H), 2.72Ϫ2.81 (m, 1 H), 3.05 (dtr, J ϭ 12/6 Hz, 1
H), 3.28Ϫ3.41 (m, 1 H), 3.74 (s, 3 H), 3.90 (ABq, J ϭ 8.3 Hz, 2 ment as riding H’s. There are two symmetrically independent mole-
H), 4.37 (dd, J ϭ 4.4/9.3 Hz, 1 H), 6.09 (d, J ϭ 6.0 Hz, 1 H), 6.19 cules in the asymmetric unit of compound 20. They differ mainly
positions were calculated geometrically and included in the refine-
(d, J ϭ 6.0 Hz, 1 H), 6.85 (d, J ϭ 9.0 Hz, 2 H), 6.95 (dtr, J ϭ 1/ in the atomic displacement parameters of the acetoxy group at
7 Hz, 1 H), 7.02 (dtr, J ϭ 1/7 Hz, 1 H), 7.18Ϫ7.25 (m, 3 H), 7.38 C(15). The displacement parameters of the acetoxy group in the
(d, J ϭ 7.6 Hz, 1 H), 10.72 (s, 1 H). Ϫ 1H NMR (400 MHz, second molecule had abnormally high values in the first refinement.
CD2Cl2): δ ϭ 0.39 (d, J ϭ 13.0 Hz, 1 H), 0.77 (s, 3 H), 1.15Ϫ1.44
A split atom model was therefore introduced and refined with ap-
(m, 3 H), 1.51 (dtr, J ϭ 3.5/13 Hz, 1 H), 1.68 (d, J ϭ 13.0 Hz, 1 plication of isotropic displacement parameters and some further
H), 1.87 (dtr, J ϭ 3.7/13 Hz, 1 H), 2.22 (d, J ϭ 11.0 Hz, 1 H), 2.51 restraints. The Flack x parameter does not allow the determination
(d, J ϭ 6.5 Hz, 2 H), 2.77 (dtr, J ϭ 15/5.5 Hz, 1 H), 2.87 (dtr, J ϭ
of the absolute structures of both compounds; the configuration
15/5 Hz, 1 H), 3.11 (dtr, J ϭ 12.3/5.5 Hz, 1 H), 3.42 (ddd, J ϭ 5/ was chosen in agreement with earlier investigations of related sub-
Eur. J. Org. Chem. 2001, 4051Ϫ4060
4059

M. Wolter, C. Borm, E. Merten, R. Wartchow, E. Winterfeldt
FULL PAPER
Table 1. X-ray crystallography
Compound
20
25
Empirical formula
Molecular mass
Temperature
C32H36O5
500.26
C38H39NO5
589.70
300 K
300(2) K
˚
˚
Wavelength
0.71073 A
0.71073 A
Crystal system
Space group
Unit cell dimensions
Monoclinic
P 21 (No. 4)
a ϭ 17.658(3) A,
α ϭ 90°
b ϭ 6.354(1) A,
Orthorhombic
P 21 21 21
a ϭ 9.1580(10) A,
α ϭ 90°
˚
˚
˚
˚
b ϭ 16.123(2) A,
β ϭ 104.48(2)°
c ϭ 25.158(4) A,
β ϭ 90°
c ϭ 20.245(3) A,
˚
˚
γ ϭ 90°
γ ϭ 90°
3
3
˚
˚
Volume
Z
Calculated density
Absorption coefficient
F(000)
2733.0(8) A
4
2989.3(7) A
4
1.217 g/cm3
0.081 mmϪ1
1072
1.310 Mg/m3
0.086 mmϪ1
1256
Crystal size
0.33 ϫ 1.0 ϫ 0.09 mm
Stoe IPDS area detector
1.79° to 24.03°
0.74 ϫ 0.37 ϫ 0.06 mm
Stoe IPDS area detector
2.01° to 24.08°
Diffractometer
Theta range for data
collection
Reflections collected
Reflections unique
Rint
20990
8491
0.0897
None
2870
660
0.0397
0.64
20763
4601
0.0886
None
2213
401
0.0335
0.72
Absorption correction
Reflections with I Ͼ 2σ(I)
Refined variables
R[F2 Ͼ 2σ(F2)]
Goodness-of-fit
wR(F2), all data
0.0669
0.18, Ϫ0.14
0.0495
0.12, Ϫ0.13
Ϫ3
˚
∆ρmax,min [e·A
]
stances. The program PLATON was used for checks and graphics.
Crystal data and experimental details are listed in Table 1. [Refer-
ences: G. M. Sheldrick, SHELXL-93, a program for refining crystal
structures, University of Göttingen, 1993. G. M. Sheldrick,
SHELXS-86, a program for crystal structure determination, Uni-
versity of Göttingen, 1986. A. L. Spek, PLATON, an integrated
tool for the analysis of the results of a single-crystal structure deter-
mination. Acta Crystallogr. Suppl. A46, 1990, C-34.]
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lication nos. CCDC-161439 for 20 and CCDC-161440 for 25. Cop-
ies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: (internat.)
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Acknowledgments
Continuous support of our work by the ‘‘Fonds der chemischen
Industrie’’ is gratefully acknowledged. We are particularly thankful
to the Deutsche Forschungsgemeinschaft (DFG) for a very valu-
able initial grant opening the road to first exploratory studies into
an exciting but by no means easily predictable field. For the experi-
ments described here we owe particular thanks to the DFG for
providing specific 14 kbar facilities.
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Received April 30, 2001
[O01213]
4060
Eur. J. Org. Chem. 2001, 4051Ϫ4060