Synthesis of novel steroid backbones via photoinduced electron transfer initiated domino cyclizations of silyl enol ethers

Article abstract of DOI:10.1055/s-2004-815956

Photoinduced electron transfer was used to activate silyl enol ethers. The generated radical cations of specifically designed precursors undergo ring closure reactions to yield novel steroid compounds. These domino reactions proceed with high stereoselectivity. The synthesis of the complex silyl enol ethers, the stereo-selective domino cyclization process and the assignment of stereochemistry of the novel steroid compounds is presented.

Full text of DOI:10.1055/s-2004-815956

FEATURE ARTICLE
619
Synthesis of Novel Steroid Backbones via Photoinduced Electron Transfer
Initiated Domino Cyclizations of Silyl Enol Ethers
PET
Dom
e
inoCycliza
n
tions s O. Bunte, Stefanie Rinne, Jochen Mattay*
Organische Chemie I, Fakultät für Chemie, Universität Bielefeld, Postfach 100131, 33501 Bielefeld, Germany
Fax +49(521)1066417; E-mail: mattay@uni-bielefeld.de
Received 28 November 2003
polycyclic hydrocarbons as shown for the cyclization re-
action of 1 (Scheme 1).7 After one-electron oxidation,
radical cation 3 undergoes a completely selective 6-endo
ring closure reaction. Saturation of the intermediate radi-
Abstract: Photoinduced electron transfer was used to activate silyl
enol ethers. The generated radical cations of specifically designed
precursors undergo ring closure reactions to yield novel steroid
compounds. These domino reactions proceed with high stereoselec-
tivity. The synthesis of the complex silyl enol ethers, the stereo- cal 4 leads to the formation of cyclization products 2a,b
selective domino cyclization process and the assignment of
(9:1 d.r.) with high stereoselectivity.
stereochemistry of the novel steroid compounds is presented.
Key words: domino reactions, cyclizations, stereoselectivity, elec-
tron transfer, steroids
Introduction
Since Schöpf and Robinson have applied the concept of
domino reactions for the synthesis of tropinone in 1917,1
it received growing attention and importance in organic
synthesis. Over the last two decades, various types of
domino reactions have been developed as is noticeable
from a number of summarizing reviews.2,3 Nevertheless, a
deeper understanding of mechanistical features is still re-
Scheme 1
quired for a successful domino reaction, especially for
combinations of cationic, radical, anionic, pericyclic,
photochemical, or transition metal-catalyzed steps. In the
field of radical domino reactions, the properties and be-
havior of the reactive intermediates are sufficiently under-
stood and thus, the ‘programming’ of suitable precursors
to obtain the desired target molecule through a domino re-
action becomes possible.3
As an extension of this concept, our strategy was to use
the cyclized radical intermediates 6a of such a reaction as
a starting point for a secondary ring closure (6a → 6b).8
By selecting an appropriate side chain, steroid frame-
works 7 could be constructed in a two step domino reac-
tion (Scheme 2). The results on the syntheses of the
precursors, the stereoselectivity of the cyclization reaction
and the formation of novel steroid compounds will be pre-
sented here.
A major drawback in radical chemistry is a suitable and
practical activation of the precursor molecule. For exam-
ple, the commonly used tin hydride as well as transition
metals in electron transfer activation counteract the effi-
ciency and attractiveness of the domino synthesis due to
environmental problems.4 Photoinduced electron transfer
(PET) activation offers an attractive alternative to these
established methods since solely catalytic amounts of a
sensitizer are required. Furthermore, PET allows selective
excitation of the sensitizer by light.5
Various studies on one-electron oxidation of silyl enol
ethers have shown that the intermediate radical cations
produced can be used as reactive intermediates in cycliza-
tion reactions.6 During our ongoing work we were able to
apply this strategy to the stereoselective construction of
SYNTHESIS 2004, No. 4, pp 0619–0633
Advanced online publication: 09.02.2004
x
x
.
x
x
.2
0
0
4
Scheme 2
DOI: 10.1055/s-2004-815956; Art ID: T11703SS
© Georg Thieme Verlag Stuttgart · New York

620
J. O. Bunte et al.
FEATURE ARTICLE
pure product, no purification was required. Again, the
structure was confirmed by NMR analysis (DEPT, CO-
Proof of the Domino Concept
For a successful domino cyclization of silyl enol ethers SY, HMQC, HMBC). Thus, 12 was subjected to cyclo-
like 5 several requirements have to be fulfilled. Besides a propylcarbinyl-homoallyl rearrangement. Treatment with
selective synthesis of the precursor with respect to all dou- a mixture of PBr3, LiBr and sym-collidine afforded a
ble bonds the saturation process has to occur only on the crude product that contained both isomers of the desired
final intermediate (6b). Quenching of uncyclized radicals alkene. Additionally, several byproducts containing bro-
like 6a would lead to a broad product spectrum and thus mine, presumably bromocyclobutanes were obtained as
an inefficient concept.
detected by GC/MS analysis of the crude mixture.10 The
crude material was treated with ZnBr2 in Et2O to yield ho-
moallylic bromide 13 E-selectively in 73% yield. As
shown by GC analysis, the crude product contained less
than 2% of the corresponding Z-isomer. Finkelstein reac-
tion with bromide 13 afforded iodide 14 in 92% yield
(Scheme 3).
In order to see if our cyclization strategy fulfilled these re-
quirements, we conducted a synthesis with an easily ac-
cessible starting material and built up a side chain from
(S)-perillyl bromide (8) (Scheme 3).9,10
The -keto ester 10 was obtained by substitution with the
enolate of ethyl-3-(1-methylcyclopropyl)-3-oxopro-
panoate 9.10b,11 Further reaction with Ba(OH)2 led to the
formation of 11 in 92% yield over two steps. The structure
of 11 was confirmed by NMR analysis (DEPT, COSY,
HMQC, HMBC). Subsequent reduction with LiAlH4 in
Et2O afforded cyclopropylcarbinol 12 in 93% yield as a
The desired side chain could be synthesized in good yields
and with the complete selectivity towards both double
bonds required for the cyclization reaction. It was coupled
with the ring-D fragment of the steroid skeleton by meta-
lation and reaction with 3-ethoxycyclohexenone 15. Met-
alation with tert-butyllithium, reaction with the carbonyl
Biographical Sketches
Jens O. Bunte was born tinuing his work in the electron transfer cycliza-
1973 in Lemgo (Germany). group of J. Mattay he ob- tions of silyl enol ethers and
He studied chemistry at the tained his PhD in 2003 from their application in organic
University of Bielefeld, the University of Bielefeld. synthesis.
where he received his Di- The main topics of his PhD
ploma degree in 2000. Con- thesis were photoinduced
Stefanie Rinne was born Bielefeld, where she joined Rotary scholar at the Uni-
1980 in Bückeburg (Germa- the group of J. Mattay for a versity of Edinburgh.
ny). She is studying chemis- research project. Currently,
try at the University of she is a visiting student as a
Jochen Mattay received his appointed associate profes- istry at the University of
PhD in 1978 from RWTH sor at the universities of Bielefeld. His main research
Aachen under the supervi- Aachen (1985–1989) and interests focus on photo-
sion of H.-D. Scharf. After Münster (1989–1995) and chemistry and supramolecu-
postdoctoral studies at Co- full professor at the Univer- lar chemistry with special
lumbia University with N. J. sity of Kiel (1995–1998). emphasis on electron trans-
Turro, he returned to He also was visiting profes- fer processes, self-organiza-
Aachen in 1980 and finished sor at Osaka University tion
and
molecular
his habilitation in 1983. Be- (1995) and the University of recognition as well as mo-
fore joining the University Bern (1996). He is currently lecular
of Bielefeld in 1998 he was dean of the faculty of chem- fullerenes.
switches
and
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

FEATURE ARTICLE
PET Domino Cyclizations
621
Scheme 3
compound and acidic work-up afforded enone 16 in 64% cular weight could not be separated by distillative meth-
yield after chromatographic purification (Scheme 4). ods. Best work-up conditions were found to be extraction
Even under these optimized conditions, the reaction al- with ice-cold aq HCl and ice-cold n-pentane. Following
ways yielded the reduction product of 14 (X = H) as a re- this strategy, both components of the product, the homoal-
sult of the highly basic lithium compound. Attempts to lylic side chain and the ring fragment can be varied. Silyl
add less basic cerium organic species to the carbonyl enol ethers can be isolated in good yield and high purity
group were, however, not successful.12 Additionally, met- by introducing a commercially available organometallic
alation of 13 with magnesium was not as efficient as the compound in the last step.
metal halogen exchange with tert-butyllithium since a
considerable amount of Wurtz-coupling product was ob-
tained.
PET Domino Cyclization
Silyl enol ether 17 was subjected to PET oxidation with
9,10-dicyanonthracene (DCA) as a sensitizer. DCA is
electronically excited with light of = 420 nm and thus
able to oxidize the electron rich silyl enol ether.5
The radical ion pair formed through oxidation needs to be
separated by solvent molecules in order to increase the
lifetime of the reactive intermediates. The formation of
such a solvent-separated radical ion pair is most common-
ly achieved by the use of polar solvents as e.g. acetoni-
trile.5 Unfortunately, 17 did not sufficiently dissolve in the
latter solvent. Furthermore, the desired cyclization did not
occur in less polar solvents. After steady optimization, a
3:1 mixture of acetonitrile and propionitrile was found to
be a suitable reaction medium for the preparative cycliza-
tion of 17.
Scheme 4
PET cyclization of 17 afforded three products 18a–c in
26% yield after chromatographic purification
(Equation 1). The product ratio was determined by GC as
47:41:12 (18a:18b:18c).
The silyl enol ether functionality, as well as the methyl
group was introduced by cuprate addition in the presence
of TMSCl. A threefold excess of dimethyl cuprate was
used and the silyl enol ether 17 was isolated in 84% yield.
Isomerization of the double bond did not occur, which is
essential for the following cyclization reaction.13 Com-
plete reaction and clean work-up are required in this step
since the product is unstable to standard chromatography
conditions. Furthermore, by-products of the same mole-
This first domino cyclization of silyl enol ethers, leading
to steroid compounds proceeded in a highly selective
manner. Only fully cyclized products were obtained,
which is an important requirement for the domino con-
cept. Furthermore, these products only cyclize in a 6-endo
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

622
J. O. Bunte et al.
FEATURE ARTICLE
Equation 1
fashion as desired. The stereoselectivity is also remark- results turned out to be problematic.7c,14 The narrow range
1
ably high. Silyl enol ether 17 is a mixture of two diastereo- of the chemical shifts in the H NMR spectra, caused by
mers with respect to the methyl group introduced by the unfunctionalized structure of the cyclization products,
cuprate addition. From these two isomers only three prod- led to a strong overlap of signals. Consequently, the cor-
uct isomers are obtained, including one byproduct in 12% relation signals were hard to interpret.
yield. It should be noted that 64 product isomers are theor-
etically possible, due to the five stereogenic centers gen-
erated during the cyclization process.
The structure of byproduct 18c was not fully assigned due
to the small amount of material. Additionally, a complete
separation from 18a was not accomplished. The compari-
The structure of 18b was unambiguously determined by son of 13C-DEPT spectra nevertheless gave strong indica-
X-ray crystal structure analysis (Figure 1).7c Apart from tion towards a tetracyclic framework as in 18a and 18b.
the stereochemistry between rings C and D, all ring con- Conformational analysis of the radical intermediate prior
nections are trans. The cis-connection at the former silyl to radical quenching suggests a preference for a cis-selec-
enol ether site (12a-4a) is a common feature in the PET tivity between 6a and 10a, since the isopropenyl group is
cyclizations of silyl enol ethers and occurs with complete trying to avoid an axial position. The product ratio is a fur-
selectivity.
ther argument for 18c to be the 6a-epimer of 18b. The ra-
tio between the diastereomers 18a and 18b is expected to
be 1:1, due to the same common cyclization pathway.
Branching of the pathway at the radical saturation step
would result in a smaller amount of 18b in the reaction
mixture.14
In conclusion, the synthesis and cyclization of silyl enol
ether 17 fulfilled all requirements for the domino concept:
a versatile, selective synthesis of the precursor and a se-
lective domino cyclization in a reaction, which drastically
increases the molecular complexity by the generation of
five additional stereogenic centers in one reaction step.
Figure 1
Synthesis of Novel Steroid Compounds
The stereochemistry of 18a was determined by NMR
With this promising results in hand we went on with a syn-
thesis of properly functionalized precursors for the syn-
thesis of novel steroid compounds. Variations in the
precursors have to be a variation of the ring size of ring D
of the steroid skeleton and an inert oxygen function in ring
A (carbon 3). Following this strategy a new variety of the
tetracyclic steroid should be accessible since the methyl
group of 19 will be attached at carbon 9. On the contrary,
naturally occurring steroids commonly carry this methyl
methods. We used heteronuclear correlation NMR (HM-
1
QC, HMBC) for the complete assignment of 13C and H
1
signal groups. Extensive and careful analysis of the H
coupling constants, and correlation of the vicinal coupling
constants with calculated geometries of possible
diastereomeric products obtained by force field confor-
mational analysis led to reasonable and successful assign-
ment of the stereochemistry of the cyclization products.14
In our previous studies NOESY experiments were ap- group at carbon 10 of the skeleton (Equation 2).
plied, but the outcome and thus the interpretation of the
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

FEATURE ARTICLE
PET Domino Cyclizations
623
Acidic work-up afforded enones 34 and 35 in 35% and
49% yield after chromatographic purification (Scheme 7).
Equation 2
The oxygen functionalized ring-A fragment 26 was syn-
thesized according to known methods and starting from
m-anisic acid (23).15 Birch reduction, double bond
isomerization, and hydrolysis of the enol ether afforded
keto acid 24 with the double bond in the proper position.
Functional group transformation led to the formation of
the allylic alcohol 26.16 Treatment with PBr3 in Et2O gave
the allylic bromide 27 in 77% yield (Scheme 5).
Scheme 7
The synthesis of homoallylic iodide 32 was conducted
analogous to the synthesis of 14 (Scheme 6).10 The struc-
tures of 29, 30, and 31 were confirmed by NMR analysis
(DEPT, COSY, HMQC, HMBC).
Silyl enol ethers 19 and 20 were prepared according to the
successful method developed for the synthesis of 17. The
yields were very good with 93% (19) and 96% (20) af-
fording the precursors for the domino cyclization in high
purity.
As for the synthesis of 16, 32 was metalated with tert-bu-
tyllithium and then reacted with 3-ethoxy-cyclopentenone
(33) and 3-ethoxycyclo-hexenone (15), respectively.17
Scheme 5
Scheme 6
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

624
J. O. Bunte et al.
FEATURE ARTICLE
For the cyclization of silyl enol ether 20, the same opti-
mized reaction conditions as for the cyclization of 17 were
used. Use of DCA as a sensitizer in a 75:25 mixture of
acetonitrile and propionitrile and irradiation with light of
= 420 nm resulted in the formation of two cyclization
products 22a and 22b, obtained in 27% yield. The product
ratio was determined by GC to be 50:50, as would be ex-
pected for an epimeric pair (Equation 3). Only one enan-
tiomer is displayed in the following schemes for clarity.
Equation 4
Radical cation 36, primarily generated by PET, undergoes
two different ring closure reactions with a 1:0.72 selectiv-
ity (calcd from product ratio) favoring the cis-transoid
pathway following 37a.
Equation 3
Remarkably, only fully cyclized products are obtained in
high stereoselectivity. Cyclohexanone silyl enol ether 20
cyclized in a completely selective manner. Only two dia-
stereomeric products were formed from the diastereo-
meric starting material although five stereogenic centers
are built up. In other words, only one out of 32 possible
cyclization pathways is followed in this domino cycliza-
tion, resulting in a 1:1 transformation of the starting mate-
rial.
PET cyclization of 19 afforded four products 21a–d in
44% yield after chromatographic purification
(Equation 4). The product ratio was determined by GC as
30:28:21:21 (21a:21b:21c:21d).
In this domino cyclization only fully cyclized products
were obtained in high stereoselectivity, as well. The silyl
enol ether 19 obtained through cuprate addition is a mix-
ture of two diasteromers with respect to the methyl group
and the methoxy group in the ring-A fragment. Conse-
quently, the cyclization products are epimeric pairs: 21a,
21b and 21c, 21d, respectively.
Both epimeric pairs result from a single cyclization path-
way. The 21a/21b pair shows a cis-connection between
ring C and D, a transoid-stereochemistry between 3a and
3b, as well as an all-trans-orientation of the remaining
ring junctions. This cis-transoid-connection at the previ-
ous silyl enol ether site is typically observed. In line with
our earlier results on cyclizations of cyclopentanone silyl
enol ethers,7c the 21c/21d pair additionally afforded the
cis-cisoid-orientation. This finding reduces the observed
stereoselectivity to a 1:2 transformation of the starting
material, due to branching of the cyclization pathways
(Scheme 8).
Scheme 8
Because of the radical cationic character of the intermedi-
ate, the branching of cyclization pathways (37a, 37b)
solely occurs in the primary cyclization step (bond forma-
tion 3a–3b). The secondary cyclization step (9b–9a), as
well as the saturation of the remaining radical center (5a),
is completely selective. As a consequence, the domino cy-
clization of 19 produces five new stereogenic centers with
only two diastereomeric patterns.
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

FEATURE ARTICLE
PET Domino Cyclizations
625
es to 2.75 ppm without any functionality nearby. This is
Proof of Stereochemistry
only possible with a cis-cisoid stereochemistry, as shown
Based on our experiences from the structure determina- in Figure 2.
tion of the cyclization products obtained from 17
(Equation 1) and the result from the x-ray structure analy-
sis of 18b, it was possible to assign the stereochemistry of
the cyclization products 21a–d and 22a,b by NMR-anal-
ysis.
Conclusion
We have shown that domino cyclizations of PET generat-
ed silyl enol ether radical cations can be used for the con-
struction of novel steroid backbones. These compounds
include an arrangement of methyl substituents in the ste-
roid skeleton, which was previously unknown. We have
devised a versatile synthesis of homoallylic side chains,
their coupling with ethoxy-cycloalkenones and the effi-
cient synthesis of complex trimethylsilyl ethers. Subse-
quent domino cyclizations of these specifically designed
precursors proceeded in a highly stereoselective manner
to yield products with five additional stereogenic centers
in one reaction step, a dramatic increase in molecular
complexity. The reaction conditions to achieve this trans-
formation are simple irradiation in the presence of a cata-
lytic amount of sensitizer.
Again, we applied heteronuclear correlation NMR (HM-
1
QC, HMBC) for the complete assignment of 13C and H
1
signal groups. As for 18a, extensive analysis of H cou-
pling constants and correlation of the vicinal coupling
constants with geometries of possible diastereomeric
products, obtained by force field conformational analysis,
led to a successful assignment of the stereochemistry of
the cyclization products. In Figure 2, the geometries of
21a and 21c obtained via this strategy are displayed. Free
positions should be regarded as hydrogen atoms.
1H NMR and 13C NMR spectra were recorded at 300 K using a
Bruker DRX 500 or Bruker Avance 600. Spectra were recorded in
CDCl3 or C6D6; chemical shifts were calibrated to the residual pro-
ton and carbon resonance of the solvent: CDCl3 ( H = 7.26 ppm,
C = 77.00 ppm), C6D6 ( H = 7.20 ppm, C = 128.0 ppm). Assign-
ments with a * are interchangeable. Additional NMR experiments
were conducted to determine structures APT: 10; APT, H/H-COSY,
HMQC: 11, 12; H/H-COSY: 13, 14, 32, 35; H/H-COSY, DEPT
135, HMBC: 17; H/H-COSY, DEPT-135, HMQC, HMBC: 29, 30,
34, 19; DEPT-135, H/H-COSY: 18a; DEPT 135: 18c; H/H-COSY,
DEPT 135, HMQC: 31; HMQC, HMBC, H/H-COSY: 22a, 21a–d,
22b. IR spectra were recorded on a Perkin-Elmer 841. HRMS were
recorded on an Autospec X, Vacuum Generators, Manchester. GC/
MS were recorded on a Shimadzu GC 17A/QP 5050A with a capil-
lary column 5MS, Hewlett-Packard. Analytical thin layer chroma-
tography was performed on silica gel 60 F254, Merck. Column
chromatography was performed on silica gel MN60 (63–200 m),
Macherey & Nagel. HPLC was performed on a silica gel column RT
250-25, LiChrosorb Si60 (7 m), Merck using a Merck L6000 pump
and a RI detector RI Bischoff 8110, Bischoff. Photochemical reac-
tions were performed using a RPR-100 Rayonet photochemical
chamber reactor, Southern New England Ultraviolet Company with
RPR-4190 Å lamps having an emission maximum at 419 nm 15
nm at half band width. All reactions were carried out under an at-
mosphere of argon. Starting materials and solvents were purified
using standard laboratory techniques.18
Figure 2
The coupling constants of the bridgehead hydrogens, as
well as the adjacent protons are of special importance for
the determination of the stereochemistry of the cyclization
products.
Ethyl-2-[(4-isopropenyl-1-cyclohexenyl)methyl]-3-(1-methylcy-
clopropyl)-3-oxo-propanoate (10)
The coupling constants between H-5a and H-9a, for ex-
ample, correspond to a trans-connection at rings A and B
in both 21a and 21c. The same is true for the stereochem-
istry between 3a and 3b in 21a. In 21c, the signals of the
important bridgehead protons 3a and 3b could not be re-
solved, due to almost identical chemical shifts. A special
feature of the geometry, discovered in model studies,
helped us to determine the stereochemistry.14 The axial
proton at C-4 lies within close proximity of the carbonyl
group and due to its anisotropy, the chemical shift increas-
A suspension of NaH (55%; 4.48 g, 103 mmol) in paraffin was
washed under an argon atmosphere with n-pentane (3 × 20 mL) and
suspended in anhyd THF (50 mL). The mixture was cooled to 0 °C
and a solution of ethyl-3-(1-methylcyclopropyl)-3-oxopropanoate
(9; 5.81 g, 34.2 mmol) in anhyd THF (20 mL) was added dropwise.
After stirring at r.t. for 15 min a solution of 1-(bromomethyl)-4-iso-
propenyl-1-cyclohexene (8; 20.1 g, 93.4 mmol) in anhyd THF (50
mL) was added dropwise and stirred for 10 h at r.t. and for 1 h under
reflux. The reaction mixture was cooled with ice and treated with
H2O (25 mL). After phase separation the aqueous layer was extract-
ed with Et2O (50 mL), the combined organic layers were washed
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

626
J. O. Bunte et al.
FEATURE ARTICLE
with brine (50 mL), dried (MgSO4), and filtered. Concentration in
vacuo and column filtration with EtOAc afforded crude 10 (27.8 g,
98%).
3-(4-Isopropenyl-1-cyclohexenyl)-1-(1-methylcyclopropyl)-1-
propanol (12)
3-(4-Isopropenyl-1-cyclohexenyl)-1-(1-methylcyclopropyl)-1-pro-
panone (11; 19.88 g, 85.6 mmol) in anhyd Et2O (30 mL) was added
dropwise to a suspension of LiAlH4 (3.26 g, 90.7 mmol) in anhyd
Et2O (250 mL) at 0 °C. The reaction mixture was stirred at 0 °C for
1 h and treated with concd aq Na2SO4 (20 mL). After stirring at r.t.
for 15 min it was dried (Na2SO4), and filtered. Concentration in vac-
uo afforded 12 (18.6 g, 93%) as a colorless oil.
IR (film): 3087, 2971, 2926, 2842, 1745, 1693, 1644, 1438, 1389,
1367, 1327, 1260, 1214, 1174, 1082, 1033, 949, 915, 887, 814 cm–1.
1H NMR (500 MHz, CDCl3): = 0.71–0.76 (m, 2 H, H-18, H-19),
1.16–1.47 (m, 9 H, H-9ax, H-14, H-17, H-18, H-19), 1.70 (m, 3 H,
H-3), 1.73-2.11 (m, 6 H, H-4, H-5, H-8, H-9eq), 2.35–2.55 (m, 2 H,
H-10), 3.76–3.81 (m, 1 H, H-11), 4.10–4.11 (m, 2 H, H-13), 4.64–
4.70 (m, 2 H, H-1), 5.39–5.43 (m, 1 H, H-6).
13C NMR (125.8 MHz, CDCl3): = 14.07 (q, C-14), 18.04/18.08 (t,
C-18*1), 18.12/18.13 (t, C-19*1), 19.64/19.67 (q, C-17), 20.73 (q,
C-3), 26.91/26.99 (s, C-16), 27.62/27.63 (t, C-9), 28.80/28.84 (t, C-
5*2), 30.60 (t, C-8*2), 36.43/36.58 (t, C-10), 40.76 (d, C-4), 51.39/
51.61 (d, C-11), 61.12 (t, C-13), 108.52 (t, C-1), 122.97/123.08 (d,
C-6), 133.72/133.82 (s, C-2), 169.34/169.25 (s, C-12), 205.94 (s, C-
15).
IR (film): 3394, 3076, 2924, 1774, 1700, 1643, 1452, 1437, 1375,
1317, 1138, 1044, 1015, 966, 952, 938, 914, 886, 858, 816 cm–1.
1H NMR (500 MHz, CDCl3): = 0.25–0.40 (m, 4 H, H-15, H-16),
1.02 (s, 3 H, H-14), 1.40–1.50 (m, 1 H, H-9ax), 1.55 (m, 1 H, OH),
1.60–1.69 (m, 2 H, H-11), 1.70–1.74 (m, 3 H, H-3), 1.77–1.83 (m,
1 H, H-9eq), 1.84–2.15 (m, 7 H, H-4, H-5, H-8, H-10), 2.80 (tm,
J = 6.5 Hz, 1 H, H-12), 4.63–4.71 (m, 2 H, H-1), 5.39–5.47 (m, 1
H, H-6).
13C NMR (125.8 MHz, CDCl3): = 11.18 (t, C-15*1), 11.90/11.91
(t, C-16*1), 17.15/17.18 (q, C-14), 20.56/20.57 (s, C-13), 20.76/
20.80 (q, C-3), 27.79/27.82 (t, C-9), 28.70/28.83 (t, C-5*2), 30.68/
30.72 (t, C-8*2), 32.07/32.10 (t, C-10*3), 34.27/34.29 (t, C-11*3),
41.10/41.19 (d, C-4), 78.69/78.82 (d, C-12), 108.39 (t, C-1), 120.50
(d, C-6), 137.31/137.35 (s, C-7), 150.08, 150.12 (s, C-2).
GC/MS (EI, 70 eV): m/z (%) = 305 (0.2), 304 (2), 176 (16),
175 (15), 171 (4), 134 (19), 119 (13), 91 (10), 83 (80), 79 (11),
67 (12), 55 (100), 53 (12), 41 (13), 29 (18).
GC/MS (CI, isobutane): m/z (%) = 306 (19), 305 (100), 135 (12).
3-(4-Isopropenyl-1-cyclohexenyl)-1-(1-methylcyclopropyl)-1-
propanone (11)
GC/MS (EI, 70 eV): m/z (%) = 234 (0.5), 201 (11), 188 (18),
187 (13), 175 (10), 174 (10), 173 (33), 161 (23), 159 (15), 147 (11),
145 (28), 136 (10), 134 (21), 133 (22), 131 (19), 119 (30), 117 (23),
107 (17), 106 (14), 105 (30), 98 (19), 95 (12), 94 (12), 93 (48),
92 (20), 91 (48), 83 (48), 82 (12), 81 (43), 80 (32), 79 (70), 77 (31),
71 (19), 70 (10), 69 (38), 68 (38), 67 (100), 65 (23), 57 (47),
56 (29), 55 (79), 53 (35), 43 (35), 41 (76), 39 (22), 29 (37).
Ba(OH)2·H2O (69.2 g, 364 mmol) was suspended in a mixture of
H2O (120 mL) and EtOH (50 mL). Ethyl-2-[(4-isopropenyl-1-cy-
clohexenyl)-methyl]-3-(1-methylcyclopropyl)-3-oxo-propanoate
(10; 27.8 g, 91.0 mmol) was added under an argon atmosphere. The
reaction mixture was stirred for 19 h under reflux, cooled to r.t., and
then added to a mixture of H2O (500 mL) and Et2O (200 mL). Con-
cd HCl was added until all solids had dissolved. The layers were
separated and the aqueous layer was extracted with Et2O (100 mL).
The combined organic layers were washed with H2O, sat. aq
NaHCO3 (100 mL), and brine (100 mL), dried (MgSO4), and fil-
tered. Concentration in vacuo afforded 11 (19.9 g, 94%) as a yel-
lowish oil.
GC/MS (CI, isobutane): m/z (%) = 233 (3), 218 (14), 217 (100),
161 (36), 135 (13), 121 (12).
HRMS: m/z calcd for C16H26O (M+), 234.1984; found, 234.1981.
Anal. Calcd for C16H26O: C, 81.99; H, 11.18. Found: C, 81.52; H,
11.27.
[ ]D25 –67.5 (c = 1.0, CHCl3).
(E)-1-Bromo-6-(4-isopropenyl-1-cyclohexenyl)-3-methyl-3-
hexene (13)
IR (film): 3088, 3008, 2969, 2923, 2841, 1739, 1692, 1643, 1437,
1415, 1388, 1364, 1328, 1287, 1245, 1140, 1085, 1050, 1020, 994,
947, 914, 887, 823 cm–1.
1H NMR (500 MHz, CDCl3): = 0.64–0.74 (m, 2 H, H-15/16),
1.15–1.25 (m, 2 H, H-15/16), 1.34 (s, 3 H, H-14), 1.44 (dddd,
J = 5.6, 11.4, 11.4, 12.8 Hz, 1 H, H-9ax), 1.71 (dd, J = 1.2, 1.2 Hz,
3 H, H-3), 1.78 (dddd, J = 2.6, 4.6, 5.6, 12.7 Hz, 1 H, H-9eq), 1.84–
2.12 (m, 5 H, H-4, H-5, H-8), 2.17 (tm, 2 H, J = 7.6 Hz, H-10),
2.40–2.52 (m, 2 H, H-11), 4.66–4.70 (m, 2 H, H-1), 5.36–5.40 (m,
1 H, H-6).
13C NMR (125.8 MHz, CDCl3): = 17.93 (t, C-15*1), 17.94 (t, C-
16*1), 19.76 (q, C-14), 20.72 (q, C-3), 26.41 (s, C-13), 27.73 (t, C-
9), 28.92 (t, C-5*2), 30.63 (t, C-8*2), 31.54 (t, C-10), 36.25 (t, C-11),
41.03 (d, C-4), 108.41 (t, C-1), 120.53 (d, C-6), 136.40 (s, C-7),
149.96 (s, C-2), 211.42 (s, C-12).
3-(4-Isopropenyl-1-cyclohexenyl)-1-(1-methylcyclo-propyl)-1-
propanol (12; 9.38 g, 40.0 mmol) and sym-collidine (7.27 g, 60.0
mmol) were successively added dropwise to a suspension of LiBr
(11.9 g, 200 mmol) in anhyd Et2O (300 mL). The mixture was
cooled to –78 °C and PBr3 (4.44 mL, 46.8 mmol) was added drop-
wise. After stirring for 10 h with slow warming to r.t., the solution
was cooled with an ice/NaCl slurry and a mixture of sym-collidine
(22.7 g, 188 mmol) and H2O (2.75 mL, 150 mmol) was added. After
stirring for 10 min n-pentane (400 mL) and sat. aq NaHCO3 (125
mL) were added to the reaction mixture. The layers were separated
and the organic layer was washed successively with 5% aq HCl
(150 mL), sat. aq NaHCO3 (150 mL), and brine (150 mL), dried
(MgSO4), filtered, and concentrated in vacuo. The product was di-
rectly used for the next reaction.
A solution of the crude material in anhyd Et2O (100 mL) was added
dropwise to a suspension of ZnBr2 (27.0 g, 120 mmol) in anhyd
Et2O (40 mL) cooled to –78 °C. After stirring for 1 h at –78 °C the
mixture was stirred for 14 h under slow warming to 0 °C. 0.75 mL
H2O were added and after stirring for 45 min pyridine (18.8 g, 238
mmol) was added and the mixture was stirred for 15 min at 0 °C. n-
Hexane (600 mL) and sat. aq NaHCO3 (200 mL) were added, the
layers were separated and the organic layer was washed successive-
ly with 5% aq HCl (80 mL), brine (80 mL), sat. aq NaHCO3 (80
mL), and brine (80 mL), dried (MgSO4), and filtered Concentration
in vacuo and column filtration with Et2O afforded 13 (8.71 g, 73%)
as a colorless oil.
GC/MS (EI, 70 eV): m/z (%) = 233 (0.5), 232 (2), 149 (14),
134 (23), 119 (13), 105 (10), 91 (15), 83 (100), 79 (15), 77 (11),
67 (16), 55 (85), 53 (17), 41 (23), 39 (11), 29 (14), 27 (10).
GC/MS (CI, isobutane): m/z (%) = 234 (17), 233 (100).
HRMS: m/z calcd for C16H24O (M+), 232.1827; found, 232.1828.
Anal. Calcd for C16H24O: C, 82.70; H, 10.41. Found: C, 82.62; H,
10.69.
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

FEATURE ARTICLE
PET Domino Cyclizations
627
IR (film): 3085, 2923, 1782, 1714, 1643, 1436, 1375, 1311, 1266,
1208, 1137, 1049, 1013, 961, 913, 887, 802, 758, 653 cm–1.
organic layer was successively washed with sat. aq NaHCO3 (100
mL), H2O (100 mL), and brine (100 mL), dried (MgSO4), and fil-
tered. Concentration in vacuo and column filtration with cyclohex-
ane–EtOAc (90:10) afforded 16 (3.46 g, 64%) as a colorless oil.
1H NMR (500 MHz, CDCl3): = 1.41–1.49 (m, 1 H, H-9ax), 1.61–
1.63 (m, 3 H, H-14), 1.73–1.75 (m, 3 H, H-3), 1.77–1.83 (m, 1 H,
H-9eq), 1.85–2.17 (m, 9 H, H-4, H-5, H-8, H-10, H-11), 2.53 (tm,
J = 7.5 Hz, 2 H, H-15), 3.43 (t, J = 7.5 Hz, 2 H, H-16), 4.67–4.75
(m, 2 H, H-1), 5.20–5.24 (m, 1 H, H-12), 5.39–5.44 (m, 1 H, H-6).
13C NMR (125.8 MHz, CDCl3): = 15.60 (q, C-14), 20.80 (q, C-3),
26.30 (t, C-11), 27.87 (t, C-9), 28.81 (t, C-5*1), 30.75 (t, C-8*1),
31.72 (t, C-16), 37.26 (t, C-10), 41.18 (d, C-4), 42.90 (t, C-15),
108.38 (t, C-1), 120.55 (d, C-6), 127.69 (d, C-12), 131.77 (s, C-13),
136.98 (s, C-7), 150.17 (s, C-2).
25
[ ]D –47.1 (c = 1.0, CHCl3).
IR (film): 2922, 1673, 1644, 1626, 1452, 1434, 1373, 1346, 1324,
1252, 1191, 1130, 1086, 1049, 963, 913, 885, 823, 755 cm–1.
1H NMR (500 MHz, CDCl3): = 1.42–1.47 (m, 1 H, H-9ax), 1.60–
1.62 (m, 3 H, H-14), 1.72–1.74 (m, 3 H, H-3), 1.77–1.83 (m, 1 H,
H-9eq), 1.85–2.14 (m, 11 H, H-4, H-5, H-8, H-10, H-11, H-21),
2.13–2.20 (m, 2 H, H-15), 2.26–2.33 (m, 4 H, H-16, H-22), 2.33–
2.37 (m, 2 H, H-20), 4.68–4.72 (m, 2 H, H-1), 5.12–5.16 (m, 1 H,
H-12), 5.38–5.42 (m, 1 H, H-6), 5.84–5.88 (m, 1 H, H-18).
13C NMR (125.8 MHz, CDCl3): = 15.81 (q, C-14), 20.76 (q, C-3),
22.65 (t, C-21), 26.25 (t, C-11), 27.81 (t, C-9), 28.79 (t, C-5*1),
29.59 (t, C-22), 30.69 (t, C-8*1), 36.60 (t, C-16), 36.97 (t, C-15),
37.29 (C-20), 37.42 (t, C-10), 41.14 (d, C-4), 108.34 (t, C-1), 120.33
(d, C-6), 125.44 (d, C-12), 125.78 (d, C-18), 133.41 (s, C-13),
137.11 (s, C-7), 150.12 (s, C-2), 166.26 (s, C-17), 199.84 (s, C-19).
GC/MS (EI, 70 eV): m/z (%) = 298 (7), 296 (7), 189 (37), 162 (11),
161 (88), 135 (13), 133 (14), 121 (11), 119 (16), 107 (24), 105 (15),
94 (11), 93 (100), 91 (41), 81 (60), 80 (16), 79 (78), 77 (30),
69 (20), 68 (18), 67 (85), 65 (22), 55 (78), 53 (36), 41 (63),
39 (19), 29 (14), 27 (15).
GC/MS (CI, isobutane): m/z (%) = 355 (11), 353 (11), 300 (13),
299 (73), 298 (23), 287 (100), 296 (16), 295 (14), 243 (24),
241 (18), 218 (11), 217 (51), 215 (22), 203 (14), 189 (11), 175 (13),
161 (43), 150 (10), 149 (44), 147 (11), 137 (10), 135 (32), 133 (11),
123 (20), 121 (15), 111 (10), 109 (23).
GC/MS (EI, 70 eV): m/z (%) = 312 (0.01), 135 (17), 133 (10),
110 (100), 107 (11), 93 (25), 91 (21), 81 (14), 79 (35), 77 (20),
67 (27), 65 (11), 55 (46), 53 (27), 41 (31), 39 (11).
HRMS: m/z calcd for C22H32O (M+), 312.2453; found, 312.2441.
HRMS: m/z calcd for C16H25Br (M+), 296.1134; found, 296.1133.
Anal. Calcd for C16H25Br: C, 64.65; H, 8.48. Found: C, 64.20; H,
8.26.
3-[(E)-6-(4-Isopropenyl-1-cyclohexenyl)-3-methyl-3-hexenyl]-
3-methyl-1-cyclohexenyl-trimethylsilylether (17)
(E)-1-Iodo-6-(4-isopropenyl-1-cyclohexenyl)-3-methyl-3-hex-
ene (14)
In a flame dried flask CuI (4.22 g, 22.1 mmol) was suspended in an-
hyd THF (75 mL) and the mixture was cooled with an ice/NaCl slur-
ry. MeLi (27.6 mL, 44.2 mmol of a 1.6 M solution in Et2O) was
added dropwise and it was stirred until the yellow precipitate is
completely dissolved. The reaction mixture was cooled to –78 °C
and a solution of TMSCl (2.38 g, 22.04 mmol) and 3-[(E)-6-(4-iso-
propenyl-1-cyclohexenyl)-3-methyl-3-hexenyl]-2-cyclohexen-1-
one (16; 2.30 g, 7.37 mmol) in anhyd THF (20 mL) was added drop-
wise. After stirring for 2 h the cooled reaction mixture was placed
in a separation funnel, ice-cold 0.1 N aq HCl (180 mL) and ice-cold
n-pentane (225 mL) were added. After shaking for a short time the
layers were separated and the organic layer was washed with ice-
cold sat. aq NaHCO3, dried (Na2SO4), and filtered. Concentration in
vacuo afforded 17 (2.48 g, 84%) as a colorless oil.
A solution of NaI (14.83 g, 93.83 mmol) and (E)-1-bromo-6-(4-iso-
propenyl-1-cyclohexenyl)-3-methyl-3-hexene (13; 5.72 g, 19.24
mmol) in acetone (50 mL) was thoroughly degassed with argon and
stirred under reflux for 2.5 h. It was cooled to r.t., n-hexane (250
mL) was added and the mixture was filtered. The filter cake was
washed with n-hexane (2 × 100 mL) and the combined filtrates
were washed with brine (100 mL), dried (MgSO4), and filtered.
Concentration in vacuo afforded 14 (6.07 g, 92%) as a yellowish oil.
1H NMR (500 MHz, CDCl3): = 1.41–1.49 (m, 1 H, H-9ax), 1.61–
1.63 (m, 3 H, H-14), 1.72–1.75 (m, 3 H, H-3), 1.77–1.83 (m, 1 H,
H-9eq), 1.85–2.15 (m, 9 H, H-4, H-5, H-8, H-10, H-11), 2.53 (t,
J = 7.7 Hz, 2 H, H-15), 3.21 (t, J = 7.7 Hz, 2 H, H-16), 4.67–4.73
(m, 2 H, H-1), 5.19–5.22 (m, 1 H, H-12), 5.40–5.44 (m, 1 H, H-6).
IR (film): 2934, 1661, 1644, 1453, 1374, 1364, 1340, 1263, 1251,
1205, 1132, 1058, 988, 965, 934, 887, 842, 753, 665 cm–1.
13C NMR (125.8 MHz, CDCl3): = 5.15 (t, C-16), 15.32 (q, C-14),
20.81 (q, C-3), 26.29 (t, C-11), 27.86 (t, C-9), 28.81 (t, C-5*1),
30.75 (t, C-8*1), 37.23 (t, C-10), 41.18 (d, C-4), 43.79 (t, C-15),
108.37 (t, C-1), 120.54 (d, C-6), 127.35 (d, C-12), 133.41 (s, C-13),
137.00 (s, C-7), 150.18 (s, C-2).
1H NMR (500 MHz, CDCl3): = 0.178 (s, 9 H, H-TMS), 0.951 (s,
3 H, H-23), 1.20–1.50 (m, 5 H, H-9ax, H-16, H-22), 1.58–1.59 (m,
3 H, H-14), 1.63–1.70 (m, 2 H, H-21), 1.73–1.74 (m, 3 H, H-3),
1.77–1.83 (m, 1 H, H-9eq), 1.85–2.15 (m, 13 H, H-4, H-5, H-8, H-
10, H-11, H15, H-20), 4.66 (dd, J = 1.3, 1.3 Hz, 1 H, H-18), 4.68–
4.72 (m, 2 H, H-1), 5.08–5.13 (m, 1 H, H-12), 5.39–5.43 (m, 1 H,
H-6).
13C NMR (125.8 MHz, CDCl3): = 0.33 (q, C-TMS), 16.15 (q, C-
14), 19.63 (t, C-21), 20.79 (q, C-3), 26.39 (t, C-11), 27.90 (t, C-9),
28.02 (q, C-23), 28.86 (t, C-5*1), 29.87 (t, C-20), 30.76 (t, C-8*1),
34.48 (s, C-17), 34.52 (t, C-15+C-22), 37.59 (t, C-10), 41.22 (d, C-
4), 42.12 (t, C-16), 108.35 (t, C-1), 114.49 (d, C-18), 120.25 (d, C-
6), 123.67 (d, C-12), 135.94 (s, C-13), 137.36 (s, C-7), 149.25 (s, C-
19), 150.23 (s. C-2).
GC/MS (EI, 70 eV): m/z (%) = 345 (0.1), 344 (0.7), 217 (11),
189 (29), 161 (42), 135 (16), 133 (11), 119 (14), 107 (26), 105 (19),
95 (11), 94 (10), 93 (99), 91 (46), 82 (17), 81 (85), 80 (17), 79 (87),
77 (41), 69 (21), 68 (18), 67 (100), 68 (18), 67 (100), 65 (26),
55 (86), 54 (11), 53 (45), 43 (13), 41 (72), 39 (27), 29 (18).
3-[(E)-6-(4-Isopropenyl-1-cyclohexenyl)-3-methyl-3-hexenyl]-
2-cyclohexen-1-one (16)
To a solution of 2,2 -bipyridine (26 mg) in anhyd THF (200 mL)
cooled to –78 °C t-BuLi (22.7 mL, 38.5 mmol of a 1.7 M solution
in n-pentane) was added. Subsequently a solution of (E)-1-iodo-6-
(4-isopropenyl-1-cyclohexenyl)-3-methyl-3-hexene (14; 5.94 g,
17.25 mmol) in anhyd THF (10 mL) was added dropwise. The reac-
tion mixture was stirred for 1.5 h at –78 °C before a solution of 3-
ethoxycyclohex-2-enone (15; 2.94 g, 21.0 mmol) in anhyd THF (10
mL) was added dropwise. After stirring for 1 h at –78 °C it was
warmed to 0 °C, Et2O (100 mL) and 2 N aq HCl (100 mL) were add-
ed, it was stirred for 20 min at r.t. and the layers were separated. The
13C NMR (125.8 MHz, C6D6): = 0.47, 16.34, 19.98, 20.89, 26.89,
28.25, 28.40, 29.12, 30.36, 31.17, 34.81, 34.89, 35.13, 38.12, 41.59,
42.75, 108.94, 113.74, 120.82, 124.31, 135.98, 137.28, 149.95,
150.05.
GC/MS (EI, 70 eV): m/z (%) = 400 (0.2), 184 (16), 183 (100),
73 (55), 55 (14).
HRMS: m/z calcd for C26H44OSi (M+), 400.3162; found, 400.3152.
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

628
J. O. Bunte et al.
FEATURE ARTICLE
Anal. Calcd for C26H44OSi: C, 77.93; H, 11.07. Found: C, 76.06; H,
10.48.
IR (film): 3090, 2926, 2864, 1702, 1641, 1447, 1382, 1349, 1309,
1293, 1260, 1225, 1169, 1147, 1116, 1069, 1023, 993, 957, 888,
786, 727 cm–1.
PET Cyclization of 3-[(E)-6-(4-Isopropenyl-1-cyclohexenyl)-3-
methyl-3-hexenyl]-3-methyl-1-cyclohexenyl-trimethylsilyl-
ether (17)
1H NMR (500 MHz, CDCl3): = 0.72 (s, 3 H), 0.85–0.95 (m, 3 H),
0.87 (s, 3 H), 0.96–1.02 (m, 1 H), 1.05–1.20 (m, 3 H), 1.21–1.50 (m,
6 H), 1.55–1.66 (m, 3 H), 1.71–1.73 (m, 3 H), 1.81 (ddddd, J = 4.5,
4.5, 13.6, 13.6, 13.6 Hz, 1 H), 1.87–2.00 (m, 3 H), 2.03 (dddd,
J = 2.4, 2.4, 2.4, 13.4 Hz, 1 H), 2.06–2.13 (m, 1 H), 2.22–2.35 (m,
2 H), 2.35–2.41 (m, 1 H, H-9), 4.74–4.84 (m, 1 H, H-16), 4.88–4.96
(m, 1 H, H-16).
13C NMR (125.8 MHz, CDCl3): = 12.08 (q), 22.53 (t, C-2), 22.77
(q), 25.08 (t), 27.31 (t), 27.77 (t), 27.89 (q), 29.34 (t), 30.12 (t),
33.26 (t), 34.37 (t), 35.05 (t), 36.15 (s), 37.03 (d), 37.58 (t, C-3),
37.79 (s), 39.04 (d), 44.23 (d), 48.14 (d), 60.59 (d), 110.73 (t, C-16),
146.96 (s, C-15), 216.61 (s, C-4).
A solution of 3-[(E)-6-(4-isopropenyl-1-cyclohexenyl)-3-methyl-3-
hexenyl]-3-methyl-1-cyclohexenyl-trimethylsilylether (17; 361
mg, 0.90 mmol), DCA (300 mg, 1.30 mmol) and n-decane (200 L)
in anhyd MeCN–anhyd propionitrile (3:1, 100 mL) was placed in ir-
radiation tubes (11 mL each, pyrex glass, 12 mm diameter), de-
gassed with argon for 20 min and irradiated with light of 420 nm
until complete consumption of the starting material had occured.
Concentration in vacuo and column filtration with cyclohexane–
EtOAc (95:5) afforded 18a–c as a mixture of diastereomers (77 mg,
26%).
GC/MS (EI, 70 eV): m/z (%) = 329 (4), 328 (22), 313 (23),
187 (10), 149 (10), 145 (10), 135 (12), 133 (14), 121 (16), 119 (18),
111 (100), 109 (14), 107 (30), 105 (31), 95 (32), 93 (37), 91 (32),
82 (27), 81 (34), 79 (40), 77 (17), 69 (17), 67 (38), 65 (10), 55 (70),
53 (24), 43 (21), 41 (49), 39 (10), 29 (19), 28 (14).
The diastereomers were separated by HPLC (cyclohexane–EtOAc,
95:5) affording pure 18b. Fractional crystallization from MeCN af-
forded pure 18a. Compound 18c could only be obtained in a 1:1
mixture with 18a.
HRMS: m/z calcd for C23H36O (M+), 328.27607; found, 328.27616.
(4aS,4bS,6aR,9S,10aS,10bS,12aR)-9-Isopropenyl-10b,12a-di-
methylhexadecahydro-benzo[a]phenanthren-4(1H)-one (18a)
IR (film): 3084, 2922, 2308, 1693, 1642, 1451, 1380, 1344, 1311,
1295, 1261, 1241, 1229, 1190, 1170, 1157, 1087, 979, 956, 929,
905, 881, 847, 798, 756, 730, 665 cm–1.
(9S)-9-Isopropenyl-10b,12a-dimethylhexadecahydro-benzo-
[a]phenanthren-4(1H)-one (18c)
13C NMR (150.96 MHz, C6D6): = 17.69 (q), 20.72 (q), 21.83 (t),
22.50 (t, C-2), 27.94 (q), 29.47 (t), 30.22 (t), 30.94 (t), 31.65 (t),
33.34 (t), 34.62 (t), 35.41 (t), 36.41 (d), 37.69 (t, C-3), 37.84 (s),
37.98 (s), 40.88 (d), 45.22 (d), 46.68 (d), 59.92 (d), 107.95 (t, C-16),
151.22 (s, C-15), 216.40 (s, C-4).
1H NMR (600 MHz, C6D6): = 0.58 (d, J = 0.6 Hz, 3 H, H-14), 0.67
(ddd, J = 3.1, 10.5, 11.9 Hz, 1 H, H-10a), 0.70 (ddddd, J = 1.3, 1.3,
2.3, 5.7, 13.8 Hz, 1 H, H-1eq), 0.81 (dddd, J = 5.3, 12.0, 12.3, 12.6
Hz, 1 H, H-5ax), 0.86 (d, J = 0.7 Hz, 3 H, H-13), 0.87 (ddd,
J = 12.1, 12.1, 12.1 Hz, 1 H, H-10ax), 0.95 (dddd, J = 3.5, 11.2,
12.7, 12.7 Hz, 1 H, H-7ax), 1.01 (ddddd, J = 3.5, 3.5, 11.0, 11.2,
11.7 Hz, 1 H, H-6a), 1.06 (ddd, J = 4.2, 13.9, 13.9 Hz, 1 H, H-11ax),
1.12 (ddd, J = 2.9, 4.1, 13.9 Hz, 1 H, H-12eq), 1.08–1.18 (m, 2 H,
H-6ax, H-6eq), 1.16 (dddd, J = 3.5, 12.4, 12.4, 12.4 Hz, 1 H, H-
8ax), 1.27 (ddd, J = 4.3, 14.1, 14.1 Hz, 1 H, H-12ax), 1.36 (dddd,
J = 1.0, 4.3, 11.6, 11.6 Hz, 1 H, H-4b), 1.39 (ddd, J = 2.8, 4.3, 13.2
Hz, 1 H, H-11eq), 1.53 (dddd, J = 2.8, 3.9, 3.9, 3.0 Hz, 1 H, H-5eq),
1.57 (ddddd, J = 2.4, 2.4, 4.6, 7.1, 13.5 Hz, 1 H, H-2eq), 1.62 (dddd,
J = 3.3, 3.3, 3.3, 12.5 Hz, 1 H, H-7eq), 1.66 (ddddd, J = 4.9, 4.9,
13.5, 13.5, 13.5 Hz, 1 H, H-2ax), 1.73–1.79 (m, 1 H, H-8eq), 1.75–
1.77 (m, 3 H, H-17), 1.80 (dddd, J = 2.1, 3.1, 3.1, 12.5 Hz, 1 H, H-
10eq), 1.92 (ddddd, J = 0.9, 3.3, 3.3, 12.0, 12.0 Hz, 1 H, H-9), 1.95
(ddd, J = 4.9, 13.7, 13.7 Hz, 1 H, H-1ax), 2.06 (ddd, J = 7.1, 13.5,
13.5 Hz, 1 H, H-3ax), 2.10 (ddd, J = 1.2, 1.2, 12.2 Hz, 1 H, H-4a),
2.12 (ddddd, J = 1.3, 1.3, 2.4, 5.1, 13.4 Hz, 1 H, H-3eq), 4.86–4.90
(m, 2 H, H-16).
GC/MS (EI, 70 eV): m/z (%) = 329 (7), 328 (9), 313 (33), 295 (17),
281 (17), 201 (26), 189 (13), 188 (21), 187 (34), 163 (11), 159 (11),
149 (16), 147 (16), 135 (22), 133 (24), 131 (14), 121 (24), 119 (19),
112 (10), 111 (92), 109 (17), 108 (11), 107 (44), 106 (11), 105 (46),
96 (14), 95 (73), 94 (10), 93 (55), 91 (51), 83 (14), 82 (24), 81 (40),
79 (59), 77 (27), 70 (13), 69 (15), 68 (12), 67 (61), 65 (12), 57 (15),
56 (12), 55 (100), 53 (36), 43 (17), 42 (18), 41 (59), 39 (13),
29 (27), 28 (54).
1-(Bromomethyl)-5-methoxy-1-cyclohexene (27)
A solution of (5-methoxy-1-cyclohexenyl) methanol (26; 6.27 g,
44.2 mmol) in anhyd Et2O (250 mL) was cooled with dry ice–ace-
tone. PBr3 (4.88 g, 18.0 mmol) was added dropwise. After complete
addition, the reaction mixture was allowed to warm to r.t. and stirred
for 5 h. The solution was added to ice (100 g), washed successively
with H2O (80 mL) and sat. aq NaHCO3 (80 mL) and dried (Na2SO4).
Filtration and concentration an vacuo afforded 27 (7.0 g, 77%) as a
yellowish oil. It should be stored at –18 °C and used for further re-
actions within days of preparation.
13C NMR (150.96 MHz, C6D6): = 12.36 (q, C-14), 20.91 (q, C-
17), 22.51 (t, C-2), 25.12 (t, C-6), 27.88 (q, C-13), 29.29 (t, C-1),
30.65 (t, C-10), 31.30 (t, C-8), 33.41 (t, C-11), 34.29 (t, C-5), 34.78
(t, C-7), 35.04 (t, C-12), 36.05 (d, C-6a), 36.36 (s, C-10b), 37.58 (t,
C-3), 37.75 (s, C-12a), 44.26 (d, C-4b), 45.81 (d, C-9), 53.94 (d, C-
10a), 60.57 (d, C-4a), 108.02 (t, C-16), 151.03 (s, C-15), 216.53 (s,
C-4).
IR (film): 2930, 2658, 2429, 2090, 1729, 1715, 1661, 1437, 1376,
1364, 1308, 1246, 1209, 1163, 1097, 1052, 994, 897, 879, 825, 789,
728, 688, 640 cm–1.
1H NMR (500 MHz, CDCl3): = 1.56–1.65 (m, 1 H), 1.78–1.86 (m,
1 H), 2.00–2.25 (m, 3 H), 2.45–2.52 (m, 1 H), 3.38 (s, 3 H, OMe),
3.51–3.56 (m, H-3), 3.90–3.97 (m, 2 H, H-7), 5.83–5.87 (m, 1 H, H-
6).
GC/MS (EI, 70 eV): m/z (%) = 329 (3), 328 (18), 313 (39),
189 (10), 121 (11), 119 (11), 111 (100), 109 (10), 107 (20),
105 (17), 95 (23), 93 (29), 91 (23), 81 (26), 79 (30), 77 (11),
69 (14), 67 (30), 55 (53), 53 (15), 43 (17), 41 (37), 29 (12).
13C NMR (125.8 MHz, CDCl3): = 23.19, 26.25, 32.17, 38.97,
55.84, 75.15, 127.44, 132.00.
HRMS: m/z calcd for C23H36O (M+), 328.27607; found, 328.27644.
GC/MS (EI, 70 eV): m/z (%) = 125 (10), 95 (17), 94 (22), 93 (68),
91 (26), 83 (12), 79 (15), 77 (33), 67 (35), 65 (18), 58 (100), 53 (12),
45 (15), 43 (15), 41 (23), 39 (21), 27 (12).
(4aR,4bR,6aS,9S,10aR,10bR,12aS)-9-Isopropenyl-10b,12a-
dimethylhexadecahydro-benzo[a]phenanthren-4(1H)-one (18b)
[ ]D25 –85.7 (c = 0.88, CHCl3).
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

FEATURE ARTICLE
PET Domino Cyclizations
629
3-(5-Methoxy-1-cyclohexenyl)-1-(1-methylcyclopropyl)-1-pro-
panone (29)
(E)-1-Bromo-6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-hexene
(31)
As described for the synthesis of 10 and 11, 29 was synthesized via
ethyl-2-[(5-methoxy-1-cyclohexenyl)methyl]-3-(1-methylcyclo-
propyl)-3-oxopropanoate 28. Compound 28 was formed from ethyl-
3-(1-methylcyclopropyl)-3-oxopropanoate (9; 5.81 g, 34.2 mmol)
and 1-(bromomethyl)-5-methoxy-1-cyclohexene (27; 7.0 g, 34.3
mmol) affording crude 28 (9.41 g).
As described for the synthesis of 13, 31 was prepared from 3-(5-
methoxy-1-cyclohexenyl)-1-(1-methylcyclopropyl)-1-propanol
(30; 4.73 g, 21.1 mmol), affording 31 (4.79 g, 79%) as a colorless
oil.
IR (film): 2926, 2656, 2352, 1740, 1729, 1715, 1702, 1668, 1561,
1441, 1373, 1311, 1267, 1194, 1122, 1099, 991, 932, 897, 828, 782
cm–1.
GC/MS (EI, 70 eV): m/z (%) = 179 (11), 171 (15), 133 (13), 92 (11),
91 (10), 83 (100), 79 (14), 77 (11), 55 (84), 41 (11), 29 (21), 27 (10).
1H NMR (500 MHz, CDCl3): = 1.46–1.56 (m, 1 H, H-4), 1.61 (dd,
J = 1.0, 1.3 Hz, 3 H, H-11), 1.82–2.06 (m, 5 H, H-2, H-4, H-5, H-
7), 2.06–2.18 (m, 3 H, H-5, H-8), 2.21–2.28 (m, 1 H, H-2), 2.51 (tm,
J = 7.5 Hz, 2 H, H-12), 3.37 (s, 3 H, OMe), 3.41 (t, J = 7.5 Hz, 2 H,
H-13), 3.40–3.48 (m, 1 H, H-3), 5.19 (qt, J = 1.2, 7.0 Hz, 1 H, H-9),
5.35–5.39 (m, 1 H, H-6).
13C NMR (125.8 MHz, CDCl3): = 15.56 (q, C-11), 23.38 (t, C-5),
26.08 (t, C-8), 27.01 (t, C-4), 31.65 (t, C-13), 34.38 (t, C-2), 37.26
(t, C-7), 42.83 (t, C-12), 55.71 (q, OMe), 76.18 (d, C-3), 120.55 (d,
C-6), 127.44 (d, C-9), 131.87 (s, C-10), 134.67 (s, C-1).
GC/MS analysis showed that the crude product already contained
29, apart from 28.
Further reaction as described for 11 afforded 29 (5.73 g, 75%) as a
colorless oil.
IR (film): 3362, 3092, 2928, 2845, 1690, 1441, 1415, 1371, 1315,
1246, 1194, 1122, 1098, 1058, 994, 947, 898, 866, 837, 796 cm–1.
1H NMR (500 MHz, CDCl3): = 0.62–0.73 (m, 2 H, H-12/H13),
1.13–1.24 (m, 2 H, H-12/H-13), 1.32 (s, 3 H, H-11), 1.44–1.55 (m,
1 H), 1.80–1.87 (m, 1 H), 1.88–2.04 (m, 2 H), 2.06–2.26 (m, 4 H),
2.43–2.48 (m, 2 H, H-8), 3.35 (s, 3 H, OMe), 3.41–3.48 (m, 1 H, H-
3), 5.32–5.36 (m, 1 H, H-6).
13C NMR (125.8 MHz, CDCl3): = 17.93/17.95 (t, C-12/C13),
19.73 (q, C-11), 23.20 (t), 26.41 (s, C-10), 26.82 (t), 31.56 (t, C-7),
34.46 (t), 36.02 (t, C-8), 55.70 (q, OMe), 75.94 (d, C-3), 120.58 (d,
C-6), 134.11 (s, C-1), 211.21 (s, C-9).
GC/MS (EI, 70 eV): m/z (%) = 147 (35), 119 (32), 106 (17), 95 (10),
94 (16), 93 (100), 92 (19), 91 (43), 81 (41), 79 (34), 77 (37), 67 (29),
65 (14), 58 (19), 55 (38), 53 (24), 45 (15), 41 (44), 39 (16), 29 (11),
27 (13).
HRMS: m/z calcd for C14H22OBr (M+ – H),285.08540; found,
285.08521.
Anal. Calcd for C14H23OBr: C, 58.54; H, 8.07. Found: C, 57.67; H,
7.55.
GC/MS (EI, 70 eV): m/z (%) = 222 (<0.1), 190 (21), 92 (24), 91
(19), 84 (11), 83 (100), 79 (21), 77 (16), 71 (10), 67 (12), 58 (13),
56 (10), 55 (79), 53 (17), 43 (21), 41 (22), 39 (13), 29 (17), 27 (13).
(E)-1-Iodo-6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-hexene
(32)
As described for the synthesis of 14, 32 was prepared from (E)-1-
HRMS: m/z calcd for C14H22O2 (M+), 222.16198; found,
222.16197.
bromo-6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-hexene
yielding 32 (2.20 g, 86%) as a yellowish oil.
(31),
3-(5-Methoxy-1-cyclohexenyl)-1-(1-methylcyclopropyl)-1-pro-
panol (30)
As described for the synthesis of 12, 3-(5-methoxy-1-cyclohexe-
nyl)-1-(1-methylcyclopropyl)-1-propanone (29; 5.08 g, 22.9 mmol)
was reduced, yielding 30 (4.91 g, 96%) as a colorless oil.
IR (film): 2927, 2655, 1729, 1701, 1668, 1439, 1373, 1304, 1243,
1193, 1169, 1121, 1099, 990, 931, 896, 829, 783, 733 cm–1.
1H NMR (500 MHz, CDCl3): = 1.47–1.56 (m, 1 H), 1.60 (s, 3 H,
H-11), 1.83–1.90 (m, 1 H), 1.91–2.18 (m, 7 H), 2.20–2.30 (m, 1 H),
2.51 (t, J = 7.6 Hz, 2 H, H-12), 3.20 (t, J = 7.6 Hz, 2 H, H-13), 3.37
(s, 3 H, OMe), 3.41–3.50 (m, 1 H, H-3), 5.17–5.19 (m, 1 H, H-9),
5.37–5.38 (m, 1 H, H-6).
13C NMR (125.8 MHz, CDCl3): = 5.00 (t, C-13), 15.31 (q, C-11),
23.42 (t, C-5), 26.11 (t, C-8), 27.06 (t, C-4), 34.43 (t, C-2), 37.25 (t,
C-7), 43.76 (t, C-12), 55.72 (q, OMe), 76.23 (d, C-3), 120.57 (d, C-
6), 127.13 (d, C-9), 133.54 (s, C-10), 134.72 (s, C-1).
IR (film): 3453, 3076, 2933, 2660, 2049, 1735, 1723, 1701, 1668,
1560, 1453, 1373, 1316, 1247, 1194, 1122, 1099, 1015, 955, 938,
858, 830, 794 cm–1.
1H NMR (500 MHz, CDCl3): = 0.23–0.41 (m, 4 H, H-12/H-13),
1.00 (s, 3 H, H-11), 1.43–1.73 (m, 4 H), 1.80–2.30 (m, 7 H), 2.73–
2.83 (m, 1 H, H-9), 3.35 (s, 3 H, OMe), 3.39–3.50 (m, 1 H, H-3),
5.35–5.42 (m, 1 H, H-6).
13C NMR (125.8 MHz, CDCl3): = 11.09/11.13 (t, C-12/C-13),
11.88/11.90 (t, C-12/C-13), 17.14, 20.53/20.54, 23.17/23.37, 26.85/
27.04, 31.88/32.00, 34.28/34.29, 34.33, 55.69 (q, OMe), 76.02/
76.15 (d, C-3), 78.49/78.69, 120.45/120.48, 134.92/134.98.
GC/MS (EI, 70 eV): m/z (%) = 334 (<0.1), 302 (11), 175 (36), 147
(34), 119 (29), 106 (15), 105 (10), 95 (12), 94 (14), 93 (100), 91
(47), 82 (12), 81 (51), 79 (34), 77 (36), 67 (51), 65 (15), 58 (17), 55
(37), 53 (24), 45 (15), 41 (44), 39 (16), 29 (11), 27 (13).
GC/MS (EI, 70 eV): m/z (%) = 225 (<0.1), 224 (0.3), 192 (12), 174
(13), 164 (15), 159 (20), 149 (10), 146 (12), 145 (20), 131 (13), 124
(11), 120 (10), 119 (15), 117 (12), 109 (10), 108 (11), 107 (15),
106 (22), 105 (14), 99 (11), 98 (32), 97 (11), 95 (36), 94 (50), 93
(62), 92 (45), 91 (68), 85 (14), 83 (78), 82 (18), 81 (37), 80 (24), 79
(100), 78 (24), 77 (48), 71 (48), 70 (11), 69 (21), 68 (23), 67 (99),
66 (17), 65 (28), 59 (13), 58 (43), 57 (60), 56 (38), 55 (84), 54 (11),
53 (41), 45 (30), 43 (52), 41 (98), 39 (31), 29 (50), 28 (14), 27 (28).
HRMS: m/z calcd for C14H22OI (M+ – H), 333.07154; found,
333.07153.
Anal. Calcd for C14H23OI: C, 50.31; H, 6.94. Found: C, 51.03; H,
6.96.
3-[(E)-6-(5-Methoxy-1-cyclohexenyl)-3-methyl-3-hexenyl]-2-
cyclohexen-1-one (35)
As described for the synthesis of 16, 35 was prepared from (E)-1-
iodo-6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-hexene (32; 2.20
g, 6.59 mmol) and 3-ethoxycyclohex-2-enone (15; 1.11 g, 7.90
mmol). Column chromatography (cyclohexane–EtOAc, 75:25) af-
forded 35 (975 mg, 49%) as a colorless oil.
HRMS: m/z calcd for C14H24O2 (M+), 224.17763; found, 224.17813.
Anal. Calcd for C14H24O2: C, 74.95; H, 10.78. Found: C, 74.70; H,
10.70.
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

630
J. O. Bunte et al.
FEATURE ARTICLE
(4aR*,4bR*,6aR*,8S*,10aR*,10bS*,12aS*)-8-Methoxy-
10b,12a-dimethylhexadecahydro-benzo[a]phenanthren-4(1H)-
one (22a)
IR (film): 2928, 2662, 1672, 1626, 1453, 1373, 1347, 1324, 1252,
1192, 1122, 1099, 1058, 990, 963, 931, 886, 828, 782, 756, 734, 665
cm–1.
IR (film): 2926, 2655, 2001, 1707, 1445, 1382, 1360, 1309, 1292,
1280, 1242, 1224, 1212, 1191, 1168, 1146, 1091, 1046, 1022, 1007,
972, 958, 912, 898, 860, 840, 787, 727, 665 cm–1.
1H NMR (500 MHz, CDCl3): = 1.41–1.51 (m, 1 H, H-4), 1.54–
1.57 (m, 3 H, H-11), 1.76–2.35 (m, 19 H), 3.32 (s, 3 H, OMe), 3.37–
3.44 (m, 1 H, H-3), 5.04–5.13 (m, 1 H, H-9), 5.27–5.36 (m, 1 H, H-
6), 5.78–5.82 (m, 1 H, H-15).
13C NMR (125.8 MHz, CDCl3): = 15.78 (q, C-11), 22.60 (t, C-18),
23.30 (t, C-5), 26.03 (t, C-8), 26.96 (t, C-4), 29.55 (t, C-19), 34.36
(t, C-2), 36.55 (t, C-12)*1, 36.92 (t, C-13)*1, 37.25 (t, C-7)*2, 37.41
(t, C-17)*2, 55.66 (q, OMe), 76.11 (d, C-3), 120.33 (d, C-6), 125.19
(d, C-9)*3, 125.72 (d, C-15)*3, 133.51 (s, C-10), 134.78 (s, C-1),
166.23 (s, C-14), 199.80 (s, C-16).
1H NMR (600 MHz, C6D6): = 0.61 (ddd, J = 3.9, 11.5, 11.5 Hz, 1
H, H-10a), 0.65 (d, J = 0.7 Hz, 3 H, H-14), 0.70 (ddddd, J = 1.2,
1.2, 2.4, 4.5, 13.8 Hz, 1 H, H-1eq), 0.78 (dddd, J = 4.7, 12.2, 13.1,
13.1 Hz, 1 H, H-6ax), 0.84 (d, J = 0.7 Hz, 3 H, H-13), 0.91 (ddd,
J = 2.6, 11.9, 13.6 Hz, 1 H, H-7ax), 1.06–1.15 (m, 3 H, H-5eq, H-
11ax, H-12eq), 1.15–1.25 (m, 2 H, H-5ax, H-9ax), 1.26 (ddd,
J = 4.2, 14.2, 14.2 Hz, 1 H, H-12ax), 1.38 (ddd, J = 3.4, 12.1, 12.1
Hz, 1 H, H-4b), 1.38–1.47 (m, 3 H, H-10ax, H-10eq, H-11eq), 1.50
(dddd, J = 2.7, 4.1, 4.1, 13.0 Hz, 1 H, H-6eq), 1.57 (ddddd, J = 2.4,
2.4, 4.8, 6.9, 13.6 Hz, 1 H, H-2eq), 1.65 (ddddd, J = 4.5, 5.3, 13.4,
13.4, 13.4 Hz, 1 H, H-2ax), 1.75 (ddddd, J = 3.9, 3.9, 11.6, 11.6,
11.6 Hz, 1 H, H-6a), 1.88 (dddd, J = 2.7, 3.3, 3.3, 13.6 Hz, 1 H, H-
7eq), 1.97 (ddd, J = 4.8, 13.6, 13.6 Hz, 1 H, H-1ax), 2.04 (ddddd,
J = 3.1, 3.1, 3.1, 3.1, 13.6 Hz, 1 H, H-9eq), 2.07 (ddd, J = 6.9, 13.2,
13.2 Hz, 1 H, H-3ax), 2.09 (dd, J = 1.5, 11.9 Hz, 1 H, H-4a), 2.12
(ddddd, J = 1.3, 1.3, 2.4, 5.2, 13.4 Hz, 1 H, H-3eq), 3.17 (s, 3 H, H-
15), 3.33 (dddd, J = 2.8, 2.8, 2.8, 2.8 Hz, 1 H, H-8).
GC/MS (EI, 70 eV): m/z (%) = 303 (<0.1), 302 (0.2), 161 (20), 160
(13), 110 (100), 93 (40), 91 (28), 81 (13), 79 (27), 77 (26), 67 (21),
65 (10), 55 (31), 53 (22), 45 (10), 41 (29), 39 (10).
HRMS: m/z calcd for C20H30O2 (M+), 302.22458; found, 302.22437.
3-[(E)-6-(5-Methoxy-1-cyclohexenyl)-3-methyl-3-hexenyl]-3-
methyl-1-cyclohexenyl-trimethylsilyl Ether (20)
As described for the synthesis of 17, 20 was prepared from 3-[(E)-
6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-hexenyl)-2-cyclohex-
en-1-one (35; 890 mg, 2.95 mmol), affording 20 (1.10 g, 96%) as a
colorless oil.
13C NMR (150.96 MHz, C6D6): = 12.52 (q, C-14), 19.41 (t, C-10),
22.65 (t, C-2), 25.59 (t, C-5), 28.00 (q, C-13), 29.61 (t, C-1), 30.31
(t, C-9), 30.43 (d, C-6a), 33.71 (t, C-11), 34.85 (t, C-6), 35.40 (t, C-
12), 36.42 (s, C-10b), 37.53 (s, C-12a), 37.59 (t, C-3), 38.50 (t, C-
7), 44.38 (d, C-4b), 54.26 (d, C-10a), 55.50 (q, C-15), 60.48 (d, C-
4a), 75.09 (d, C-8), 215.55 (s, C-4).
IR (film): 2935, 2661, 1941, 1715, 1661, 1453, 1365, 1252, 1193,
1100, 1058, 1036, 989, 965, 934, 891, 840, 753, 690, 665 cm–1.
1H NMR (500 MHz, CDCl3): = 0.17 (s, 9 H, SiMe3), 0.94 (s, 3 H,
H-20), 1.23–1.44 (m, 4 H), 1.47–1.56 (m, 1 H), 1.56–1.59 (m, 3 H,
H-11), 1.82–2.30 (m, 15 H), 3.37 (s, 3 H, OMe), 3.42–3.48 (m, 1 H,
H-3), 4.64–4.66 (m, 1 H, H-15), 5.05–5.12 (m, 1 H, H-9), 5.32–5.39
(m, 1 H, H-6).
13C NMR (125.8 MHz, CDCl3): = 0.31 (q, SiMe3), 16.14 (q, C-
11), 19.61 (t, C-18), 23.44 (t, C-5), 26.21 (t, C-8), 27.10 (t, C-4),
27.99 (q, C-20), 29.85 (t, C-17), 34.44, 34.46, 34.49 (integral for 2
13C-signals), 37.61 (t, C-7), 42.09 (t, C-13), 55.71 (q, OMe), 76.28
(d, C-3), 114.47 (d, C-15), 120.26 (d, C-6), 123.46 (d, C-9), 135.09
(s, C-1)*1, 136.08 (s, C-10)*1, 149.25 (s, C-16).
GC/MS (EI, 70 eV): m/z (%) = 319 (10), 318 (43), 304 (23), 303
(100), 300 (14), 271 (12), 253 (12), 163 (13), 161 (11), 147 (21),
111 (92), 107 (10), 105 (12), 95 (16), 93 (17), 91 (19), 81 (24), 79
(34), 77 (18), 71 (17), 69 (18), 68 (10), 67 (44), 65 (10), 55 (58), 53
(14), 43 (16), 41 (42), 29 (13).
HRMS: m/z calcd for C21H34O2 (M+), 318.25533; found, 318.25561.
(4aR*,4bR*,6aR*,8R*,10aR*,10bS*,12aS*)-8-Methoxy-
10b,12a-dimethylhexadecahydro-benzo[a]phenanthren-4(1H)-
one (22b)
IR (film): 2929, 2672, 2383, 2349, 2021, 1707, 1450, 1381, 1309,
1293, 1260, 1242, 1223, 1198, 1169, 1145, 1105, 1052, 1024, 994,
956, 942, 925, 904, 888, 855, 834, 786, 727, 674 cm–1.
GC/MS (EI, 70 eV): m/z (%) = 390 (0.1), 184 (17), 183 (100), 73
(42).
HRMS: m/z calcd for C24H42O2Si (M+), 390.29541; found,
390.29645.
1H NMR (600 MHz, C6D6): = 0.50 (ddd, J = 3.3, 10.3, 12.1 Hz, 1
H, H-10a), 0.54 (d, J = 0.7 Hz, 3 H, H-14), 0.69 (dddd, J = 1.3, 2.5,
5.7, 13.8 Hz, 1 H, H-1eq), 0.77 (dddd, J = 3.4, 12.0, 13.3, 13.3 Hz,
1 H, H-10ax), 0.78-0.84 (m, 1 H, H-6ax), 0.85 (d, J = 0.7 Hz, 3 H,
H-13), 0.96–1.02 (m, 1 H, H-6a), 0.96 (ddd, J = 11.1, 11.1, 11.1 Hz,
1 H, H-7ax), 1.02–1.15 (m, 4 H, H-5ax, H-5eq, H-11ax, H-12eq),
1.24 (dddd, J = 3.8, 11.0, 12.3, 13.5 Hz, 1 H, H-9ax), 1.27 (ddd,
J = 4.3, 14.0, 14.0 Hz, 1 H, H-12ax), 1.29 (ddd, J = 3.5, 12.5, 12.5
Hz, 1 H, H-4b), 1.33 (ddd, J = 2.8, 4.3, 13.1 Hz, 1 H, H-11eq), 1.45
(dddd, J = 3.4, 3.4, 3.4, 13.1 Hz, 1 H, H-6eq), 1.57 (ddddd, J = 2.5,
2.5, 4.9, 7.3, 13.6 Hz, 1 H, H-2eq), 1.60 (dddd, J = 3.4, 3.4, 3.4, 13.1
Hz, 1 H, H-10eq), 1.64 (dddd, J = 4.7, 4.7, 13.5, 13.5 Hz, 1 H, H-
2ax), 1.93 (ddd, J = 5.1, 13.8, 13.8 Hz, 1 H, H-1ax), 1.96 (dddd,
J = 2.5, 2.5, 4.0, 11.2 Hz, 1 H, H-7eq), 2.05 (ddd, J = 8.1, 13.4, 13.4
Hz, 1 H, H-3ax), 2.08 (ddd, J = 1.2, 1.2, 12.2 Hz, 1 H, H-4a), 2.10
(ddddd, J = 1.3, 1.3, 2.4, 5.0, 13.4 Hz, 1 H, H-3eq), 2.14 (ddddd,
J = 2.5, 3.5, 3.5, 4.3, 12.3 Hz, 1 H, H-9eq), 2.92 (dddd, J = 4.3, 4.3,
10.8, 10.8 Hz, 1 H, H-8), 3.29 (s, 3 H, H-15).
Anal. Calcd for C24H42O2Si: C, 73.84; H, 10.84. Found: C, 73.25;
H, 10.74.
PET Cyclization of 3-[(E)-6-(5-Methoxy-1-cyclohexenyl)-3-me-
thyl-3-hexenyl)-3-methyl-1-cyclohexenyl-trimethylsilyl Ether
(20)
A solution of 3-[(E)-6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-
hexenyl)-3-methyl-1-cyclohexenyl-trimethylsilyl ether (20; 135
mg, 0.42 mmol), DCA (60 mg, 0.26 mmol) and n-decane (60 L) in
anhyd MeCN–anhyd propionitrile (3:1, 66 mL) was placed in irra-
diation tubes (11 mL each, pyrex glass, 12 mm diameter), degassed
with argon for 20 min and irradiated with light of 420 nm until com-
plete consumption of the starting material had occurred. The reac-
tion mixture was concentrated in vacuo and the residue was
subjected to column chromatography (cyclohexane–EtOAc, 85:15)
in order to isolate the mixture of diastereomers. The diastereomers
were separated by HPLC (cyclohexane–EtOAc, 92.5:7.5) yielding
22a (19.4 mg, 0.061 mmol) and 22b (16.4 mg, 0.052 mmol) in 27%
combined isolated yield. The diastereomeric ratio was determined
by GC directly from the reaction mixture (22a:22b, 50:50).
13C NMR (150.96 MHz, C6D6): = 12.24 (q, C-14), 22.61 (t, C-2),
23.60 (t, C-10), 25.48 (t, C-5), 28.03 (q, C-13), 29.54 (t, C-1), 32.83
(t, C-9), 33.82 (t, C-11), 34.53 (t, C-6)*, 34.65 (d, C-6a)*, 35.39 (t,
C-12), 36.18 (s, C-10b), 37.55 (t, C-3 und s, C-12a), 40.62 (t, C-7),
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

FEATURE ARTICLE
PET Domino Cyclizations
631
44.11 (d, C-4b), 53.43 (d, C-10a), 55.55 (q, C-15), 60.44 (d, C-4a),
79.05 (d, C-8), 212.57 (s, C-4).
PET Cyclization of 3-[(E)-6-(5-methoxy-1-cyclohexenyl)-3-me-
thyl-3-hexenyl)-3-methyl-1-cyclopentenyl-trimethylsilylether
(19)
GC/MS (EI, 70 eV): m/z (%) = 319 (10), 318 (37), 303 (10), 287
(11), 286 (44), 272 (15), 271 (64), 268 (26), 253 (20), 190 (12), 188
(15), 178 (12), 175 (13), 173 (13), 172 (14), 161 (14), 159 (17),
147 (23), 146 (10), 145 (16), 133 (11), 121 (10), 119 (15), 111
(100), 107 (14), 105 (18), 95 (24), 93 (25), 91 (23), 81 (37), 79 (50),
77 (23), 71 (23), 69 (22), 68 (13), 67 (66), 65 (10), 55 (82), 53 (23),
45 (13), 43 (24), 42 (12), 41 (65), 29 (20).
A solution of 3-[(E)-6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-
hexenyl]-3-methyl-1-cyclopentenyl-trimethylsilylether (19; 264
mg, 0.70 mmol) and DCA (60 mg, 0.26 mmol) in anhyd MeCN–an-
hyd propionitrile (3:1, 132 mL) was placed in irradiation tubes (11
mL each, pyrex glass, 12 mm diameter), degassed with argon for 20
min and irradiated with light of 420 nm until complete consumption
of the starting material had occurred. The reaction mixture was con-
centrated in vacuo and the residue was subjected to column chroma-
tography (cyclohexane–EtOAc, 85:15) in order to isolate the
mixture of diastereomers. The combined isolated yield of cycliza-
tion products was 94 mg, 44%. The separation of diastereomers was
accomplished by HPLC (cyclohexane–EtOAc 92.5:7.5) The diaste-
reomeric ratio was determined by GC directly from the reaction
mixture (21a:21b:21c:21d, 30:28:21:21).
HRMS: m/z calcd for C21H34O2 (M+), 318.25533; found, 318.25579.
3-[(E)-6-(5-Methoxy-1-cyclohexenyl)-3-methyl-3-hexenyl]-2-
cyclopenten-1-one (34)
As described for the synthesis of 16, 34 was prepared from (E)-1-
iodo-6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-hexene (32; 1.70
g, 5.08 mmol) and 3-ethoxycyclopent-2-enone (33; 0.78 g, 6.20
mmol). Column chromatography (cyclohexane–EtOAc, 75:25) af-
forded 34 (507 mg, 35%) as a colorless oil,
(3aR*,3bR*,5aR*,7S*,9aR*,9bS*,11aR*)-7-Methoxy-9b,11a-
dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one
(21a)
IR (film): 2928, 1712, 1677, 1617, 1438, 1409, 1373, 1283, 1231,
1184, 1121, 1099, 1058, 989, 932, 840, 783 cm–1.
IR (film): 2930, 2102, 1732, 1642, 1446, 1381, 1360, 1237, 1188,
1H NMR (500 MHz, CDCl3): = 1.45–1.54 (m, 1 H), 1.50–1.60 (m,
3 H, H-11), 1.80–2.16 (m, 8 H), 2.18–2.26 (m, 3 H), 2.34–2.40 (m,
2 H), 2.49 (tm, J = 7.7 Hz, 2 H), 2.53–2.59 (m, 2 H), 3.35 (s, 3 H,
OMe), 3.40–3.46 (m, 1 H, H-3), 5.09–5.16 (m, 1 H, H-9), 5.31–5.37
(m, 1 H, H-6), 5.88–5.95 (m, 1 H, H-15).
13C NMR (125.8 MHz, CDCl3): = 15.81 (q, C-11), 23.31 (t, C-5),
26.02 (t, C-8), 26.96 (t, C-4), 31.46 (t, C-18)*1, 31.90 (t, C-13)*1,
34.38 (t, C-2), 35.20 (t, C-12)*2, 36.80 (t, C-17)*2, 37.38 (t, C-7),
55.67 (q, OMe), 76.13 (d, C-3), 120.39 (d, C-6), 125.25 (d, C-9),
129.50 (d, C-15), 133.36 (s, C-10), 134.76 (s, C-1), 182.68 (s, C-
14), 210.03 (s, C-16).
1111, 1093, 913 cm–1.
1H NMR (600 MHz, C6D6): = 0.49–0.56 (m, 2 H, H-9a), 0.61 (d,
J = 0.5 Hz, 3 H, H-13), 0.74 (d, J = 0.9 Hz, 3 H, H-12), 0.79 (dddd,
J = 4.1, 12.2, 13.3, 13.3 Hz, 1 H, H-5ax), 0.88 (ddd, J = 2.6, 12.0,
13.6 Hz, 1 H, H-6ax), 0.89 (ddd, J = 3.1, 12.2, 12.2 Hz, 1 H, H-3b),
0.94 (ddd, J = 4.3, 13.5, 13.5 Hz, 1 H, H-10ax), 1.05 (dddd, J = 1.3,
3.8, 7.6, 12.9 Hz, 1 H, H-1), 1.12–1.22 (m, 2 H, H-11eq, H-8ax),
1.17 (dddd, J = 3.9, 13.6, 13.6, 13.6 Hz, 1 H, H-4ax), 1.34 (ddd,
J = 4.7, 14.1, 14.1 Hz, 1 H, H-11ax), 1.40-1.46 (m, 2 H, H-9), 1.49
(ddd, J = 2.6, 4.7, 13.3 Hz, 1 H, H-10eq), 1.55 (dd, J = 1.1, 12.2 Hz,
1 H, H-3a), 1.56 (dddd, J = 2.9, 4.0, 4.0, 13.2 Hz, 1 H, H-5eq), 1.77
(ddddd, J = 3.9, 3.9, 11.6, 11.6, 11.6 Hz, 1 H, H-5a), 1.87 (dddd,
J = 3.1, 3.1, 3.1, 13.6 Hz, 1 H, H-6eq), 1.91 (ddd, J = 10.3, 10.3,
12.9 Hz, 1 H, H-1), 2.01 (dddd, J = 2.8, 2.8, 4.1, 14.0 Hz, 1 H, H-
4eq), 2.03 (ddddd, J = 3.1, 3.1, 3.1, 3.1, 13.7 Hz, 1 H, H-8eq), 2.06–
2.12 (m, 2 H, H-2), 3.17 (s, 3 H, H-14), 3.31 (dddd, J = 2.8, 2.8, 2.8,
2.8 Hz, 1 H, H-7).
GC/MS (EI, 70 eV): m/z (%) = 289 (0.1), 288 (0.4), 147 (20), 134
(11), 96 (100), 93 (61), 91 (34), 81 (13), 80 (11), 79 (31), 77 (34),
67 (33), 65 (18), 58 (11), 55 (41), 53 (19), 45 (14), 41 (41), 39 (14),
29 (10).
HRMS: m/z calcd for C19H28O2 (M+), 288.20893; found, 288.20992.
13C NMR (150.96 MHz, C6D6): = 12.24 (q, C-13), 19.62 (t, C-9),
24.80 (t, C-4), 29.24 (q, C-12), 29.86 (t, C-1), 30.36 (t, C-8), 30.67
(d, C-5a), 31.31 (t, C-11), 33.53 (t, C-10), 34.39 (t, C-2), 34.67 (t,
C-5), 35.63 (s, C-9b), 37.68 (s, C-11a), 38.42 (t, C-6), 42.84 (d, C-
3b), 53.68 (d, C-9a), 55.50 (q, C-14), 58.10 (d, C-3a), 75.10 (d, C-
7), 218.29 (s, C-3).
3-[(E)-6-(5-Methoxy-1-cyclohexenyl)-3-methyl-3-hexenyl]-3-
methyl-1-cyclopentenyl-trimethylsilylether (19)
As described for the synthesis of 17, 19 was prepared from 3-[(E)-
6-(5-methoxy-1-cyclohexenyl)-3-methyl-3-hexenyl]-2-cyclopent-
en-1-one (34; 400 mg, 1.40 mmol), affording 19 (488 g, 93%) as a
colorless oil.
IR (film): 3058, 2930, 2850, 1714, 1643, 1453, 1372, 1342, 1312,
1252, 1194, 1121, 1100, 993, 930, 871, 845, 782, 757, 690 cm–1.
GC/MS (EI, 70 eV): m/z (%) = 305 (8), 304 (37), 289 (43), 273 (15),
272 (86), 257 (34), 254 (13), 215 (13), 178 (24), 176 (10), 163 (17),
161 (16), 159 (13), 149 (13), 148 (15), 147 (27), 145 (16), 133 (11),
121 (16), 119 (11), 107 (15), 105 (17), 97 (100), 95 (16), 94 (11), 93
(18), 91 (27), 81 (33), 80 (10), 79 (47), 77 (27), 71 (24), 69 (18), 68
(12), 67 (56), 65 (11), 57 (10), 56 (10), 55 (74), 53 (26), 43 (22), 41
(63), 29 (19), 28 (22).
1H NMR (500 MHz, CDCl3): = 0.20 (s, 9 H, SiMe3), 1.01 (s, 3 H,
H-19), 1.30–1.44 (m, 2 H, H-13), 1.46–1.63 (m, 2 H), 1.57–1.58 (m,
3 H, H-11), 1.66–1.74 (m, 1 H), 1.82–2.19 (m, 10 H), 2.21–2.34 (m,
3 H), 3.37 (s, 3 H, OMe), 3.41–3.48 (m, 1 H, H-3), 4.48 (dd, J = 1.6,
1.6 Hz, 1 H, H-15), 5.04–5.12 (m, 1 H, H-9), 5.34–5.39 (m, 1 H, H-
6).
HRMS: m/z calcd for C20H32O2 (M+),304.24023; found 304.23988.
13C NMR (125.8 MHz, CDCl3): = –0.03 (q, SiMe3), 16.16 (q, C-
11), 23.43 (t, C-5), 26.21 (t, C-8), 27.09 (t, C-4), 27.97 (q, C-19),
33.18 (t), 34.45 (t), 34.91 (t), 35.33 (t, C-12), 37.62 (t, C-7), 41.42
(t, C-13), 44.94 (s, C-14), 55.70 (q, OMe), 76.28 (d, C-3), 112.22 (d,
C-15), 120.23 (d, C-6), 123.33 (d, C-9), 135.11 (s, C-10)*1, 136.09
(s, C-1)*1, 152.87 (s, C-16).
(3aR*,3bR*,5aR*,7R*,9aR*,9bS*,11aR*)-7-Methoxy-9b,11a-
dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one
(21b)
IR (film): 2929, 2864, 2403, 2349, 2112, 1736, 1678, 1451, 1408,
1380, 1258, 1236, 1160, 1142, 1113, 1098, 992, 961, 920, 664 cm–1.
1H NMR (600 MHz, C6D6): = 0.42 (ddd, J = 3.2, 10.7, 11.7 Hz, 1
H, H-9a), 0.50 (s, 3 H, H-13), 0.75 (dddd, J = 3.3, 13.0, 13.0, 13.0
Hz, 1 H, H-9ax), 0.76 (s, 3 H, H-12), 0.80 (ddd, J = 3.2, 12.3, 12.3
Hz, 1 H, H-3b), 0.81 (dddd, J = 4.8, 12.4, 12.4, 12.4 Hz, 1 H, H-
5ax), 0.88 (ddd, J = 4.4, 13.5, 13.5 Hz, 1 H, H-10ax), 0.94 (ddd,
J = 11.5, 11.5, 11.5 Hz, 1 H, H-6ax), 0.97–1.14 (m, 3 H, H-1, H-
GC/MS (EI, 70 eV): m/z (%) = 170 (22), 169 (100), 73 (40).
HRMS: m/z calcd for C23H40O2Si (M+), 376.27976; found,
376.28053.
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

632
J. O. Bunte et al.
FEATURE ARTICLE
4ax, H-5a), 1.16–1.26 (m, 2 H, H-8ax, H-11eq), 1.34 (ddd, J = 4.8,
14.0, 14.0 Hz, 1 H, H-11ax), 1.40 (ddd, J = 2.6, 4.6, 13.1 Hz, 1 H,
H-10eq), 1.50 (dddd, J = 3.5, 3.5, 3.5, 13.1 Hz, 1 H, H-5eq), 1.56
(d, J = 12.3 Hz, 1 H, H-3a), 1.61 (dddd, J = 3.5, 3.5, 3.5, 13.2 Hz, 1
H, H-9eq), 1.87 (ddd, J = 10.3, 10.3, 12.7 Hz, 1 H, H-1), 1.96 (dddd,
J = 3.4, 3.4, 3.4, 11.5 Hz, 1 H, H-6eq), 1.98 (dddd, J = 3.4, 3.4, 3.4,
13.7 Hz, 1 H, H-4eq), 2.06–2.18 (m, 3 H, H-2, H-2, H-8eq), 2.93
(dddd, J = 4.2, 4.2, 10.8, 10.8 Hz, 1 H, H-7), 3.28 (s, 3 H, H-14).
13C NMR (150.96 MHz, C6D6): = 11.95 (q, C-13), 23.76 (t, C-9),
24.71 (t, C-4), 29.26 (q, C-12), 29.80 (t, C-1), 31.26 (t, C-11), 32.82
(t, C-8), 33.61 (t, C-10), 34.33 (t, C-2)*1, 34.34 (t, C-5)*1, 34.90 (d,
C-5a), 35.36 (s, C-9b), 37.67 (s, C-11a), 40.53 (t, C-6), 42.52 (d, C-
3b), 52.81 (d, C-9a), 55.41 (q, C-14), 58.08 (d, C-3a), 79.07 (d, C-
7), 218.29 (s, C-3).
1156, 1125, 1107, 1092, 1043, 982, 965, 945, 927, 904, 857, 834,
820, 735 cm–1.
1H NMR (600 MHz, C6D6): = 0.58 (ddd, J = 3.3, 10.9, 12.1 Hz, 1
H, H-9a), 0.79 (s, 3 H, H-13), 0.88–1.00 (m, 4 H, H-5ax, H-6ax, H-
10ax, H-11), 0.95 (s, 3 H, H-12), 1.17 (ddd, J = 8.9, 12.4, 12.4 Hz,
1 H, H-1), 1.20 (dddd, J = 2.3, 4.1, 13.6, 13.6 Hz, 1 H, H-8ax),
1.31–1.42 (m, 5 H, H-1, H-3a, H-3b, H-9eq, H-11), 1.45 (ddd,
J = 2.6, 4.1, 12.6 Hz, 1 H, H-10eq), 1.50 (dddd, J = 3.6, 12.5, 12.5,
13.6 Hz, 1 H, H-9ax), 1.56 (dddd, J = 2.6, 2.6, 4.4, 14.0 Hz, 1 H, H-
4eq), 1.74 (dddd, J = 2.6, 4.0, 4.0, 12.8 Hz, 1 H, H-5eq), 1.87
(ddddd, J = 3.8, 3.8, 11.5, 11.5, 11.5 Hz, 1 H, H-5a), 1.94 (dddd,
J = 3.1, 3.1, 3.1, 13.6 Hz, 1 H, H-6eq), 1.96 (dddd, J = 1.4, 1.4, 8.9,
18.8 Hz, 1 H, H-2), 2.03 (ddddd, J = 3.1, 3.1, 3.1, 3.1, 13.6 Hz, 1 H,
H-8eq), 2.12 (ddd, J = 9.2, 12.1, 18.8 Hz, 1 H, H-2), 2.75 (dddd,
J = 3.9, 13.3, 13.3, 13.3 Hz, 1 H, H-4ax), 3.17 (s, 3 H, H-14), 3.32
(dddd, J = 2.8, 2.8, 2.8, 2.8 Hz, 1 H, H-7).
13C NMR (150.96 MHz, C6D6): = 14.11 (q, C-13), 19.45 (t, C-9),
26.12 (q, C-12), 26.64 (t, C-4), 29.65 (t, C-11), 30.37 (t, C-8), 31.07
(d, C-5a), 34.37 (t, C-10), 35.47 (t, C-1), 36.14 (t, C-5), 36.19 (t, C-
2), 37.15 (s, C-9b), 38.54 (t, C-6), 38.97 (s, C-11a), 44.73 (d, C-3b),
54.71 (d, C-9a), 55.47 (q, C-14), 58.90 (d, C-3a), 75.15 (d, C-7),
218.53 (s, C-3).
GC/MS (EI, 70 eV): m/z (%) = 305 (10), 304 (29), 281 (11), 273
(15), 272 (100), 258 (15), 257 (84), 215 (19), 189 (15), 178 (19),
176 (12), 163 (15), 161 (14), 159 (16), 149 (22), 147 (21), 145 (20),
133 (14), 121 (15), 119 (10), 109 (10), 107 (18), 105 (19), 97 (61),
95 (19), 94 (13), 93 (26), 91 (24), 81 (42), 79 (45), 77 (17), 71 (28),
67 (56), 65 (15), 55 (63), 53 (18), 45 (15), 43 (22), 41 (55), 32 (23),
29 (17), 28 (21).
HRMS: m/z calcd for C20H32O2 (M+), 304.24023; found, 304.23976.
GC/MS (EI, 70 eV): m/z (%) = 305 (10), 304 (42), 287 (10), 286
(41), 272 (35), 258 (10), 257 (46), 254 (33), 247 (11), 233 (24), 232
(96), 221 (36), 220 (54), 216 (13), 215 (25), 201 (16), 190 (10),
179 (12), 178 (18), 177 (12), 173 (11), 169 (25), 167 (23), 165 (11),
164 (22), 163 (24), 160 (13), 159 (24), 148 (11), 147 (18), 146 (12),
135 (14), 134 (16), 133 (14), 131 (13), 122 (12), 121 (26), 120 (11),
119 (25), 111 (11), 109 (18), 108 (13), 107 (31), 105 (14), 97 (48),
95 (56), 94 (19), 93 (43), 91 (46), 84 (11), 82 (11), 81 (71), 80 (18),
79 (65), 77 (50), 73 (20), 71 (51), 69 (44), 67 (84), 65 (26), 58 (11),
57 (14), 56 (13), 55 (76), 54 (11), 53 (30), 45 (11), 44 (17), 43 (46),
41 (100), 40 (13), 39 (11), 32 (31), 29 (36), 27 (14).
(3aS*,3bR*,5aR*,7R*,9aR*,9bS*,11aS*)-7-Methoxy-9b,11a-
dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one
(21c)
IR (film): 2929, 2863, 2390, 2353, 2329, 2013, 1735, 1714, 1702,
1677, 1656, 1600, 1537, 1449, 1378, 1316, 1265, 1109, 1095, 1039,
918, 814 cm–1.
1H NMR (600 MHz, C6D6): = 0.48 (ddd, J = 3.3, 11.1, 11.1 Hz, 1
H, H-9a), 0.68 (s, 3 H, H-13), 0.79 (dddd, J = 3.5, 12.1, 13.3, 13.3
Hz, 1 H, H-9ax), 0.86–0.98 (m, 3 H, H-5ax, H-10, H-11), 0.93 (s, 3
H, H-12), 0.98 (ddd, J = 11.0, 11.0, 11.0 Hz, 1 H, H-6ax), 1.15
(ddddd, J = 3.7, 3.7, 11.4, 11.4, 11.4 Hz, 1 H, H-5a), 1.18 (ddd,
J = 9.0, 12.3, 12.3 Hz, 1H, H-1), 1.18–1.26 (m, 1 H, H-8ax), 1.28–
1.39 (m, 5 H, H-1, H-3a, H-3b, H-10, H-11), 1.51 (dddd, J = 2.4,
2.4, 4.6, 14.0 Hz, 1 H, H-4eq), 1.56 (dddd, J = 3.5, 3.5, 3.5, 13.1 Hz,
1 H, H-9eq), 1.70 (dddd, J = 2.6, 4.0, 4.0, 12.8 Hz, 1 H, H-5eq), 1.98
(dddd, J = 1.3, 1.3, 9.0, 18.9 Hz, 1 H, H-2), 2.00 (dddd, J = 2.5, 3.7,
3.7, 12.0 Hz, 1 H, H-6eq), 2.10–2.16 (m, 1 H, H-8eq), 2.14 (ddd,
J = 9.2, 12.1, 18.8 Hz, 1 H, H-2), 2.68 (dddd, J = 3.9, 12.4, 13.7,
13.7 Hz, 1 H, H-4ax), 2.92 (dddd, J = 4.3, 4.3, 11.0, 11.0 Hz, 1 H,
H-7), 3.33 (s, 3 H, H-14).
13C NMR (150.96 MHz, C6D6): = 13.95 (q, C-13), 23.60 (t, C-9),
26.07 (q, C-12), 26.50 (t, C-4), 29.63 (t, C-11), 32.73 (t, C-8), 34.48
(t, C-10), 35.33 (C-5a)*, 35.43 (C-1)*, 35.83 (t, C-5), 36.19 (t, C-
2), 36.89 (s, C-9b), 39.02 (s, C-11a), 40.81 (t, C-6), 44.42 (d, C-3b),
53.91 (d, C-9a), 55.41 (q, C-14), 58.80 (d, C-3a), 79.08 (d, C-7),
218.69 (s, C-3).
HRMS: m/z calcd for C20H32O2 (M+), 304.24023; found, 304.23963.
Acknowledgment
Financial support by the Ministerium für Schule, Wissenschaft und
Forschung des Landes Nordrhein-Westfalen (MSWF-NRW), the
Deutsche Forschungsgemeinschaft (DFG), the Fonds der Chemi-
schen Industrie and the Innovationsfonds der Universität Bielefeld
is gratefully acknowledged. We also thank the state of Nordrhein-
Westfalen for granting a predoctoral scholarship for JOB. We wish
to thank Thomas Geisler for his synthetic work and Dr. Michael
Oelgemöller for his help in preparation of the manuscript.
References
(1) (a) Robinson, R. J. Chem. Soc. 1917, 762. (b) Robinson, R.
J. Chem. Soc. 1917, 867. (c) Schöpf, C.; Lehmann, G.;
Arnold, W. Angew. Chem. 1937, 50, 779.
(2) (a) Tietze, L. F.; Beifuss, U. Angew. Chem. Int. Ed. 1993, 32,
131; Angew. Chem. 1993, 105, 137;. (b) Tietze, L. F. Chem.
Rev. 1996, 96, 136. (c) Malacria, M. Chem. Rev. 1996, 96,
306. (d) Hudlicky, T. Chem. Rev. 1996, 96, 3.
(3) (a) Curran, D. P. Synthesis 1988, 417. (b) Curran, D. P.
Synthesis 1988, 489. (c) Jasperse, C. P.; Curran, D. P.;
Fevig, T. L. Chem. Rev. 1991, 91, 1237. (d) McCarroll, A.
J.; Walton, J. C. Angew. Chem. Int. Ed. 2001, 40, 2224;
Angew. Chem. 2001, 113, 2282.
(4) (a) Baguley, P. A.; Walton, J. C. Angew. Chem. Int. Ed.
1998, 37, 3072; Angew. Chem. 1998, 110, 3272. (b) Snider,
B. B. Chem. Rev. 1996, 96, 339. (c) Molander, G. A.;
Harris, C. R. Chem. Rev. 1996, 96, 307.
GC/MS (EI, 70 eV): m/z (%) = 305 (3), 304 (17), 272 (37), 258 (19),
257 (100), 254 (20), 232 (27), 216 (11), 215 (20), 207 (24), 189
(13), 176 (15), 164 (12), 163 (13), 161 (12), 159 (17), 147 (15),
145 (21), 133 (17), 121 (15), 119 (11), 109 (11), 108 (10), 107 (20),
105 (10), 97 (38), 95 (13), 94 (13), 93 (25), 91 (29), 81 (50), 79 (52),
77 (18), 71 (34), 69 (22), 67 (54), 65 (20), 55 (70), 53 (30), 45 (13),
43 (16), 41 (59), 32 (18), 29 (22).
HRMS: m/z calcd for C20H32O2 (M+), 304.24023; found, 304.24027.
(3aS*,3bR*,5aR*,7S*,9aR*,9bS*,11aS*)-7-Methoxy-9b,11a-
dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one
(21d)
IR (film): 2930, 2868, 2656, 2398, 2354, 2138, 1734, 1701, 1642,
1445, 1411, 1387, 1376, 1357, 1315, 1265, 1245, 1231, 1212, 1190,
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York

FEATURE ARTICLE
PET Domino Cyclizations
633
(5) (a) Kovarnos, G. J.; Turro, N. J. Chem. Rev. 1986, 86, 401.
(b) Mattay, J.; Vondenhof, M. Top. Curr. Chem. 1991, 159,
219. (c) Kovarnos, G. J. Fundamentals of Photoinduced
Electron Transfer; VCH Publishers: New York, 1993.
(d) Electron Transfer in Chemistry, Vol. 1 and 2; Balzani,
V., Ed.; Wiley-VCH: Weinheim, 2001. (e) Heinemann, C.;
Demuth, M. J. Am. Chem. Soc. 1999, 121, 4894. (f) Hintz,
S.; Heidbreder, A.; Mattay, J. Top. Curr. Chem. 1996, 177,
77. (g) Oelgemöller, M.; Bunte, J. O.; Mattay, J. In Synthetic
Organic Photochemistry; Ramamurthy, V.; Schanze, K.,
Eds.; Marcel & Dekker: New York, in press.
(11) (a) Barco, A.; Benetti, S.; Pollini, G. P. Synthesis 1973, 316.
(b) De Silva, A. N.; Francis, C. L.; Ward, A. D. Aust. J.
Chem. 1993, 46, 1657.
(12) (a) Imamoto, T. Comprehensive Organic Synthesis –
Organocerium Reagents, Vol. 1; Trost, B. M.; Fleming, I.;
Schreiber, S. L., Eds.; Pergamon Press: Oxford, 1991, 231.
(b) Takeda, N.; Imamoto, T. Org. Synth. 1999, 76, 228.
(c) Panev, S.; Dimitrov, V. Tetrahedron: Asymmetry 2000,
11, 1517.
(13) Bergdahl, M.; Eriksson, M.; Nilsson, M.; Olsson, T. J. Org.
Chem. 1993, 58, 7238.
(6) Bunte, J. O.; Mattay, J. In CRC Handbook of Organic
Photochemistry and Photobiology, 2nd Ed.; Horspool, W.
M.; Lenci, F., Eds.; CRC Press: Boca Raton, 2004, Chap. 10.
(7) (a) Ackermann, L.; Heidbreder, A.; Wurche, F.; Klärner,
F.-G.; Mattay, J. J. Chem. Soc., Perkin Trans. 2 1999, 863.
(b) Hintz, S.; Mattay, J.; van Eldik, R.; Fu, W.-F. Eur. J.
Org. Chem. 1998, 1583. (c) Bunte, J. O.; Rinne, S.; Schäfer,
C.; Neumann, B.; Stammler, H.-G.; Mattay, J. Tetrahedron
Lett. 2003, 45.
(8) Boehm, H. M.; Handa, S.; Pattenden, G.; Roberts, L.; Blake,
A. J.; Li, W. S. J. Chem. Soc., Perkin Trans. 1 2000, 3522.
(9) Buchecker, R.; Marti, U.; Eugster, C. H. Helv. Chim. Acta
1982, 65, 896.
(14) Bunte, J. O. PhD thesis; Universität Bielefeld: Germany,
2003.
(15) Webster, F. X.; Silverstein, R. M. Synthesis 1987, 922.
(16) (a) Johnstone, R. A. W.; Rose, M. E. Tetrahedron 1979, 35,
2169. (b) Giuliano, R. M.; Jordan, A. D. Jr.; Gauthier, A. D.;
Hoogsteen, K. J. Org. Chem. 1993, 58, 4979.
(17) (a) Kikani, B. B.; McKee, J. T.; Zanger, M. Synthesis 1990,
176. (b) Campaigne, E.; Selby, T. P. J. Heterocycl. Chem.
1980, 17, 1255. (c) Fuchs, R.; McGarrity, J. F. Synthesis
1992, 373. (d) Duc, L.; McGarrity, J. F.; Meul, T.; Warm, A.
Synthesis 1992, 391.
(18) Armarego, W. L. F.; Perrin, D. D. In Purification of
Laboratory Chemicals, 4th Ed.; Butterworth-Heinemann:
Oxford, 1996.
(10) (a) Johnson, W. S.; Bartlett, W. R.; Czeskis, B. A.; Gautier,
A.; Lee, C. H.; Lemoine, R.; Leopold, E. J.; Luedtke, G. R.;
Bancroft, K. J. J. Org. Chem. 1999, 64, 9587. (b) Brady, S.
F.; Ilton, M. A.; Johnson, W. S. J. Am. Chem. Soc. 1968, 90,
2882.
Synthesis 2004, No. 4, 619–633 © Thieme Stuttgart · New York