Asymmetric synthesis of 3,4-annulated cyclopentenones from cycloalkenyl ketones and vinyl carbamates by diastereoselective carbonyl addition/conrotatory 4π ring closure

Article abstract of DOI:10.1055/s-2008-1067150

1-Lithiated O-vinyl carbamates add with high induced diastereoselectivity onto enantiomerically pure cycloalk-1-enyl (1-dibenzylamino)alkyl ketones. Subsequent O-carbamoyl migration, followed by a torquoselective, antarafacial 4π ring closure, leads to ho

Full text of DOI:10.1055/s-2008-1067150

2264
PAPER
Asymmetric Synthesis of 3,4-Annulated Cyclopentenones from Cycloalkenyl
Ketones and Vinyl Carbamates by Diastereoselective Carbonyl Addition/
Conrotatory 4p Ring Closure
A
symmetric Synthesis
i
of 3,4-
c
Annulated
h
C
yclopenten
a
ones el Siemer, Roland Fröhlich, Dieter Hoppe*
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstr. 40, 48149 Münster, Germany
Fax +49(251)8336531; E-mail: dhoppe@uni-muenster.de
Received 10 March 2008
Dedicated to Prof. Dr. Reinhard W. Hoffmann on the occasion of his 75th birthday
enone 3 and the reaction mixture was allowed to warm up
Abstract: 1-Lithiated O-vinyl carbamates add with high induced
diastereoselectivity onto enantiomerically pure cycloalk-1-enyl (1-
dibenzylamino)alkyl ketones. Subsequent O-carbamoyl migration,
followed by a torquoselective, antarafacial 4p ring closure, leads to
homochiral 2-substituted bicyclo[n.3.0]alk-1-ene-2-ones.
slowly to room temperature. During this period, the alkox-
ide 4, formed with high substrate-directed diastereoselec-
tivity,10 rearranges by carbamoyl migration6 to release
two hidden reactive functionalities from 4, namely a lith-
ium enolate and an allylic carbamoyloxy group in 5.
Key words: carbanion, cyclopentenones, asymmetric synthesis,
electrocyclic reaction, torquoselectivity
The intramolecular substitution step proceeds as a pericy-
clic 4p electrocyclization with strict conrotatory torquose-
lectivity in which the substitution of the carbamoyloxy
group in the allylic position takes place as an antarafacial
process; bicyclic cyclopentenones 6 result with complete
diastereoselectivity (Scheme 1, Table 1).
The synthesis of cyclopent-2-en-1-ones finds consider-
able interest due to their occurrence in physiologically ac-
tive compounds1 or their utilization in synthesis.2 There is
no ‘silver bullet’ for the construction of enantiopure cy-
clopentenones from two starting materials by formation of
two C–C bonds. The latter was accomplished by Pauson–
Khand reaction3 ([2+2+1] mode), the Nazarov cyclization
from an in situ generated divinyl ketone4 ([3+2] mode), or
by the Danheiser method ([4+1] mode) by nucleophilic
attack of a d1-synthon onto a silylketene and subsequent
ring formation to yield racemic cyclopentenones.5
O
i-Pr2N
O
i-Pr2N
O
R2
n
X
O
O
Li
a
3
b
R1
R1
1
2
A novel addition-cyclization reaction, leading to 5-alky-
lidenecyclopent-2-en-1-ones, utilizing 1-lithioallenyl car-
bamates and ketones, following the [3+2] mode, had been
developed in a cooperation between the Tius research
group and our own.6 Quantum chemical calculation by
Lera et al.7 substantiated our previous assumption that the
4p process does not proceed through a Nazarov interme-
diate, but is better described as a hybrid of a pericyclic and
an ionic process, which is the origin of the observed high
torquoselectivity.
O
O
X
R2
carbamoyl
group
migration
i-Pr2N
R1
R2
O
O
Ni-Pr2
n
OLi
LiO
n
R1
X
5
4
R2
torquoselective,
conrotatory 4π
cyclization
X
O
n
This publication deals with the highly diastereoselective
cyclopentenone annulation onto chiral 1-acylcycloalk-1-
enes 3 making use of a 4p cyclization step. (Z)-Alk-1-enyl
carbamates 1 are rapidly deprotonated in the vinylic posi-
– LiOCONi-Pr2
R1
6
tion by means of alkyllithium (Scheme 1).8 Enantioen- Scheme 1 Synthesis of highly substituted, enantiopure cyclopen-
tenones 6. Reagents and conditions: a) s-BuLi, LiCl, THF, –78 °C,
riched ketones 3 were prepared by acylation of cycloalk-
1 h; b) –78 °C, 10 h, r.t., 2 h.
1-enyllithiums with the appropriate N-methoxy-N-meth-
ylcarboxamides according to the Weinreb method.9
The products 6 usually are obtained with an essentially
To the 1-lithioalk-1-enyl carbamate 2 (1.5 equiv) and LiCl
perfect diastereomeric ratio (dr >98:2). The high stereose-
(1.5 equiv) in THF solution was added at –78 °C the
lectivity is the result of the efficient diastereofacial selec-
tion at the carbonyl group adjacent to a dibenzylamino
group (enones 3a–d,g,j) or a tert-butyldiphenylsilyloxy
group (enones 3e,f) combined with a stereocontrolled
pericyclic reaction. Only compound 6ca is a notable ex-
SYNTHESIS 2008, No. 14, pp 2264–2270
Advanced online publication: 18.06.2008
DOI: 10.1055/s-2008-1067150; Art ID: C00608SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
8

PAPER
Asymmetric Synthesis of 3,4-Annulated Cyclopentenones
2265
R2
O
Table 1 Enones 6 Prepared
Li
R2
Entry 1
R1
3
R2
6
n
X
Yield dra
(%)
O
+
CbO
n
R1
n
n
R1
1
2
a
a
a
a
a
a
b
b
b
c
Et
Et
Et
Et
Et
Et
H
a
b
c
d
e
f
Ph
Ph
i-Pr
i-Pr
H
aa
ab
ac
ad
ae
afc
ba
bg
2
1
2
1
2
1
2
1
1
2
2
NBn2
NBn2
NBn2
NBn2
85 >98:2
72 >98:2
63 >98:2
49 >98:2
^
^
C
=
=
R2
+
3
O
Cb = i-Pr2NC(O)
R1
4
A
B
5
OTPSb 88 >98:2
OTPSb 60 >98:2
Scheme 2 Retrosynthetic presentation of the reaction
6
H
gon) through Kieselgur, and the concentration was determined by
titration against diphenylacetic acid.13 Vinyllithium reagents were
titrated with butan-2-ol in anhyd xylene against phenanthrolidine as
indicator.14 Silica gel (40–63 mm) for flash chromatography15 was
purchased from E. Merck Company (Darmstadt). TLC analysis: sil-
ica gel cards 60 F254, detection by UV light (254 nm) and stained
with vanillin reagent, KMnO4 reagent, I2 vapor, or molybdatophos-
phoric acid. GC analysis: HP 6890 (Hewlett-Packard) on the capil-
lary column HP 5 (30 m, ∆ 0.3 mm, Phase 0.25 mm).
Determination of er: column Chira Grom ODH, 250 × 2 mm or on
HPLC (Waters 717). Mps: MFB 595, Gallenkamp, or Stuart Melt-
ing Point Apparatus SMP3; Bibby, UK; not corrected. Optical rota-
tions: polarimeter PerkinElmer 341. Mass spectra: EI, Finnigan
MAT 8200; HRMS, Varian Saturn II. NMR: ARX 300, AM 360, or
AMX 400 (Bruker, Karlsruhe), in CDCl3 with TMS or CHCl3 as in-
ternal standard, assignment of 13C signals (in part) by 90° and
135° DEPT, (H,H)- or (H,C)-COSY experiments. The numbering
used for the interpretation of NMR data of compounds 6 are shown
in Figure 2.
7
a
g
j
Ph
H
NBn2
NBn2
NBn2
NBn2
NBn2
85 >98:2
85 >98:2
69 >98:2
8
H
9
H
OBn bj
10
11
Me
Bn
a
a
Ph
Ph
ca
82
93:7d
d
da
94 >98:2
a In the 1H NMR spectrum of each enone (except for 6ca), only one
diastereomer was observed.
b TPS = t-BuPh2Si.
c X-ray crystal structure analysis.
d Minor product: epimer at C-3.
Crystallographic data: Data sets were collected with a Nonius Kap-
paCCD diffractometer. Programs used: data collection COLLECT
(Nonius B.V., 1998), data reduction Denzo-SMN,16 absorption cor-
rection SORTAV,17 Denzo,18 structure solution SHELXS-97,19
structure refinement SHELXL-97,20 graphics Mopict.21
The (Z)-alk-1-enyl carbamates 1a,22 1c,23 and 1d22,24 are reported.
Compound 1b8b was prepared by base-induced elimination (vide in-
fra).25 Some of the Weinreb amides, used for ketone preparation, are
known:
(S)-2-(dibenzylamino)-N¢-methoxy-N¢-methylpropane
amide,26 (S)-2-(dibenzylamino)-N¢-methoxy-4,N¢-dimethylpentane
amide,27 (S)-2-(dibenzylamino)-N¢-methoxy-N¢-methyl-3-phenyl-
propane amide,28 (S)-3-benzyloxy-2-(dibenzylamino)-N¢-methoxy-
N¢-methylpropane amide,28 and 2-(tert-butyldiphenylsilyloxy)-N-
methoxy-N-methylpropane amide.29
Figure 1 Structure of enone 6af
ception, dr = 93:7.11 The structure of bicyclic enone 6af,
and, thus, the mechanistic pathway, was confirmed by an
X-ray crystal structure analysis under anomalous disper-
sion (Figure 1).12
Vinyl N,N-Diisopropylcarbamate (1b)
2-Chloroethyl N,N-diisopropylcarbamate (31.15 g, 0.15 mol) was
added dropwise to a solution of t-BuOK (33.7 g, 0.30 mol) in THF
(400 mL). After stirring for 24 h at r.t., H2O (200 mL) was added
and the phases were separated. The aqueous phase was extracted
with tert-butyl methyl ether (3 × 100 mL), the combined organic
From the view of synthesis strategy (Scheme 2), the new
reaction corresponds to the cycloaddition of a d1d2 syn-
thon A and an a1a3 synthon B, thereby shifting the enone phases were dried (MgSO4), and the solvent was distilled off at
100 mbar. Short-path distillation (63 °C/5 mbar) yielded pure 1b;
moiety into the newly attached five-membered ring C. All
yield: 21.8 g (85%); colorless oil.
together, the method represents a unique and simple route
for the construction of chiral bicyclic cyclopentenones.
1H NMR (400 MHz): d = 1.24 [d, 3J (CH3)2CH,(CH3)2CH = 7.2 Hz, 12 H,
(H3C)2CH], 3.85 [ps-s, 1 H, (H3C)2CH], 4.05 [ps-s, 1 H, (H3C)2CH],
2
3
4.41 (dd, J2a,2b = 1.4 Hz, J1,2a = 6.1 Hz, 1 H, H-2a), 4.75 (dd,
3J1,2b = 13.9 Hz, 1 H, H-2b), 7.25 (dd, 1 H, H-1).
Reactions with organometallic reagents were carried out under ar-
gon in flasks, sealed with a rubber septum. n-Pentane (P), Et2O (E),
and toluene were dried by refluxing over sodium wire. THF was
dried over potassium metal. CH2Cl2 was distilled over CaH2. s-BuLi
(~1.3 M in hexanes) was purchased from Acros, filtered (under ar-
Ketones 3; General Procedure (GP)
Cycloalk-1-en-1-yllithium (6.0 mmol, 0.1–0.65 M in Et2O) in THF
(15 mL) under argon was cooled to –40 °C before the Weinreb
Synthesis 2008, No. 14, 2264–2270 © Thieme Stuttgart · New York

2266
M. Siemer et al.
PAPER
O
NBn2
O
NBn2
O
NBn2
51
2
3
OBn
51
1
Ph
5
2
21
22
1
5
21
22
2
3
22
21
5
4
1
23
52
52
24
4
4
3
34
33
31
31
33
31
32
32
33
32
6aa
6ad
6bj
O
O
NBn2
NBn2
O
OSiC(C6H5)2(CH3)3
51
51
51
Ph
5
4
Ph
2
2
5
1
1
2
5
1
21
21
21
22
Ph
22
22
52
52
3
4
3
4
3
34
31
33
31
33
31
32
33
32
32
6ab
6af
6da
O
O
O
NBn2
NBn2
NBn2
51
51
Ph
2
5
4
Ph
2
5
1
1
2
1
21
22
23
21
22
5
4
21
22
52
24
3
3
4
3
34
31
34
31
34
31
33
32
32
33
33
32
6ac
6ba
6ca
O
OSiC(C6H5)2(CH3)3
O
NBn2
51
5
2
3
1
21
22
2
3
1
21
22
5
52
4
4
34
31
31
33
32
33
32
6ae
6bg
Figure 2
amide (3.0 mmol) dissolved in THF (6 mL) was added. Stirring at
–40 °C was continued for 5 h. For workup, the mixture was
quenched with aq sat. NH4Cl (20 mL) and H2O (20 mL). Extraction
of the aqueous phase with tert-butyl methyl ether (3 × 20 mL), dry-
ing (MgSO4), filtration, removal of solvent, and column chromato-
graphic purification on silica gel (P:E, 20–3:1) afforded ketones 3.
(S)-1-Cyclopent-1-en-1-yl-2-(dibenzylamino)-3-phenylpropan-
1-one (3b)
According to GP, 3b was obtained from (S)-2-(dibenzylamino)-N¢-
methoxy-N¢-methyl-3-phenylpropane amide28 and cyclopent-1-en-
1-yllithium;31 yield: 58%; viscous oil; [a]D20 +5.4 (c = 0.8, CHCl3).
IR (KBr): 3084, 3062, 3027, 2924, 2837, 1659, 1608 cm–1.
1H NMR (400 MHz): d = 1.65–1.83 (m, 1 H, CH2), 2.14–2.41 (m, 4
(S)-1-Cyclohex-1-en-1-yl-2-(dibenzylamino)-3-phenylpropan-
1-one (3a)
H, CH2), 2.93 (dd, 2JPhCHH,PhCHH = 13.5 Hz, 3JCH,PhCHH = 5.4 Hz, 1 H,
2
3
PhCHH), 3.09 (dd, JPhCHH,PhCHH = 13.5 Hz, JCH,PhCHH = 9.0 Hz, 1
According to GP, 3a was obtained from (S)-2-(dibenzylamino)-N¢-
2
methoxy-N¢-methyl-3-phenylpropane amide28 and cyclohex-1-en-
H, PhCHH), 3.64 (d, JHaNBn,HbNBn = 14.0 Hz, 2 H, CHaNBn), 3.72
20
1-yllithium;30 yield: 80%; colorless oil; [a]D +9.3 (c = 1.0,
(d, 2 H, CHbNBn), 4.13 (dd, 1 H, CNH), 5.84 (m, 1 H, H-1), 7.00–
7.25 (m, 15 H, C6H5).
CHCl3).
13C NMR (100 MHz): d = 22.6 (CH2), 30.4 (CH2), 32.2 (CH2), 33.8
(PhCH2), 54.4 (CH2NBn), 63.1 (CHN), 125.9, 126.9, 128.1, 128.2,
128.8, 129.4, 139.0, 139.7 (C6H5), 144.2 (C=CH), 145.6 (C=CH),
198.5 (C=O).
IR (film): 3084, 3062, 3026, 2939, 2856, 2838, 1740, 1662, 1637,
1601 cm–1.
1H NMR (400 MHz): d = 1.42–1.65 (m, 4 H, CH2), 1.86–2.23 (m, 4
H, CH2), 3.0 (dd, 2JPhCHH,PhCHH = 13.6 Hz, 3JCH,PhCHH = 5.3 Hz, 1 H,
3
Anal. Calcd for C28H29NO: C, 85.02; H, 7.39; N, 3.54. Found: C,
84.76; H, 7.48; N, 3.33.
PhCHH), 3.17 (dd, JCH,PhCHH = 8.9 Hz, 1 H, PhCHH), 3.67 (d,
2JHaNBn,HbNBn = 14.2 Hz, 2 H, CHaNBn), 3.77 (d, 2 H, CHbNBn),
4.26 (dd, 1 H, CNH), 6.00–6.10 (m, 1 H, C=CH), 7.07–7.33 (m, 15
H, C6H5).
(S)-1-Cyclohex-1-en-1-yl-2-(dibenzylamino)-4-methylpentan-1-
one (3c)
According to GP, 3c was obtained from (S)-2-(dibenzylamino)-N¢-
methoxy-4,N¢-dimethylpentane amide27 and cyclohex-1-en-1-yl-
lithium;30 yield: 52%; colorless oil; [a]D20 +1.5 (c = 1.0, CHCl3).
13C NMR (100 MHz): d = 21.4, 21.9, 23.0, 25.7 (CH2), 32.0
(PhCH2), 54.3 (CH2NBn), 60.8 (CNH), 125.9, 126.9, 128.0, 128.1,
128.8, 129.4, 139.2 (C6H5), 139.7 (C=CH), 140.2 (C=CH), 200.9
(C=O).
IR (film): 3084, 3062, 3028, 2932, 2866, 1663, 1635, 1603 cm–1.
Anal. Calcd for C29H31NO: C, 85.04; H, 7.63; N, 3.42. Found: C,
84.96; H, 7.71; N, 3.29.
1H NMR (400 MHz): d = 0.81 [d, 3J(CHa3)2CH,(CH3)2CH = 6.2 Hz, 3 H,
(CHa3)2CH], 0.84 [d, 3J(CHb3)2CH,(CH3)2CH = 6.2 Hz, 3 H, (CHb3)2CH],
1.44–1.73 [m, 7 H, (H3C)2CH, CH2], 1.93–2.12, 2.15–2.25 (m, 4 H,
CH2), 3.59 (d, 2JHaNBn,HbNBn¢ = 14.0 Hz, 2H, CHaNBn), 3.75 (d, 2 H,
Synthesis 2008, No. 14, 2264–2270 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of 3,4-Annulated Cyclopentenones
2267
3
3
CHbNBn), 4.06 (dd, JCNH,CH2 = 5.9 Hz, JCNH,CH2 = 7.7 Hz, 1 H,
133.6, 134.1, 136.2, 136.3, 142.5, 144.8 (C6H5, C=CH), 142.5
(C=CH), 200.0 (C=O).
CNH), 6.15–6.25 (m, 1 H, C=CH), 7.17–7.41 (m, 10 H, C6H5).
13C NMR (100 MHz): d = 22.0, 22.5, 23.1, 23.3, 23.5, 25.4
[(H3C)2CH, CH2], 26.3 [(H3C)2CH], 35.9 (CH2), 54.7 (CH2NBn),
57.0 (CNH), 127.2, 128.5, 129.3, 140.2 (C6H5), 139.8 (C=CH),
140.7 (C=CH), 203.1 (C=O).
Anal. Calcd for C24H30O2Si: C, 76.14; H, 7.99. Found: C, 76.03; H,
8.21.
[6S,7S,9(1S)]-9-[1-(Dibenzylamino)-2-phenylethyl]-7-ethyl-
bicyclo[4.3.0]non-1(9)-en-8-one (6aa); Typical Procedure (TP)
A round-bottomed flask sealed with a septum containing LiCl
(21 mg, 0.5 mmol, 1.5 equiv) was flame-dried in vacuum and filled
with argon. To this were added THF (2 mL) and (Z)-but-1-enyl
carbamate (1a; 100 mg, 0.5 mmol, 1.5 equiv) by a syringe. After
cooling to –78 °C, a 1.38 M solution of s-BuLi in hexane–
cyclohexane (92:8) (0.31 mL, 0.43 mmol, 1.3 equiv) was added.
After 1 h, ketone 3a (135 mg (0.33 mmol, 1.0 equiv) dissolved in
THF (2 mL) was slowly injected. After 10 h at –78 °C, the mixture
was allowed to warm to r.t. over 2 h followed by 2 h stirring at r.t.
H2O (5 mL) was added, the phases were separated, and the aqueous
phase was extracted with tert-butyl methyl ether (3 × 5 mL). After
drying the organic phases (MgSO4), the crude product was purified
by flash chromatography (E:P = 1:30); yield: 130 mg (85%); color-
less solid; mp 81 °C; [a]D20 –9.5 (c = 0.8, CHCl3); dr >98:2.
Anal. Calcd for C26H33NO: C, 83.15; H, 8.86; N, 3.73. Found: C,
82.94; H, 8.99; N, 3.64.
(S)-1-Cyclopent-1-en-1-yl-2-(dibenzylamino)-4-methylpentan-
1-one (3d)
According to GP, 3d was obtained from (S)-2-(dibenzylamino)-N¢-
methoxy-4,N¢-dimethylpentane amide27 and cyclopent-1-en-1-yl-
lithium;31 yield: 73%; colorless oil; [a]D20 +1.3 (c = 1.2, CHCl3).
IR (film): 3084, 3062, 3028, 2956, 2868, 2839, 2806, 1663, 1609
cm-1.
1H NMR (400 MHz): d = 0.81 [d, 3J(CHa3)2CH,(CH3)2CH = 5.0 Hz, 3 H,
3
(CHa3)2CH], 0.85 [d, J(CHb3)2CH,(CH3)2CH = 5.2 Hz,
3
H,
(CHb3C)2CH], 1.53–1.71 [m, 3 H, CH2, (H3C)2CH], 1.82–1.99 (m,
H, CH2), 2.36–2.60 (m, H, CH2), 3.64 (d,
2JHaNBn,HbNBn = 14.2 Hz, 2 H, CHaNBn), 3.79 (d, 2 H, CHbNBn),
2
4
IR (KBr): 3083, 3061, 3025, 2924, 2856, 2796, 1688, 1623, 1601
cm–1.
1H NMR (400 MHz): d = 0.23 (m, 1 H, H-32a), 0.52 (m, 1 H, H-
34a), 0.88 (t, 3J51,52 = 7.4 Hz, 3 H, H-52), 1.19 (m, 1 H, H-33a), 1.39
(m, 1 H, H-51a), 1.44 (m, 1 H, H-33b), 1.47 (m, 1 H, H-32b), 1.60
(m, 1 H, H-5), 1.64 (m, 1H, H-31a), 1.66 (m, 1 H, H-51b), 1.92 (m,
3
3
4.01 (dd, JCNH,CHaHb = 5.6 Hz, JCNH,CHaHb = 7.3 Hz, 1 H, CNH),
6.05 (s, 1 H, C=CH), 7.19–7.34 (m, 10 H, C6H5).
13C NMR (100 MHz): d = 22.5 (CH2), 22.6 [(H3C)2CH], 24.9
[(H3C)2CH], 27.8 [(H3C)2CH], 30.5 (CH2), 33.9 (CH2), 35.7 (CH2),
54.3 (CH2NBn), 59.0 (CNH), 122.7, 126.8, 128.0, 128.8 (C6H5),
143.5 (C=CH), 145.6 (C=CH), 200.0 (C=O).
1 H, H-34b), 1.99 (m, 1 H, H-31b), 2.10 (m, 1 H, H-4), 3.15 (dd,
3
2J22a,22b = 12.7 Hz, J21,22a = 5.2 Hz,
1 H, H-22a), 3.29 (d,
Anal. Calcd for C25H31NO: C, 83.06; H, 8.64; N, 3.87. Found: C,
82.67; H, 8.62; N, 3.74.
2JHaNBn,HbNBn = 14.6 Hz,
2
H, NCHa), 3.47 (dd,
1
H,
3J21,22b = 10.8 Hz, H-22b), 3.70 (dd, 1 H, H-21), 3.99 (d, 2 H,
NCHb), 6.92–7.25 (m, 15 H, C6H5).
2-(tert-Butyldiphenylsilyloxy)-1-cyclohex-1-en-1-ylpropan-1-
one (3e)
13C NMR (100 MHz): d = 11.5 (C-52), 24.3 (C-51), 25.1 (C-33),
26.5 (C-32), 28.9 (C-31), 35.2 (C-34), 35.7 (C-22), 46.5 (C-5), 53.8
(C-4), 55.3 (CH2NBn), 57.0 (C-21), 125.6, 126.4, 127.9, 128.0,
128.3, 129.2, 140.2, 140.8 (C6H5), 132.9 (C-2), 180.5 (C-3), 210.8
(C-1).
According to GP, 3e was obtained from 2-(tert-butyldiphenyl-
silyloxy)-N-methoxy-N-methylpropane amide and cyclohex-1-en-
20
1-yllithium;30 yield: 65%; colorless oil; [a]D –17.9 (c = 1.1,
CHCl3).
IR (film): 3071, 2933, 2858, 1680, 1635 cm–1.
Anal. Calcd for C33H37NO: C, 85.48; H, 8.04; N, 3.02. Found: C,
85.23; H, 8.15; N, 2.97.
1H NMR (400 MHz): d = 1.08 [s, 9 H, C(CH3)3], 1.35 (d,
3JCHOSi,CH3 = 6.8 Hz, 3 H, CH3), 1.47–1.58 (m, 4 H, CH2), 1.90–2.28
(m, 4 H, CH2), 6.68 (s, 1 H, C=CH), 7.31–7.46, 7.60–7.72 (m, 10 H,
C6H5).
13C NMR (100 MHz): d = 19.1 [C(CH3)3], 21.2, 21.4, 23.2, 25.80
(CH2), 21.8 (CH3), 26.8 [C(CH3)3], 69.0 (CHOSi), 127.4, 127.5,
129.5, 129.6, 133.2, 133.70, 135.7, 135.9 (C6H5), 136.6 (C=CH),
140.3 (C=CH) 201.6 (C=O).
[4S,5S,2(1S)]-2-[1-(Dibenzylamino)-2-phenylethyl]-4-ethyl-
bicyclo[3.3.0]oct-1-en-3-one (6ab)
According to TP, 6ab was obtained from carbamate 1a and ketone
3b; yield: 72%; colorless solid; mp 92 °C (E–P); [a]D –8.3
(c = 1.3, CHCl3); dr >98:2.
20
IR (KBr): 3080, 3059, 3023, 2964, 2928, 2865, 2789, 2715, 1692,
1642 cm–1.
1H NMR (400 MHz): d = 0.72 (m, 1 H, H-33a), 0.98 (t,
3J51,52 = 7.3 Hz, 3 H, H-52), 1.45 (m, 1 H, H-51a), 1.70 (m, 1 H, H-
31a), 1.77–1.87 (m, 3 H, H-5, H-32), 1.94 (m, 1 H, H-51b), 2.03 (m,
Anal. Calcd for C25H32O2Si: C, 76.48; H, 8.22. Found: C, 76.23; H,
8.32.
2-(tert-Butyldiphenylsilyloxy)-1-cyclopent-1-en-1-ylpropan-1-
one (3f)
According to GP, 3f was obtained from 2-(tert-butyldiphenyl-
silyloxy)-N-methoxy-N-methylpropane amide and cyclopent-1-en-
1-yllithium;31 yield: 55%; slightly yellow oil; [a]D20 –21.1 (c = 1.4,
CHCl3).
1 H, H-33b), 2.18 (m, 1 H, H-31b), 2.48 (m, 1 H, H-4), 3.23 (dd,
3
2J22a,22b = 13.2 Hz, J21,22a = 6.4 Hz,
1 H, H-22a), 3.33 (dd,
3J21,22b = 9.4 Hz, 1 H, H-22b), 3.42 (d, 2JCHaNBn, CHbNBn = 14.3 Hz, 2
H, NCHa), 3.72 (dd, 1 H, H-21), 4.04 (d, 2 H, NCHb), 6.99–7.31
(m, 15 H, C6H5).
13C NMR (100 MHz): d = 11.9 (C-52), 22.3 (C-51), 25.68, 25.73
(C-31, C-32), 31.3 (C-33), 35.4 (C-22), 50.6 (C-5), 55.3 (NCH2),
56.3 (C-4), 58.1 (C-21), 125.7, 127.1, 127.8, 127.9, 128.3, 129.1,
139.9, 140.6 (C6H5), 133.1 (C-2), 187.1 (C-3), 211.6 (C-1).
IR (film): 3071, 2958, 2932, 2893, 2858, 1679, 1611 cm–1.
1H NMR (300 MHz): d = 1.00 [s, 9 H, C(CH3)3], 1.27 (d,
3JCHOSi,CH3 = 6.8 Hz, 3 H, CH3), 1.70–1.76 (m, 2 H, CH2), 2.21–2.47
(m, 4 H, CH2), 4.54 (q, 1 H, CHOSi), 6.59 (t, 3JC=CH,CH2 = 4.3 Hz, 1
H, C=CH), 7.15–7.40, 7.48–7.64 (m, 10 H, C6H5).
13C NMR (75 MHz): d = 19.6 [C(CH3)3], 22.4 (CH3), 22.5, 31.5,
34.6 (CH2), 27.3 [C(CH3)3], 73.7 (CHOSi), 127.0, 128.0, 130.1,
Anal. Calcd for C32H35NO: C, 85.48; H, 7.85; N, 3.12. Found: C,
85.20; H, 7.86; N, 2.99.
Synthesis 2008, No. 14, 2264–2270 © Thieme Stuttgart · New York

2268
M. Siemer et al.
PAPER
[6S,7S,9(1S)]-9-[1-(Dibenzylamino)-3-methylbutyl]-7-ethylbi-
cyclo[4.3.0]non-1(9)-en-8-one (6ac)
129.5, 133.9, 133.9, 135.6, 135.7, 135.8, 135.8, 139.3 (C6H5), 133.9
(C-2), 175.8 (C-3), 207.9 (C-1).
According to TP, 6ac was obtained from carbamate 1a and ketone
3c; yield: 63%; amorphous solid; [a]D20 –11.2 (c = 0.9, CHCl3); dr
>98:2.
Anal. Calcd for C29H38O2Si: C, 77.97; H, 8.57. Found: C, 77.71; H,
8.31.
IR (KBr): 3084, 3062, 3028, 2957, 2930, 2860, 2801, 1694, 1622
cm–1.
[2(1S),4S]-2-[1-(tert-Butyldiphenylsilyloxy)ethyl]-4-ethyl-
bicyclo[3.3.0]oct-1-en-4-one (6af)
According to TP, 6af was obtained from carbamate 1a and ketone
3f; yield: 88%; amorphous solid; [a]D –66 (c = 0.9, CHCl3); dr
>98:2.
3
1H NMR (400 MHz): d = 0.67 (d, J23,24a = 6.7 Hz, 3 H, H-24a),
20
0.73 (d, 3J23,24b = 6.5 Hz, 3 H, H-24b), 0.92 (m, 3 H, H-52), 0.99 (m,
1 H, H-32a), 1.01 (m, 1 H, H-34a), 1.32–1.46, 1.71–1.82 (m, 4 H,
H-31, H-51), 1.64 (m, 1 H, H-22a), 1.81 (m, 1 H, H-34b), 1.87 (m,
1 H, H-33a), 2.10 (m, 1 H, H-22b), 2.15 (m, 1 H, H-32b), 2.24 (m,
1 H, H-4), 2.37 (m, 1 H, H-33b), 3.17 (d, 2JCHaNBn,CHbNBn = 14.3 Hz,
2 H, NCHa), 3.56 (dd, 3J21,22a = 9.6 Hz, 3J21,22b = 6.2 Hz, 1 H, H-21),
3.86 (d, 2 H, NCHb), 7.01–7.27 (m, 5 H, C6H5).
13C NMR (100 MHz): d = 12.3 (C-52), 22.8 (C-24a), 24.0 (C-24b),
24.9, 26.0, 26.1 (C-23, C-31, C-51), 27.7 (C-34), 30.0 (C-33), 36.1
(C-32), 39.0 (C-22), 47.3 (C-4), 54.5 (C-21), 55.6 (C-5), 55.7
(NCH2), 127.1, 128.5, 128.6, 129.0, 129.1, 129.3, 141.7 (C6H5),
134.6 (C-2), 180.2 (C-3), 211.5 (C-1).
IR (film): 3071, 3041, 2962, 2859, 1702, 1662, 1431, 1375, 1287,
1256, 1108, 1072, 1002, 947, 913, 822, 736, 704, 436 cm–1.
1H NMR (400 MHz): d = 1.19 (t, 3J51,52 = 7.5 Hz, 3 H, H-52), 1.53
3
(d, J21,22 = 6.4 Hz, 3 H, H-22), 1.33 [s, 9 H, C(CH3)3], 1.86–3.14
(m, 10 H, H-4, H-5, H-31, H-32, H-33, H-51), 5.07 (q, 1 H, H-21),
7.52–7.71, 7.82–8.01 (m, 10 H, C6H5).
13C NMR (100 MHz): d = 112.0 (C-52), 18.3 (C-22), 22.1
[C(CH3)3], 24.0, 26.4, 27.0, 30.9 (C-31, C-32, C-33, C-51), 27.0
[C(CH3)3], 51.8 (C-4), 55.4 (C-5), 64.7 (C-21), 122.7, 127.3, 127.4,
127.6, 129.4, 129.5, 133.9, 134.0, 134.4, 134.7, 135.6, 135.7
(C6H5), 138.1 (C-2), 181.9 (C-3), 209.7 (C-1).
Anal. Calcd for C30H39NO: C, 83.87; H, 9.15; N, 3.26. Found: C,
83.56; H, 9.00; N, 3.33.
Anal. Calcd for C28H36O2Si: C, 77.73; H, 8.39. Found: C, 77.92; H,
8.51.
[2(1S),4S,5S]-2-[1-(Dibenzylamino)-3-methylbutyl]-4-ethylbi-
cyclo[3.3.0]oct-1-en-3-one (6ad)
According to TP, 6ad was obtained from carbamate 1a and ketone
[6S,9(1S)]-9-[1-(Dibenzylamino)-2-phenylethyl]bi-
cyclo[4.3.0]non-1(9)-en-8-one (6ba)
20
3d; yield: 49%; amorphous solid; [a]D –7.0 (c = 1.1, CHCl3); dr
According to TP, 6ba was obtained from carbamate 1b and ketone
>98:2.
20
3a; yield: 75%; amorphous solid; [a]D –13.4 (c = 0.9, CHCl3);
IR (KBr): 3085, 3062, 3028, 2957, 2931, 2869, 2801, 1698, 1641,
1603 cm–1.
dr = 99:1.
IR (KBr): 3081, 3062, 3015, 2932, 2865, 2799, 1695, 1614, 1605
cm–1.
3
1H NMR (400 MHz): d = 0.64 (d, J23,24a = 6.5 Hz, 3 H, H-24a),
3
3
0.67 (d, J23,24b = 6.7 Hz, 3 H, H-24b), 0.93 (dd, J51,52 = 7.2 Hz, 3
H, H-52), 0.98 (m, 1 H, H-33a), 1.33–1.48 (m, 2 H, H-51a, H-23),
1.62–1.82 (m, 2 H, H-22), 1.84–1.96 (m, 4 H, H-5, H-51b, H-32),
1H NMR (400 MHz): d = 0.21 (m, 1 H, H-32a), 0.56 (m, 1 H, H-
34a), 1.23–1.95 (m, 8 H, H-5, H-31, H-32b, H-33, H-34b), 2.12 (m,
2
3
1 H, H-4), 3.09 (dd, J22a,22b = 12.6 Hz, J21,22a = 5.4 Hz, 1 H, H-
2
2.06–2.13 (m, 1 H, H-33b), 2.18 (ddd, J31a,31b = 19.0 Hz,
2
22a), 3.23 (d, JHaNBn,HbNBn = 14.6 Hz, 2 H, NCHa), 3.56 (dd,
3J31a,32a = 8.1 Hz, J31a,32b = 8.5 Hz, 1 H, H-31a), 2.37 (ddd,
3
3J21,22b = 10.6 Hz, 1 H, H-22b), 3.77 (dd, 1 H, H-21), 4.01 (d, 2 H,
3J31b,32a = 7.4 Hz, 3J31b,32b = 6.4 Hz, 1 H, H-31b), 2.47 (m, 1 H, H-4),
NCHb), 6.75–7.18 (m, 15 H, C6H5).
3.25 (d, 2JNCHa, NCHa¢ = 14.2 Hz,
2 H, NCHa), 3.49 (dd,
13C NMR (100 MHz): d = 23.2, 26.7, 29.3 (C-31, C-32, C-33), 34.9
(C-34), 36.6 (C-22), 46.3 (C-5), 55.1 (C-4), 55.4 (CH2NBn), 56.2
(C-21), 125.8, 126.3, 127.9, 128.1, 128.2, 129.9, 140.3, 140.8
(C6H5), 133.2 (C-2), 180.6 (C-3), 212.2 (C-1).
3J21,22a = 6.8 Hz, 3J21,22b = 8.4 Hz, 1 H, H-21), 3.78 (d, 2 H, NCHb),
7.08–7.18 (m, 2 H, CHarom-para), 7.16–7.23 (m, 4 H, CHarom-ortho),
7.26–7.31 (m, 4 H, CHarom-meta).
13C NMR (100 MHz): d = 11.9 (C-52), 22.3 (C-51), 22.4 (C-24b),
22.7 (C-24a), 25.1 (C-23), 26.0 (C-32), 26.3 (C-31), 31.6 (C-33),
38.3 (C-22), 51.1 (C-5), 53.2 (C-21), 55.1 (NCH2), 56.3 (C-4),
126.4 (CHarom-para), 127.8 (CHarom-ortho), 128.5 (CHarom-meta), 134.0
(C-2), 140.8 (Carom-ipso), 185.2 (C-3), 211.8 (C-1).
Anal. Calcd for C31H33NO: C, 85.48; H, 7.64; N, 3.22. Found: C,
85.11; H, 7.55; N, 3.23.
[2(1S),5S]-2-[1-(Dibenzylamino)ethyl]bicyclo[3.3.0]oct-1-en-3-
one (6bg)
Anal. Calcd for C29H37NO: C, 83.81; H, 8.97; N, 3.37. Found: C,
84.02; H, 9.15; N, 3.11.
According to TP, 6bg was obtained from carbamate 1b and ketone
20
3g; yield: 85%; colorless oil; [a]D –25.3 (c = 1.2, CHCl3); dr
>98:2.
[4S,7S,9(1S)]-9-[1-(tert-Butyldiphenylsilyloxy)ethyl]-7-ethylbi-
cyclo[4.3.0]non-1(9)-en-8-one (6ae)
According to TP, 6ae was obtained from carbamate 1a and ketone
IR (film): 3083, 3059, 3027, 2963, 2869, 2802, 1697, 1642, 1601
cm–1.
20
1H NMR (300 MHz): d = 0.86 (m, 1 H, H-33a), 1.37 (d,
3J21,22 = 7.1 Hz, 3 H, H-22), 1.89 –2.00 (m, 2 H, H-32), 1.96 (dd,
2J5a,5b = 17.3 Hz, 3J4,5a = 3.2 Hz, 1 H, H-5a), 2.07 (m, 1 H, H-33b),
2.33–2.52 (m, 2 H, H-31), 2.57 (dd, 3J4,5b = 6.3 Hz, 1 H, H-5b), 2.73
(m, 1 H, H-4), 3.51 (d, 2JHaNBn,HbNBn = 14.4 Hz, 2 H, CHaNBn), 3.72
(d, 1 H, H-21), 3.74 (d, 2 H, CHbNBn), 7.14–7.38 (m, 10 H, C6H5).
13C NMR (75 MHz): d = 14.6 (C-22), 25.7 (C-32), 26.3 (C-31),
31.1 (C-33), 42.5 (C-5), 44.5 (C-4), 50.8 (C-21), 55.1 (CH2NBn),
126.5, 127.9, 128.3, 140.7 (C6H5), 136.3 (C-2), 186.3 (C-3), 210.1
(C-1).
3e; yield: 60%; colorless solid; mp 103 °C; [a]D –59 (c = 0.34,
CHCl3); dr >98:2.
IR (film): 3071, 3051, 2931, 2858, 1694, 1646, 1428, 1110, 910,
760, 823, 735, 704, 471 cm–1.
1H NMR (400 MHz): d = 0.81 (t, 3J51,52 = 6.8 Hz, 3 H, H-52), 0.99
[s, 9 H, C(CH3)3], 1.18 (d, 3J21,22 = 6.6 Hz, 3 H, H-22), 1.12–2.06,
3.44 (m, 12 H, H-4, H-5, H-31, H-32, H-33, H-34, H-51), 4.76 (q, 1
H, H-21), 7.17–7.35, 7.46–7.57 (m, 10 H, C6H5).
13C NMR (100 MHz): d = 11.5 (C-52), 23.5, 25.3, 26.0, 28.6, 29.6,
34.6 [C-31, C-32, C-33, C-34, C-51, C(CH3)3], 23.9 (C-22), 26.9
[C(CH3)3], 46.9 (C-4), 53.2 (C-5), 63.8 (C-22), 127.3, 127.4, 129.4,
Synthesis 2008, No. 14, 2264–2270 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of 3,4-Annulated Cyclopentenones
2269
Anal. Calcd for C24H27NO: C, 83.44; H, 7.88; N, 4.05. Found: C,
83.32; H, 8.16; N, 3.81.
Anal. Calcd for C38H39NO: C, 86.82; H, 7.48; N, 2.66. Found: C,
86.47; H, 7.54; N, 2.33.
[2(1S),5S]-2-[1-(Dibenzylamino)-2-benzyloxyethyl]bi-
cyclo[3.3.0]oct-1-en-3-one (6bj)
Acknowledgment
According to TP, 6bj was obtained from carbamate 1b and ketone
3j; yield: 69%; colorless oil; [a]D –23.1 (c = 0.6, CH2Cl2);
dr = 98:2.
The work was funded by the Deutsche Forschungsgemeinschaft
(SFB 424) and the Fonds der Chemischen Industrie (grant to M.S.).
We acknowledge the careful experimental work by the research stu-
dents Ms. Susanne Dammers, Ms. Yvonne Fricke, and Ms. Tina
Dunckerberg.
20
IR (film): 3082, 3061, 3028, 2957, 2865, 2799, 1696, 1643, 1608
cm–1.
1H NMR (300 MHz): d = 0.91 (m, 1 H, H-33a), 1.81–1.93 (m, 2 H,
2
3
H-32), 1.99 (dd, J5a,5b = 17.8 Hz, J4,5a = 3.2 Hz, 1 H, H-5a), 2.07
References
(m, 1 H, H-33b), 2.16–2.46 (m, 2 H, H-31), 2.59 (dd, 3J4,5b = 6.5 Hz,
1 H, H-5b), 2.78 (m, 1 H, H-4), 3.41 (d, JHaNBn,HbNBn = 14.1 Hz, 2
H, CHaNBn), 3.78 (t, J21,22b = 7.2 Hz, 1 H, H-21), 3.87 (d, 2 H,
CHbNBn), 3.92 (dd, J22a,22b = 9.6 Hz, J21,22a = 7.2 Hz, 1 H, H-
22a), 3.93 (dd, 2 H, H-22b), 4.40 (s, 2 H, CH2OBn), 7.10–7.35 (m,
15 H, C6H5).
2
(1) Cyclopentenone-derived prostaglandins: (a) Rossi, A.;
Kapahi, P.; Natoli, G.; Takahashi, T.; Chen, Y.; Karin, M.;
Santoro, M. G. Nature 2000, 403, 103. (b) Willboughby, D.
A.; Moore, A. R.; Colville-Nash, P. R. Nat. Med. 2000, 6,
137.
3
2
3
13C NMR (100 MHz): d = 25.6 (C-32), 26.2 (C-31), 31.2 (C-33),
42.5 (C-5), 44.8 (C-4), 55.5 (C-21), 55.7 (CH2NBn), 69.4 (C-22),
73.0 (CH2OBn), 126.6, 126.8, 127.3, 127.4, 128.0, 128.2, 128.4,
128.8, 128.9, 138.7, 140.5 (C6H5), 133.1 (C-2), 188.8 (C-3), 210.2
(C1).
(2) Corey, E. J.; Cheng, X.-M. The Logic of Chemical
Synthesis; Wiley: New York, 1995, 250.
(3) (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.;
Formann, M. I. J. Chem. Soc., Perkin Trans. 1 1973, 977.
Review: (b) Blanco-Urgoiti, J.; Anorbe, L.; Pérez-Serrano,
L.; Dominguez, G.; Pérez-Castells, J. Chem. Soc. Rev. 2004,
33, 32. (c) Gibson, S. E.; Lewis, S. E.; Mainolfi, N.
J. Organomet. Chem. 2004, 689, 3873.
Anal. Calcd for C31H33NO2: C, 82.45; H, 7.37; N, 3.10. Found: C,
82.21; H, 7.12; N, 3.33.
(4) Review: (a) Tius, M. A. Acc. Chem. Res. 2003, 36, 284.
(b) Tius, M. A. Eur. J. Org. Chem. 2005, 2193. For further
reading on the Nazarov cyclization, see also: (c) Frontier,
A. J.; Collison, C. Tetrahedron 2005, 61, 7577.
[6S,7S,9(1S)]-9-[1-(Dibenzylamino)-2-phenylethyl]-7-methyl-
bicyclo[4.3.0]non-1(9)-en-8-one (6ca)
According to TP, 6ca was obtained from 1c and ketone 3a; yield:
82%; colorless solid; [a]D20 –5.4 (c = 0.9, CHCl3); dr = 93:7.
(d) Pellissier, H. Tetrahedron 2005, 61, 6479.
IR (KBr): 3090, 3056, 3020, 2927, 2858, 2795, 1691, 1619 cm–1.
(e) Habermas, K. L.; Denmark, S. E. Org. React. 1994, 45,
1. In a more general way the Piancatelli reaction can be
considered as a Nazarov reaction (transformation of furfuryl
alcohols to cyclopentenones); review: (f) Piancatelli, G.;
D’Auria, M.; D’Onofrio, F. Synthesis 1994, 867.
(5) (a) Loebach, J. L.; Bennett, D. M.; Danheiser, R. L. J. Am.
Chem. Soc. 1998, 120, 9690. (b) Dalton, A. M.; Zhang, Y.;
Davie, C. P.; Danheiser, R. L. Org. Lett. 2002, 15, 2465.
(c) Davie, C. P.; Danheiser, R. L. Angew. Chem. Int. Ed.
2005, 44, 5890; Angew. Chem. 2005, 117, 6017. Another
example for the addition of a nucleophilic carbene to a vinyl
ketene: (d) Rigby, J. H.; Wang, Z. Org. Lett. 2003, 3, 263.
(6) Schultz-Fademrecht, C.; Tius, M. A.; Grimme, S.;
Wibbeling, B.; Hoppe, D. Angew. Chem. Int. Ed. 2002, 41,
1532; Angew. Chem. 2002, 114, 1610.
1H NMR (400 MHz): d = 0.29 (m, 1 H, H-32a), 0.49 (m, 1 H, H-
34a), 0.91–2.13 (m, 11 H, H-4, H-5, H-31, H-32b, H-33, H-34b, H-
51), 3.17 (dd, 2J22a,22b = 12.5 Hz, 3J21,22a = 5.4 Hz, 1 H, H-22a), 3.30
(d, 2JHaNBn,HbNBn = 14.5 Hz, 2 H, NCHa), 3.43 (dd, 3J21,22b = 10.6 Hz,
1 H, H-22b), 3.70 (dd, 1 H, H-21), 3.97 (d, 2 H, NCHb), 6.85–7.31
(m, 15 H, C6H5).
13C NMR (100 MHz): d = 15.9 (C-51), 24.9, 26.4, 28.5 (C-31, C-
32, C-33), 34.3, 35.6 (C-22, C-34), 47.4 (C-5), 49.0 (C-4), 55.3
(CH2NBn), 57.0 (C-21), 125.6, 126.5, 127.9, 128.1, 128.4, 129.0,
140.8 (C6H5), 132.3 (C-2), 179.8 (C-3), 211.8 (C-1).
Anal. Calcd for C32H35NO: C, 85.48; H, 7.85; N, 3.12. Found: C,
85.33; H, 7.99; N, 3.55.
(7) (a) Faza, O. N.; López, C. S.; Álvarez, R.; de Lera, A. R.
Chem. Commun. 2005, 4285. Further articles about
torquoselectivity in the synthesis of cyclopentenones:
(b) López, C. S.; Faza, O. N.; York, D. M.; de Lera, A. R.
J. Org. Chem. 2004, 69, 3635. (c) Faza, O. N.; López, C. S.;
Álvarez, R.; de Lera, A. R. Chem. Eur. J. 2004, 10, 4324.
(8) (a) Kocienski, P.; Dixon, N. J. Synlett 1989, 52.
(b) Sengupta, S.; Snieckus, V. J. Org. Chem. 1990, 55,
5680. (c) Peschke, B.; Lüßmann, J.; Dyrbusch, M.; Hoppe,
D. Chem. Ber. 1992, 117, 1421.
(9) (a) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22,
3815. For reviews, see: (b) Sibi, M. P. Org. Prep. Proced.
Intl. 1993, 25, 15. (c) Mentzel, M.; Hoffmann, H. M. R.
J. Org. Chem. 2004, 339, 517.
(10) (a) Reetz, M. T. Chem. Rev. 1999, 99, 1121. For 3e, a high
diastereoselectivity in the reduction with LiAlH4 is
described: (b) Hart, S. A.; Sabat, M.; Etzkorn, F. A. J. Org.
Chem. 1998, 63, 7580.
(11) A partial base-induced epimerization of 6ca may be the
origin.
[6S,7S,9(1S)]-7-Benzyl-9-[1-(dibenzylamino)-2-phenylethyl]bi-
cyclo[4.3.0]non-1(9)-en-8-one (6da)
According to TP, 6da was obtained from 1d and ketone 6a; yield:
94%; colorless solid; [a]D20 –15.6 (c = 1.1, CHCl3); dr = 99:1.
IR (KBr): 3085, 3055, 3028, 2927, 2852, 2801, 1690, 1622, 1605
cm–1.
1H NMR (400 MHz): d = 0.17 (m, 1 H, H-32a), 0.41 (m, 1 H, H-
34a), 1.01–1.61, 1.91 (m, 7 H, H-5, H-31, H-32b, H-33, H-34b),
2.11 (m, 1 H, H-4), 2.51 (dd, 2J51a,51b = 9.9 Hz, 3J5,51a = 7.4 Hz, 1 H,
H-51a), 3.09 (dd, 2J22a,22b = 12.6 Hz, 3J21,22a = 5.1 Hz, 1 H, H-22a),
3.17 (dd, 3J5,51b = 4.9 Hz,
1
H, H-51b), 3.29 (d,
2JHaNBn,HbNBn = 14.6 Hz, 2 H, NCHa), 3.47 (dd, 1 H, H-22b), 3.69
(dd, 3J21,22b = 11.0 Hz, 1 H, H-21), 3.99 (d, 2 H, NCHb), 6.81–7.16
(m, 20 H, C6H5).
13C NMR (100 MHz): d = 24.9, 26.3, 28.9 (C-31, C-32, C-33), 34.7,
35.6, 36.8 (C-34, C-22, C-51), 46.0 (C-5), 54.1 (C-4), 55.3
(CH2NBn), 57.1 (C-21), 125.7, 125.9, 126.2, 126.5, 127.9, 128.0,
128.2, 128.27, 128.33, 129.2, 139.7, 140.1, 140.7 (C6H5), 133.0 (C-
2), 180.7 (C-3), 209.5 (C-1).
Synthesis 2008, No. 14, 2264–2270 © Thieme Stuttgart · New York

2270
M. Siemer et al.
PAPER
(12) X-ray crystal structure analysis for 6af: formula C29H38O2Si,
M = 446.68, colorless crystal 0.30 × 0.25 × 0.10 mm, a =
10.154 (1), b = 16.328 (1), c = 15.949 (1) Å, b = 94.90 (1)°,
V = 2634.6 (3) Å3, rcalc = 1.126 g cm–3, m = 0.943 mm–1,
empirical absorption correction (0.765 £ T £ 0.912), Z = 4,
monoclinic, space group P21 (No. 4), l = 1.54178 Å,
T = 223 K, w and j scans, 21759 reflections collected ( h,
k, l), [(sin q)/l] = 0.60 Å–1, 7576 independent
(Rint = 0.034) and 7417 observed reflections [I 2 s(I)], 587
refined parameters, R = 0.035, wR2 = 0.094, Flack parameter
0.04 (2), max. residual electron density 0.16 (–0.13) eÅ–3,
two almost identical molecules in the asymmetric unit,
hydrogen atoms calculated and refined as riding atoms.
CCDC 670192 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44(1223)336033, E-mail:
deposit@ccdc.cam.ac.uk.
(13) Kofron, W. G.; Baclawski, L. M. J. Org. Chem. 1976, 41,
1879.
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(25) (a) Siemer, M. Diploma Thesis; University of Münster:
Münster, 2001. (b) See also ref. 8b for comparison.
(26) (a) Hoffmann, R. W.; Rühl, T.; Chemla, F.; Zahneisen, T.
Liebigs Ann. Chem. 1992, 719. (b) Velluz, L.; Amiard, C.;
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(b) Blessing, R. H. J. Appl. Cryst. 1997, 30, 421.
(31) Paquette, L. A. Eur. J. Org. Chem. 1998, 1709; and
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Synthesis 2008, No. 14, 2264–2270 © Thieme Stuttgart · New York