3-Substituted and 2,3-Disubstituted Cyclopentanones via an Asymmetric Tandem 1,4-Addition/Dieckmann Cyclization

Article abstract of DOI:10.1055/s-2003-45008

A new stereoselective method for the synthesis of 3-substituted and 2,3-disubstituted cyclopentanones is described. The key step is the 1, 4-addition of a cuprate to a chilar Michael-acceptor derived from (-)-8-phenylmenthol or the Helmchen auxiliary followed by Dieckmann cyclization of the obtained chiral enolates. The resultant 2,3-cyclopentanones can be transformed after methanolysis and demethoxycarbonylation to the related 3-substituted cyclopentanones.

Full text of DOI:10.1055/s-2003-45008

LETTER
291
3-Substituted and 2,3-Disubstituted Cyclopentanones via an Asymmetric
Tandem 1,4-Addition/Dieckmann Cyclization1
C
yclopentanone
s
v
l
ia
A
sy
r
m
metric
i
T
ande
c
1,4-Addi
h
tion/Dieckmann Cy
G
clization roth,* Wolfgang Halfbrodt, Aris Kalogerakis, Thomas Köhler, Paul Kreye
Fachbereich Chemie der Universität Konstanz, Universitätsstrasse 10, Postfach M-720, 78457 Konstanz, Germany
Fax +49(7531)884155; E-mail: ulrich.groth@uni-konstanz.de
Received 21 October 2003
thesis of (–)-8-phenylmenthol.13 The other chiral acceptor
5b was synthesized in a similar way starting from 1 and
alcohol B – the Helmchen auxiliary – in 51% yield over 3
steps. While reaction of the organocuprates RCu-
Abstract: A new stereoselective method for the synthesis of 3-sub-
stituted and 2,3-disubstituted cyclopentanones is described. The
key step is the 1,4-addition of a cuprate to a chilar Michael-acceptor
derived from (–)-8-phenylmenthol or the Helmchen auxiliary fol-
lowed by Dieckmann cyclization of the obtained chiral enolates. Li·nBu3·PBF3, which were prepared according to
Oppolzer14 from MeLi or PhLi, copper(I)iodide, tributyl
The resultant 2,3-cyclopentanones can be transformed after metha-
nolysis and demethoxycarbonylation to the related 3-substituted
cyclopentanones.
phosphine and BF3·Et2O, with 5a gave the cyclopen-
tanones 7a and 7b in goods yields and with high diastere-
oselectivity, the analogue organocuprate t-BuCuLi·n-
Bu3P·BF3 generated from t-BuLi did not react (Table 1,
Key words: asymmetric synthesis, cyclopentanones, cuprate,
chiral auxiliary, 1,4-addition, Dieckmann cyclization, natural prod-
ucts
entry 3). We were able to synthesize the cyclopentanone
7c by changing from copper(I)iodide to copper(I)cya-
nide.15 In this case the use of the tributyl phosphine is not
2,3-Disubstituted and 2,2¢,3-trisubstituted cyclopen-
tanones such as jasmonic acid and its related compounds,2
chokol A,3 sarkomycin,4 dactylol,5 confertin,6 11-
deoxyprostaglandines7 and steroids8 are attractive target
molecules in organic synthesis due to their biological ac-
tivity and pharmaceutical importance. Consequently, a
number of methods have been applied for the asymmetric
construction of cyclopentanones.9 Since some conjugate
addition/cyclization reactions have been reported10 in
connection with our own studies in steroid synthesis11 we
have developed a versatile applicable method for the
asymmetric synthesis of 3-substituted-2-carbomethoxy-
and 3-substituted-cyclopentanones. We were able to syn-
thesize two different chiral enoates 5a and 5b, which al-
lowed the conjugate addition of various organocopper
compounds. The intermediates 6 of this addition led via an
intramolecular cyclization (Dieckmann cyclization) to
2,3-disubstituted cyclopentanones 7 in good yields and
with high diastereoselectivity (Scheme 1). These gave
upon methanolysis the enantiopure 2-carbomethoxycy-
clopentanones 8 (Scheme 2), which can be used as start-
ing materials in the synthesis of natural products
containing a cyclopentane moiety.
necessary, which makes the purification of the synthe-
sized cyclopentanone by column chromatography easier.
Next, we studied the reaction of allylcuprates with 5a by
choosing three different cuprate adducts, but unfortunate-
ly the 3-allyl-substitued cyclopentanone 7d could not be
obtained. In the course of our synthetic studies towards
R*-OH
O
O
O
O
P(OEt)3
(EtO)2P
Cl
Cl
OR*
OR*
Cl
C6H5N(CH3)2
1
2a,b
3a,b
O
1. NaH
H3CO
"R-cuprate"
OR*
2.
H3CO
O
O
5a,b
O
4
O
O
OR*
R
R
O
H3CO
OR*
O
The (–)-8-phenylmenthol-derived Michael-acceptor 5a
was prepared in a Wittig–Horner reaction from methyl-4-
oxo-butanoate 4 and the diethoxy phosphonic ester 3a in
87% yield; as a by-product the corresponding cis-isomer
of 5a was isolated in 4% yield. Compound 4 was obtained
in two steps by an improved synthesis according to Saji.12
Compund 3a was prepared in a Michael–Arbuzov reac-
tion from the chloroacetate 2a, an intermediate in the syn-
7
6
R*-OH =
A
B
HO
N
SO2Ph
OH
SYNLETT 2004, No. 2, pp 0291–0294
0
2.
0
2.
2
0
0
4
Ph
Advanced online publication: 19.12.2003
DOI: 10.1055/s-2003-45008; Art ID: G29703ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 1

292
U. Groth et al.
LETTER
Table 1 1,4-Addition/Dieckmann Cyclization of Cuprates with the Chiral Acceptors17
Entry
1
R
5, R*
A
Cuprate
7 (%)
7a (79)
7b (67)
–
de (%)a
CH3
RCuLi·n-Bu3P·BF3
RCuLi·n-Bu3P·BF3
RCuLi·n-Bu3P·BF3
R2Cu(CN)Li2·BF3
RCuLi·nBu3P·BF3
R2CuLi2·n-Bu3P·BF3
R2Cu(CN)Li2·BF3
RCuLi·nBu3P·BF3
R2CuLi2·nBu3P·BF3
R2Cu(CN)Li2·BF3
78
76
–
2
Ph
A
3
t-Bu
A
4
t-Bu
A
7c (85)
–
75
–
5
CH2=CH2CH2
CH2=CH2CH2
CH2=CH2CH2
CH2=CH
CH2=CH
CH2=CH
CH2=CH
CH2=CH
A
6
A
–
–
7
A
–
–
8
A
–
–
9
A
7e (78)
7f (79)
7f (88)
7f (78)
82
78
89
89
10
11
12
B
b
B
R2Cu(CN)Li2·BF3
c
B
R2Cu(CN)Li2·BF3
a Determined by 13C NMR spectroscopy.
b The cuprate was added at –95 °C.
c The cuprate was added at –116 °C.
the sesquiterpenes chokols we investigated the synthesis auxiliaries, in 83–95% yield. Obviously, the major dia-
of the 2-carbomethoxy-3-vinyl-cyclopentanone 8e stereomers 7 undergo a methanolysis much faster than
(Scheme 2, Table 2, entries 4 and 5) starting from the pre- their C-3 epimers, so that the b-keto esters 8 can be
vious using chiral acceptor 5a and the camphor derivative obtained virtually in enantiomerically pure form. As a by-
5b by reaction with a vinylcuprate. The Oppolzer organo- product of the methanolysis an almost 1:1 mixture of 7
cuprate (CH2=CH)CuLi·n-Bu3P·BF3 generated from and its epimers was obtained in 6–11%. The enantiomeric
vinyllithium16 did not react with 5a, but the reaction of excess and the absolute configuration of 8a at C-3 were
the cuprate (CH2=CH)2CuLi2·n-Bu3P·BF3 yielded 78% of determined by comparison of its optical rotation with an
the 3-vinyl-b-keto-ester 7e with 82% de. Similarly, the authentic sample prepared from (R)-pulegone.18 The
chiral enoate 5b derived from the Helmchen auxiliary,9b absolute configuration of 8b19 and 8c20 was determined by
after reaction with vinylcuprates also gave the vinyl- comparison of the optical rotation of the prepared 3-sub-
cyclopentanone 7f in good yields and with high stituted-cyclopentanones 9 with the reported value. For
diastereoselectivity.
Indeed,
addition
of the determination of the absolute configuration of 8e we
15
(CH2=CH)2Cu(CN)Li2·BF3 at –85 °C to 5b afforded 7f compared the optical rotation of our 2-carbomethoxy-3-
in 79% yield and with 78% de. We also observed that the vinylcyclopentanone 8e17 with the reported value of the
20
yield and the diastereomeric excess of 7f can be increased same compound ([a]D = +85.05) synthesized from
(88% yield and 89% d.e.) by addition of the cuprate at Helmchen and co-workers.9b The enantiomeric excess of
–95 °C. However, addition at lower temperatures (–116 the cyclopentanones 8b–e and 9b–e was obtained by de-
°C) had no effect on the de, but the yield decreased to termination of the diastereomeric excess of the diastereo-
78%.
meric ketals 10 by analysis of their 13C NMR spectra.21
These were prepared after demethoxycarbonylation of 8
with DABCO22 (1,4-diazabicyclo[2.2.2]octane) in DMSO
and reaction of the obtained cyclopentanones 9 with
(2R,3R)-(–)-2,3-butanediol 11.
Methanolysis of the cyclopentanones 7 at 120 °C in a
sealed tube afforded the 2-carbomethoxycyclopentanones
8 in 86–95% ee and, in addition, enantiomerically pure
(–)-8-phenylmenthol A or camphor alcohol B, the chiral
O
O
O
HO OH
O
O
DABCO
CO2R*
CO2Me
MeOH
120 °C
11
DMSO
120°C, 1 h
cat. p-TsOH
R
R
R
R
7
8
9
10
Scheme 2
Synlett 2004, No. 2, 291–294 © Thieme Stuttgart · New York

LETTER
Cyclopentanones via Asymmetric Tandem 1,4-Addition/Dieckmann Cyclization
293
Table 2 Synthesis of the 3-Substituted Cyclopentanones
Entry
7, R
8 (%)
R*OH (%)
A (84)
ee (%)
89
9 (%)
–
10 (%)
–
1
7a, CH3
7b, Ph
8a (84)
8b (91)
8c (60)
8e (77)
8e (78)
2
A (95)
> 95b
86
76
96
3
7c, t-Bu
7e, CH2=CH
7f, CH2=CHa
A (92)
89
84
4
A (83)
> 95b
> 95b
85
90
5
B (86)
88
94
a Table 1, entry 11.
b Only one diastereomer was detected.
(6) (a) Quinkert, G.; Müller, T.; Königer, A.; Schultheis, O.;
Sickenberger, B.; Dürner, G. Tetrahedron Lett. 1992, 33,
3469. (b) The Total Synthesis of Natural Products, Vol. 11;
John Wiley & Sons, Inc.: New York, 1994, 148–150.
(c) Confertin can also be synthesized from a 2,3-
disubstituted cyclopentanone.
(7) (a) Noyori, R.; Suzuki, M. Angew. Chem. Int. Ed. Engl.
1984, 23, 847; Angew. Chem. 1984, 96, 854. (b) Steglich,
W.; Fugmann, B.; Lang-Fugmann, S. RÖMPP Natural
Products; Thieme: Stuttgart, 2000, 517–518.
(8) (a) Wiechert, R. Angew. Chem. Int. Ed. Engl. 1970, 9, 321;
Angew. Chem. 1970, 82, 331. (b) Wiechert, R. Angew.
Chem. Int. Ed. Engl. 1970, 16, 506; Angew. Chem. 1977, 89,
513. (c) Quinkert, G.; Stark, H. Angew. Chem. Int. Ed. Engl.
1983, 22, 637; Angew. Chem. 1983, 95, 651. (d) Steglich,
W.; Fugmann, B.; Lang-Fugmann, S. RÖMPP Natural
Products; Thieme: Stuttgart, 2000, 608–611.
In summary, we have developed a new access to substitut-
ed cyclopentanones by employing a tandem reaction of
cuprates with chiral Michael acceptors via an asymmetric
1,4-addition and a Dieckmann cyclization. The prepared
2,3-substituted cyclopentanones were then transformed
into the related enantiopure 2-carbomethoxycyclopen-
tanones and 3-substituted cyclopentanones. The synthesis
of cyclopentanoid natural products using this new
methodology is currently under investigation.
Acknowledgment
The authors are grateful to the Fonds der Chemischen Industrie
and the EU Commission, Directorate XII, for financial support.
P. K. is grateful to the Cusanuswerk – Bischöfliche Hochbegabten-
förderung – for a PhD fellowship.
(9) (a) Yamamoto, Y. In Houben–Weyl, Methods of Organic
Chemistry, Vol. E 21b; Thieme: Stuttgart, 1995, 2041–
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1996, 52, 971. (c) Kanai, M.; Tomioka, K. Tetrahedron Lett.
1994, 35, 895. (d) Hailes, H. C.; Isaac, B.; Javaid, M. H.
Tetrahedron Lett. 2001, 42, 7325. (e) Denmark, S. E.; Kim,
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(g) Hua, D. H.; Chan-Yu-King, R.; McKie, J. A.; Myer, L.
J. Am. Chem. Soc. 1987, 109, 5026. (h) Barnhart, R. W.;
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(j) Moritani, Y.; Appella, D. H.; Jurkauskas, V.; Buchwald,
S. L. J. Am. Chem. Soc. 2000, 122, 6797. (k) Liang, L.;
Au-Yeung, T. T.-L.; Chan, A. S. C. Org. Lett. 2002, 4, 3799.
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5364. (b) Nugent, W. A.; Hobbs, F. W. Jr. Org. Synth. 1988,
66, 52. (c) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed.
Engl. 1993, 32, 131; Angew. Chem. 1993, 105, 137.
(d) Rossiter, B. E.; Swingle, N. M. Chem. Rev. 1992, 92,
771.
(11) (a) Groth, U.; Köhler, T.; Taapken, T. Tetrahedron 1991, 47,
7583. (b) Groth, U.; Huhn, T.; Richter, N. Liebigs Ann.
Chem. 1993, 49. (c) Groth, U.; Köhler, T.; Taapken, T.
Liebigs Ann. Chem. 1994, 665. (d) Groth, U.; Taapken, T.
Liebigs Ann. Chem. 1994, 669.
(12) Sumitomo, H.; Kobayashi, K.; Saiji, T. J. Polym. Sci. 1972,
10, 3421.
(13) (a) Ort, O. Org. Synth. 1987, 65, 203. (b) Scharf, H.-D.;
Buschmann, H. Synthesis 1988, 827; and references cited
therein.
References
(1) Stereoselective Synthesis of Steroids and Related
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N.; Kalogerakis, A. Eur. J. Org. Chem. 2003, 23, 4634.
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Elsevier Science Ltd.: Amsterdam, 1999, 108–136.
(b) Ernst, M.; Helmchen, G. Angew. Chem. Int. Ed. 2002, 41,
4054; Angew. Chem. 2002, 114, 4231. (c) Helmchen, G.;
Gocke, A.; Lauer, G.; Urmann, M. Angew. Chem., Int. Ed.
Engl. 1990, 29, 1024; Angew. Chem. 1990, 102, 1079(3).
(3) (a) Oppolzer, W.; Cunningham, F. Tetrahedron Lett. 1986,
26, 5467. (b) Mash, E. A. J. Org. Chem. 1987, 52, 4142.
(c) Lawler, D. M.; Simpkins, N. S. Tetrahedron Lett. 1988,
29, 1207. (d) Suzuki, T.; Tada, H.; Unno, K. J. Chem. Soc.,
Perkin Trans. 1 1992, 2017. (e) Groth, U.; Halfbrodt, W.;
Köhler, T.; Kreye, P. Liebigs Ann. Chem. 1994, 885.
(f) Urban, E.; Knühl, G.; Helmchen, G. Tetrahedron 1995,
51, 13031.
(4) Helmchen, G.; Ihrig, K.; Schindler, H. Tetrahedron Lett.
1987, 28, 183.
(5) (a) Fürstner, A.; Müller, T. Synlett 1997, 1010. (b)Fürstner,
A.; Langenmann, K. J. Org. Chem. 1996, 61, 8746. (c) The
Total Synthesis of Natural Products, Vol. 11; John Wiley &
Sons, Inc.: New York, 1994, 172–173. (d) Dactylol is a
bicyclic sesquiterpene, which can be synthesized starting
from a 2,3-disubstituted cyclopentanone.
(14) Oppolzer, W.; Moretti, R.; Godel, T.; Meunier, A.; Löher, H.
Tetrahedron Lett. 1983, 24, 4971.
Synlett 2004, No. 2, 291–294 © Thieme Stuttgart · New York

294
U. Groth et al.
LETTER
(15) (a) Lipshutz, B. H. Synlett 1990, 119. (b) Lipshutz, B. H.
Org. React. 1992, 41, 135.
(16) Vinyllithium was prepared via reaction of tetravinyltin with
n-BuLi.
115.38 (CH=CH2), 127.49, 128.12, 129.33, 129.89, 132.46
(arom. C), 138.64 (CH=CH2), 136.98, 137.05, 138.16,
139.04 (arom. C), 167.88 (CHCOO), 210.70 [212.35] (C=O)
(signals of the 2¢R,3¢S-configured diastereomer in brackets).
EI-MS (70 eV): m/z (%) = 549 (3) [M+], 395(11) [M+ –
C8H10O3], 254 (100) [M+ – C8H10O3 – SO2C6H5], 105 (22)
(17) Experimental Procedure: A solution of 10.0 mmol
organolithium compound in Et2O (10 mL) was added to a
solution of 5.0 mmol copper(I) cyanide in Et2O (10 mL)at
–80 °C. After 2 h stirring 5.0 mmol BF3·Et2O were added
and the resultant mixture was cooled at –95 °C. A solution of
1.0 mmol chiral enoate 5 in Et2O (10 mL) was added via
canulla and the obtained mixture was allowed to warm under
stirring to r.t. (18 h). The reaction mixture was quenched
with aq sat. NH4Cl solution (30 mL), extracted with Et2O (2
× 20 mL), the combined organic layer dried over MgSO4 and
evaporated in vacuum. Purification of the residue by flash
chromatography provided the 2,3-substituted
+
[C8H9 ]. Anal. Calcd for C32H39O5NS (549.7): C, 69.92; H,
7.15. Found: C, 69.87; H, 7.28.
Compound 8e (Table 2, entry 5): Rf 0.31 (Et2O–petroleum
ether, 1:2). [a]D20 +82.3 (c 1.5, CHCl3). Bp. 65–70 °C (2
torr). IR(film): 3065 (alkene CH), 1750 (C=O), 1730
(OC=O), 1635 (C=C) cm–1. 1H NMR (250 MHz, CDCl3):
d = 1.54–1.86 (m, 1 H, CH), 2.16–2.60 (m, 3 H, CH, CH2),
3.03 (dd, 3J = 11.6 Hz, 4J = 0.6 Hz, 1 H, C-2-H), 3.14–3.29
(m, 1 H, C-3-H), 3.76 (s, 3 H, OCH3), 5.10 (ddd, 3Jcis = 10.0
Hz, 2J = 1.2 Hz, 4J = 1.2 Hz, 1 H, CH=CH2), 5.17 (ddd,
3Jtrans = 17.0 Hz, 2J = 1.2 Hz, 4J = 1.2 Hz, 1 H, CH=CH2),
5.84 (ddd, 3Jtrans = 17.0 Hz, 3Jcis = 10.0 Hz, 3J = 6.6 Hz, 1 H,
CH=CH2). 13C NMR (62.5 MHz, CDCl3): d = 27.25 (C-4),
38.12 (C-5), 44.83 (C-3), 52.48 (OCH3), 60.77 (C-2), 115.95
(CH=CH2), 135.95 (CH=CH2), 169.10 (COOCH3), 210.71
(C-1). EI-MS (70 eV): m/z (%) = 168 (86) [M+], 137 (85)
[M+ – OCH3], 109 (90) [M+ – COOCH3], 81 (100) [M+ –
C2H3O2 – C2H3 – H]. HRMS: m/z calcd for C9H12O3 (168.2):
168.0786; found: 168.0786.
Compound 10e (Table 2, entry 5): Rf 0.41 (Et2O–
petroleum ether, 1:10). [a]D20 +3.3 (c 1.4, CHCl3). IR(film):
3065 (alkene CH), 1635 (C=C) cm–1. 1H NMR (250 MHz,
CDCl3): d = 1.21–1.27 (m, 6 H, CH3), 1.31–2.08 (m, 6 H,
CH2), 2.46–2.74 (m, 1 H, CHCH=CH2), 3.47–3.66 (m, 2 H,
OCH), 4.91 (ddd, 3Jcis = 10.0 Hz, 2J = 1.5 Hz, 4J = 1.5 Hz, 1
H, CH=CH2), 5.00 (ddd, 3Jtrans = 17.2 Hz, 2J = 1.5 Hz, 4J =
cyclopentanone 7.
Analytical data of selected compounds (Figure 1).
Compound 7e: Rf 0.41 (Et2O–petroleum ether, 1:5).
IR(film): 3040 (alkene CH), 1740 (C=O), 1725 (OC=O),
1650 (alkene C=C), 1610 (arom. C=C) cm–1. 1H NMR (250
MHz, CDCl3): d = 0.87 (d, 3J = 6.5 Hz, 1 H, H-5¢), 1.19 (s, 3
H, CH3), 1.27 (s, 3 H, CH3), 0.80–1.84 (m, 7 H, H-1¢, H-3¢,
H-4¢, H-6¢), 1.88–2.40 (m, 3 H, H-4, H-5, H-2¢), 3.46 (d,
3J = 11 Hz, 1 H, H-2), 2.83–3.05 (m, 1 H, H-3), 4.81 (ddd,
3J = 10.5, 10.5, 4 Hz, 1 H, COOCH, H-1¢), 5.09 (ddd, Jcis
=
10 Hz, J = 1.5, 1.5 Hz, 1 H, CH=CH2), 5.125 (ddd, Jtrans = 17
Hz, J = 1.5, 1.5 Hz, 1 H, CH=CH2), 5.745 (ddd, Jtrans = 17
Hz, Jcis = 10 Hz, J = 7 Hz, 1 H, CH=CH2), 7.06–7.20 (m, 1
H, arom. H), 7.23–7.38 (m, 4 H, arom. H). 13C NMR (62.5
MHz, CDCl3): d = 21.74 [22.75] (CH3), 25.68 (CH3), 26.58
(cyclopentane-CH2), [26.43] 26.65 (cyclohexane-CH2),
27.37 [27.51] (CH3), [29.52] 31.28 (CHCH3, C-5¢), 34.52
[34.68] (cyclohexane-CH2), 37.79 [38.25] (cyclopentane-
CH2), 39.70 [39.87] (C(CH3)2), 41.38 [41.73] (cyclohexane-
CH2), 43.73 [46.20] (CHCH=CH2, C-3), 49.96 [50.48] (C-
2¢), 60.90 [62.07] (COCHCO, C-2), 75.96 [76.30] (C-1¢),
115.78 [116.24] (CH = CH2), 124.87 [125.18], 125.45
[125.56], [127.84] 127.97 (3 × C-arom.), 138.62 [140.67]
(CH=CH2), 151.51 (C-arom.), 167.34 [168.13] (COO),
210.22 (CO) (signals of the 2R,3S-configured diastereomer
in brackets). EI-MS (70 eV): m/z (100) = 119 [PhC(CH3)2]
(100), 249 (4) [M+ – PhC(CH3)2)], 368 (2) [M+]. Anal. Calcd
for C24H32O3 (368.5): C, 78.22; H, 8.75. Found: C, 78.39; H,
8.85.
1.5 Hz, 1 H, CH=CH2), 5.79 (ddd, 3Jtrans = 17.2 Hz, 3Jcis
=
10.0 Hz, 3J = 7.2 Hz, 1 H, CH=CH2). 13C NMR (62.5 MHz,
CDCl3): d = 16.86 (CH3), 16.95 (CH3), 30.57, 37.98 (CH2),
42.16 (C-7), 44.43 (CH2), 78.21 (CHCH3), 78.26 (CHCH3),
113.07 (CH=CH2), 116.84 (OCO), 141.98 (CH=CH2). EI-
MS (70 eV): m/z (%) = 182 (3) [M+], 114 (100) [C6H10O2 ],
+
+
54 (26) [C4H8 ]. Anal. Calcd for C11H18O2 (182.3): C, 72.49;
H, 9.95. Found: C, 72.36; H, 9.84.
3
1
5'
3
O
2
O
N
O
1
O
2
O
O
SO2Ph
1
O
O
5
1'
2'
2
3
2'
Compound 7f (Table 1, entry 11): Rf 0.46 (Et2O–
petroleum ether, 1:1); mp: 59–63 °C. IR(nujol): 3060, 3040
(arom. CH), 1750 (C=O), 1730 (OC=O), 1640 (C=C), 1610,
1595 (arom. C=C), 1350, 1165 (CSO2N) cm–1. 1H NMR
(250 MHz, CDCl3): d = 0.82 (s, 3 H, CH3), 0.88 (s, 3 H, C-
1-CH3), 1.04 (s, 3 H, CH3), 0.90–2.45 (m, 9 H, CH, CH2),
2.02 (s, 3 H, arom. CH3), 2.32 (s, 3 H, arom. CH3), 3.33 (d,
O
O
OCH3
3
3'
7
Ph
8e
10e
7e
7f
Figure 1
Jtrans = 11.2 Hz, 1 H, H-2¢), 3.34–3.50 (m, 1 H, H-3¢), 4.25
(ddd, J = 8.8 Hz, J = 3.4 Hz, 4J = 1.0 Hz, 1 H, H-3), 5.11
(ddd, Jcis = 10.6 Hz, 2J = 1.2 Hz, 4J = 1.2 Hz, 1 H, CH=CH2),
5.27 (ddd, Jtrans = 17.0 Hz, 2J = 1.2 Hz, 4J = 1.2 Hz, 1 H,
CH=CH2), 5.46 (d, J = 8.8 Hz, 1 H, H-2), 5.78 (s, 1 H, arom.
H), 5.98 (ddd, Jtrans = 17.0 Hz, Jcis = 10.6 Hz, J = 6.6 Hz, 1
H, CH=CH2), 6.83 (s, 1 H, arom. H), 7.11 (s, 1 H, arom. H),
7.28–7.57 (m, 5 H, arom. H). 13C NMR (62.5 MHz, CDCl3):
d = 14.30 (C-10), 19.41 (C-8), 19.51 (C-9), 19.69 (C-5),
20.98, 21.29 (2 × arom. CCH3), 26.59 (C-6), 26.62 (C-4¢),
38.13 (C-5¢), [35.53] 43.46 (C-3¢), 45.71 (C-7), 49.38 (C-4),
51.30 (C-1), 59.35 (C-3), 60.77 [63.27] (C-2¢), 77.59 (C-2),
(18) Marx, J. N.; Norman, L. R. J. Org. Chem. 1975, 40, 1602.
(19) (a) For 9b (R = Ph): [a]D20 = +83.4 (c 0.3, CHCl3).
(b) Taber, D. F.; Raman, K. J. Am. Chem. Soc. 1983, 105,
5935. (c) Taura, Y.; Tanaka, M.; Wu, X.-M.; Funakoshi, K.;
Sakai, K. Tetrahedron 1991, 47, 4879.
(20) For 9c (R = t-Bu): [a]D20 = +134.8 (c 1.13, CHCl3); ref.19b
(21) Hiemstra, H.; Wynberg, H. Tetrahedron Lett. 1977, 25,
2183.
(22) (a) Parish, E. J.; Mody, N. V.; Hedin, P. A.; Miles, D. H. J.
Org. Chem. 1974, 39, 1592. (b) Huang, B.-S.; Parish, E. J.;
Miles, D. H. J. Org. Chem. 1974, 39, 2647.
Synlett 2004, No. 2, 291–294 © Thieme Stuttgart · New York