Diastereoselective domino heck-suzuki reaction: Synthesis of substituted methylenetetrahydrofurans

Article abstract of DOI:10.1055/s-0028-1088217

In a palladium-catalyzed reaction of dienyl ethers with boronic acids, a diastereoselective cyclization occurs to give methylenetetrahydrofurans. They can be obtained as pure enantiomers and their conversion into dihydro-3(2H)-furanones and dioxanones is

Full text of DOI:10.1055/s-0028-1088217

968
LETTER
Diastereoselective Domino Heck–Suzuki Reaction: Synthesis of Substituted
Methylenetetrahydrofurans
S
ynthesis of Substitute
a
d
Methylen
n
etetrahydrofu
f
rans red Braun,* Brigitte Richrath
Institut für Organische Chemie und Makromolekulare Chemie, Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany
Fax +49(211)8115079; E-mail: braunm@uni-duesseldorf.de
Received 25 November 2008
In memoriam Professor Dr. Hans-Dieter Martin
X
R2
Abstract: In a palladium-catalyzed reaction of dienyl ethers with
boronic acids, a diastereoselective cyclization occurs to give meth-
ylenetetrahydrofurans. They can be obtained as pure enantiomers
and their conversion into dihydro-3(2H)-furanones and dioxanones
is demonstrated.
Br
+
(HO)2BR2
R1
R1
O
O
3
4
1: X = CH2
2: X = O
Key words: palladium, catalysis, cyclizations, stereoselectivity,
chirality
Scheme 1 Retrosynthetic approach of a diastereoselective domino
Heck–Suzuki reaction
cially available allylic alcohol (R)-6a. The palladium-
catalyzed coupling with boronic acids 4a–e, which were
present in the reaction mixture from the beginning, along
with cesium carbonate, gave the heterocyclic five-mem-
bered products 1aa–1ca (Table 1).
Domino reactions have developed into an exceptionally
efficient tool in organic synthesis by taking advantage of
the fact that two or more bonds can be formed in a consec-
utive manner without isolating the intermediate products.
In the individual steps of domino reactions, different
mechanisms can be combined in various transformations.
Transition-metal-mediated, particularly palladium-cata-
lyzed conversions are increasingly used in domino reac-
tions.1 Especially the Heck reaction has been applied in
multifold consecutive carbon–carbon bond formations.2
When a different palladium-catalyzed conversion is
planned to succeed the Heck reaction, the intermediate
palladium species has to be trapped in order to avoid the
final b-elimination.3–7 A very useful carbon–carbon bond
formation will result if boronic acids serve as trapping
agents. However, this sequence, a domino Heck–Suzuki
reaction, has been realized rarely and was applied in syn-
theses of several carbocyclic and heterocyclic compounds
only recently.8 In none of those, however, the problem of
stereoselective formation of contiguous chiral centers has
been addressed.
Both tetrakis(triphenylphosphino)palladium [Pd(Ph3P)4]
and Herrmann’s catalyst10 generated from palladium ace-
tate and tri-o-tolylphosphane were found to be suitable to
bring about the domino sequence. The latter catalyst pro-
vided slightly higher yields, as shown in Table 2 (entries
1 vs. 2 and 7 vs. 8). Fair yields were usually obtained from
substrate 1a when coupled with arylboronic acids 4a–c
(entries 1–4). The protocol could also be applied to vinyl
and alkyl boronic acids 4d and 4e; however, the products
1ad and 1ae were formed in moderate yields only (entries
5 and 6). Substrates 3b and 3c also underwent the domino
reaction and gave methylenetetrahydrofurans 1ba, 1bb,
1bc, and 1ca (entries 7–11). Minor amounts (15–25%) of
noncyclized products arising from a direct Suzuki cou-
pling as well as dienes originating from final b-elimina-
tion could be removed by column chromatography.
In view of the formation of a second stereogenic carbon
center in the course of the domino Heck–Suzuki reaction
of ethers 3, the problem of diastereoselectivity was ad-
dressed. It turned out that the cyclization reactions of
phenyl-substituted ethers 3a occurred with remarkably
high stereoselectivity, giving in each case essentially a
single diastereomer 1aa–1ae. The NMR spectra and GC-
MS detection of the crude products revealed diastereo-
meric ratios up to >98:2, as shown in Table 2 (entries 1–
6). Lager amounts of the cis-isomer were found in the
product 1ab (entry 3). For substrates 3b,c, which have a
methyl or isopropyl residue at the stereogenic carbon cen-
ter, lower diastereoselectivity was also obtained (entries
7–11). In some cases, the diastereomeric purity could be
enhanced by column chromatography of the crude cy-
clization product. Thus, tetrahydrofuran 1aa was obtained
as a pure diastereomer (entries 1, 2, and 12). The 13C
In this communication, we describe the first diastereo-
selective domino Heck–Suzuki reaction. It permits to ob-
tain 2,3-disubstituted 4-methylenetetrahydrofurans 1 and
3(2H)-dihydrofuranones 2 from readily accessible ethers
3 and boronic acids 4 according to retrosynthetic
Scheme 1. It involves a disconnection of the 3,4-bond in
the heterocyclic ring and the 1¢,2¢-bond in the side chain.9
The precursors of the conceived domino sequence, racem-
ic dienes 3a–c, were obtained from a Williamson etherifi-
cation of 2,3-dibromopropene (5) with allylic alcohols
(rac)-6a–c through the corresponding alkoxides. In an
analogous manner, (R)-3a was prepared form commer-
SYNLETT 2009, No. 6, pp 0968–0972
x
x.
x
x.
2
0
0
9
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088217; Art ID: G36608ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Substituted Methylenetetrahydrofurans
969
Table 1 Synthesis of Ethers 3 and Diastereoselective Cyclization to Methylenetetrahydrofurans 1a
R2
R1
Br
Br
R2B(OH)2 (4)
a
+
HO
R1
b
R1
Br
O
O
5
6
3
1
3, 6
R1
4
R2
Ph
1
R1
R2
3a, 6a
3b, 6b
3c, 6c
Ph
4a
4b
4c
4d
4e
1aa
1ab
1ac
1ad
1ae
1ba
Ph
Ph
Me
i-Pr
4-MeSC6H4
4-ClC6H4
Ph
4-MeSC6H4
4-ClC6H4
Ph
(E)-n-HexCH=CH
i-Pr
Ph
(E)-n-HexCH=CH
Ph
i-Pr
Me
Me
Me
i-Pr
Ph
1bb
1bc
1ca
4-MeSC6H4
4-ClC6H4
Ph
a Reaction conditions: (a) NaH, THF, reflux, 3a: 93%, 3b: 59%, 3c: 36%; (b) [Pd(PPh3)4] (3 mol%) or (2-MeC6H4)3P (2.5 mol%), Pd(OAc)2
(2.5 mol%); (c) Cs2CO3 (150 mol%), EtOH, 25 °C, 24 h.
NMR spectroscopy served for the determination of the
relative configuration in the products 1aa–1ca. In dia-
stereomeric 2,3-disubstituted tetrahydrofurans, the chem-
ical shifts of carbon atoms 2 and 3 differ in a characteristic
manner: both carbon atoms appear at lower field in the
trans-diastereomers, whereas the resonances are high-
field-shifted in the cis-diastereomers.11 This assignment
of the configuration, illustrated for trans- and cis-1ba in
Figure 1, also applies to the other methylenetetrahydro-
furans 1. In accordance with reported data7, the vicinal 2-
H,3-H coupling constants are substantially smaller in the
cis-diastereomers compared with the trans-diastereomers.
As a result, the main products formed by the domino
Heck–Suzuki protocol turned out to be trans configured.
This is also in accordance with the stereochemical out-
come in nickel-mediated Heck carbonylation sequences
of 3a that deliver trans products albeit with moderate dia-
stereoselectivty.7
Table 2 Diastereoselective Domino Heck–Suzuki Reaction of
Ethers 3 to 2,3-Disubstituted 4-Methylenetetrahydrofurans 1
Entry Substrate Boronic Product
Yield dr (trans-1/
3
acid 4
1
(%)a
54b
61c
52c
51c
32c
31c
28b
48c
52c
31c
51c
cis-1)d
1
2
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3c
4a
1aa
1aa
1ab
1ac
1ad
1ae
1ba
1ba
1bb
1bc
1ca
98:2 (>99:1)e
98:2 (>99:1)e
83:17 (89:11)e
97:3
4a
3
4b
4c
4
5
4d
4e
96:4
6
>98:2
7
4a
83:17 (88:12)e
83:17
8
4a
9
4b
4c
89:11
10
11
12
83:17
Ph
Ph
48.4
78.1
51.2
81.3
4a
82:18
Me
15.9
Me
20.3
O
O
(R)-3a
4a
(2R,3R)-1aa 54c
98:2 (>99:1)e
trans-1ba
cis-1ba
a Isolated products, purified by column chromatography.
b Catalyst: [Pd(Ph3P)4].
c Catalyst: (2-MeC6H4)3P, Pd(OAc)2.
Figure 1 Relevant 13C shift values in diastereomeric methylene-
tetrahydrofurans trans-1ba and cis-1ba
d Determined in the crude product.
e Values in parentheses: trans/cis ratio after column chromatography.
The predominant formation of the trans-diastereomers is
plausibly explained by considering the transition state
models 7a and 7b, as outlined in Scheme 2. In the dia-
stereoselectivity determining step of the domino se-
quence, cyclization of 7a and 7b occurs to give the alkyl
palladium intermediates trans-8 and cis-8, respectively. It
seems to be plausible that the chairlike transition state 7a
is favored compared with the boatlike 7b. During the final
coupling of the diastereomers 8 with boronic acids 4, a
competing b-elimination accounts for the formation of
dienes as byproducts.12 Thus, there are, aside from the di-
rect Suzuki reaction without cyclization, altogether four
Synlett 2009, No. 6, 968–972 © Thieme Stuttgart · New York

970
M. Braun, B. Richrath
LETTER
heterocyclic compounds 1. By using enantiomerically
pure allylic alcohols, the protocol readily leads to tetra-
hydrofurans 1, dihydro-3-furanone 2, and dioxanone 9
that form as single stereoisomers.
O
O
O
Ph
Ph
a
b
Ph
O
Ph
Ph
O
O
Ph
1aa
2
9
Acknowledgment
Scheme 3 Conversion of methylenetetrahydrofuran 1aa into fura-
none 2 and dioxanone 9. Reagents and conditions: (a) O3, CH2Cl2,
–78 °C; 60%; (b) 3-chloroperbenzoic acid, Li2CO3, CH2Cl2, 0–25 °C,
51%.
We are grateful to Dr. Andreas Hohmann for preliminary experi-
ments.
References and Notes
competing reactions with different rate constants. This
easily explains that products from an individual bro-
moalkene 3 and different boronic acids 4 form in not equal
diastereomeric ratios (entries 1–6 and 7–10). If, for exam-
ple, the reaction of the boronic acid with trans-8 is slow
compared with that of cis-8, the former may undergo b-
elimination to a higher degree, so that a higher amount of
the cis-configured Heck–Suzuki product results (entries 3
vs. 2 or 8 vs. 9).
(1) (a) Tietze, L.-F.; Brasche, G.; Gericke, K. M. Domino
Reactions in Organic Synthesis; Wiley-VCH: Weinheim,
2006. (b) Tietze, L. F. Chem. Rev. 1996, 96, 115.
(2) For a review, see: (a) Negishi, E.-I.; Copéret, C.; Ma, S.;
Liou, S.-Y.; Liu, F. Chem. Rev. 1996, 96, 365. For early
examples, see: (b) Narula, C. K.; Mak, K. T.; Heck, R. F.
J. Org. Chem. 1983, 48, 2792. (c) Shi, L.; Narula, C. K.;
Mak, K. T.; Kao, L.; Xu, Y.; Heck, R. F. J. Org. Chem. 1983,
48, 3894. (d) Grigg, R.; Stevenson, P.; Worakun, T. J.
Chem. Soc., Chem. Commun. 1984, 1073. (e) Grigg, R.;
Stevenson, R.; Worakun, T. Tetrahedron 1988, 44, 2033.
(f) Negishi, E.; Tour, J. M. J. Am. Chem. Soc. 1985, 107,
8289.
(3) Trapping by reduction: (a) Trost, B. M.; Fleitz, F. J.;
Watkins, W. J. J. Am. Chem. Soc. 1996, 118, 5146.
(b) Ojima, I.; Donovan, R. J.; Shay, W. R. J. Am. Chem. Soc.
1992, 114, 6580. (c) Oh, C. H.; Rhim, C. Y.; Kang, J. H.;
Kim, A.; Park, B. S.; Seo, Y. Tetrahedron Lett. 1996, 37,
8875. (d) Kulagowski, J. J.; Curtis, N. R.; Swain, C. J.;
Williams, B. J. Org. Lett. 2001, 3, 667.
PdXLn
trans-1
O
R1
O
R1
PdXLn
7a
7b
trans-8
cis-8
cis-1
PdXLn
O
O
R1
PdXLn
R1
(4) Trapping by Stille coupling: (a) Yamada, H.; Aoyagi, S.;
Kibayashi, C. Tetrahedron Lett. 1997, 38, 3027.
Scheme 2 Transition-state models 7a and 7b and rationale of the
diastereoselective formation of trans-1 in the Heck–Suzuki reaction
(b) Negishi, E.; Noda, Y.; Lamaty, F.; Vawter, E. J.
Tetrahedron Lett. 1990, 31, 4393. (c) Luo, F.-T.; Wang,
R.-T. Tetrahedron Lett. 1991, 32, 7703. (d) Salem, B.;
Delort, E.; Klotz, P.; Suffert, J. Org. Lett. 2003, 5, 2307.
(5) Trapping by Sonogashira coupling: (a) D’Souza, D. M.;
Rominger, F.; Müller, T. J. J. Angew. Chem. Int. Ed. 2005,
44, 153; Angew. Chem. 2005, 117, 156. (b) Teplý, F.; Stará,
I. G.; Starý, I.; Kollárovič, A. Šaman, D.; Fiedler, P.
Tetrahedron 2002, 58, 9007.
(6) Trapping with organozinc reagents: (a)Burns, B.;Grigg, R.;
Sridharan, V.; Stevenson, P.; Sukirthalingam, S.; Worakun,
T. Tetrahedron Lett. 1989, 30, 1135. (b) Luo, F.-T.; Wang,
R.-T. Heterocycles 1990, 31, 2181. (c) Wang, R.-T.; Chou,
F.-L.; Luo, F.-T. J. Org. Chem. 1990, 55, 4846.
In order to demonstrate the synthetic significance of the
diastereoselective domino Heck–Suzuki reaction, it was
applied to enantiomerically pure ether (R)-3. As a result,
methylenetetrahydrofuran (2R,3R)-1aa was obtained as a
single stereoisomer (Table 2, entry 12). The exocyclic
double bond can be used for further transformations
(Scheme 3). Thus, ozonolysis of (2R,3R)-1aa gave 3-
furanone 2 in 60% yield. Its CD spectrum displays a char-
acteristic positive Cotton effect at 289 nm. When ketone
2 was submitted to a Baeyer–Villiger oxidation with 3-
chloroperbenzoic acid, dioxanone 9 resulted in a com-
pletely regioselective manner.13 It can be considered as a
protected form of a 2,3-disubstituted 3-hydroxypropanoic
acid, which, under retrosynthetic aspects, originates from
a C-1–C-2 carbon–carbon bond disconnection and a C-1¢–
C-2¢ disconnection of the side chain attached in 2-posi-
tion, thus being complementary to the aldol transform.14
The heterocyclic derivatives 2 and 9 are also obtained as
pure enantiomers and diastereomers.
(7) For a related nickel-catalyzed cyclization–carbonylation,
see: Delgado, A.; Llebaria, A.; Camps, F.; Moreto, J. M.
Tetrahedron Lett. 1994, 35, 4011.
(8) (a) Oh, C. H.; Sung, H. R.; Park, S. J.; Ahn, K. H. J. Org.
Chem. 2002, 67, 7155. (b) Couty, S.; Liegault, B.; Meyer,
C.; Cossy, J. Org. Lett. 2004, 6, 2511. (c) Couty, S.; Meyer,
C.; Cossy, J. Tetrahedron Lett. 2006, 47, 767. (d) Yanada,
R.; Obika, S.; Inokuma, T.; Yanada, K.; Yamashita, M.;
Ohta, S.; Takemoto, Y. J. Org. Chem. 2005, 70, 6972.
(e) Cheung, W. S.; Patch, R. J.; Player, M. R. J. Org. Chem.
2005, 70, 3741. (f) Yu, H.; Richey, R. N.; Carson, M. W.;
Coghlan, M. J. Org. Lett. 2006, 8, 1685. (g) Arthuis, M.;
Pontikis, R.; Florent, J.-C. Tetrahedron Lett. 2007, 48,
6397. (h) Marchal, E.; Cupif, J.-F.; Uriac, P.; van de Weghe,
P. Tetrahedron Lett. 2008, 49, 3713. (i) Guo, L.-N.; Duan,
X.-H.; Hu, J.; Bi, H.-P.; Liu, X.-Y.; Liang, Y.-M. Eur. J.
Org. Chem. 2008, 1418.
In summary, a protocol for a diastereoselective cycliza-
tion has been elaborated that leads to the formation of
novel methylenetetrahydrofurans15,16 from readily avail-
able starting materials, the allylic alcohols 6 and commer-
cially available dibromide 5. For the first time, a domino
Heck–Suzuki reaction has been applied that permits to
build up contiguous stereogenic carbon centers in the
Synlett 2009, No. 6, 968–972 © Thieme Stuttgart · New York

LETTER
Synthesis of Substituted Methylenetetrahydrofurans
971
(9) For overviews on the synthesis of tetrahydrofurans, see:
(a) Kröper, H. In Houben Weyl, 4th ed., Vol. 3; Müller, E.,
Ed.; Thieme: Stuttgart, 1965, 517. (b) Eberbach, W. In
Houben-Weyl, Vol. E6a; Kreher, R. P., Ed.; Thieme:
Stuttgart, 1994, 16. For different approaches to racemic 2,3-
disubstituted-4-methylenetetrahydrofurans, see: (c) Jana,
S.; Guin, C.; Roy, S. C. Tetrahedron Lett. 2005, 46, 1155.
(d) Ranu, B. C.; Mandal, T. Tetrahedron Lett. 2006, 79,
2859. (e) Tang, F.; Chen, C.; Moeller, K. D. Synthesis 2007,
3411.
(10) Herrmann, W. A.; Broßmer, C.; Öfele, K.; Reisinger, C.-P.;
Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1844; Angew. Chem. 1995, 107, 1989.
(11) (a) Frauenrath, H.; Philipps, T. Liebigs Ann. Chem. 1985,
1951. (b) Hartung, J.; Kneuer, R. Eur. J. Org. Chem. 2000,
1677.
H, CH2Ar), 2.98 (m, 1 H, 3-H), 4.50 (m, 1 H, 5-H), 4.64 (m,
1 H, 5-H), 4.65 (d, J = 6.0 Hz, 1 H, 2-H), 4.84 (d, J = 1.89
Hz, 1 H, C=CHH), 5.01 (d, J = 1.58 Hz, 1 H, C=CHH), 7.09
(d, J = 8.20 Hz, 2 H, m-ArCl), 7.28 (m, 7 H, arom. H). 13
C
NMR (125 MHz, CDCl3): d = 22.02, 27.96, 31.83, 35.68,
69.25, 86.53, 101.37, 124.51, 127.04, 129.65, 130.51,
141.74, 154.69. GC-MS (tR = 10.70 min): m/z (%) = 284 (5)
[M]+, 158 (72), 143 (100).
Compound 1ad: 1H NMR (500 MHz, CDCl3): d = 0.81 (m,
3 H, CH3), 1.21 (m, 10 H, CH2), 1.87 (m, 1 H, CHCHH),
2.33 (m, CHCHH), 2.58 (m, 1 H, 3-H), 4.35 (dq, Jd = 13.24
Hz, Jq = 2.21 Hz, 1 H, 5-H), 4.54 (m, 1 H, 5-H), 4.92 (q,
J = 2.05 Hz, 1 H, 2-H), 5.27 (m, 2 H, C=CHH, CH=CH),
5.41 (m, 2 H, C=CHH, CH=CH), 7.27 (d, J = 4.10 Hz, 2 H,
o-arom. H), 7.38 (t, J = 7.72 Hz, 2 H, m-arom. H), 7.53 (dd,
J = 1.10, 8.35 Hz, 1 H, p-arom. H). 13C NMR (125 MHz,
CDCl3): d = 15.0, 21.2, 24.4, 27.9, 31.5, 33.1, 34.7, 58.1,
70.5, 90.3, 109.6, 125.0, 126.1, 127.6, 129.2, 130.0, 136.5,
149.9. GC-MS (tR = 10.70 min): m/z (%) = 284 (32) [M]+,
269 (38), 172 (45), 158 (100).
(12) The latter reaction predominates, when (8S,9E,11S)-10-
bromo-8-methyl-11-phenyl-2,5,7,12-tetraoxopentadeca-
9,14-diene is submitted to the protocol: Hohmann, A.
Dissertation; University of Düsseldorf: Germany, 2006.
(13) Confer: Trost, B. M.; Yang, H.; Probst, G. D. J. Am. Chem.
Soc. 2004, 126, 48.
Compound 1ae: 1H NMR (500 MHz, CDCl3): d = 1.25 (d,
J = 6.31 Hz, 6 H, CH3), 1.29 (m, 2 H, CH2Ph), 1.38 (m, 1 H,
CHCH3), 2.94 (q, J = 7.25 Hz, 1 H, 3-H), 4.75 (m, 2 H, 5-H),
5.13 (d, J = 10.40 Hz, 1 H, 2-H), 5.27 (t, J = 1.42 Hz 1 H,
C=CHH), 5.30 (t, J = 1.42 Hz, 1 H, C=CHH), 7.25 (m, 5 H,
arom. H). 13C NMR (125 MHz, CDCl3): d = 22.02, 27.96,
31.83, 35.68, 69.25, 86.53, 101.37, 124.51, 127.04, 129.65,
130.51, 141.74, 154.69. GC-MS (tR = 10.70 min): m/z (%) =
165 (10) [M – C4H3]+, 139 (12), 123 (85), 97 (100).
Compound 1ba: 1H NMR (500 MHz, CDCl3): d = 0.93 (d,
J = 6.31 Hz, 3 H, CH3), 2.63 (m, 2 H, CH2Ph), 2.87 (m, 1 H,
3-H), 3.68 (quint, J = 6.46 Hz, 1 H, 2-H), 4.21 (dq, Jd = 13.24
Hz, Jq = 2.21 Hz, 1 H, 5-H), 4.35 (dt, Jd = 13.24 Hz, Jt = 1.42
Hz, 1 H, 5-H), 4.79 (q, J = 2.21 Hz, 1 H, C=CHH), 4.78 (q,
(14) (a) Corey, E. J.; Cheng, X. M. The Logic of Chemical
Synthesis; Wiley: New York, 1989. (b) Modern Aldol
Reactions; Mahrwald, R., Ed.; Wiley-VCH: Weinheim,
2004. (c) For a different approach to b-hydroxycarboxylic
acids via diastereoselective conversions of dioxanones, see:
Herradón, B.; Seebach, D. Helv. Chim. Acta 1989, 72, 690.
(15) Typical Procedure for the Preparation of Compound 1aa
To a stirred solution of 3a (0.253 g, 1.00 mmol) in EtOH (10
mL) under an argon atmosphere were added PhB(OH)2 (4a,
0.183 g, 1.50 mmol), Cs2CO3 (0.489 g, 1.5 mmol), Pd(OAc)2
(5.5 mg, 0.0025 mmol), and tri-o-tolylphosphane (5.1 mg,
0.0025 mmol). After stirring for 24 h at 25 °C, the solvent
was removed in a rotary evaporator. The residue was
dissolved in a mixture of Et2O (40 mL) and deionized H2O
(40 mL). The aqueous layer was separated and extracted
with three 20 mL portions of Et2O. The combined organic
layers were dried with anhyd MgSO4, and the solvent was
evaporated under reduced pressure. The yellow-brown crude
product was purified by column chromatography on SiO2
(hexane–EtOAc, 6:1) to give yellowish, oily 1aa (0.153 g,
61%).
J = 2.05 Hz, 1 H, C=CHH), 7.17 (m, 5 H, arom. H). 13
C
NMR (125 MHz, CDCl3): d = 15.87 (cis), 20.30 (trans),
38.58, 51.75, 70.78, 81.29, 104.65, 115.70, 126.64, 128.81,
129.44, 130.05, 140.08, 152.57. GC-MS [tR = 10.70
min(trans), 6.71 min(cis)]: m/z (%) = 188 (5) [M]+, 143 (17),
129 (100), 97 (70).
Compound 1bb: 1H NMR (500 MHz, CDCl3): d = 0.96
(d, J = 6.31 Hz, 3 H, CH3), 2.41 (s, 3 H, SCH3), 2.58 (dd,
J = 14.03, 8.04 Hz, 2 H, CH2Ar), 2.81 (dd, J = 14.19, 6.13
Hz, 1 H, 3-H), 3.66 (quint, J = 6.38 Hz, 1 H, 2-H), 4.19 (q,
J = 2.21 Hz, 1 H, 5-H), 4.21 (q, J = 2.21 Hz, 1 H, 5-H), 4.78
(q, J = 2.36 Hz, 1 H, C=CHH), 4.87 (q, J = 2.21 Hz, 1 H,
C=CHH), 7.13 (m, 4 H, arom. H.). 13C NMR (125 MHz,
CDCl3): d = 11.12, 21.17, 38.03, 44.76, 70.85, 79.92,
114.87, 127.57, 128.73, 130.37, 138.39, 149.53. GC-MS
[tR = 10.70 min, 9.09 min(trans), 9.30 min(cis)]: m/z (%) =
234 (12) [M]+, 137 (100), 122 (8).
(16) Spectroscopic Data
Compound 1aa: 1H NMR (500 MHz, CDCl3): d = 2.38 (m,
2 H, CH2Ph), 2.93 (m, 1 H, 3-H), 4.41 (dq, Jd = 13.16 Hz,
Jq = 2.13 Hz, 1 H, 5-H), 4.54 (dt, Jd = 13.24 Hz, Jt = 1.66 Hz,
1 H, 5-H), 4.61 (d, J = 6.31 Hz, 1 H, 2-H), 4.75 (q, J = 2.36
Hz, 1 H, C=CHH), 4.90 (q, J = 2.05 Hz, 1 H, C=CHH), 7.19
(m, 10 H, arom. H). This cis-diastereomer differs in d = 4.63
(d, J = 1.90 Hz, 1 H, 2-H). 13C NMR (125 MHz, CDCl3):
d = 38.7, 53.0, 71.9, 86.4, 105.5, 115.7, 121.1, 126.6, 126.7,
128.0, 128.7, 129.6, 130.1, 139.7, 141.8, 151. 3. GC-MS (tR
= 9.71 min): m/z (%) = 250 (2) [M]+, 158 (43), 129 (100).
Compound (2R,3R)-1aa: [a]D20 –3.1 (c 1, CHCl3).
Compound 1ab: 1H NMR (500 MHz, CDCl3): d = 2.80 (m,
2 H, CH2Ar), 2.89 (m, 1 H, 3-H), 4.40 (m, 1 H, 5-H), 4.53
(m, 1 H, 5-H), 4.57 (d, J = 6.31 Hz, 1 H, 2-H), 4.76 (q,
J = 2.21 Hz, 1 H, C=CHH), 4.90 (q, J = 1.26 Hz, 1 H,
C=CHH), 7.22 (m, 9 H, arom. H). This cis-diastereomer
differs in d = 4.61 (d, J = 1.58 Hz, 1 H, 2-H). 13C NMR (125
MHz, CDCl3): d = 16.57, 32.94, 41.62, 71.83, 85.27, 105.52,
125.82, 126.77, 127.35, 128.73, 129.57, 130.08, 131.97,
130.06, 144.22, 152.99. GC-MS [tR = 12.06 min(trans); tR =
12.10 min(cis)]: m/z (%) = 296 (23) [M]+, 158 (50), 137
(100).
Compound 1bc: 1H NMR (500 MHz, CDCl3): d = 0.96 (d,
J = 6.31 Hz, 3 H, CH3), 2.41 (m, 1 H, CHHPh), 2.59 (m, 1
H, CHHPh), 2.81 (dd, J = 14.03, 6.46 Hz, 1 H, 3-H), 3.66
(quint, J = 6.31 Hz, 1 H, 2-H), 4.20 (dq, Jd = 13.24 Hz,
Jq = 2.21 Hz, 1 H, 5-H), 4.34 (dt, Jd = 13.03 Hz, Jt = 1.85 Hz,
1 H, 5-H), 4.76 (q, J = 2.21 Hz, 1 H, C=CHH), 4.78 (q,
J = 2.21 Hz, 1 H, C=CHH), 7.07 (m, 2 H, o-arom. H), 7.19
(m, 2 H, m-arom. H). 13C NMR (125 MHz, CDCl3):
d = 20.33, 37.92, 51.69, 70.81, 81.07, 104.89, 128.92,
130.77, 132.92, 138.55, 153.58. GC-MS [tR = 7.75
min(trans), 7.98 min(cis)]: m/z (%) = 222 (1) [M]+, 143 (70),
125 (100), 97 (75).
Compound 1ca: 1H NMR (500 MHz, CDCl3): d = 0.71 (d,
J = 6.94 Hz, 3 H, CH3), 0.78 (d, J = 6.94 Hz, 3 H, CH3), 1.48
(m, 1 H, CHCH3), 2.71 (m, 2 H, CH2Ph), 3.39 (m, 1 H, 3-H),
3.42 (m, 1 H, 2-H), 4.26 (m, 2 H, 5-H), 4.67 (d, J = 2.21 Hz,
Compound 1ac: 1H NMR (500 MHz, CDCl3): d = 2.90 (m, 2
Synlett 2009, No. 6, 968–972 © Thieme Stuttgart · New York

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M. Braun, B. Richrath
LETTER
1 H, C=CHH), 4.83 (d, J = 1.58 Hz, 1 H, C=CHH), 7.23 (m,
5 H, arom. H). 13C NMR (125 MHz, CDCl3): d = 17.93,
19.60, 31.63, 40.89, 48.30, 70.88, 89.81, 105.17, 126.57,
127.66, 128,68, 129.65, 140.31, 141.65, 152.27. GC-MS
[tR = 7.21 min(trans), 7.31 min(cis)]: m/z (%) = 216 (7) [M]+,
173 (15), 155 (45), 143 (45), 129 (85), 91 (100).
129.07, 129.76, 130.25, 131.88, 140.08, 142.04, 216.12.
GC-MS (tR = 9.91 min): m/z (%) = 252 (1) [M]+, 193 (10),
161 (100).
Compound 9: 1H NMR (500 MHz, CDCl3): d = 2.68 (m, 2 H,
CH2Ph), 3.28 (m, 1 H, 5-H), 4.55 (d, J = 10.09 Hz, 1 H, 6-
H), 5.18 (d, J = 5.67 Hz, 1 H, 2-H), 5.35 (d, J = 5.67 Hz,
1 H, 2-H), 7.22 (m, 10 H, arom. H). 13C NMR (125 MHz,
CDCl3): d = 33.30, 49.61, 80.49, 93.20, 127.34, 127.81,
129.11, 129.41, 129.76, 129.99, 137.93, 137.97, 170.04.
GC-MS (tR = 10.82 min): m/z (%) = 268 (13) [M]+, 238 (13),
193 (22) [M], 176 (72), 91 (100).
Compound 2: 1H NMR (500 MHz, CDCl3): d = 2.73 (m, 1 H,
3-H), 2.92 (m, 2 H, CH2Ph), 3.84 (d, J = 17.34 Hz, 1 H, 5-
H), 4.25 (d, J = 16.08 Hz, 1 H, 5-H), 4.73 (d, J = 9.48 Hz,
1 H, 2-H), 7.30 (m, 10 H, arom. H). 13C NMR (125 MHz,
CDCl3): d = 32.58, 56.36, 72.13, 84.00, 126.80, 127.07,
Synlett 2009, No. 6, 968–972 © Thieme Stuttgart · New York