Remote substituent effect favoring the formation of syn-adducts in the chelation controlled radical reactions of γ-benzyloxy-α-methylenecarboxylic acid esters

Article abstract of DOI:10.1016/S0040-4020(03)00421-6

The chelation controlled radical reactions of ethyl γ-benzyloxy-α-methylenecarboxylates bearing a bulky γ-substituent, such as CHMe₂, CHPh₂, c-C₆H₁₁ and CH(Ph)OTBDMS, with alkyl iodides gave the syn-adducts with high diastereoselectivities. However, the diastereoselectivity for the substrates bearing a γ-substituent CH(i-Pr)OTBDMS depended critically on the configuration of the substituent; the substrate bearing the OTBDMS group anti to the γ-benzyloxy group showed poor diastereoselectivity, but its diastereomer gave syn-adduct exclusively. The high syn-selectivitiy is referred to the H-atom transfer to the outside face of radical center in the sharply folded seven-membered chelate intermediate bearing the ethoxy group with Z-geometry. The corner flapping of the radical center atom of the global minimum energy conformer generates a local minimum conformer and the H-atom transfer to the outside face of the radical center of the newly formed structure gives the anti-adduct. The poor diastereoselectivity is due to the very small energy difference between the two conformers and consequently both the syn- and anti-adducts are yielded in nearly equal amounts.

Full text of DOI:10.1016/S0040-4020(03)00421-6

Tetrahedron 59 (2003) 3649–3663
Remote substituent effect favoring the formation of syn-adducts in
the chelation controlled radical reactions of
g-benzyloxy-a-methylenecarboxylic acid esters
*
Hajime Nagano, Hisako Ohkouchi and Tomoko Yajima
Department of Chemistry, Faculty of Science, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan
Received 4 February 2003; accepted 12 March 2003
Abstract—The chelation controlled radical reactions of ethyl g-benzyloxy-a-methylenecarboxylates bearing a bulky g-substituent, such as
CHMe2, CHPh2, c-C6H11 and CH(Ph)OTBDMS, with alkyl iodides gave the syn-adducts with high diastereoselectivities. However, the
diastereoselectivity for the substrates bearing a g-substituent CH(i-Pr)OTBDMS depended critically on the configuration of the substituent;
the substrate bearing the OTBDMS group anti to the g-benzyloxy group showed poor diastereoselectivity, but its diastereomer gave syn-
adduct exclusively. The high syn-selectivitiy is referred to the H-atom transfer to the outside face of radical center in the sharply folded
seven-membered chelate intermediate bearing the ethoxy group with Z-geometry. The corner flapping of the radical center atom of the global
minimum energy conformer generates a local minimum conformer and the H-atom transfer to the outside face of the radical center of the
newly formed structure gives the anti-adduct. The poor diastereoselectivity is due to the very small energy difference between the two
conformers and consequently both the syn- and anti-adducts are yieldedinnearly equalamounts. q 2003ElsevierScience Ltd. All rights reserved.
1. Introduction
g-hydroxy, g-methoxy and g-methoymethoxy esters with
methyl, ethyl or isopropyl iodide (R3¼Me, Et or i-Pr)
performed in the presence of Lewis acid gave syn-II
predominantly. In the addition of bulky tert-butyl radical,
however, the selectivity was reversed and the major product
was anti-II. In contrast to the substrates mentioned above,
g-benzyloxy esters I (R2¼Bn) showed syn-selectivity
irrespective of the bulk of alkyl iodides. Furthermore, we
have reported the origin of diastereoselectivities based on
the conformational analysis of the chelated radical inter-
mediates obtained by combination of CONFLEX and PM3
calculations.4d,6 The H-atom transfer reaction to the
sharply folded seven-membered chelate intermediate4d,7,8
bearing an ethoxy group with Z-geometry (dihedral angle
OvC–O–C of ester moiety: ca. 08) and CH2–R3 bond
parallel to the radical face occurs exclusively on the exposed
outside face of radical center to afford the highest syn-
selectivity.
During the past decade the stereochemical control of acyclic
radical reactions has been received considerable attention
and significant levels of diastereoselectivity have been
achieved when they adopt preferred conformations.1 The
use of Lewis acids offers the possibility to regulate
conformations and improve the stereoselectivity in acyclic
radical reactions.2 The bulk of substituents at the stereo-
genic center is, as well, an important factor controlling the
stereoselectivity as represented by the exocyclic effect in
1,2-asymmetric induction.3
We have recently reported the chelation-controlled 1,3-
asymmetric induction in the radical-mediated additions to
a-methylene-g-oxycarboxylic acid esters I (Scheme 1).4,5
The diastereoselectivity depended on the substituents R1
and R2 and the alkyl iodides R3I. The radical reactions of
Scheme 1. Radical reactions of a-methylene-g-oxycarboxylic acid esters I with alkyl iodides.
Keywords: radical reaction; 1,3-asymmetric induction; remote substituent effect; Lewis acid; CONFLEX-PM3.
*
Corresponding author. Tel.: þ81-3-5978-5348; fax: þ81-3-5978-5715; e-mail: nagano@cc.ocha.ac.jp
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00421-6

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H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
Scheme 2.
In the radical reactions of the steroidal g-benzyloxy-a-
methylenecarboxylic acid esters 1 and 2 with alkyl iodides
R3I performed in the presence of MgB2·OEt2, we have
observed that the diastereoselectivity depends on the
configuration at C-22 (i.e. the relative stereochemistry of
g- and d-substituents) and the bulk of R3 group
(Scheme 2).4c,d The results suggest that there may exist
stereochemical relationships between the g- and d-sub-
stituents that exert either complementary or opposing
influences on the facial bias of the radical center.
2. Results and discussion
2.1. Preparations of the substrates 9, 10 and 15–25
2.1.1. Preparation of 9, 10 and 15–17. Substrates 9 and 10
were prepared from octanal and ethyl 2-(bromomethyl)pro-
penoate following the procedures reported previously.4d
Substrates 15–17 were prepared from isobutyl aldehyde,
diphenylacetaldehyde,
and
cyclohexylcarbaldehyde,
respectively, following the procedures reported previous-
ly.4c
We report herein the effect of substituents at the d-position
and their configurations affecting the diastereoselectivity in
the chelation controlled radical addition reactions to
g-benzyloxy-a-methylenecarboxylic acid esters 8, 9 and
15–25 (Scheme 4 and Tables 1 and 2). This work was
performed to find out the radical reactions with reliably high
level of diastereoselectivity.
2.1.2. Preparation of 18 and 22. The alcohol 469 was
transformed to the silyl ether 47 with tert-butyldimethylsilyl
chloride and imidazole in 47% yield (Scheme 3). The
oxidative cleavage of the thioacetal 47 with N-bromo-
succimide in acetone gave the aldehyde 52 in 77% yield.10
The Reformatsky reaction of the aldehyde with ethyl
2-(bromomethyl)propenoate and zinc11 gave the hydroxy
esters 56 and 57 in 81% yield with 3.3:1 diastereomer
ratio.12 The benzylation of the alcohols 56 and 57 with
benzyl 2,2,2-trichloroacetimidate and trifluoromethane-
sulfonic acid gave the benzyl ethers 18 (87% yield) and
22 (62% yield), respectively.13
Table 1. Diastereoselectivity in the radical reactions of a-methylene-g-
benzyloxycarboxylic acid esters 9 and 10 with isopropyl or t-butyl iodide in
the presence of MgBr2·OEt2
Entry
Substrate
R0
Product
Yield (%)
syn:anti
1
2
3
4
9
9
10
10
i-Pr
t-Bu
i-Pr
t-Bu
11
12
13
14
88
99
100
97
.50:1
7.6:1
.50:1
9.2:1
2.1.3. Preparation of 19 and 23. Usual treatment of the
alcohol 489 with tert-butyldimethylsilyl chloride and
imidazole gave the silyl ether 49 in 99% yield. The

H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
3651
Table 2. Diastereoselectivity in the radical reactions of a-methylene-g-oxycarboxylic acid esters 15–25 with alkyl iodides R3I in the presence of MgBr2·OEt2
Entry
Substrate
R1
R2
Product
R3
Yield (%)
syn:antia
1
2
3
4
5
6
7
8
15
15
16
16
17
17
18
19
19
19
19
20
21
Me
Ph
Me
Ph
26
27
28
29
30
31
32
33
34
35
36
37
38
i-Pr
t-Bu
Et
i-Pr
Et
i-Pr
i-Pr
Me
Et
i-Pr
t-Bu
i-Pr
i-Pr
75
67
82
88
98
92
94
66
93
87
86
90
89
11:1
3.7:1
18:1
.50:1
17:1
40:1
1.2:1
19:1
35:1
–CH2(CH2)3CH2–
i-Pr
Ph
OTBDMS
OTBDMS
9
10b
11
12c
13d
50:1
.50:1
10:1
6.7:1
Ph
Ph
OBn
Ome
14
15
16
17
22
23
23
23
23
24
25
i-Pr
Ph
OTBDMS
OTBDMS
39
40
41
42
43
44
45
i-Pr
Me
Et
i-Pr
t-Bu
i-Pr
i-Pr
95
54e
95
87
90
90
89
.50:1
11.5:1
24:1
.50:1
.50:1
6.7:1
9:1
18
19c
20d
Ph
Ph
OBn
OMe
R3I (3 equiv.), n-Bu3SnH (2 equiv.), Et3B (1 equiv.), MgBr2·OEt2 (3 equiv.), CH2Cl2, 08C.
a
syn and anti denote the diastereomers bearing the CH2R3 group syn and anti to the benzyloxy group, respectively.
Without Lewis acid, 40% yield and syn/anti¼1:1.
b
c
d
e
Reaction performed for the mixture of 20 and 24.
Reaction performed for the mixture of 21 and 25.
Conversion yield 72%.
oxidative cleavage of the thioacetal 49 with N-bromo-
Reformatsky reaction of the aldehyde with ethyl 2-(bromo-
methyl)propenoate and zinc, followed by benzylation with
benzyl 2,2,2-trichloroacetimidate and trifluoromethane-
sulfonic acid gave the esters 21 and 25 as an inseparable
mixture in 25% yield (not optimized).11–13
succimide in acetone gave the aldehyde 53 in 89% yield.10
The Reformatsky reaction of the aldehyde with ethyl
2-(bromomethyl)propenoate and zinc11 gave the hydroxy
esters 58 and 59 in 89% yield with 1.7:1 diastereomer
ratio.12 The benzylation of the alcohols 58 and 59 with
benzyl 2,2,2-trichloroacetimidate and trifluoromethane-
sulfonic acid gave the benzyl ethers 19 (58% yield) and
23 (58% yield), respectively.13
2.2. Radical reactions
The reactions of g-benzyloxy-a-methylenecarboxylic acid
esters 9 and 10 bearing a bulky heptyl group on the g-carbon
atom with isopropyl iodide gave the syn-products
exclusively, but the syn-selectivities in the reactions with
tert-butyl iodide were lower probably because of the
shielding of the radical face by the bulky tert-butyl group
(Scheme 4 and Table 1). As we have previously reported,4d
the diastereoselectivity of cyclohexyl ester 10 was higher
than that of methyl ester 9 (entries 2 and 4).
2.1.4. Preparation of 20 and 24. The benzylation of the
alcohol 489 with benzyl bromide and sodium hydride gave
benzyl ether 50 in 73% yield. The benzyl ether was then
transformed into the aldehyde 54 in 71% yield. The
Reformatsky reaction of the aldehyde with ethyl 2-(bromo-
methyl)propenoate and zinc, followed by benzylation with
benzyl 2,2,2-trichloroacetimidate and trifluoromethane-
sulfonic acid gave the bisbenzyl ether 20 and 24 as an
inseparable mixture in 80% yield with 1.7:1 diastereomer
ratio.11–13
In the case of ester 15 where both the substituents R1 and R2
were small methyl group, however, their selectivities were
lower (Table 2, entries 1 and 2). For the substrates 16 and 17
with large d-substituents extremely high syn-selectivities
were attained (entries 3–6). We also examined the radical
reactions of the esters 18 and 22 bearing a bulky tert-
butyldimethylsiloxy and a smaller isopropyl groups at the
2.1.5. Preparation of 21 and 25. The methylation of the
alcohol 489 with methyl iodide and sodium hydride gave
methyl ether 51 in 70% yield. The ether 51 was then
transformed into the aldehyde 55 in quantitative yield. The

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H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
Scheme 3. Preparations of the a-methylene-g-oxycarboxylic acid esters 18–25. Reagents: (a) TBDMSCl, imidazole; (b) PhCH2Br, NaH, THF; (c) CH3I, NaH,
THF; (d), NBS, BaCO3, acetone; (e) BrCH2C(vCH2)CO2CH2CH3, Zn, THF–NH4Cl aq., (f) separation of diastereomers 56–59 using SiO2 chromatography;
(g) BnOC(vNH)CCl3, TfOH, cyclohexane–CH2Cl2.
d-position. The reaction of 18 showed no diastereo-
selectivity, but its diastereomer 22 gave the diastereomer
39 bearing the b-CH2CH(CH3)2 syn to the g-benzyloxy
group with excellent diastereoselectivity (entries 7 vs. 14).
The configuration of the d-substituents critically affects the
diastereoselectivity in the reactions of esters 18 and 22 as
well as the steroidal esters 1 and 2. The stereochemistry of
ester 22 with a smaller R1¼i-Pr and a larger R2¼OTBDMS
corresponds to that of 1 with a small R1¼Me and a large
R2¼St. The radical reactions of g-benzyloxy-a-methylene-
carboxylic acid esters 19 and 23 bearing two bulky groups
(R1¼phenyl and R2¼OTBDMS) at the d-carbon atom
showed extremely high syn-selectivities (entries 8–11 and
15–18). The reactions were syn-selective irrespective of the
bulk of alkyl R3 groups and the selectivity increased in the
order of Me, Et, i-Pr and t-Bu.
We carried out subsequently the radical reaction of the
inseparable mixture of bisbenzyloxy esters 20 and 24
(diastereomer ratio 1.7:1) with isopropyl iodide in the
presence of MgBr2·OEt2. Among the four possible dia-
stereomeric adducts 37 and 44, two diastereomers bearing
the isobutyl group syn to the benzyloxy group were obtained
preferentially (entries 12 and 19), but the syn-selectivities
Scheme 4.

H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
3653
Scheme 5. Determination of the stereochemistry of 34, 35 and 42. Reagents: (a) n-Bu4NF, THF; (b) p-TsOH, benzene; (c) H2, Pd–C, ethanol.
were lower than those of 19 and 23. The reaction of the
g-benzyloxy-d-methoxy esters 21 and 25 with isopropyl
iodide also gave predominantly syn adducts 38 and 45,
respectively (entries 13 and 20). In the case of the ester 25,
high syn-selectivity has been observed despite the presence
of a small methoxy group as R2 (entry 20). The five
membered chelate ring formed by the coordination of
d-benzyloxy (or d-methoxy) and g-benzyloxy groups to a
magnesium ion may attribute to the high syn-selectivities in
the reactions of esters 20, 21, 24 and 25.3 The methyl and
methoxymethyl ethers corresponding to the benzyl ethers 1,
2, 9 and 10 showed low syn-selectivities.4a,c,d This may be
due to the lack of an oxygen function on the d-carbon atom
necessary for the chelate ring formation mentioned above.
via g-hydroxy ester 67. The NOE difference spectra showed
the side chains are in anti relation, and consequently the 2,4-
syn stereochemistry of 34 was established without
ambiguity.
The transformation of the 4,5-syn diastereomer 42 into the
corresponding d-lactone 70 proceeded without epimeriza-
tion. The 2,4-syn stereochemistry of 42 was assigned by the
NOE difference spectra of 70.
The NOE experiments suggest that the lactone 65 may adopt
twist-chair conformation, and the lactones 66 and 70 may
adopt twist-boat conformations. The exhaustive searches of
low-energy conformers of the d-lactones were performed
with CONFLEX program using the MM2 force field for
energy minimization.6 The calculated global minimum
energy structures of 65 and 70 agree to the NOE
experiments. The calculations for 66 showed the presence
of a twist-boat conformer, which is 0.2 kcal mol21 higher in
energy than the global minimum structure adopting a twist-
chair conformation. The twist-boat conformer contributes
probably to the NOE enhancement of a-H (8%) observed by
irradiating d-H.
2.3. Determination of the diastereomer ratios of
products 11–14 and 26–45 and their stereochemistry
In order to determine the stereochemistry of the products,
we attempted initially the transformation of the adduct 35
into the d-lactone 65 via d-hydroxy ester 64 (Scheme 5).
However, the cleavage of the silyl ether with tetrabutyl-
ammonium fluoride gave the d-hydroxy ester 64
accompanying the d-lactone 65 and its epimer 66. Treat-
ment of the hydroxy ester 64 with p-toluenesulfonic acid
gave the lactones 65 and 66. The NOE difference spectra of
the d-lactones 65 and 66 established the 4,5-anti stereo-
chemistry of 35, but the distinction between the 2,4-syn and
2,4-anti diastereomers was not accomplished because of the
epimerization during lactonization.
The stereochemistries of the other products 11–14, 26–33,
36–41 and 43–45 were determined by comparing their
chemical shifts of 2-H and 3-H with those of 34, 35 and 42.
The diastereomer ratios of the products were determined by
the integrations of 2-H in the 1H NMR spectra. The methine
protons of 2,4-syn-adducts resonated in lower field than
those of 2,4-anti adducts.4
The adduct 34 was then transformed into the g-lactone 68

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H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
Scheme 6. The structures of chelated radical intermediates A–D and their diastereoselectivities.
2.4. Origin of the diastereoselectivity
Z-geometry in the global minimum energy0 conformer A-1
(Fig. 1, dihedral angle C1–C2–C10 –C2 ¼122.28). The
local minimum energy conformers B and C (R¼
CH(OTMS)i-Pr) were 3.8 and 2.9 kcal mol21 higher in
energy, respectively. The poor diastereoselectivities in the
reactions of 1 (Scheme 2, entry 1) and 2 have been referred
to the global minimum energy conformers C (R¼St–
CHMe) with E-geometry (calculated for ethyl esters),4d and
not to the conformers B (R¼St–CHMe) yielding anti
adduct. However, in the case of the ester 18 (entry 7), the
poor selectivity was found to be due to the low energy
conformer B (R¼CH(OTMS)i-Pr) being 0.3 kcal mol21
higher in energy than the global minimum energy conformer
A (R¼CH(OTMS)i-Pr).
The diastereoselectivities in the chelation-controlled radical
reactions of a-methylene-g-oxycarboxylic acid esters have
been rationalized based on the conformational analysis of
the chelated transition state models A–D using CONFLEX
and subsequent PM3 calculations (Scheme 6).4d,7,8 The
H-atom transfer reaction to the sharply folded seven-
membered chelate model A bearing an ethoxy group with
Z-geometry occurs on the exposed outside face of radical
center to afford the syn-selectivity,4d whereas the H-atom
transfer to the model B afford the anti-selectivity. The
intermediate model C bearing a methoxy group with
E-geometry shows poor diastereoselectivity due to the
shielding of the radical face by the methoxy group.4d
The PM3 calculations for the model of the ester 19 were
abandoned because the CONFLEX calculations gave too
many structures to be calculated. However, the confor-
mational analysis of the intermediate model A (R¼
CH(OTMS)Ph) for the methyl radical addition to the ester
23 was achieved (entry 15). The global energy minimum
conformer A-2 bearing the methoxy group with Z-geometry
(dihedral angle OvC–O–C of ester moiety:0.18) showed
that the H-atom transfer reaction proceeds exclusively on
the exposed outside face of radical center to afford the high
syn-selectivity (Fig. 1). The high diastereoselectivity in the
reaction of 23 is furthermore referred to the geometry of the
ethyl group attached to 0the radical center in A-2 (dihedral
angle C1–C2–C10 –C2 ¼246.98) where the ethyl group
does not shield the outside face of radical center, despite the
To account for the experimental observations mentioned
above, the conformational analyses of the radical inter-
mediate models in the methyl radical addition to 15, 18, 19,
22 and 23 were performed. To simplify the calculations, the
ethoxy and tert-butyldimethylsilyl groups were replaced
with methoxy and trimethylsilyl groups, respectively. In the
case of ester 15, the energy difference between the global
minimum energy conformer A (R¼CHMe2) and the local
1.0 kcal mol21 and the high syn selectivity (Table 2, entry
1) was attained. The extremely high syn-selectivity in the
reaction of the ester 22 with isopropyl iodide (entry 14) can
be referred to the geometry of the benzyl group shielding the
inside radical face as well to the methoxy group with
minimum energy conformer
B
(R¼CHMe2) was
Figure 1. Global minimum energy conformers of the chelated radical intermediate models A-1 and A-2.

H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
3655
presence of the local minimum energy conformer with
E-geometry C (R¼CH(OTMS)Ph; 0.7 kcal mol21 higher in
energy) inducing a poor diastereoselectivity.
(13), 158 (18), 130 (38), 127 (21), 105 (21) and 91 (100);
HRMS calcd for C20H30O3 [Mþ] 318.2195, found 318.2182.
4.2.2. g-Benzyloxy-amethylene ester 10. 1H NMR
(400 MHz) d 7.32–7.24 (5H, m, Ph), 6.21 (1H, d,
J¼1.6 Hz, vCHH), 5.60 (1H, d, J¼1.6 Hz, vCHH), 4.82
(1H, m, CO2CH), 4.54 (1H, d, J¼11.6 Hz, OCHHPh), 4.49
(1H, d, J¼11.6 Hz, OCHHPh), 3.57 (1H, m, CHOBn), 2.61
(1H, dd, J¼14.0, 6.8 Hz, CHHCHOBn), 2.48 (1H, dd,
J¼14.0, 6.0 Hz, CHHCHOBn), 1.83 (2H, m, CH2), 1.72
(2H, m, CH2), 1.53–1.26 (18H, m, (CH2)3 and (CH2)6CH3)
and 0.88 (3H, d, J¼6.8 Hz, (CH2)6CH3); 13C NMR
(100.4 MHz) d 166.5, 138.8, 138.1, 128.2, 127.7, 127.3,
126.9, 77.8, 72.8, 71.3, 37.4, 34.2, 31.9, 31.6, 29.7, 29.3,
25.5, 25.4, 23.7, 22.7 and 14.2; MS m/z 287 (Mþ2Oc-
C6H11, 6%), 239 (11), 220 (12), 219 (72), 205 (13), 198
(50), 176 (36), 158 (16), 130 (90), 127 (31), 116 (26), 107
(28), 92 (69) and 91 (100); HRMS calcd for C19H27O2
[Mþ2Oc-C6H11] 287.2011, found 287.2005.
The conformers B having a bulky R group (R¼St–CHMe,
n-C7H15, CHPh2, CHc-C6H11 or CH(OTMS)Ph) syn to the
benzyl group may be disfavored because of the steric
repulsion between the bulky substituents (R and BnO)
oriented upward.
3. Conclusion
In summary, we have shown that the chelation controlled
radical reactions of g-benzyloxy-a-methylenecarboxylic
acid esters bearing a bulky g-substituent14 with alkyl
iodides gave the adducts with high syn-selectivities. The
selectivity is referred to the H-atom transfer to the outside
face of radical center in the sharply folded seven-membered
chelate intermediate A bearing the ethoxy group with
Z-geometry. However, the reaction of 18 showed poor
diastereoselectivity despite the presence of a bulky g-sub-
stituent. For the compounds 1 and 2, the intermediate C
bearing the ethoxy group with E-geometry shields the
outside face of radical center and lowered the diastereo-
selectivity. In the reaction of 18, however, the energy
difference between the intermediates A and B was very
small, and consequently both the syn- and anti-adducts were
yielded in nearly equal amounts. The work described above
emphasizes the possibility for attaining reliable radical
mediated 1,3-asymmetric induction.
4.2.3. g-Benzyloxy-a-methylene ester 15. 1H NMR
(270 MHz) d 7.36–7.24 (5H, m, Ph), 6.20 (1H, d,
J¼2.0 Hz, vCHH), 5.64 (1H, d, J¼2.0 Hz, vCHH), 4.49
(2H, dd, J¼13.2, 11.5 Hz, PhCH2), 4.18 (2H, q, J¼7.3 Hz,
CO2CH2CH3), 3.40 (1H, m, 4-H), 2.57 (1H, dd, J¼13.9,
4.3 Hz, 3-H), 2.44 (1H, dd, J¼13.9, 7.6 Hz, 3-H), 1.90 (1H,
m, (CH3)2CH), 1.28 (3H, t, J¼7.3 Hz, CO2CH2CH3), 0.97
(3H, d, J¼4.3 Hz, CH3) and 0.95 (3H, d, J¼4.3 Hz, CH3);
13C NMR (67.8 MHz) d 167.15, 138.81, 138.07, 128.08,
127.61, 127.23, 126.94, 82.51, 72.15, 60.62, 34.01, 30.98,
18.23, 17.86 and 14.28; MS m/z 276 (Mþ, 7%), 233
(Mþ2C3H7, 36), 170 (49), 163 (100), 158 (59), 130 (76),
115 (40) and 91 (100); HRMS calcd for C17H24O3 [Mþ]
276.1726, found 276.1755.
4. Experimental
4.1. General
4.2.4. g-Benzyloxy-a-methylene ester 16. 1H NMR
(400 MHz) d 7.46–7.16 (13H, m, Ph), 6.94 (2H, m, Ph),
6.19 (1H, s, vCHH), 5.56 (1H, s, vCHH), 4.38 (1H, ddd,
J¼8.0, 8.0, 4.1 Hz, CHO), 4.27 (1H, d, J¼10.4 Hz,
OCHHPh), 4.19(2H, q, J¼7.3 Hz CO2CH2CH3), 4.04 (1H,
d, J¼8.0 Hz, CH), 3.99 (1H, d, J¼10.3 Hz, OCHHPh), 2.68
(1H, dd, J¼13.9, 4.8 Hz, CHHCvCH2), 2.43 (1H, dd,
J¼13.9, 8.1 Hz, CHHCvCH2) and 1.30 (3H, t, J¼7.3 Hz
CO2CH2CH3); 13C NMR (100.4 MHz) d 167.0, 142.3,
141.9, 138.0, 137.4, 129.2 (2C), 128.5 (2C), 128.4 (2C),
128.1 (2C), 128.0 (4C), 127.8, 127.3, 126.3, 126.3, 80.9,
73.3, 60.7, 57.2, 37.3 and 14.3; MS m/z 355 (Mþ2OEt,
1%), 233(49), 167(89) and 91(100); HRMS calcd for
C25H23O2 (Mþ2C2H5O) 355.1698, found 355.1728.
1H NMR spectra were recorded on a JEOL GSX-270
(270 MHz) or GSX-400 (400 MHz) spectrometer with
CDCl3 as the solvent and tetramethylsilane as an internal
standard. 13C NMR spectra were recorded on the instru-
ments operating at 67.9 or 100.5 MHz with CDCl3 as the
solvent and internal standard (d 77.0). Mass spectra (EIþ)
were obtained on a JEOL JMS-700 mass spectrometer.
Precoated Merck Kieselgel 60 F254 and Kanto silica gel 60
(spherical neutral) were used for thin layer chromatography
and flash chromatography, respectively. All the products
reported herein were colorless oils.
4.2. Preparation of the substrates 18–25
4.2.5. g-Benzyloxy-a-methylene ester 17. 1H NMR
(400 MHz) d 7.40–7.17 (5H, m, Ph), 6.20 (1H, s,
vCHH), 5.64 (1H, s, vCHH), 4.47 (2H, s, OCH2Ph),
4.18 (2H, q, J¼7.3 Hz, CO2CH2CH3), 3.38 (1H, ddd, J¼8.3,
3.4, 3.4 Hz, CHO), 2.61 (1H, dd, J¼14.2, 3.4 Hz,
CHHCvCH2), 2.44 (1H, dd, J¼14.2, 8.3 Hz,
CHHCvCH2), 1.83–1.68 (6H, m), 1.28 (3H, t, J¼7.3 Hz,
CO2CH2CH3) and 1.25–1.10 (5H, m); 13C NMR
(67.8 MHz) d 167.1, 138.8, 138.1, 128.1 (2C), 127.6 (2C),
127.2, 126.9, 82.2, 72.3, 60.6, 41.5, 34.4, 29.0, 28.4, 26.7,
26.5 (2C) and 14.3; MS m/z 316 (Mþ, 3%), 233(15),
203(89), 92(79) and 91(100); HRMS calcd for C20H28O3
[Mþ] 316.2038, found 316.2044.
4.2.1. g-Benzyloxy-a-methylene ester 9. 1H NMR
(400 MHz) d 7.34–7.24 (5H, m, Ph), 6.20 (1H, d,
J¼1.2 Hz, vCHH), 5.63 (1H, d, J¼1.2 Hz, vCHH), 4.52
(1H, d, J¼11.2 Hz, OCHHPh), 4.49 (1H, d, J¼11.2 Hz,
OCHHPh), 3.73 (3H, s, OCH3), 3.56 (1H, m, CHOBn), 2.60
(1H, dd, J¼14.0, 6.8 Hz, CHHCHOBn), 2.50 (1H, dd,
J¼14.0, 5.6 Hz, CHHCHOBn), 1.61–1.20 (12H, m,
(CH2)6CH3) and 0.88 (3H, d, J¼6.4 Hz, (CH2)6CH3); 13C
NMR (100.4 MHz) d 167.6, 138.7, 137.4, 128.1, 127.7,
127.3, 127.2, 77.6, 71.8, 51.8, 37.3, 34.1, 31.9, 29.7, 29.3,
25.4, 22.7 and 14.2; MS m/z 318 (Mþ, 1.8%), 278 (10), 277
(21), 219 (47), 212 (20), 195 (10), 181 (27), 180 (16), 179

3656
H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
4.2.6. 1,3-Dithiane 47. Following the procedures reported
by Hazra and co-workers,9 the alcohol 46 was prepared
from isobutyraldehyde and 1,3-dithiane in 95% yield. To a
cooled (08C) solution of the alcohol 46 (463 mg, 2.4 mmol)
and imidazole (1.09 g, 16.0 mmol) in dry DMF (10 cm3)
was added tert-butylchlorodimethylsillane (759 mg,
5.04 mmol), and the solution was stirred at room tempera-
ture overnight. After addition of chilled water, the product
was extracted with hexane. The organic layer was washed
with water and saturated brine, and then dried over
anhydrous sodium sulfate. The solvent was evaporated in
vacuo and the residue was chromatographed on silica gel
(eluent: hexane–ethyl acetate (30:1, v/v)) to give the silyl
(577 mg, 2.55 mmol) and iodomethane (0.8 cm3,
12.8 mmol). The mixture was stirred at 08C for 0.5 h and
then at room temperature for 0.5 h. Water was added and the
mixture was filtered. After evaporation, the crude product
was chromatographed on silica gel (eluent: hexane–ethyl
acetate (20:1, v/v)) to give the methyl ether 51 (426 mg,
70% yield). 1H NMR (400 MHz) d 7.41–7.35 (5H, m, Ph),
4.34 (1H, s, CH), 3.29 (3H, s, OCH3), 2.89–2.77 (4H, m,
2£SCH2), 2.06 (1H, m, CHH) and 1.88 (1H, m, CHH); 13
C
NMR (100.4 MHz) d 137.9, 128.5, 128.2, 127.3, 85.7, 57.5,
53.4, 30.5, 30.2 and 25.9.
4.2.10. Aldehyde 52. To a solution of the dithiane 47
(123 mg, 0.40 mmol) in acetone (8.0 cm3) was added
BaCO3 (1.11 g, 5.6 mmol) at 08C. A solution of N-bromo-
succinimide (170 mg, 0.96 mmol) in acetone (10 cm3) was
added and the mixture was stirred at room temperature for
1 h. An excess of N-bromosuccinimide was decomposed
with 10% aqueous sodium disulfite. After filtration and
concentration, sodium chloride was added. The product was
then extracted with ether. The organic layer was washed
with water and saturated brine, and then dried over
anhydrous sodium sulfate. After evaporation in vacuo, the
residue was chromatographed on silica gel (eluent: hexane–
ethyl acetate (30:1, v/v)) to give the aldehyde 52 (67 mg,
1
ether 47 (350 mg, 47% yield). H NMR (400 MHz) d 4.22
(1H, d, J¼4.6 Hz, SCHS), 3.56 (1H, t, J¼4.6 Hz, CHO),
2.85 (4H, m, 2£CH2S), 2.08 (1H, m, CHH), 2.01 (1H, m,
CHH), 1.86 (1H, m, CH(CH3)2), 0.97 (3H, d, J¼6.8 Hz,
CHCH3), 0.94 (3H, d, J¼6.8 Hz, CHCH3), 0.94 (9H, s,
C(CH3)3), 0.19 (3H, s, SiCH3) and 0.08 (3H, s, SiCH3); 13
C
NMR (100.4 MHz) d 79.3, 54.5, 32.5, 31.4, 30.9, 26.6, 26.2,
20.3, 18.6, 17.5, 23.6 and 23.9.
4.2.7. 1,3-Dithiane 49. Following the procedures reported
by Hazra and co-workers,9 the alcohol 48 was prepared
from benzaldehyde and 1,3-dithiane in 96% yield. To a
cooled (08C) solution of the alcohol 48 (163 mg,
0.72 mmol) and imidazole (307 mg, 4.51 mmol) in dry
DMF (3 cm3) was added tert-butylchlorodimethylsillane
(220 mg, 1.46 mmol), and the solution was stirred at room
temperature overnight. After addition of chilled water, the
product was extracted with hexane. The organic layer was
washed with water and saturated brine, and then dried over
anhydrous sodium sulfate. The solvent was evaporated in
vacuo and the residue was chromatographed on silica gel
(eluent: hexane–ethyl acetate (30:1, v/v)) to give the silyl
ether 49 (242 mg, 99% yield). 1H NMR (270 MHz) d 7.37–
7.24 (5H, m, Ph), 4.72 (1H, d, J¼7.2 Hz, CH–O), 4.26 (1H,
d, J¼7.2 Hz, CHS2), 2.84–2.72 (4H, m, SCH2), 2.04 (1H,
m, CHH), 1.83 (1H, m, CHH), 0.88 (9H, s, C(CH3)3), 0.08
(3H, s, SiCH3) and 20.15 (3H, s, SiCH3); 13C NMR
(67.8 MHz) d 141.5, 128.0, 127.9, 126.8, 77.9, 55.3, 30.2,
29.9, 25.95, 25.86, 18.4, 24.5 and 24.8.
1
77% yield). H NMR (400 MHz) d 9.59 (1H, d, J¼2.2 Hz,
CHvO), 3.72 (1H, dd, J¼4.9, 2.2 Hz, CHO), 2.03 (1H, m,
CH(CH3)2), 0.97 (3H, d, J¼7.1 Hz, CHCH3), 0.93 (9H, s,
C(CH3)3), 0.92 (3H, d, J¼6.4 Hz, CHCH3) and 0.06 (3H, s,
2£SiCH3); 13C NMR (100.4 MHz) d 204.8, 82.0, 31.5, 25.8,
18.8, 18.3, 16.9, 24.5 and 25.0.
4.2.11. Aldehyde 53. To a solution of the dithiane 49
(242 mg, 0.71 mmol) in acetone (13 cm3) was added BaCO3
(1.78 g, 9.0 mmol) at 08C. A solution of N-bromosuccini-
mide (289 mg, 1.62 mmol) in acetone (20 cm3) was added
and the mixture was stirred at room temperature for 1 h.
Work-up as described above gave the aldehyde 53 (158 mg,
1
89% yield). H NMR (270 MHz) d 9.51 (1H, d, J¼2.2 Hz,
CHvO), 7.40–7.25 (5H, m, Ph), 5.00 (1H, d, J¼2.2 Hz,
CH–O), 0.95 (9H, s, C(CH3)3), 0.12 (3H, s, SiCH3) and 0.05
(3H, s, SiCH3); 13C NMR (67.8 MHz) d 199.3, 136.5, 128.6,
128.3, 126.3, 80.0, 25.8, 18.4 and 24.7.
4.2.8. 1,3-Dithiane 50. To a suspension of sodium hydride
(60% dispersion in mineral oil; 112 mg, 2.8 mmol) in dry
THF (3.0 cm3) cooled to 08C were added benzyl bromide
(0.38 cm3, 3.2 mmol) and the alcohol 48 (343 mg,
1.50 mmol). The mixture was stirred at 08C for 0.5 h and
then at room temperature for 2 h. Water was added and the
mixture was filtered. After evaporation in vacuo, the residue
was chromatographed on silica gel (eluent: hexane–ethyl
acetate (10:1, v/v)) to give the benzyl ether 50 (345 mg,
4.2.12. Aldehyde 54. Treatment of the dithiane 50 (345 mg,
1.09 mmol) with BaCO3 (2.71 g, 13.8 mmol) and N-bromo-
succinimide (377 mg, 2.10 mmol) in acetone (65 cm3) as
described above gave the aldehyde 54 (174 mg, 71% yield).
1H NMR (400 MHz) d 9.62 (1H, d, J¼1.8 Hz, CHvO),
7.43–7.24 (10H, m, 2£Ph), 4.80 (1H, d, J¼1.8 Hz, CH),
4.66 (1H, d, J¼11.7 Hz, CHHPh) and 4.54 (1H, d,
J¼11.7 Hz, CHHPh); 13C NMR (100.4 MHz) d 198.2,
136.9, 133.8, 128.95, 128.85, 128.5, 128.0, 127.9, 127.5,
85.4 and 71.1.
1
73% yield). H NMR (400 MHz) d 7.40–7.25 (10H, m,
2£Ph), 4.57 (1H, d, J¼12.0 Hz, CHHPh), 4.49 (1H, d,
J¼7.2 Hz, CHOBn), 4.36 (1H, d, J¼7.2 Hz, SCHS), 4.28
(1H, d, J¼12.0 Hz, CHHPh), 2.88–2.71 (4H, m, 2£SCH2),
2.06 (1H, m, CHH) and 1.85 (1H, m, CHH); 13C NMR
(100.4 MHz) d 138.0, 137.4, 128.6, 128.3, 128.0, 127.7,
127.6, 82.6, 70.9, 53.1, 30.3, 30.0 and 25.9.
4.2.13. Aldehyde 55. Treatment of the dithiane 51 (408 mg,
1.70 mmol) with BaCO3 (4.52 g, 22.9 mmol) and N-bromo-
succinimide (727 mg, 4.08 mmol) in acetone (23 cm3) as
described above gave the aldehyde 55 (256 mg, 100%
yield). 1H NMR (400 MHz) d 9.60 (1H, d, J¼1.7 Hz,
CHvO), 7.44–7.36 (5H, m, Ph), 4.65 (1H, d, J¼1.7 Hz,
CH) and 3.45 (3H, s, OCH3); 13C NMR (100.4 MHz) d
198.1, 133.6, 129.0, 128.9, 127.4, 88.2 and 57.3.
4.2.9. 1,3-Dithiane 51. To a suspension of sodium hydride
(60% dispersion in mineral oil; 192 mg, 4.8 mmol) in dry
THF (25 cm3) cooled to 08C were added the alcohol 48

H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
3657
4.2.14. Compounds 56 and 57. To a solution of the
aldehyde 52 (423 mg, 1.7 mmol) in THF (2.0 cm3) were
SiCH3) and 20.14 (3H, s, SiCH3); 13C NMR (67.8 MHz) d
167.5, 141.1, 137.9, 128.0, 127.4, 127.0, 126.8, 78.0, 75.3,
60.8, 34.5, 25.9, 18.3, 14.2, 24.5 and 24.9; HRMS calcd
for C16H23O4Si [Mþ2C4H9] 307.1366, found 307.1358.
added
ethyl
2-(bromomethyl)propenoate
(656 mg,
3.4 mmol) and saturated aqueous ammonium chloride
(10 cm3). Zinc powder (302 mg, 4.6 mmol) was added at
08C, and the reaction mixture was stirred at this temperature
for 2 h. The product was extracted with ethyl acetate. The
organic layer was washed with water and saturated brine,
and then dried over anhydrous sodium sulfate. The solvent
was evaporated in vacuo and the residue was chromato-
graphed on silica gel (eluent: hexane–ethyl acetate (30:1,
v/v)) to give the hydroxy esters 56 and 57 (522 mg, 81%
yield) in a ratio of 3.3:1.
1
Less polar, minor diastereomer 59. H NMR (270 MHz) d
7.39–7.26 (5H, m, Ph), 6.19 (1H, d, J¼1.7 Hz, vCHH),
5.63 (1H, d, J¼1.3 Hz, CHH), 4.47 (1H, d, J¼5.9 Hz, CH–
O), 4.14 (2H, q, J¼7.0 Hz, CH2CH3), 3.83 (1H, m, CHOH),
2.77 (1H, d, J¼3.6 Hz, OH), 2.38 (1H, dd, J¼13.7, 2.5 Hz,
CHH), 2.24 (1H, dd, J¼13.7, 9.6 Hz, CHH), 1.23 (3H, t,
J¼7.0 Hz, CH3), 0.89 (9H, s, C(CH3)3), 0.05 (3H, s, SiCH3)
and 20.20 (3H, s, SiCH3); 13C NMR (67.8 MHz) d 167.1,
141.0, 137.5, 128.0, 127.7, 127.1, 126.6, 78.8, 74.9, 60.7,
35.4, 25.9, 18.2, 14.2, 24.4 and 25.0; HRMS calcd for
C16H23O4Si [Mþ2C4H9] 307.1366, found 307.1407.
More polar, major diastereomer 56. 1H NMR (400 MHz) d
6.25 (1H, d, J¼1.5 Hz, vCHH), 5.66 (1H, s, vCHH), 4.22,
(2H, m, CH2CH3), 3.78 (1H, m, CHOH), 3.45 (1H, dd,
J¼5.6, 3.7 Hz, CH–O), 2.61 (1H, br d, J¼14.2 Hz,
CHH(CvCH2), 2.35 (1H, dd, J¼14.2, 10.2 Hz,
CHHCvCH2), 2.23 (1H, d, J¼4.9 Hz, OH), 1.81 (1H, m,
CH(CH3)2), 1.30 (3H, t, J¼7.2 Hz, CH2CH3), 0.96 (3H, d,
J¼6.8 Hz, CH3), 0.93 (3H, d, J¼6.8 Hz, CH3), 0.93 (9H, s,
4.2.16. g-Benzyloxy-a-methylene ester 18. To a solution
of the alcohol 56 (139 mg, 0.46 mmol) in cyclohexane–
dichloromethane (2:1, v/v; 5 cm3) were added successively
benzyl 2,2,2-trichloroacetimidate (0.17 cm3) and trifluoro-
methanesulfonic acid (0.03 cm3). The reaction mixture was
stirred at room temperature for 0.5 h. After dilution with
diethyl ether, the solution was washed successively with
saturated aqueous sodium hydrogencarbonate, water and
brine, and dried over anhydrous sodium sulfate. The solvent
was evaporated in vacuo and the residue was chromato-
graphed on silica gel (eluent: hexane–ethyl acetate (30:1,
v/v) and then hexane–benzene (1:1)) to give 18 (155 mg;
87% yield). 1H NMR (400 MHz) d 7.37–7.24 (5H, m, Ph),
6.16 (1H, d, J¼1.5 Hz, vCHH), 5.62 (1H, s, CHH), 4.57
(1H, d, J¼11.8 Hz, CHHPh), 4.44 (1H, d, J¼11.8 Hz,
CHHPh), 4.15, (2H, m, CH2CH3), 3.57 (1H, m, CHOBn),
3.51 (1H, t, J¼5.2 Hz, CH–OTBDMS), 2.67 (1H, dd,
J¼14.4 and 2.2 Hz, CHH), 2.46 (1H, dd, J¼14.4, 9.6 Hz,
CHH), 1.88 (1H, m, CH(CH3)2), 1.25 (3H, t, J¼7.2 Hz,
CH2CH3), 0.97 (3H, d, J¼6.8 Hz, CH3), 0.93 (3H, d,
J¼6.6 Hz, CH3), 0.91 (9H, s, C(CH3)3), 0.04 (3H, s, SiCH3)
and 0.01 (3H, s, SiCH3); 13C NMR (100.4 MHz) d 167.2,
138.8, 138.3, 128.0, 127.5, 127.2, 126.6, 81.0, 72.4, 60.6,
33.0, 30.1, 26.1, 20.7, 18.7, 18.3, 14.3, 23.8 and 24.3;
HRMS m/z calcd for C20H31O4Si [Mþ2C4H9] 363.1991,
found 363.1991.
C(CH3)3), 0.11 (3H, s, SiCH3) and 0.09 (3H, s, SiCH3); 13
C
NMR (100.4 MHz) d 167.5, 138.1, 127.2, 80.3, 72.4, 60.9,
34.8, 30.7, 26.1, 20.0, 18.8, 18.5, 14.2, 23.7 and 24.2;
HRMS calcd for C13H25O4Si [Mþ2C4H9] 273.1523, found
273.1504.
1
Less polar, minor diastereomer 57. H NMR (400 MHz) d
6.16 (1H, d, J¼1.7 Hz, vCHH), 5.53 (1H, s, vCHH), 4.21,
(2H, m, CH2CH3), 3.78 (1H, m, CHOH), 3.38 (1H, dd,
J¼4.2, 3.2 Hz, CH–O), 2.47 (1H, d, J¼7.3 Hz, OH), 2.44
(1H, dd, J¼14.2, 3.1 Hz, CHHCvCH2), 2.36 (1H, dd,
J¼14.2, 9.0 Hz, CHHCvCH2), 1.84 (1H, m, CH(CH3)2),
1.29 (3H, t, J¼7.2 Hz, CH2CH3), 0.96 (3H, d, J¼6.8 Hz,
CH3), 0.94 (9H, s, C(CH3)3), 0.90(3H, d, J¼6.8 Hz, CH3),
0.12 (3H, s, SiCH3) and 0.11 (3H, s, SiCH3); 13C NMR
(100.4 MHz) d 166.9, 139.7, 125.1,78.9, 69.5, 60.7, 32.2,
30.9, 26.1, 18.7, 18.4, 18.0, 14.3, 23.8 and 24.1; HRMS
calcd for C13H25O4Si [Mþ2C4H9] 273.1523, found
273.1528.
4.2.15. Compounds 58 and 59. To a solution of the
aldehyde 53 (252 mg, 1.0 mmol) in THF (1.0 cm3) were
added
ethyl
2-(bromomethyl)propenoate
(320 mg,
4.2.17. g-Benzyloxy-a-methylene ester 19. The benzyl-
ation of alcohol 58 performed as described above gave the
benzyl ether 19 (216 mg, 58% yield). 1H NMR (400 MHz) d
7.38–7.08 (10H, m, 2£Ph), 6.18 (1H, d, J¼1.8 Hz,
vCHH), 5.60 (1H, s, CHH), 4.67 (1H, d, J¼5.4 Hz,
PhCH–O), 4.21 (1H, d, J¼11.0 Hz, CHHPh), 4.13 (1H, d,
J¼11.0 Hz, CHHPh), 4.09 (2H, m, CHHCH3), 3.67 (1H, m,
CH–OBn), 2.78 (1H, dd, J¼14.0, 1.1 Hz, CHH), 2.36 (1H,
dd, J¼14.0, 9.8 Hz, CHH), 1.20 (3H, t, J¼7.1 Hz, CH3),
0.91 (9H, s, C(CH3)3), 0.06 (3H, s, SiCH3) and 20.17 (3H,
s, SiCH3); 13C NMR (67.8 MHz) d 167.0, 142.3, 138.1,
137.8, 128.1, 128.0, 127.8, 127.3, 127.2, 127.1, 82.9, 76.9,
73.3, 60.5, 34.4, 25.9, 18.3, 14.2, 24.5 and 24.8; MS m/z
397 (Mþ2C4H9, 2%), 221 (74) and 91 (100); HRMS calcd
for C23H29O4Si [Mþ2C4H9] 397.1835, found 397.1838.
1.7 mmol) and saturated aqueous ammonium chloride
(5.0 cm3). Zinc powder (132 mg, 2.0 mmol) was added at
08C, and the reaction mixture was stirred at this temperature
for 2 h. The product was extracted with ethyl acetate. The
organic layer was washed with water and saturated brine,
and then dried over anhydrous sodium sulfate. The solvent
was evaporated in vacuo and the residue was chromato-
graphed on silica gel (eluent: hexane–ethyl acetate (30:1,
v/v)) to give the hydroxy esters 58 and 59 (263 mg, 89%
yield) in a ratio of 1.7:1.
More polar, major diastereomer 58. 1H NMR (270 MHz) d
7.34–7.23 (5H, m, Ph), 6.19 (1H, d, J¼1.7 Hz, vCHH),
5.58 (1H, d, J¼1.3 Hz, CHH), 4.66 (1H, d, J¼5.6 Hz, CH–
O), 4.17 (2H, m, CH2CH3), 3.83 (1H, m, CHOH), 2.60 (1H,
dd, J¼14.5, 1.7 Hz, CHH), 2.35 (1H, d, J¼4.2 Hz, OH),
2.26 (1H, dd, J¼14.5, 10.2 Hz, CHH), 1.26 (3H, t,
J¼7.0 Hz, CH3), 0.92 (9H, s, C(CH3)3), 0.08 (3H, s,
4.2.18. g-Benzyloxy-a-methylene esters 20 and 24.
Treatment of the aldehyde 54 (174 mg, 0.77 mmol) with
ethyl 2-(bromomethyl)propenoate (240 mg, 1.24 mmol) and

3658
H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
zinc powder (122 mg, 1.9 mmol) in THF (0.8 cm3)-
saturated aqueous ammonium chloride (4.0 cm3) as
described above gave an inseparable mixture of the hydroxy
esters 60 and 61 (220 mg, 84% yield), in a ratio of 1.7:1.
Treatment of the alcohols (137 mg, 0.40 mmol) with benzyl
2,2,2-trichloroacetimidate (0.16 cm3) and trifluoromethane-
sulfonic acid (0.025 cm3) as described above gave an
inseparable mixture of 20 and 24 (139 mg, 80% yield) in a
ratio of 1.7:1.
(Mþ2OCH3, 1%), 91 (100) and 84 (52); HRMS calcd for
C21H23O3 [Mþ2OC3] 323.1647, found 323.1604.
4.2.20. g-Benzyloxy-a-methylene ester 22. The benzyl-
ation of alcohol 57 performed as described above gave the
benzyl ether 22 in 62% yield. 1H NMR (400 MHz) d 7.37–
7.24 (5H, m, Ph), 6.20 (1H, d, J¼1.7 Hz, vCHH), 5.63 (1H,
s, CHH), 4.56 (1H, d, J¼11.6 Hz, CHHPh), 4.32 (1H, d,
J¼11.6 Hz, CHHPh), 4.12, (2H, m, CH2CH3), 3.62 (1H, m,
CHOBn), 3.53 (1H, dd, J¼7.2, 2.0 Hz, CH–OTBDMS),
2.52 (2H, m, CH2), 1.75 (1H, m, CH(CH3)2), 1.24 (3H, t,
J¼7.3 Hz, CH2CH3), 0.97 (3H, d, J¼6.6 Hz, CH3),
0.91(3H, d, J¼6.3 Hz, CH3), 0.91 (9H, s, C(CH3)3), 0.08
(3H, s, SiCH3) and 0.04 (3H, s, SiCH3); 13C NMR
(100.4 MHz) d 167.2, 138.6, 138.0, 128.0, 127.8, 127.5,
127.2, 79.3, 78.8, 71.9, 60.5, 33.2, 31.4, 26.2, 20.0, 19.6,
18.6, 14.3, 23.6 and 24.6; HRMS m/z calcd for
C20H31O4Si [Mþ2C4H9] 363.1991, found 363.2018.
1
Compound 20. H NMR (400 MHz) d 7.42–7.02 (15H, m,
3£Ph), 6.18 (1H, d, J¼1.5 Hz, vCHH), 5.60 (1H, s,
vCHH), 4.71–4.06 (7H, m, 2£PhCH2, CHOBn and
OCH2CH3), 3.82 (1H, m, CHOBn), 2.87 (1H, dd, J¼14.0,
3.2 Hz, CHHCvCH2), 2.47 (1H, dd, J¼14.0, 8.8 Hz,
CHHCvCH2) and 1.22 (3H, t, J¼7.2 Hz, CH3).
1
Compound 24. H NMR (400 MHz) d 7.42–7.02 (15H, m,
3£Ph), 6.11 (1H, d, J¼1.5 Hz, vCHH), 5.44 (1H, s,
vCHH), 4.71–4.06 (7H, m, 2£PhCH2, CHOBn and
OCH2CH3), 3.82 (1H, m, CHOBn), 2.39 (2H, m, CH2-
CvCH2) and 1.22 (3H, t, J¼7.2 Hz, CH3). 20 and 24. MS
m/z 323 (Mþ2OC7H7, 3%), 233 (99) and 91 (100); HRMS
calcd for C21H23O3 [Mþ2OC7H7] 323.1647, found
323.1674.
4.2.21. g-Benzyloxy-a-methylene ester 23. Treatment of
the alcohol 59 (268 mg, 0.79 mmol) with benzyl 2,2,2-
trichloroacetimidate (0.3 cm3) and trifluoromethanesulfonic
acid (0.05 cm3) as described above gave the benzyl ether 23
1
in 58% yield. H NMR (400 MHz) d 7.36–7.23 (10H, m,
2£Ph), 6.10 (1H, d, J¼1.7 Hz, vCHH), 5.50 (1H, s,
vCHH), 4.75 (1H, d, J¼5.6 Hz, PhCH–O), 4.66 (1H, d,
J¼11.5 Hz, CHHPh), 4.46 (1H, d, J¼11.5 Hz, CHHPh),
4.08 (2H, q, J¼7.1 Hz, CH2CH3), 3.77 (1H, ddd, J¼10.0,
5.6, 2.9 Hz, CH–OBn), 2.42 (1H, dd, J¼13.9, 2.9 Hz,
CHH), 2.08 (1H, dd, J¼13.9, 10.0 Hz, CHH), 1.21 (3H, t,
J¼7.6 Hz, CH3), 0.88 (9H, s, C(CH3)3), 0.02 (3H, s, SiCH3)
and 20.15 (3H, s, SiCH3); 13C NMR (67.8 MHz) d 166.9,
141.5, 138.5, 137.5, 128.1, 127.9, 127.7, 127.3, 127.2,
127.1, 81.9, 77.1, 73.6, 60.5, 34.2, 25.9, 18.3, 14.3, 24.6
and 24.8; MS m/z 397 (Mþ2C4H9, 7%) and 91 (100);
HRMS calcd for C23H29O4Si [Mþ2C4H9] 397.1835, found
397.1849.
4.2.19. g-Benzyloxy-a-methylene esters 21 and 25.
Treatment of the aldehyde 55 (256 mg, 1.7 mmol) with
ethyl 2-(bromomethyl)propenoate (520 mg, 2.7 mmol) and
zinc powder (292 mg, 4.5 mmol) in THF (1.7 cm3)-
saturated aqueous ammonium chloride (8.5 cm3) as
described above gave an inseparable mixture of the hydroxy
esters 62 and 63 (277 mg, 61% yield) in a ratio of 1.3:1.
Compound 62. 1H NMR (400 MHz) d 7.40–7.26 (5H, m, 2,
Ph), 6.20 (1H, s, vCHH), 5.64 (1H, m, CHH), 4.24–3.94
(4H, m, CHOH, CHOCH3 and CH2CH3), 3.25 (3H, s,
OCH3) and 1.24 (3H, t, J¼7.1 Hz, OCH2CH3).
4.3. Radical reactions
Compound 63. 1H NMR (400 MHz) d 7.40–7.26 (5H, m, 2,
Ph), 6.22 (1H, s, vCHH), 5.63 (1H, m, CHH), 4.24–3.94
(4H, m, CHOH, CHOCH3 and CH2CH3), 3.29 (3H, s,
OCH3) and 1.26 (3H, t, J¼7.1 Hz, OCH2CH3). The
benzylation of the mixture with benzyl 2,2,2-trichloro-
acetimidate (0.33 cm3) and trifluoromethanesulfonic acid
(0.05 cm3) as described above gave an inseparable mixture
of 21 and 25 in 25% yield (not optimized) and in a ratio of
1:1.3.
General procedure of the radical reactions performed in the
presence of MgBr2·OEt2. To a solution of a-methylene ester
(0.06 mmol) in 1.5 cm3 of dry CH2Cl2 was added MgBr2·-
OEt2 (0.18 mmol, 3 equiv.), and the mixture was stirred at
room temperature for 10 min. To the suspension cooled to
08C were added alkyl iodide R3I (0.18 mmol, 3 equiv.),
n-Bu3SnH (0.12 mmol, 2 equiv.) and Et3B (1.06 mol dm23
in hexane; 0.06 mmol, 1 equiv.). The mixture was stirred at
08C for 1 h. KF and water were added and the mixture was
stirred at room temperature for 3 h. After filtration, the
solvent was evaporated in vacuo. The residue was purified
by flash chromatography on silica gel [eluent: hexane–ethyl
acetate (20:1 or 10:1)] to give the inseparable diastereo-
meric adducts.
1
Compound 21. H NMR (400 MHz) d 7.38–7.05 (10H, m,
2£Ph), 6.19 (1H, s, vCHH), 5.62 (1H, s, CHH), 4.32 (1H,
d, J¼11.2 Hz, CHHPh), 4.21–4.08 (4H, m, CHHPh,
CHOCH3 and CH2CH3), 3.73 (1H, m, CHOBn), 3.25 (3H,
s, OCH3), 2.78 (1H, dd, J¼14.2, 3.4 Hz, CHHCvCH2),
2.46 (1H, m, CHHCvCH2) and 1.20 (3H, t, J¼7.2 Hz,
CH3).
General procedure of the radical reactions performed in the
absence of MgBr2·OEt2. The radical reaction was performed
as described above except for the absence of Lewis acid.
1
Compound 25. H NMR (400 MHz) d 7.38–7.05 (10H, m,
2£Ph), 6.19 (1H, s, vCHH), 5.61 (1H, s, CHH), 4.46 (1H,
d, J¼11.5 Hz, CHHPh), 4.38 (1H, d, J¼11.5 Hz, CHHPh),
4.21–4.08 (3H, m, CHOCH3 and CH2CH3), 3.80 (1H, m,
CHOBn), 3.29 (3H, s, OCH3), 2.46 (m, CH2) and 1.24 (3H,
t, J¼7.2 Hz, CH3). Compounds 21 and 25. MS m/z 323
4.3.1. Compound 11 (2,4-syn). 1H NMR (400 MHz) d
7.36–7.24 (5H, m, Ph), 4.49 (1H, d, J¼11.2 Hz, OCHHPh),
4.42 (1H, d, J¼11.2 Hz, OCHHPh), 3.56 (3H, s, CO2CH3),
3.31 (1H, m, CHOBn), 2.76 (1H, m, CHCO2CH3), 1.87 (1H,

H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
3659
m, CHHCHOBn), 1.63–1.16 (16H, m, CHHCHOBn,
(CH2)6CH3, CH2CH(CH3)2 and CH(CH3)2), 0.90 (3H, d,
J¼6.4 Hz, CH(CH3)2), 0.88 (3H, t, J¼6.4 Hz, CH3) and
0.87 (3H, d, J¼6.4 Hz, CH(CH3)2); 13C NMR (100.4 MHz)
d 177.1, 138.7, 128.2, 127.9, 127.4, 71.3, 51.3, 42.6, 39.9,
37.6, 34.0, 31.8, 29.9, 29.3, 26.2, 25.2, 23.0, 22.7, 22.3 and
14.2; MS m/z 362 (Mþ, 1.5%), 263 (9), 239 (28), 236 (17),
130 (59), 92 (11) and 91 (100); HRMS calcd for C23H38O3
(Mþ) 362.2821, found 362.2834.
71.6, 47.4, 40.6, 38.9, 34.2, 31.9, 31.8, 31.6, 31.0, 29.8,
29.6, 29.2, 25.5, 25.2, 23.9, 23.8 and 22.7.
Compound anti-14. 1H NMR (400 MHz) d 7.40–7.26 (5H,
m, Ph), 4.72 (1H, m, CO2CH), 4.51 (1H, d, J¼11.2 Hz,
OCHHPh), 4.47 (1H, d, J¼11.2 Hz, OCHHPh), 3.33 (1H,
m, CHOBn), 2.48 (1H, m, CHCO2), 1.85–1.15 (26H, m,
(CH2)5, CH2CHOBn, CH2t-Bu and (CH2)6CH3), 0.92 (3H, t,
J¼7.2 Hz, CH3) and 0.87(9H, s, C(CH3)3); 13C NMR
(100.4 MHz) d 176.8, 138.9, 128.1, 127.7, 127.3, 77.7, 72.2,
70.4, 46.7, 40.6, 39.1, 34.2, 31.9, 31.8, 31.6, 30.9, 29.8,
29.6, 29.3, 25.4, 25.2, 23.9, 23.8 and 22.7.
4.3.2. Compound 12 (2,4-syn and 24-anti). MS m/z 277
(Mþ2C7H15, 4%), 253 (11), 149 (7), 144 (36), and 91
(100); HRMS calcd for C17H25O3 (Mþ2C7H15) 277.1804,
found 277.1810.
4.3.5. Compound 26 (2,4-syn and 2,4-anti). MS m/z 277
(Mþ2i-Pr, 43%), 275 (5.5), 250 (11), 185 (25), 183 (12),
144 (82), 101 (52) and 91 (100); HRMS calcd for C17H25O3
[Mþ2i-Pr] 277.1804, found 277.1767.
1
Compound syn-12. H NMR (400 MHz) d 7.38–7.26 (5H,
m, Ph), 4.50 (1H, d, J¼11.2 Hz, OCHHPh), 4.43 (1H, d,
J¼11.2 Hz, OCHHPh), 3.59 (3H, s, CO2CH3), 3.27 (1H, m,
CHOBn), 2.75 (1H, m, CHCO2CH3), 1.76 (1H, m, CH2-
CHOBn), 1.62–1.16 (14H, m, CH2t-Bu and (CH2)6CH3),
0.92 (3H, d, J¼7.2 Hz, (CH2)6CH3) and 0.87 (9H, s,
C(CH3)3); 13C NMR (100.4 MHz) d 177.9, 138.7, 128.2,
127.9, 127.4, 77.4, 71.4, 51.4, 47.3, 40.0, 38.3, 34.0, 31.9,
30.9, 29.8, 29.4, 29.3, 25.2, 22.7 and 14.2.
Compound 2,4-syn-26. 1H NMR (270 MHz) d 7.28 (5H, m,
Ph), 4.53 (1H, d, J¼11.2 Hz, CHHPh), 4.44 (1H, d,
J¼11.2 Hz, CHHPh), 4.09 (2H, m, CH2CH3), 3.13 (1H,
m, CHO), 2.76 (1H, m, CHCO2Et), 1.97 (1H, m,
CH(CH3)2), 1.78 (1H, ddd, J¼13.9, 11.1, 2.7 Hz,
CHCHHCH), 1.54 (3H, m), 1.23 (3H, t, J¼7.0 Hz,
CH2CH3), 1.20 (1H, m), 0.92 (3H, d, J¼7.3 Hz, CHCH3),
0.90 (6H, d, J¼7.0 Hz, CHCH3) and 0.87 (3H, d, J¼7.3 Hz,
CHCH3); 13C NMR (67.8 MHz) d 176.6, 138.8, 128.2,
127.8, 127.3, 82.5, 72.2, 59.9, 42.8, 40.3, 33.9, 30.6, 26.2,
23.1, 22.2, 18.7, 17.2 and 14.4.
Compound anti-12. 1H NMR (400 MHz) d 7.38–7.26 (5H,
m, Ph), 4.51 (1H, d, J¼11.2 Hz, OCHHPh), 4.42 (1H CH2i-
Pr, d, J¼11.2 Hz, OCHHPh), 3.54 (3H, s, CO2CH3), 3.33
(1H, m, CHOBn), 2.55 (1H, m, CHCO2CH3), 1.93 (1H, m,
CH2CHOBn), 1.62–1.16 (14H, m, CH2t-Bu and
(CH2)6CH3), 0.89 (3H, d, J¼7.2 Hz, (CH2)6CH3) and 0.86
(9H, s, C(CH3)3); 13C NMR (100.4 MHz) d 177.9, 138.7,
128.1, 127.7, 127.3, 77.2, 70.5, 51.4, 46.7, 39.5, 39.1, 33.7,
31.8, 30.8, 29.8, 29.4, 29.2, 25.0, 22.7 and 13.7.
Compound 2,4-anti-26. 1H NMR (270 MHz) d 7.28 (5H, m,
Ph), 4.52 (1H, d, J¼11.2 Hz, CHHPh), 4.41 (1H, d,
J¼11.2 Hz, CHHPh), 4.09 (2H, m, CH2CH3), 3.20 (1H,
m, CHO), 2.67 (1H, m, CHCO2Et), 1.97 (1H, m,
CH(CH3)2), 1.78 (1H, ddd, J¼13.9, 11.1, 2.7 Hz,
CHCHHCH), 1.54 (3H, m), 1.20 (1H, m), 1.18 (3H, t,
J¼7.0 Hz, CH2CH3), 0.92 (3H, d, J¼7.3 Hz, CHCH3), 0.90
(6H, d, J¼7.0 Hz, CHCH3) and 0.86 (3H, d, J¼7.3 Hz,
CHCH3); 13C NMR (67.8 Hz) d 176.6, 139.9, 128.3, 127.6,
127.2, 82.5, 72.1, 69.9, 42.0, 38.3, 31.3, 30.3, 23.1, 22.0,
20.6, 17.2 and 14.1
4.3.3. Compound 13 (2,4-syn). 1H NMR (400 MHz) d
7.38–7.26 (5H, m, Ph), 4.77 (1H, m, CO2CH), 4.51 (1H, d,
J¼11.2 Hz, OCHHPh), 4.45 (1H, d, J¼11.2 Hz, OCHHPh),
3.33 (1H, m, CHOBn), 2.76 (1H, m, CHCO2), 1.86–1.15
(27H, m, CH2CHOBn, (CH2)5, CH2CH(CH3)2 and
(CH2)6CH3), 0.91 (3H, d, J¼6.8 Hz, CH(CH3)2), 0.88
(3H, d, J¼6.8 Hz, CH3) and 0.87 (3H, d, J¼6.8 Hz,
CH(CH3)2); 13C NMR (100.4 MHz) d 176.0, 138.9, 128.2,
127.8, 127.3, 77.9, 72.1, 71.6, 42.8, 40.4, 38.2, 34.3, 31.9,
31.8, 31.7, 29.8, 29.3, 26.2, 25.5, 25.2, 23.8, 23.2, 22.7, 22.1
and 14.2; MS m/z 331 (Mþ2C7H15, 19%), 250 (12), 249
(64), 220 (20), 205 (70), 198 (58), 116 (56) and 91 (100);
HRMS calcd for C21H31O3 (Mþ2C7H15) 331.2273, found
331.2287.
4.3.6. Compound 27 (2,4-syn and 2,4-anti). MS m/z 291
(Mþ2i-Pr, 51%), 289 (7), 227 (7), 199 823), 181 (17), 158
(88), 130 (15), 101 (74) and 91 (100); HRMS calcd for
C18H27O3 [Mþ2i-Pr,] 291.2029, found 291.1995.
Compound 2,4-syn-27. 1H NMR (400 MHz) d 7.30 (5H, m,
Ph), 4.54 (1H, d, J¼11.1 Hz, CHHPh), 4.47 (1H, d,
J¼11.1 Hz, CHHPh), 4.08 (2H, m, CH2CH3), 3.09 (1H,
m, CHO), 2.74 (1H, m, CHCO2Et), 1.96 (1H, m,
CH(CH3)2), 1.78 (2H, m, CHCH2CH), 1.49 (2H, m, CH2–
t-Bu), 1.23 (3H, t, J¼7.0 Hz, CH2CH3), 0.91 (3H, d,
J¼6.8 Hz, CHCH3), 0.89 (3H, d, J¼6.8 Hz, CHCH3) and
0.88 (9H, s, t-Bu); 13C NMR (67.8 MHz) d 174.4, 138.9,
128.2, 127.8, 127.3, 82.4, 72.3, 60.0, 47.5, 38.8, 36.4, 31.0,
30.5, 29.5, 18.6, 17.2 and 14.3.
4.3.4. Compound 14 (2,4-syn and 24-anti). MS m/z 353
(Mþ2Bn, 3%), 345 (10), 263 (24), 255 (17), 253 (53), 213
(14), 212 (96), 155 (28), 130 (94), 127 (12), 92 (24) and 91
(100); HRMS calcd for C22H41O3 (Mþ2Bn) 353.3056,
found 353.3075.
1
Compound syn-14. H NMR (400 MHz) d 7.40–7.26 (5H,
m, Ph), 4.74 (1H, m, CO2CH), 4.51 (1H, d, J¼11.2 Hz,
OCHHPh), 4.50 (1H, d, J¼11.2 Hz, OCHHPh), 3.31 (1H,
m, CHOBn), 2.72 (1H, m, CHCO2), 1.85–1.15 (26H, m,
(CH2)5, CH2CHOBn, CH2t-Bu and (CH2)6CH3), 0.90 (3H, t,
J¼7.2 Hz, CH3) and 0.88 (9H, s, C(CH3)3); 13C NMR
(100.4 MHz) d 176.8, 138.9, 128.2, 127.8, 127.3, 77.7, 72.2,
Compound 2,4-anti-27. 1H NMR (400 MHz) d 7.30 (5H, m,
Ph), 4.54 (1H, d, J¼11.1 Hz, CHHPh), 4.47 (1H, d,
J¼11.1 Hz, CHHPh), 4.03 (2H, m, CH2CH3), 3.14 (1H,
m, CHO), 2.52 (1H, m, CHCO2Et), 1.96 (1H, m,
CH(CH3)2), 1.78 (2H, m, CHCH2CH), 1.30 (2H, m,

3660
H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
CH2–t-Bu), 1.19 (3H, t, J¼7.0 Hz, CH2CH3), 0.91 (3H, d,
J¼6.8 Hz, CHCH3), 0.89 (3H, d, J¼6.8 Hz, CHCH3) and
0.83 (9H, s, t-Bu); 13C NMR (100 MHz) d 177.4, 138.9,
128.1, 127.5, 127.2, 81.8, 72.2, 60.0, 46.4, 39.2, 35.8, 30.9,
30.0, 29.5, 18.0, 17.2 and 14.2.
CHCH3); 13C NMR (100 MHz) d 176.6, 138.9, 128.1 (2C),
127.7 (2C), 127.3, 82.1, 72.4, 59.9, 42.8, 41.3, 40.3, 34.7,
29.2, 28.1, 26.8, 26.5, 26.4, 26.2, 23.0, 22.2 and 14.4; MS
m/z 315 (Mþ2OC2H5, 5%), 277(55), 269(7), 250(9),
223(35), 185(27), 144(95), 101(50), 92(39) and 91(100);
HRMS calcd for C21H31O2 (Mþ2OC2H5) 315.2324, found
315.2321.
4.3.7. Compound 28 (2,4-syn). 1H NMR (400 MHz) d 7.39
(2H, d, J¼7.1 Hz, Ph), 7.30–7.17 (11H, m, Ph), 7.01 (2H,
m, Ph), 4.26 (1H, d, J¼10.3 Hz, OCHHPh), 4.16–4.04 (4H,
m, CH, CHOBn and CH2CH3), 3.87 (1H, d, J¼10.3 Hz,
OCHHPh), 2.72 (1H, m, CHCO2Et), 1. 99 (1H, ddd,
J¼14.2, 11.5, 2.5 Hz, CHCHHCH), 1.50 (m, 2H), 1.25 (3H,
t, J¼7.1 Hz, CO2CH2CH3), 1.33–1.15 (3H, m) and 0.83
(3H t, J¼7.1 Hz, CH2CH3); 13C NMR (100 MHz) d 176.5,
142.4, 142.1, 138.1, 129.0 (2C), 128.5 (4C), 128.2 (2C),
128.1 (2C), 128.0 (2C), 127.4, 126.4, 126.3, 80.9, 73.6,
60.1, 57.3, 41.6, 36.6, 35.6, 20.5, 14.4 and 14.0; MS m/z 385
(Mþ2OC2H5, 1%), 263(16), 167(24), 109(80) and 91(100);
HRMS calcd for C27H29O2 (Mþ2OC2H5) 385.2167, found
385.2203.
4.3.11. Compounds 32 (2,4-syn and 2,4-anti). MS m/z 419
(Mþ2OC2H5, 42%), 407 (100), 299 (97), 271 (75), 187 (58)
and 91 (49); HRMS calcd for C25H43O3Si [Mþ2OC2H5]
419.2981, found 419.2982.
1
Compound 2,4-syn-32. H NMR (400 MHz) d 7.37–7.25
(5H, m, Ph), 4.64 (1H, d, J¼11.6 Hz, CHHPh), 4.37 (1H, d,
J¼11.6 Hz, CHHPh), 3.95 (2H, m, CH2CH3), 3.50 (1H, m,
CHO), 3.51 (1H, t, J¼7.3 Hz, CHCHOTBDMS), 3.45 (1H,
ddd, J¼9.8, 2.7, 1.9 Hz, CHO), 2.52 (1H, m, CHCO2Et),
1.73–1.50 (6H, m, CH2CH(CH3)2, CH2 and CH(CH3)2),
1.14 (3H, t, J¼7.1 Hz, CH2CH3), 0.96 (3H, d, J¼6.6 Hz,
CHCH3), 0.90 (9H, s, C(CH3)3), 0.88–0.79 (9H, CH(CH3)2
and CHCH3), 0.07 (3H, s, SiCH3) and 0.02 (3H, s, SiCH3).
4.3.8. Compound 29 (2,4-syn). 1H NMR (400 MHz) d 7.38
(2H, d, J¼8.5 Hz, Ph), 7.30- 7.17(11H, m, Ph), 7.01 (2H, dd,
J¼7.5, 2.4 Hz, Ph), 4.28 (1H, d, J¼10.0 Hz, OCHHPh),
4.17–4.00 (4H, m, CH, CHOBn and CH2CH3), 3.87 (1H, d,
J¼10.0 Hz, OCHHPh), 2.81 (1H, m, CHCO2Et), 1.97 (1H,
ddd, J¼14.0, 11.8, 2.2 Hz, CHCHHCH), 1.52–1.40 (3H,
m), 1.24 (3H, t, J¼7.1 Hz, CH2CH3), 1.09 (1H, m), 0.85
(3H, d, J¼6.3 Hz, CHCH3) and 0.78 (3H, d, J¼6.3 Hz,
CHCH3); 13C NMR (100 MHz) d 176.5, 142.4, 142.1,
138.1, 128.9 (2C), 128.5 (4C), 128.2 (2C), 128.1 (2C),
128.0 (2C), 127.4, 126.4, 126.3, 80.9, 73.6, 60.1, 57.3, 42.6,
39.9, 37.0, 26.0, 22.9, 22.2 and 14.4; MS m/z 399
(Mþ2OC2H5, 2%), 277(61), 167(93) and 91(100); HRMS
calcd for C28H31O2 (Mþ2OC2H5) 399.2324, found
399.2349.
1
Compound 2,4-anti-32. H NMR (400 MHz) d 7.37–7.25
(5H, m, Ph), 4.63 (1H, d, J¼11.2 Hz, CHHPh), 4.36 (1H, d,
J¼11.2 Hz, CHHPh), 4.05 (2H, m, CH2CH3), 3.50 (1H, m,
CHO), 3.50 (1H, t, J¼7.3 Hz, CHCHOTBDMS), 3.36 (1H,
td, J¼6.4, 1.7 Hz, CHO), 2.74 (1H, m, CHCO2Et), 2.00 (1H,
ddd, J¼13.5, 9.6, 2.3 Hz, CHCHHCH), 1.73–1.50 (5H, m,
CH2CH(CH3)2, CHH and CH(CH3)2), 1.20 (3H, t,
J¼7.1 Hz, CH2CH3), 0.95 (3H, d, J¼6.6 Hz, CHCH3),
0.89 (9H, s, C(CH3)3), 0.88–0.79 (9H, CH(CH3)2 and
CHCH3), 0.04 (3H, s, SiCH3) and 0.02 (3H, s, SiCH3).
1
4.3.12. Compound 33 (2,4-syn). H NMR (400 MHz) d
7.37–7.16 (10H, m, 2£Ph), 4.64 (1H, d, J¼5.3 Hz,
CHOTBDMS), 4.31 (1H, d, J¼10.5 Hz, CHHPh), 4.19
(1H, d, J¼10.5 Hz, CHHPh), 4.02 (2H, m, CH2CH3), 3.43
(1H, m, CHOBn), 2.57 (1H, m, CHCO2Et), 1.98 (1H, ddd,
J¼13.8, 11.5, 2.3 Hz, CHCHHCH), 1.63–1.41 (3H, m,
CHCHHCH and CH2), 1.16 (3H, t, J¼7.2 Hz, OCH2CH3),
0.89 (9H, s, C(CH3)3), 0.86 (3H, t, J¼7.2 Hz, CH3), 0.04
(3H, s, SiCH3) and 20.18 (3H, s, SiCH3); 13C NMR
(67.8 MHz) d 175.9, 142.3, 138.3, 128.12, 128.05, 127.8,
127.3, 127.2, 127.1, 82.8, 76.9, 73.4, 59.9, 43.5, 33.8, 26.5,
25.9, 18.3, 14.4, 11.8, 24.5 and 24.8; MS m/z 413
(Mþ2C4H9, 2%), 249 (47), 221 (43), 107 (69) and 91
(100); HRMS calcd for C24H33O4Si [Mþ2C4H9] 413.2148,
found 413.2143.
4.3.9. Compound 30 (2,4-syn). 1H NMR (400 MHz) d
7.38–7.24 (5H, m, Ph), 4.51 (1H, d, J¼11.0 Hz, CHHPh),
4.43 (1H, d, J¼11.0 Hz, CHHPh), 4.08 (1H, dq, J¼10.7,
7.1 Hz, CO2CHHCH3), 4.07 (1H, dq, J¼10.7, 7.1 Hz,
CO2CHHCH3), 3.12 (1H, ddd, J¼9.0, 5.1, 2.4 Hz,
CHOBn), 2.66 (1H, dddd, J¼11.3, 8.8, 5.4, 3.4 Hz,
CHCO2Et), 1.85 (1H, ddd, J¼14.1, 11.3, 2.4 Hz,
CHCHHCH), 1.76–1.51 (8H, m), 1.22 (3H, t, J¼7.1 Hz,
CH2CH3), 1.16–1.43 (6H, m), 1.07 (2H, m) and 0.89 (3H, t,
J¼7.1 Hz, CH2CH3), 13C NMR (100 MHz) d 176.4, 138.9,
128.2 (2C), 127.7 (2C), 127.3, 82.1, 72.3, 59.9, 42.0, 41.2,
35.8, 34.2, 29.2, 28.1, 26.8, 26.5, 26.4, 20.6, 14.4 and 14.1;
MS m/z 301 (Mþ2OC2H5, 5%), 263(54), 255(8), 236(8),
209(31), 171(24), 130(98), 101(28), 92(57) and 91(100);
HRMS calcd for C20H29O2 (Mþ2OC2H5) 301.2167, found
301.2145.
1
4.3.13. Compound 34 (2,4-syn). H NMR (400 MHz) d
7.37–7.17 (10H, m, 2£Ph), 4.63 (1H, d, J¼5.4 Hz,
CHOTBDMS), 4.31 (1H, d, J¼10.5 Hz, CHHPh), 4.19
(1H, d, J¼10.5 Hz, CHHPh), 4.02 (2H, m, CH2CH3), 3.41
(1H, m, CHOBn), 2.64 (1H, m, CHCO2Et), 1.98 (1H, ddd,
J¼13.9, 11.5, 2.5 Hz, CHCHHCH), 1.58 (2H, m, CH2), 1.36
(1H, m, CHCHHCH), 1.27 (2H, m, CH2), 1.15 (3H, t,
J¼7.1 Hz, CH3), 0.89 (9H, s, C(CH3)3), 0.87 (3H, t,
J¼7.3 Hz, CH3), 0.04 (3H, s, SiCH3) and 20.19 (3H, s,
SiCH3); 13C NMR (67.8 MHz) d 176.1, 142.3, 138.3,
128.13, 128.05, 127.8, 127.3, 127.2, 127.1, 82.9, 76.9, 73.5,
59.9, 41.7, 35.6, 34.2, 25.9, 20.6, 18.3, 14.4, 14.1, 24.5 and
24.8; MS m/z 469 (Mþ2CH3, 2%), 263 (66), 181 (98) and
1
4.3.10. Compound 31 (2,4-syn). H NMR (400 MHz) d
7.38–7.25 (5H, m, Ph), 4.52 (1H, d, J¼11.0 Hz, CHHPh),
4.45 (1H, d, J¼11.0 Hz, CHHPh), 4.09 (1H, dq, J¼10.8,
7.1 Hz, CHHCH3), 4.07 (1H, dq, J¼10.8, 7.1 Hz,
CHHCH3), 3.11 (1H, ddd, J¼6.8, 5.1, 2.4 Hz, CHOBn),
2.74 (1H, m, CHCO2Et), 1.82 (1H, ddd, J¼13.9, 11.0,
2.4 Hz, CHCHHCH), 1.76–1.63 (6H, m), 1.60–1.50 (3H,
m), 1.22 (3H, t, J¼7.3 Hz, CH2CH3), 1.19–1.01 (6H, m),
0.90 (3H, d, J¼6.3 Hz, CHCH3) and 0.87 (3H, d, J¼6.3 Hz,

H. Nagano et al. / Tetrahedron 59 (2003) 3649–3663
3661
1
91 (100); HRMS calcd for C28H41O4Si [Mþ2CH3]
469.2774, found 469.2799.
Compound 38. H NMR (400 MHz) d 7.35–7.17 (10H, m,
2£Ph), 4.37 (1H, d, J¼10.7 Hz, CHHPh), 4.21 (1H, d,
J¼10.7 Hz, CHHPh), 4.16 (1H, d, J¼5.4 Hz, CHOCH3),
4.04 (2H, m, CH2CH3), 3.47 (1H, m, CHOBn), 3.25 (3H, s,
OCH3), 2.73 (1H, m, CH–CO2Et), 1.96 (1H, ddd, J¼13.9,
11.5, 2.4 Hz, CHCHHCH), 1.15 (3H, t, J¼7.1 Hz,
CH2CH3), 0.87 (3H, d, J¼6.3 Hz, CH(CH3)2) and 0.84
(3H, d, J¼6.4 Hz, CH(CH3)2).
1
4.3.14. Compound 35 (2,4-syn). H NMR (400 MHz) d
7.34–7.17 (10H, m, 2£Ph), 4.63 (1H, d, J¼5.4 Hz,
CHOTBDMS), 4.31 (1H, d, J¼10.5 Hz, CHHPh), 4.17
(1H, d, J¼10.5 Hz, CHHPh), 4.02 (2H, m, CH2CH3), 3.40
(1H, m, CHOBn), 2.74 (1H, m, CHCO2Et), 1.96 (1H, ddd,
J¼13.9, 11.5, 2.3 Hz, CHCHHCH), 1.59–1.46 (3H, m,
CHCHHCH and CH2), 1.19 (1H, m, CH), 1.15 (3H, t,
J¼7.1 Hz, CH2CH3), 0.89 (9H, s, C(CH3)3), 0.87 (3H, d,
J¼6.6 Hz, CHCH3), 0.84 (3H, d, J¼6.4 Hz, CHCH3), 0.04
(3H, s, SiCH3) and 20.19 (3H, s, SiCH3); 13C NMR
(67.8 MHz) d 176.3, 142.3, 138.3, 128.2, 128.1, 127.8,
127.4, 127.2, 127.1, 82.9, 76.9, 73.5, 59.9, 42.5, 40.0, 34.7,
26.2, 25.9, 23.1, 22.1, 18.2, 14.3, 24.5 and 24.9; MS m/z
453 (Mþ2OC2H5, 2%), 277 (87), 221 (66) and 91 (100);
HRMS calcd for C28H41O3Si [Mþ2OC2H5] 453.2825,
found 453.2838.
1
Compound 45. H NMR (400 MHz) d 7.35–7.17 (10H, m,
2£Ph), 4.67 (1H, d, J¼10.7 Hz, CHHPh), 4.49 (1H, d,
J¼10.7 Hz, CHHPh), 4.18 (1H, d, J¼5.9 Hz, CHOCH3),
4.04 (2H, m, CH2CH3), 3.57 (1H, m, CHOBn), 3.26 (3H, s,
OCH3), 2.73 (1H, m, CH–CO2Et), 1.20 (3H, t, J¼7.1 Hz,
CH2CH3), 0.84 (3H, d, J¼6.4 Hz, CH(CH3)2) and 0.80 (3H,
d, J¼6.1 Hz, CH(CH3)2).
1
4.3.18. Compound 39 (2,4-syn). H NMR (400 MHz) d
7.34–7.17 (5H, m, Ph), 4.56 (1H, d, J¼11.2 Hz, CHHPh),
4.42 (1H, d, J¼11.2 Hz, CHHPh), 4.00 (2H, m, CH2CH3),
3.41 (1H, t, J¼5.0 Hz, CHOTBDMS), 3.24 (1H, ddd,
J¼10.5, 5.0, 2.0 Hz, CHOBn), 2.66 (1H, m, CHCO2Et),
1.86 (1H, ddd, J¼13.9, 10.8, 1.9 Hz, CHCHHCH), 1.75
(1H, m, CH(CH3)2), 1.59–1.43 (3H, m, CHH and CH2),
1.15 (3H, t, J¼7.2 Hz, CH2CH3), 0.88 (3H, d, J¼6.8 Hz,
CH3), 0.83 (9H, s, C(CH3)3), 0.82 (3H, d, J¼7.1 Hz, CH3),
0.79 (3H, d, J¼6.6 Hz, CH3), 20.04 (3H, s, SiCH3) and
20.08 (3H, s, SiCH3); MS m/z 419 (Mþ2OC2H5, 4%),271
(44), 187 (94) and 91 (100); HRMS calcd for C25H43O3Si
[Mþ2OC2H5] 419.2981, found 419.2982.
1
4.3.15. Compound 36 (2,4-syn). H NMR (400 MHz) d
7.37–7.18 (10H, m, 2£Ph), 4.61 (1H, d, J¼5.4 Hz,
CHOTBDMS), 4.35 (1H, d, J¼10.5 Hz, CHHPh), 4.15
(1H, d, J¼10.5 Hz, CHHPh), 4.00 (2H, q, J¼7.1 Hz,
CH2CH3), 3.35 (1H, m, CHOBn), 2.74 (1H, m, CHCO2Et),
1.98 (1H, ddd, J¼13.7, 11.5, 2.5 Hz, CHCHHCH), 1.77
(1H, dd, J¼13.9, 10.0 Hz, CHHt-Bu), 1.54 (1H, ddd,
J¼13.7, 9.8, 3.7 Hz, CHCHHCH), 1.19 (1H, dd, J¼13.9,
2.9 Hz, CHHt-Bu), 1.15 (3H, t, J¼7.1 Hz, CH2CH3), 0.89
(9H, s, C(CH3)3), 0.85 (3H, s, C(CH3)3), 0.04 (3H, s, SiCH3)
and 20.20 (3H, s, SiCH3); 13C NMR (67.8 MHz) d 177.0,
142.3, 138.4, 128.3, 128.1, 128.0, 127.8, 127.7, 127.3,
127.2, 127.1, 82.9, 76.9, 73.5, 60.0, 47.3, 38.7, 37.2, 31.0,
29.5, 25.9, 18.2, 14.2, 24.5 and 24.8; MS m/z 467
(Mþ2OC2H5, 2%), 221 (93) and 91 (100); HRMS calcd
for C29H43O3Si [Mþ2OC2H5] 467.2981, found 467.2994.
1
4.3.19. Compound 40 (2,4-syn). H NMR (400 MHz) d
7.40–7.24 (10H, m, 2£Ph), 4.77 (1H, d, J¼11.2 Hz,
CHHPh), 4.75 (1H, d, J¼5.1 Hz, CHOTBDMS), 4.55
(1H, d, J¼11.2 Hz, CHHPh), 4.06 (2H, s, J¼7.1 Hz,
CH2CH3), 3.51 (1H, ddd, J¼10.5, 5.4, 2.2 Hz, CHOBn),
2.52 (1H, m, CHCO2Et), 1.68 (1H, ddd, J¼13.7, 11.4,
2.2 Hz, CHCHHCH), 1.53 (1H, m, CHHCH3), 1.25 (1H, m,
CHHCH3), 1.22 (1H, m, CHCHHCH), 1.20 (3H, t,
J¼7.1 Hz, OCH2CH3), 0.87 (9H, s, C(CH3)3), 0.80 (3H, t,
J¼7.4 Hz, CH3), 0.02 (3H, s, SiCH3) and 20.15 (3H, s,
SiCH3); 13C NMR (67.8 MHz) d 175.9, 141.3, 138.6, 128.2,
128.1, 127.7, 127.5, 127.2, 127.0, 81.9, 76.3, 73.8, 59.9,
43.5, 33.4, 26.3, 25.89, 25.88, 18.2, 14.4, 11.9, 24.7 and
24.9; MS m/z 425 (Mþ2OC2H5, 3%), 413 (4), 249 (58),
221 (51), 121 (56) and 91 (100); HRMS calcd for
C26H37O3Si [Mþ2OC2H5] 425.2512, found 425.2495.
4.3.16. Compounds 37 (2,4-syn) and 44 (2,4-syn). MS m/z
429 (Mþ2OC2H5, 1%), 158 (71) and 91 (100); HRMS
calcd for C29H33O3 [Mþ2OC2H5] 429.2430, found
429.2435.
1
Compound 37. H NMR (400 MHz) d 7.38–7.13 (15H, m,
3£Ph), 4.80–4.15 (5H, m, 2£CH2Ph and CHHPh), 4.09–
3.95, (2H, m, CH2CH3), 3.54 (1H, ddd, J¼9.3, 5.6, 2.4 Hz,
CHOBn), 2.74 (1H, m, CH–CO2Et), 2.02 (1H, ddd, J¼13.7,
11.0, 2.3 Hz, CHCHHCH), 1.65–1.35 (5H, m, CH2i-Pr,
CHH and CH(CH3)2), 1.14 (3H, t, J¼7.1 Hz, CH2CH3),
0.86 (3H, d, J¼6.4 Hz, CH3) and 0.84 (3H, d, J¼6.6 Hz,
CH3).
1
4.3.20. Compound 41 (2,4-syn). H NMR (400 MHz) d
7.40–7.24 (10H, m, 2£Ph), 4.77 (1H, d, J¼11.0 Hz,
CHHPh), 4.74 (1H, d, J¼5.4 Hz, CHOTBDMS), 4.55
(1H, d, J¼11.0 Hz, CHHPh), 4.05 (2H, d, J¼7.1 Hz,
CH2CH3), 3.50 (1H, ddd, J¼10.2, 5.4, 2.4 Hz, CHOBn),
2.58 (1H, m, CHCO2Et), 1.67 (1H, ddd, J¼12.7, 11.2,
2.4 Hz, CHCHHCH), 1.51 (1H, m, CHH), 1.30–1.15
(4H, m, CHH and CH2), 1.19 (3H, q, J¼7.1 Hz,
CH2CH3), 0.87 (9H, s, C(CH3)3), 0.82 (3H, t, J¼7.2 Hz,
CH3), 0.16 (3H, s, SiCH3) and 20.15 (3H, s, SiCH3); 13C
NMR (67.8 MHz) d 176.1, 141.3, 138.6, 128.2, 128.1,
127.7, 127.5, 127.2, 127.0, 81.9, 76.3, 73.9, 59.9, 41.7, 35.4,
33.8, 25.9, 20.6, 18.2, 14.4, 14.0, 24.7 and 24.9; HRMS
calcd for C27H39O3Si [Mþ2OC2H5] 439.2668, found
439.2637.
1
Compound 44. H NMR (400 MHz) d 7.38–7.13 (15H, m,
3£Ph), 4.80–4.15 (5H, m, 2£CH2Ph and CHHPh), 4.09–
3.95, (2H, m, CH2CH3), 3.64 (1H, ddd, J¼10.2, 6.6, 2.7 Hz,
CHOBn), 2.74 (1H, m, CH–CO2Et), 1.65–1.35 (6H, m,
CH2i-Pr, CH2 and CH(CH3)2), 1.17 (3H, t, J¼7.1 Hz,
CH2CH3), 0.84 (3H, d, J¼6.3 Hz, CH3) and 0.80 (3H, d,
J¼6.3 Hz, CH3).
4.3.17. Compounds 38 (2,4-syn) and 45 (2,4-syn). MS m/z
367 (Mþ2OCH3, 5%), 271 (99), 121 (100), 181 (39) and 91
(77); HRMS calcd for C24H31O3 [Mþ2OCH3] 367.2273,
found 367.2276.

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1
4.3.21. Compound 42 (2,4-syn). H NMR (400 MHz) d
7.41–7.24 (10H, m, 2£Ph), 4.79 (1H, d, J¼11.0 Hz,
CHHPh), 4.73 (1H, d, J¼5.6 Hz, CHOTBDMS), 4.56
(1H, d, J¼11.0 Hz, CHHPh), 4.05 (2H, q, J¼7.1 Hz,
CH2CH3), 3.48 (1H, m, CHOBn), 2.67 (1H, m, CHCO2Et),
1.64 (1H, ddd, J¼13.4, 11.2, 2.0 Hz, CHCHHCH), 1.54–
1.38 (2H, m, CH2), 1.19 (3H, t, J¼7.1 Hz, CH2CH3), 1.05
(1H, m, CH(CH3)2), 0.88 (9H, s, C(CH3)3), 0.82 (3H, d,
J¼6.6 Hz, CHCH3), 0.79 (3H, d, J¼6.4 Hz, CHCH3), 0.02
(3H, s, SiCH3) and 20.15 (3H, s, SiCH3); 13C NMR
(67.8 MHz) d 176.2, 141.3, 138.6, 128.2, 128.1, 127.7,
127.4, 127.2, 127.0, 82.1, 76.4, 73.9, 59.9, 42.4, 40.1, 34.4,
26.2, 25.9, 23.1, 22.1, 18.3, 14.4, 24.6 and 24.8; MS m/z
453 (Mþ2OC2H5, 2%), 277 (92), 221 (85) and 91 (100);
HRMS calcd for C28H41O3Si [Mþ2OC2H5] 453.2825,
found 453.2823.
4.4.3. g-Hydroxy ester 67. H NMR (400 MHz) d 7.44–
7.33 (5H, m, Ph), 4.01 (1H, d, J¼5.1 Hz, CHOTBDMS),
4.19 (2H, m, CH2CH3), 3.73 (1H, m, CHOH), 2.74 (1H, m,
CHCO2Et), 1.30 (3H, q, J¼7.1 Hz, CH2CH3), 1.15 (3H, t,
J¼7.1 Hz, CH3), 0.97 (9H, s, C(CH3)3), 0.94 (3H, t,
J¼7.3 Hz, CH2CH3), 0.11 (3H, s, SiCH3) and 20.09 (3H,
s, SiCH3).
4.4.4. g-Lactone 68. 1H NMR (400 MHz) d 7.40–7.25 (5H,
m, Ph), 5.04 (1H, d, J¼2.4 Hz, CHPh), 4.51 (1H, dt, J¼8.5,
3.0 Hz, g-H), 2.70 (1H, m, a-H), 2.43 (1H, ddd, J¼13.0,
9.8, 3.5 Hz, b-H), 1.79 (1H, m, CHH), 1.57 (1H, dt, J¼13.0,
8.6 Hz, b-H), 1.43–1.28 (3H, m, CHH and CH2), 0.91 (3H,
t, J¼6.8 Hz, CH3), 0.90 (9H, s, C(CH3)3), 0.08 (3H, s,
SiCH3) and 20.08 (3H, s, SiCH3); MS m/z 291 (Mþ2t-Bu,
81%) and 221 (100); HRMS calcd for C16H23O3Si (Mþ2t-
Bu) 291.1417, found 291.1425.
1
4.3.22. Compound 43 (2,4-syn). H NMR (400 MHz) d
1
7.43–7.23 (10H, m, 2£Ph), 4.80 (1H, d, J¼11.0 Hz,
CHHPh), 4.73 (1H, d, J¼5.6 Hz, CHOTBDMS), 4.60
(1H, d, J¼11.9 Hz, CHHPh), 4.05 (2H, q, J¼7.1 Hz,
CH2CH3), 3.43 (1H, m, CHOBn), 2.67 (1H, m, CHCO2Et),
1.70 (2H, m, CH2), 1.25–1.00 (2H, m, CH2), 1.20 (3H, t,
J¼7.1 Hz, CH2CH3), 0.88 (9H, s, C(CH3)3), 0.80 (3H, s,
C(CH3)3), 0.02 (3H, s, SiCH3) and 20.15 (3H, s, SiCH3);
13C NMR (100.4 MHz) d 177.1, 141.2, 138.7, 128.2, 128.1,
127.7, 127.5, 127.2, 127.0, 82.1, 76.0, 73.9, 60.1, 47.2, 38.5,
36.6, 30.9, 29.5, 25.9, 18.2, 14.2, 24.7 and 24.9; MS m/z
467 (Mþ2OC2H5, 2%), 291 (79), 221 (68) and 91 (100);
HRMS calcd for C29H43O3Si [Mþ2OC2H5] 467.2981,
found 467.2992.
4.4.5. d-Hydroxy ester 69. H NMR (400 MHz) d 7.38–
7.25 (10H, m, 2£Ph), 4.63 (1H, d, J¼4.1 Hz, CHOH), 4.54
(1H, d, J¼10.7 Hz, CHHPh), 4.38 (1H, d, J¼10.7 Hz,
CHHPh), 4.04 (2H, m, CH2CH3), 3.59 (1H, m, CHOBn),
2.67 (1H, m, CHCO2Et), 1.17 (3H, t, J¼7.1 Hz, CH2CH3),
0.88 (3H, d, J¼6.3 Hz, CHCH3) and 0.84 (3H, d, J¼6.4 Hz,
CHCH3).
4.4.6. d-Lactone 70. 1H NMR (400 MHz) d 7.44–6.91 (5H,
m, Ph), 5.32 (1H, d, J¼2.0 Hz, d-H), 4.26 (1H, d,
J¼12.2 Hz, CHHPh), 4.12 (1H, d, J¼12.2 Hz, CHHPh),
3.94 (1H, dt, J¼6.8, 2.8 Hz, g-H), 2.59 (1H, m, a-H), 2.45
(1H, ddd, J¼14.2, 8.6, 7.2 Hz, b-H), 1.90 (1H, CHHi-Pr),
1.77 (1H, m, CH(CH3)2), 1.71 (1H, ddd, J¼14.2, 10.5,
3.4 Hz, b-H), 1.39 (1H, m, CHH), 0.95 (3H, d, J¼6.6 Hz,
CHCH3) and 0.92 (3H, d, J¼6.6 Hz, CHCH3); 13C NMR
(100.4 MHz) d 174.3, 137.4, 136.0, 128.2, 128.1, 128.06,
128.0, 127.4, 127.3, 126.7, 80.5, 74.0, 71.2, 40.1, 35.2, 31.6,
25.0, 23.2 and 21.7; MS m/z 281 (Mþ2CH2CH(CH3)2, 1%),
247 (Mþ2C7H7, 15), 141 (100) and 91 (76); HRMS calcd
for C15H19O3 (Mþ2C7H7) 247.1334, found 247.1345.
4.4. Determination of the diastereomer ratios and
stereochemistries
1
4.4.1. d-Hydroxy ester 64. H NMR (400 MHz) d 7.35–
7.26 (10H, m, 2£Ph), 4.95 (1H, d, J¼4.1 Hz, CHOH), 4.54
(2H, s, CH2Ph), 4.00 (2H, m, CH2CH3), 3.58 (1H, m,
CHOBn), 2.72 (1H, m, CHCO2Et), 1.14 (3H, t, J¼7.1 Hz,
CH2CH3), 0.86 (3H, d, J¼6.4 Hz, CHCH3) and 0.83 (3H, d,
J¼6.1 Hz, CHCH3).
4.4.2. d-Lactones 65 and 66. Compound 65. 1H NMR
(400 MHz) d 7.42–7.06 (5H, m, Ph), 5.22 (1H, d, J¼8.1 Hz,
d-H), 4.35 (1H, d, J¼11.7 Hz, CHHPh), 4.25 (1H, d,
J¼11.7 Hz, CHHPh), 3.75 (1H, m, g-H), 2.59 (1H, m, a-H),
2.29 (1H, ddd, J¼13.4, 6.8, 4.4 Hz, b-H), 1.91 (1H, ddd,
J¼13.9, 9.3, 4.9 Hz, CHHi-Pr), 1.75 (2H, m, b-H
and CH(CH3)2), 1.51 (1H, ddd, J¼13.9, 9.2, 5.2 Hz,
CHHi-Pr), 0.95 (3H, d, J¼6.6 Hz, CHCH3) and 0.88 (3H,
d, J¼6.6 Hz, CHCH3); MS m/z 281 (Mþ2CH2CH(CH3)2,
4%), 247 (Mþ2C7H7, 13), 141 (97) and 91 (100);
HRMS calcd for C15H19O3 (Mþ2C7H7) 247.1334, found
247.1345.
References
1. For reviews and books, see: (a) Smadja, W. Synlett 1994,
1–26. (b) Porter, N. A.; Giese, B.; Curran, D. P. Acc. Chem.
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1
Compound 66. H NMR (400 MHz) d 7.41–7.06 (5H, m,
Ph), 5.34 (1H, d, J¼6.3 Hz, d-H), 4.46 (1H, d, J¼11.7 Hz,
CHHPh), 4.36 (1H, d, J¼11.7 Hz, CHHPh), 3.81 (1H, m,
g-H), 2.87 (1H, m, a-H), 2.14 (1H, ddd, J¼14.2, 6.8,
3.9 Hz, b-H), 1.88 (1H, ddd, J¼14.2, 9.1, 5.2 Hz, CHHi-Pr),
1.72 (2H, m, b-H and CH(CH3)2), 1.32 (1H, ddd, J¼14.2,
8.6, 5.9 Hz, CHHi-Pr), 0.95 (3H, d, J¼6.6 Hz, CHCH3) and
0.92 (3H, d, J¼6.6 Hz, CHCH3).
´
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