Stereoselective synthesis of 4-alkoxy-3-methylidenealkanols using reactions between 2-(1-alkoxyalkyl)propenylstannanes and aldehydes: X-ray crystal structure of (1R,4R)-3-methylidene-1-(4-nitrophenyl)-pentane-1,4-diol

Article abstract of DOI:10.1039/a702256e

The 2-(1-hydroxy- and 1-alkoxy-alkyl)propenylstannanes 9 and 11-15, react with aldehydes to form 4-hydroxy- and 4-alkoxy-3-methylidenealkanols 23, 24 and 36-53. The stereoselectivity of these reactions has been investigated. If the reactions are carried out by transmetallation of the stannane using a tin(IV) halide before addition of the aldehyde, modest stereoselectivity in favour of the 1,4-anti-products 23, 36 and 37 is observed for the hydroxystannane 9, whereas the alkoxystannanes 11-15 give rise preferentially to the 1,4-syn-diastereoisomers 47-53, selectivity 75-85:25-15. It should be noted that these stereochemical assignments are the reverse of those reported in the preliminary communication on this work. The structure of the 1,4-anti-product 36 from the reaction between the hydroxystannane 9 and p-nitrobenzaldehyde was established by X-ray diffraction. The stereoselectivity of BINOL-titanium(IV) catalysed reactions of the (R)-SEM-stannane (R)-12 with benzaldehyde is controlled by the configuration of the BINOL and can be used to synthesize either the 1,4-anti- or 1,4-syn-isomers 40 and 47.

Full text of DOI:10.1039/a702256e

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Stereoselective synthesis of 4-alkoxy-3-methylidenealkanols using
reactions between 2-(1-alkoxyalkyl)propenylstannanes and aldehydes:
X-ray crystal structure of (1R,4R)-3-methylidene-1-(4-nitrophenyl)-
pentane-1,4-diol
Pedro Almendros, Michelangelo Gruttadauria, Madeleine Helliwell and
Eric J. Thomas*
The Department of Chemistry, The University of Manchester, Manchester, UK M13 9PL
The 2-(1-hydroxy- and 1-alkoxy-alkyl)propenylstannanes 9 and 11–15, react with aldehydes to form 4-
hydroxy- and 4-alkoxy-3-methylidenealkanols 23, 24 and 36–53. The stereoselectivity of these reactions has
been investigated. If the reactions are carried out by transmetallation of the stannane using a tin(IV) halide
before addition of the aldehyde, modest stereoselectivity in favour of the 1,4-anti-products 23, 36 and 37
is observed for the hydroxystannane 9, whereas the alkoxystannanes 11–15 give rise preferentially to the
1,4-syn-diastereoisomers 47–53, selectivity 75–85 :25–15. It should be noted that these stereochemical
assignments are the reverse of those reported in the preliminary communication on this work. The
structure of the 1,4-anti-product 36 from the reaction between the hydroxystannane 9 and p-nitrobenz-
aldehyde was established by X-ray diffraction. The stereoselectivity of BIN OL–titanium(IV) catalysed
reactions of the (R)-SEM -stannane (R)-12 with benzaldehyde is controlled by the configuration of the
BIN OL and can be used to synthesize either the 1,4-anti- or 1,4-syn-isomers 40 and 47.
Introduction
R
Br
Reactions of propenylmetal reagents with aldehydes are of con-
siderable interest.1 For example, useful 1,4-asymmetric induc-
tion in favour of the 1,4-syn-product 2 over the 1,4-anti-isomer
3 has been observed for the chromium() and indium mediated
coupling of 1-bromo-2-(1-alkoxyalkyl)propenes 1 with alde-
hydes (selectivity 85–95:15–5).2 2-(1-Substituted-alkyl)prop-
enyl-stannanes and -silanes 4 (M = SiMe3, SnBu3) react with
aldehydes to give preferentially either the 1,4-syn- or 1,4-anti-
products 2 or 3 depending on the 1Ј-substituent and the Lewis
acid used to promote the reaction.3,4 Very high asymmetric
induction has been observed for reactions between the prop-
enylstannane 5 and aldehydes in the presence of BINOL–
titanium() and related metal catalysts.5–7 For example the
homoallylic alcohols 6 were obtained with excellent ees using
the catalyst formed from (S)-BINOL and TiCl2(OPri)2 in the
presence of molecular sieves.5 We now report full details of
a study of the stereoselectivity of reactions between 2-(1-
alkoxyalkyl)prop-2-enylstannanes 4 (M = SnBu3) and aldehydes
promoted by tin() halides together with preliminary results on
the influence of BINOL–metal catalysts on the stereoselectivity
of these reactions.†,8
OP
1
(P = Bn, SiMe2But, MOM)
OH
OH
R
R
R′
R′
OP
OP
2
3
R
M
OP
4
M = SiMe3, SnBu3;
P = Ac, Me
OH
(S)-BINOL, TiCl2(OPri)2
SnBu3
>95% ee
R
RCHO
5
6
Results and discussion
Racemic 2-(1-hydroxyethyl)- and 2-(1-hydroxy-2-methylpropyl)-
prop-2-enyl(tributyl)stannanes 99 and 10 were prepared by stan-
nylation of the alkenols 7 and 8, and were converted into the
benzyl, (2-trimethylsilylethoxy)methoxy (SEM) and methoxy-
methoxy (MOM) ethers 11–15, respectively (Scheme 1). The
(R)-enantiomer of the alcohol (R)-7 was prepared from 2-
methylbut-2-enol 16 via Sharpless epoxidation using (Ϫ)-
diisopropyl tartrate, formation of the toluene-p-sulfonate, and
reductive elimination, following the procedure reported in the
literature.4 Stannylation gave the (R)-enantiomer of the hydroxy-
alkylstannane (R)-9. The absolute configurations of both the
alkenol (R)-7 and the stannane (R)-9 were assigned on the basis
that (Ϫ)-diisopropyl tartrate had been used in the Sharpless
epoxidation,10 and were checked by comparison of the 1H
† The stereochemical assignments made in this paper are the reverse of
those reported in the preliminary publication.8 The original assign-
ments were made by correlation of the racemic products with known
compounds prepared following a literature reaction 3 and were sup-
ported by preliminary results of an X-ray crystal structure of the major
diol from the reaction of the racemic hydroxystannane 9 with benzalde-
hyde. However, these X-ray data were found to be unreliable because of
disorder in the crystals and when the chemistry reported in this paper
was carried out using enantiomerically enriched stannanes it was
apparent that the structures of the products assigned previously had to
be revised. The results reported herein, including the stereochemical
assignments, are entirely consistent with the results of Maguire et al.,2
the X-ray crystal structure for the 1,4-anti-diol 36, and the results of
Nishigaichi.3 It should be noted that the relative 1H NMR chemical
shift of the benzylic protons for the 1,4-syn- and 1,4-anti-alkoxyalco-
hols referred to in the text 2 is a useful check of relative stereochemistry.
J. Chem. Soc., Perkin Trans. 1, 1997
2549

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R
i
R
SnBu3
Me
SnBu3
Me
OH
OH
OH
7 R = Me
8 R = Pri
9 R = Me
10 R = Pri
9
i
OH
OH
Ph
ii–iv
Me
Me
+
Ph
R
SnBu3
OH
OH
60 : 40
24
23
OP
iv–v
11 R = Me, P = Bn
12 R = Me, P = SEM
13 R = Me, P = MOM
14 R = Pri, P = SEM
15 R = Pri, P = MOM
OSiMe2But
Ph
OR
Me
Me
+
Ph
Me
Me
OSiMe2But
26 R = H
27 R = (R)-PhCH(OAc)CO
28 R = (S)-PhCH(OAc)CO
OH
v, vi
ii, iii
Me
OH
Me
OR
29
O
16
17 R = H
18 R = SO2C6H4Me
OH
vii
HO
Ph
+
i, iii
25
Me
Me
SnBu3
Me
OSiMe2But
Ph
OR
OH
OP
iv, v
Me
Me
24
(R)-9 P = H
(R)-12 P = SEM
(R)-7
Ph
OSiMe2But
30 R = H
31 R = (R)-PhCH(OAc)CO
32 R = (S)-PhCH(OAc)CO
OR
33 R = H
viii
viii
34 R = (R)-PhCH(OAc)CO
35 R = (S)-PhCH(OAc)CO
OH
OH
Me
Me
SnBu3
9, SnCl4
Me
O
Me
Me
ArCHO
+
Ar
Ar
O
O
O
OH
60 : 40
OH
38 Ar = p-NO2C6H4
39 Ar = 2-naphthyl
36 Ar = p-NO2C6H4
37 Ar = 2-naphthyl
Ph
OAc
Ph
OAc
19 (R,R)
20 (R,S)
21 (R,R)
22 (R,S)
Scheme 2 Reagents and conditions: i, SnX4, CH2Cl2, Ϫ78 ЊC, 5 min,
then PhCHO (70%); ii, O3, Me2S, MeOH, Ϫ78 ЊC, then NaBH4 (70%);
iii, NaIO4 followed by NaBH4 (70%); iv, tert-butyldimethylsilyl trifluoro-
methanesulfonate, 2,6-lutidine (26, 54%; 29, 12%; 30, 25%; 33, 25%); v,
(R)- or (S)-acetylmandelic acid, dicyclohexylcarbodiimide (27, 70%; 28,
76%; 31, 70%; 32, 72%; 34, 70%; 35, 70%)
Scheme 1 Reagents and conditions: i, 2 BuLi, Bu3SnCl (9, 46%; 10,
40%); ii, NaH, Bu4NI, BnBr; iii, SEMCl, Pri2NEt (12, 89%; 14, 70%); iv,
MOMCl, Pri2NEt (13, 76%; 15, 65%); v, Ti(OPri)4, (Ϫ)-diisopropyl tar-
trate, ButOOH, CH2Cl2, Ϫ20 ЊC (55%); vi, toluene-p-sulfonyl chloride,
Et3N; vii, NaI, Zn–Cu, ethylene glycol, 80 ЊC (35% from 17); viii, (R)-
or (S)-acetylmandelic acid, dicyclohexylcarbodiimide (DCC) (19, 80%;
20, 80%; 21, 70%; 22, 70%)
1-phenylpropane-1,3-diol which is known to correspond to the
1
(R)-enantiomer 25.12 Comparisons of the H NMR spectra of
the (R)- and (S)-acetylmandelates 27 and 28, prepared from the
monosilyl ether 26 of the major product, and the regioisomeric
monosilyl ethers 30 and 33 of the minor product 24 were also
consistent with the assigned structures.
NMR spectra of their (R)- and (S)-acetylmandelates 19–22,
which indicated that the ee of the (R)-stannane (R)-9 was ca.
92%.11
Similar stereoselectivity in favour of the 1,4-anti-products
was observed for reactions of the propenylstannane 9 with p-
nitrobenzaldehyde and 2-naphthaldehyde. The structure of the
major product from the reaction with p-nitrobenzaldehyde was
confirmed by X-ray diffraction. Fig. 1 shows a projection of the
major product as determined by an X-ray crystal study which
clearly establishes the structure as the 1,4-anti-diastereoisomer
36.†
In contrast to the stereoselectivity observed with the 2-(2-
hydroxyethyl)propenylstannane 9, the 2-(1-alkoxyethyl)prop-
enylstannanes 11, 12 and 13 were found to react with aldehydes
after transmetallation with either tin() bromide or chloride to
give mixtures of the 1,4-syn- and 1,4-anti-products in which the
1,4-syn-diastereoisomers 47–51 accounted for 75–85% of the
products formed. The results obtained are summarised in Table
1. Similar stereoselectivity was observed using the 2-(1-alkoxy-
2-methylpropyl)propenylstannanes 14 and 15.
Tin(IV) halide promoted reactions of the propenylstannanes
The tin() halide promoted reactions of the propenylstannanes
with aldehydes were carried out by adding the tin halide to a
solution of the stannane in dichloromethane at Ϫ78 ЊC and
stirring for a few minutes at this temperature to effect transmet-
allation before the addition of the aldehyde. Using either tin()
bromide or tin() chloride, 2-(1-hydroxyethyl)propenylstan-
nane 9 reacted with benzaldehyde to give a mixture of the 1,4-
anti- and 1,4-syn-diastereoisomers 23 and 24 with modest stereo-
selectivity in favour of the 1,4-anti-isomer 23 (23:24 = 60:40),
see Scheme 2. The structures of these products were established
by chemical correlation of the optically active compounds pre-
pared using the (R)-stannane (R)-9. Ozonolysis of the major
product with a reductive work-up gave a mixture of the epi-
meric diols which were cleaved using sodium periodate followed
by reduction using sodium borohydride to give dextrorotatory
2550
J. Chem. Soc., Perkin Trans. 1, 1997

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consistent with those established independently by chemical
correlation for the enantiotopically enriched products obtained
using the (R)-stannane (R)-12 and reactions catalysed by
BINOL catalysts, vide infra.
It would appear that 2-(1-alkoxyalkyl)propenylstannanes are
transmetallated with tin() halides to generate propenyltin tri-
halides which react with aldehydes with reasonable levels,
80(±5):20(±5), of 1,4-asymmetric induction in favour of the
syn-diastereoisomer. For the stannanes 11–15, this stereo-
selectivity is not affected significantly by the nature of the 2-
(1-alkoxyalkyl) group or by the choice of tin() halide. How-
ever, reactions with functionalised aldehydes are less stereo-
selective. For example, ethyl glyoxalate, on treatment with the
(R)-SEM-stannane (R)-12 and tin() chloride, gave rise to the
anti- and syn-products 56 and 57, ratio 37:63, with the use of
OHCCO2Et
12, SnCl4
OH
OH
Me
Me
+
CO2Et
CO2Et
OSEM
OSEM
56
57
Fig. 1 Projection of a molecule of the 1,4-anti-diol 36 as determined
by X-ray crystallography
(ϩ)- and (Ϫ)-menthyl glyoxalates having little effect on the
stereoselectivity.
The syn- and anti-products prepared using the 2-(1-alkoxy-
alkyl)propenylstannanes could not be separated and were
characterised as mixtures. For the products prepared from
aromatic aldehydes, stereochemical assignments were made by
1H NMR spectroscopy since it is known that for any pair of
syn- and anti-diastereoisomers, the benzylic (1-H) hydrogen of
the syn-isomer is ca. 0.1–0.2 ppm downfield of the analogous
hydrogen of the anti-isomer.2 This assignment of stereo-
chemistry was confirmed for the products 40 and 47 by SEM-
protection of the anti- and syn-1,4-diols 23 and 24. The anti-
Asymmetric catalysis of reactions of 2-(1-alkoxyalkyl)-
propenylstannanes with aldehydes
Since excellent asymmetric induction is observed for reactions
between propenylstannane 5 and aromatic and α,β-unsaturated
aldehydes in the presence of BINOL-based catalysts,5–7 it was
decided to see whether these catalysts would control the stereo-
selectivity of reactions of 2-(1-alkoxyalkyl)propenylstannanes
with aldehydes. Would the stereoselectivity be controlled by the
catalyst, in which case either the 1,4-syn- or the 1,4-anti-isomer
should be the major product depending on the choice of cata-
lyst and chirality of the stannane, or would the configuration of
the stannane control the facial selectivity, in which case match-
ing and mis-matching with the catalyst would be observed?
In the event, useful stereocontrol by the catalyst was
observed, but the reactions were slow with only modest conver-
sions to products, although slightly better conversions were
obtained using the catalyst prepared using titanium() bro-
mide rather than titanium() chloride.5 The catalyst prepared
from (R)-BINOL and equimolar amounts of titanium() iso-
propoxide and titanium() bromide promoted the reaction
between the (R)-SEM-stannane (R)-12 and benzaldehyde to
give predominantly the 1,4-anti-product, 40:47 = 92:8, where-
as (S)-BINOL, under the same conditions, gave mainly the 1,4-
syn-product, 40:47 = 12:88 (Table 2). Since the enantiomeric
excess of the stannane is only of the order of 92%, these cata-
lysed reactions are proceeding with ca. 95% asymmetric induc-
tion by the catalyst with the chirality of the stannane having
little effect on the overall stereoselectivity.
OH
OH
SEMCl
Pri2NEt
Me
Me
Ph
Ph
OH
OSEM
40
23
+
OSEM
Ph
Me
OH
54
OH
OH
Ph
SEMCl
Pri2NEt
Me
Me
Ph
OH
OSEM
47
24
The structures of the products 40 and 47 from the catalysed
reactions were identified by comparison of their spectroscopic
data with those of products obtained from the tin() chloride
promoted reactions, and the absolute configurations of the
alcohol groups were consistent with the asymmetric induction
previously observed for BINOL–titanium() catalysed
allylstannane reactions.5–7 Since these products could not be
separated, the (R)-BINOL-based catalysts provided the first
access to the SEM-anti-product 40 of reasonable diastereoiso-
meric purity. The structures of products 40 and 47 were checked
by conversion into their acetylmandelates whose 1H NMR
spectra were consistent with the assigned configurations at the
alcohol centres, and by deprotection which gave the anti- and
syn-diols 23 and 24, respectively (Scheme 3). The enantiomeri-
+
OSEM
Ph
Me
OH
55
diol 23 (the major diol from the reaction of the hydroxystan-
nane 9 and benzaldehyde) gave 40 (i.e. the minor product from
the reaction of the SEM-stannane 12) together with its regio-
isomer 54. Conversely, the minor syn-diol 24 gave the major
product from the reaction of the SEM-stannane, i.e. 47, and
its regioisomer 55. These stereochemical assignments are
J. Chem. Soc., Perkin Trans. 1, 1997
2551

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Table 1 syn/anti-Stereoselectivity in tin() halide promoted reactions of 2-(1-alkoxyalkyl)propenylstannanes with aldehydes
OH
OH
SnX4
R1
SnBu3
R1
R1
R2
+
R2
R2CHO
OP
11–15
OP
OP
40–46
47–53
Product
Stannane
R1
R2
P
SnX4
anti
syn
Yield (%)
anti:syn
12
12
13
13
11
12
12
14
15
Me
Me
Me
Me
Me
Me
Me
Pri
Ph
Ph
Ph
Ph
Ph
H2C᎐CH
Me2CH
Ph
SEM
SEM
MOM
MOM
Bn
SEM
SEM
SEM
MOM
SnBr4
SnCl4
SnBr4
SnCl4
SnBr4
SnBr4
SnBr4
SnBr4
SnBr4
40
40
41
41
42
43
44
45
46
47
47
48
48
49
50
51
52
53
71
79
70
82
62
77
75
69
60
15:85
17:83
14:86
20:80
15:85
23:77
13:87
14:86
19:81
᎐
Pri
Ph
SiMe3,15 gave similar results. Reactions with ethyl glyoxalate7
gave ca. 75:25 mixtures of the 1,4-syn- and anti-
diastereoisomers 57 and 56 (the configuration of the major
product depending upon the chirality of the BINOL- or
BINAP-containing catalyst used).
O2CCH(OAc)Ph
Ph
Me
40
OSEM
58 (R)-acetylmandelate
59 (S)-acetylmandelate
23
47
Conclusions
O2CCH(OAc)Ph
Ph
This work has shown that modest 1,4-asymmetric induction is
possible in reactions between 2-(1-hydroxy- and 1-alkoxyalkyl)-
propenylstannanes and aldehydes promoted by an initial
transmetallation using a tin() halide. Of interest is the dif-
ferent stereoselectivity observed for the hydroxy- and alkoxy-
substituted stannanes. The preferred formation of the 1,4-syn-
products 47–53 from the reactions of the alkoxystannanes and
aldehydes is inconsistent with participation of the bicyclic tran-
sition structure 65 involving the co-ordinated allyltin trihalide
67. It may be that the co-ordinated tin trihalide 67 is unable,
without undue strain, to align its C᎐Sn bond parallel to the π-
orbitals of the double-bond as would be required for reaction
Me
OSEM
60 (R)-acetylmandelate
61 (S)-acetylmandelate
24
O
i, ii
Me
47
Ph
OSEM
62
vii
R1
H
H
H
PO
R1
O
X
X
H
Sn
O
SnCl3
O
R
O
R
X
iii–vi
PPh3
Me
Me
O
OBui
R2
65
66
OSEM
OH
64
63
R1
Scheme 3 Reagents and conditions: i, O3, Me2S; ii, methanesulfonyl
chloride, Et3N; iii, SEMCl, Pri2NEt; iv, LiOH, THF, H2O; v, Me3C-
PO SnX3
COCl; vi, Ph3P᎐CH2; vii, PhCHO, benzene, reflux
᎐
67
cally enriched syn-SEM-product 47 containing ca. 15% of its
anti-isomer 40 was prepared using the (R)-SEM-stannane (R)-
12 and tin() chloride, and had the same optical rotation as the
sample prepared using (S)-BINOL. The absolute configuration
at C(4) in this compound was also checked by ozonolysis and
dehydration to give the unsaturated ketone 62 which was also
prepared from (R)-isobutyl lactate 63 by way of the keto ylide
64.
O
OH
OH
OH
Me
Me
51
Me
Me
OSEM
Me
OSEM
Me
68
69
Although the stereoselectivities of the BINOL–TiBr2(OPri)2
catalysed reactions of the (R)-SEM-stannane 12 and benzalde-
hyde were very promising, the conversions and yields were
rather modest (30–40%). Preliminary investigations using other
OH
OH
Me
Me
published catalyst systems and reaction conditions, including
OSEM
Me
13
(R)-BINOL–Ti(OPri)4,6 (R)-BINOL–Zr(OPri)4
and (R)-
BINAP–AgO2CCF3,14 in some cases in the presence of PriS-
70
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J. Chem. Soc., Perkin Trans. 1, 1997

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Table 2 Stereoselectivity using BINOL-based catalysts
OH
OH
Me
SnBu3
catalyst
PhCHO
Me
Me
+
Ph
Ph
OSEM
OSEM
40
OSEM
47
(R)-12
Catalyst
Yield (%)
Selectivity 40:47
(R)-BINOL, TiBr2(OPri)2
(S)-BINOL, TiBr2(OPri)2
40
30
92:8
12:88
with an aldehyde. However, the 1,4-syn-stereoselectivity is
consistent with participation of the transition structure 66
involving a non-coordinated allyltin trihalide. The reactions
controlled by BINOL-based catalysts proceed with excellent
stereoselectivity, and have the major advantage that either the
1,4-syn- or the 1,4-anti-products are obtained depending upon
the choice of catalyst. However, further work is required to
optimise the chemical conversions and yields in these reactions.
To illustrate the use of this chemistry in synthesis, the syn-
product 51 was ozonolysed with a reductive work-up using
dimethyl sulfide to give the hydroxy ketone 68. Reduction of the
ketone with sodium borohydride–methoxydiethylborane16 and
with tetramethylammonium triacetoxyborohydride17 then gave
the 1,3-syn- and 1,3-anti-diols 69 and 70, selectively.
was allowed to warm to room temp. and was stirred for 30 min.
The reaction mixture was added to ether (210 cm3) and washed
with saturated aqueous copper sulfate (2 × 40 cm3), water (50
cm3) and brine (2 × 40 cm3). The organic layer was dried
(K2CO3) and concentrated under reduced pressure. Chroma-
tography of the residue using light petroleum–ether (50:1 con-
taining 1% of triethylamine) as eluent gave the title compound
10 (3.74 g, 40%) as a colourless oil (Found: Mϩ Ϫ C4H9,
347.1396. C15H31OSn requires M, 347.1397); νmax/cmϪ1 3487,
1627, 1464, 1377, 1291, 1248, 1073, 1003 and 874; δH 0.83 (18
H, m, 3 × CH2CH3 and CH3), 1.25 (9 H, m, 3 × CH2 and CH3),
1.41 (7 H, m, 3 × CH2 and OH), 1.54 and 1.71 (each 1 H, d, J
11, 1-H), 1.74 (1 H, m, 4-H), 3.59 (1 H, dd, J 6.5, 4, 3-H) and
4.58 and 4.64 (each 1 H, s, 1Ј-H); δC 10.5, 14.4, 15.2, 17.8, 20.5,
28.1, 29.8, 32.1, 82.0, 106.6, 152.3; m/z 405 (Mϩ ϩ 1, 1%), 347
(97) and 291 (95).
Experimental
Melting points were determined on a Buchi 510 apparatus and
are uncorrected. IR spectra were recorded on Perkin-Elmer 297
and 1710 spectrometers as liquid films unless otherwise stated.
Low and high resolution mass spectra were taken on a Kratos
Concept mass spectrometer using the chemical ionisation mode
(CI) unless otherwise stated. Characteristic clumps of isotope
peaks were observed for the propenylstannanes; those quoted
3-Benzyloxy-2-methylidenebutyl(tributyl)stannane 11
The hydroxybutylstannane 99 (1 g, 2.67 mmol) was added to a
suspension of sodium hydride (60% in mineral oil; 114 mg, 2.86
mmol) in anhydrous N,N-dimethylformamide (1.6 cm3) at 0 ЊC.
The mixture was stirred for 1 h at 20 ЊC then a solution of
tetrabutylammonium iodide (39 mg, 0.103 mmol) and benzyl
bromide (499 mg, 2.86 mmol) in tetrahydrofuran was added.
The reaction mixture was stirred for 12 h, poured into water (40
cm3) and extracted with ethyl acetate (3 × 40 cm3). The com-
bined extracts were washed with brine, dried (MgSO4) and con-
centrated under reduced pressure. Chromatography of the resi-
due using light petroleum containing 1% of triethylamine gave
the title compound 11 (124 mg, 10%) as a colourless oil (Found:
1
correspond to 120Sn. H NMR spectra were recorded on a Var-
ian Unity 500 (500 MHz), Bruker AC-300 or Varian INOVA
300 (300 MHz) spectrometer. 13C NMR spectra were recorded
on a Bruker AC 300 or INOVA 300 instrument. Optical rota-
tions were measured at 20 ЊC and are given in units of 10Ϫ1 deg
cm2 gϪ1. Flash chromatography was carried out using Merck
silica gel 60 (40–63 µm, 230–400 mesh) or May and Baker Sorbsil
C60 silica gel (40–60 µm). All solvents were dried and distilled
before use. HPLC was carried out using a Pump Controlled
Gilson Assembly with a Rainin Dynamax 60A silica column
with dimensions of 21.4 × 250 mm and a guard column, moni-
toring at 254 nm using a Gilson 115 UV detector. Light pet-
roleum refers to the fraction boiling in the range 40–60 ЊC.
Ether refers to diethyl ether.
M
ϩ Ϫ C4H9, 409.1548. C20H33OSn requires M, 409.1553); νmax
/
cmϪ1 1629, 1455, 1075, 875, 733 and 697; δH 0.94 (15 H, m,
3 × CH2CH3), 1.35 (9 H, m, 3 × CH2 and CH3), 1.52 (6 H, m,
3 × CH2), 1.74 and 1.87 (each 1 H, d, J 12, 1-H), 3.90 (1 H, q, J
6.5, 3-H), 4.38 and 4.58 (each 1 H, d, J 12, PhCHH), 4.73 and
4.87 (each 1 H, s, 1Ј-H) and 7.30 (5 H, m, aromatic H); δC 9.8,
13.0, 13.7, 20.4, 27.4, 29.1, 70.0, 78.9, 106.8, 127.3, 127.6, 128.4,
139.0 and 155.4; m/z 409 (Mϩ Ϫ 57, 50%) and 291 (40).
The (2R,3R)-hydroxy epoxide 17 was prepared from 2-
methylbut-2-enol following the literature procedure18 and had
[α]D ϩ19.4 (c 2.3, CH2Cl2) {lit.,18 [for the (2S,3S)-enantiomer]
Ϫ22.2 (c 3, CH2Cl2)}. (R)-3-Methylbut-3-en-2-ol 7 was pre-
pared from the toluene-p-sulfonate 18 by reductive elimination
using a zinc–copper couple and oven dried sodium iodide in
ethylene glycol at 80 ЊC following the literature procedure4 and
had [α]D ϩ5.8 (c 1, CHCl3) [lit.,19 ϩ6.2 (c 2.1, CHCl3)]. The (R)-
stannane 9 was prepared from (R)-3-methylbut-3-en-2-ol 7 by
using the procedure reported in the literature for the racemic
compound 9 and had [α]D Ϫ17.0 (c 1, CH2Cl2).
2-Methylidene-3-(2-trimethylsilylethoxymethoxy)butyl-
(tributyl)stannane 12
N,N-Diisopropylethylamine (950 mg, 7.35 mmol) was added to
a solution of the hydroxyalkylstannane 9 (540 mg, 1.44 mmol)
in dichloromethane (2 cm3). The solution was cooled at 0 ЊC
then 2-trimethylsilylethoxymethyl chloride (753 mg, 4.52 mmol)
was added and the reaction mixture was stirred at 0 ЊC for 2 h.
The reaction mixture was added to light petroleum and
extracted twice with cooled aqueous hydrogen chloride (0.5 ),
water and saturated aqueous sodium hydrogen carbonate. The
organic layer was dried (K2CO3) and concentrated under
reduced pressure. Chromatography of the residue using light
petroleum–ether (100:1 containing 1% triethylamine) as eluent
gave the title compound 12 (647 mg, 89%) as a colourless oil
(Found: Mϩ Ϫ C4H9, 449.1903. C19H41O2SiSn requires M,
449.1898); νmax/cmϪ1 1630, 1464, 1377, 1249, 1101, 1030, 861
and 836; δH 0.09 [9 H, s, Si(CH3)3], 0.92 (17 H, m, 3 × CH2CH3
3-Hydroxy-4-methyl-2-methylidenepentyl(tributyl)stannane 10
2,4-Dimethylpent-1-en-3-ol (2.65 g, 23.2 mmol) was added to a
solution of butyllithium (10  in hexane; 61.5 mmol) and
tetramethylethylenediamine (8.47 g, 72.9 mmol) in ether (30
cm3) at 0 ЊC. The reaction mixture was stirred at 0 ЊC for 6 h
then tributyltin chloride (8.58 g, 26.4 mmol) in tetrahydrofuran
(7 cm3) was added rapidly at 0 ЊC. The solution became clear,
J. Chem. Soc., Perkin Trans. 1, 1997
2553

View Article Online
and CH2Si), 1.33 (9 H, m, 3 × CH2 and CH3), 1.51 (6 H, m,
3 × CH2), 1.68 and 1.81 (each 1 H, d, J 12, 1-H), 3.58 and 3.75
[each 1 H, m, OHCHCH2Si(CH3)3], 4.11 (1 H, q, J 6.5, 3-H),
4.64 and 4.79 (each 1 H, s, 1Ј-H) and 4.66 (2 H, s, OCHHO); δC
Ϫ1.4, 9.7, 13.9, 13.7, 18.1, 20.3, 27.4, 29.1, 65.0, 75.8, 92.4, 106.6
and 150.2; m/z 507 (Mϩ ϩ 1, 34%), 449 (61) and 306 (100).
The (R)-stannane (R)-12 was prepared following this pro-
cedure and had [α]D ϩ28.4 (c 2.6, CHCl3).
(2R,3R)-2,3-Epoxy-2-methylbutyl toluene-p-sulfonate 18
A solution of toluene-p-sulfonyl chloride (2.65 g, 14 mmol) and
triethylamine (2.82 g, 30 mmol) in dichloromethane (25 cm3)
was added dropwise to a stirred solution of the alcohol 17 (1.40
g, 14 mmol) in dichloromethane (25 cm3) at 0 ЊC and the mix-
ture was stirred for 12 h at room temperature. The organic
phase was washed with water (2 × 5 cm3), dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the
residue eluting with ether–light petroleum (4:6), gave the tolu-
ene p-sulfonate 18 (2.81 g, 80%); νmax/cmϪ1 1598, 1360, 1177,
1097, 974, 953, 840, 816 and 773; δH (200 MHz) 1.25 (3 H, d, J
6.5, CH3), 1.29 (3 H, s, CH3), 2.44 (3 H, s, ArCH3), 2.92 (1 H, q,
J 6.5, CH), 3.94 (2 H, s, CH2) and 7.36 and 7.8 (each 2 H, d, J 8,
ArH); m/z 274 (Mϩ ϩ 18, 100%) and 257 (Mϩ ϩ 1, 38).
3-(Methoxymethoxy)-2-methylidenebutyl(tributyl)stannane 13
N,N-Diisopropylethylamine (1.76 g, 13.6 mmol) was added to a
solution of the hydroxystannane 9 (1 g, 2.67 mmol) in dichloro-
methane (4 cm3). The solution was cooled at 0 ЊC, methoxy-
methyl chloride was added (870 mg, 10.8 mmol) and the reac-
tion mixture was allowed to warm to room temp. and stirred
for 1 h. The reaction mixture was added to light petroleum and
extracted twice with cooled aqueous hydrogen chloride (0.5 ),
water and saturated aqueous sodium hydrogen carbonate.
The organic layer was dried (K2CO3) and concentrated under
reduced pressure. Chromatography of the residue using light
petroleum–ether (100:1 containing 1% triethylamine) as eluent
gave the title compound 13 (848 mg, 76%) as a colourless oil
Preparation of O-acetylmandelates
General procedure: preparation of (R)-3-methylbut-3-en-2-yl
(R)-O-acetylmandelate 19. (R)-O-Acetylmandelic acid (49 mg,
0.25 mmol) and 4-dimethylaminopyridine (DMAP, cat.) were
added to a solution of (R)-3-methylbut-3-en-2-ol 7 (20 mg, 0.23
mmol) in dichloromethane (0.5 cm3) followed by a solution of
dicyclohexylcarbodiimide (DCC) (95 mg, 0.46 mmol) in dichlo-
romethane (0.5 cm3) at 0 ЊC. The reaction mixture was allowed
to warm to room temperature and stirred for 16 h. The solvent
was removed under reduced pressure and ether was added. The
mixture was filtered and the filtrate concentrated under reduced
pressure. Chromatography of the residue using ether–light pet-
roleum (3:7) as eluent gave the title compound 19 as a colour-
less oil (49 mg, 80% yield) (Found: Mϩ ϩ NH4, 280.1559.
C15H22NO4 requires M, 280.1549); [α]D Ϫ89.7 (c 3.5, CH2Cl2);
νmax/cmϪ1 1746, 1374, 1233, 1211, 1179, 1085, 1054, 910, 740
and 697; δH 1.38 (3 H, d, J 6.5, 1-H3), 1.51 (3 H, s, 3-CH3), 2.24
(3 H, s, OCOCH3), 4.74 (2 H, s, vinylic H), 5.33 (1 H, q, J 6.5, 2-
H), 5.96 (1 H, s, CHOCOCH3), 7.41 (3 H, m, ArH) and 7.5 (2
H, m, ArH); δC 17.9, 18.9, 20.7, 74.7, 74.8, 111.9, 127.7, 128.7,
129.2, 133.9, 143.7, 168.0 and 170.4; m/z 281 (Mϩ ϩ 19, 40%),
280 (Mϩ ϩ 18, 100) and 263 (Mϩ ϩ 1, 10).
(Found:
M
ϩ Ϫ C4H9, 363.1343. C15H31O2Sn requires M,
363.1346); νmax/cmϪ1 1630, 1464, 1376, 1157, 1098, 1039, 957,
921 and 875; δH 0.92 (15 H, m, 3 × CH2CH3), 1.31 (9 H, m,
3 × CH2 and CH3), 1.50 (6 H, m, 3 × CH2), 1.69 and 1.82 (each
1 H, d, J 12, 1-H), 3.40 (3 H, s, OCH3), 4.09 (1 H, q, J 6.5, 3-H),
4.59 and 4.66 (each 1 H, d, J 7, OCHHO) and 4.65 and 4.80
(each 1 H, s, 1Ј-H); δC 9.7, 13.4, 13.7, 20.3, 27.4, 29.0, 55.2, 75.9,
94.1, 106.6 and 150.1; m/z 421 (Mϩ ϩ 1, 65%) and 308 (100).
4-Methyl-3-(2-trimethylsilylethoxymethoxy)-2-methylidene-
pentyl(tributyl)stannane 14
Following the procedure outlined for the synthesis of the stan-
nane 12, the hydroxyalkylstannane 10 (500 mg, 1.24 mmol) in
dichloromethane (3 cm3), N,N-diisopropylethylamine (801 mg,
6.20 mmol) and 2-trimethylsilylethoxymethyl chloride (620 mg,
3.72 mmol) gave, after chromatography using light petroleum–
ether (100:1 containing 1% triethylamine) as eluent, the title
compound 14 (529 mg, 80%) as a colourless oil (Found:
The following O-acetylmandelates were prepared following
this procedure using the appropriate enantiomer of O-
acetylmandelic acid.
M
ϩ Ϫ C4H9, 477.2216. C21H45O2SiSn requires M, 477.2211);
(R)-3-Methylbut-3-en-2-yl (S)-O-acetylmandelate 20. (80%)
νmax/cmϪ1 1627, 1463, 1377, 1248, 1095, 1030, 860 and 835; δH
0.05 [9 H, s, Si(CH3)3], 0.97 (23 H, m, 3 × CH2CH3, CH2Si and
2 × CH3), 1.34 (6 H, m, 3 × CH2), 1.52 (6 H, m, 3 × CH2), 1.61
and 1.72 (each 1 H, d, J 12.5, 1-H), 1.85 (1 H, m, 4-H), 3.52 [1
H, ddd, J 10, 10, 6.5, OCHHCH2Si(CH3)3], 3.61 (1 H, d, J 7, 3-
H), 3.85 [1 H, ddd, J 10, 10, 6.5, OCHHCH2Si(CH3)3], 4.60 and
4.63 (each 1 H, d, J 7, OCHHO) and 4.76 (2 H, narrow m, 1Ј-
H); δC Ϫ1.4, 9.6, 12.8, 13.7, 17.8, 18.1, 19.9, 27.4, 29.1, 30.1,
65.0, 85.8, 92.1, 110.0 and 147.2; m/z 535 (Mϩ ϩ 1, 2%), 477
(20) and 308 (100).
(Found: M
ϩ ϩ NH4, 280.1561. C15H22NO4 requires M,
280.1549); [α]D ϩ108.3 (c 2.3, CH2Cl2); νmax/cmϪ1 1746, 1374,
1233, 1211, 1179, 1085, 1052, 738 and 697; δH 1.24 (3 H, d, J
6.5, 1-H3), 1.77 (3 H, s, 3-CH3), 2.24 (3 H, s, OCOCH3), 4.91
and 5.02 (each 1 H, s, vinylic H), 5.33 (1 H, q, J 6.5, 2-H), 5.96
(1 H, s, CHOCOCH3), 7.43 (3 H, m, ArH) and 7.52 (2 H, m,
ArH); δC 18.2, 18.7, 20.7, 74.7, 74.9, 112.1, 127.5, 128.7, 129.1,
133.9, 143.7, 168.1 and 170.3; m/z 280 (Mϩ ϩ 18, 100%), 263
(Mϩ ϩ 1, 5) and 212 (70).
(R)-3-(Tributylstannylmethyl)but-3-en-2-yl (R)-O-acetylman-
delate 21. (70%) (Found: Mϩ Ϫ C4H9, 495.1560. C23H35O4Sn
requires M, 495.1556); [α]D Ϫ53.3 (c 1, CH2Cl2); νmax/cmϪ1 1748,
1633, 1455, 1373, 1233, 1210, 1056, 875, 745 and 695; δH 0.80–
1.54 [32 H, m, Sn(CH2CH2CH2CH3)3, 1Ј-H2 and 1-H3], 2.24 (3
H, s, OCOCH3), 4.48 (2 H, s, vinylic H), 5.17 (1 H, q, J 6.5, 2-
H), 5.96 (1 H, s, CHOCOCH3), 7.40 (3 H, m, ArH) and 7.51 (2
H, m, ArH); δC 9.5, 13.7, 14.7, 19.3, 27.3, 29.0, 74.3, 74.7, 77.2,
105.8, 127.8, 128.7, 129.2, 133.9, 148.3, 168.0 and 170.4; m/z
(EI) 495 (Mϩ Ϫ 57, 8%), 427 (10) and 179 (100).
(R)-3-(Tributylstannylmethyl)but-3-en-2-yl (S)-O-acetylman-
delate 22. (70%) (Found: Mϩ Ϫ C4H9, 495.1549. C23H35O4Sn
requires M, 495.1556); [α]D ϩ28.4 (c 2.7, CH2Cl2); νmax/cmϪ1
2120, 1748, 1632, 1453, 1372, 1231, 1178, 1048, 876 and 695; δH
0.85–1.99 [32 H, m, Sn(CH2CH2CH2CH3)3, 1Ј-H2 and 1-H3],
2.22 (3 H, s, OCOCH3), 4.67 and 4.82 (each 1 H, s, vinylic H),
5.22 (1 H, q, J 6.5, 2-H), 5.97 (1 H, s, CHOCOCH3), 7.41 (3 H, m,
ArH) and 7.51 (2 H, m, ArH); δC 9.6, 13.7, 24.7, 25.5, 29.0, 34.9,
55.8, 74.5, 74.6, 106.3, 127.6, 128.7, 129.1, 134.0, 148.3, 168.1
and 170.1; m/z (EI) 495 (Mϩ Ϫ 57, 8%), 149 (90) and 49 (100).
3-(Methoxymethoxy)-4-methyl-2-methylidenepentyl(tributyl)-
stannane 15
Following the procedure outlined for the synthesis of the stan-
nane 13, the hydroxyalkylstannane 10 (778 mg, 1.93 mmol) in
dichloromethane (3 cm3), N,N-diisopropylethylamine (1.27 g,
9.87 mmol) and methoxymethyl chloride (615 mg, 7.64 mmol)
gave, after chromatography using light petroleum–ethyl acetate
(100:1 containing 1% triethylamine) as eluent, the title com-
pound 15 (560 mg, 65%) as a colourless oil (Found: Mϩ Ϫ C4H9,
391.1662. C17H35O2Sn requires M, 391.1659); νmax/cmϪ1 1627,
1463, 1377, 1154, 1092, 1039 and 878; δH 0.92 (18 H, m,
3 × CH2CH3 and CH3), 1.01 (3 H, d, J 7, CH3), 1.35 (6 H, m,
3 × CH2), 1.5 (7 H, m, 3 × CH2 and 1-H), 1.73 (1 H, d, J 12.5, 1-
H), 1.86 (1 H, m, 4-H), 3.42 (3 H, s, OCH3), 3.59 (1 H, d, J 7, 3-
H), 4.48 and 4.65 (each 1 H, d, J 6.5, OCHHO) and 4.77 (2 H,
m, vinylic H); δC 9.7, 12.9, 13.7, 18.2, 19.9, 27.4, 29.1, 30.1, 55.7,
85.9, 94.0, 110.1 and 147.1; m/z 449 (Mϩ ϩ 1, 24%), 391 (50)
and 308 (100).
2554
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
(1R,4R)-3-Methylidene-1-phenyl-4-(tert-butyldimethylsilyl-
oxy)pentyl (R)-O-acetylmandelate 27. Eluted using ether–light
petroleum (2:8) (70%) (Found:
C28H42NO6Si requires M, 516.2781); [α]D ϩ36.0 (c 1.2, CH2Cl2);
νmax/cmϪ1 1751, 1455, 1373, 1232, 1207, 1175, 1103, 1082, 1056,
1028, 920, 860, 836, 755 and 697; δH Ϫ0.01 [9 H, s, Si(CH3)3],
0.90 [2 H, m, CH2Si(CH3)3], 1.19 (3 H, d, J 6.5, 5-H3), 2.14 (3 H,
s, OCOCH3), 2.42 (1 H, dd, J 15.5, 5.5, 2-H), 2.61 (1 H, dd, J
15.5, 8.5, 2-HЈ), 3.49 and 3.67 [each 1 H, td, J 10, 7, OCH-
HCH2Si(CH3)3], 4.11 (1 H, q, J 6.5, 4-H), 4.51 and 4.55 (each 1
H, d, J 7, OCHHO), 4.92 and 5.09 (each 1 H, s, vinylic H), 5.92
(1 H, m, 1-H), 5.94 (1 H, s, CHOCOCH3), 6.96 (2 H, m, ArH),
7.14 (3 H, m, ArH) and 7.33 (5 H, m, ArH); δC Ϫ1.4, 18.1, 20.1,
20.7, 37.4, 65.1, 74.4, 75.2, 76.2, 92.2, 114.6, 126.2, 127.9, 128.0,
128.2, 128.7, 129.1, 133.6, 139.5, 144.3, 167.8 and 170.2; m/z
516 (Mϩ ϩ 18, 40%) and 370 (10).
M
ϩ ϩ NH4, 500.2843.
C28H42NO5Si requires M, 500.2832); [α]D Ϫ40.0 (c 0.2, CH2Cl2);
νmax/cmϪ1 1755, 1253, 1231, 1116, 1085, 1058 and 836; δH Ϫ0.03
and Ϫ0.02 (each 3 H, s, CH3Si), 0.85 [9 H, s, SiC(CH3)3], 1.14 (3
H, d, J 5, 5-H3), 2.14 (3 H, s, OCOCH3), 2.41 (1 H, dd, J 11.5, 4,
2-H), 2.65 (1 H, dd, J 11.5, 6.5, 2-HЈ), 4.12 (1 H, q, J 5, 4-H),
4.78 and 5.06 (each 1 H, s, vinylic H), 5.89 (1 H, dd, J 6.5, 4, 1-
H), 5.95 (1 H, s, CHOCOCH3), 6.94 (2 H, m, ArH), 7.14 (3 H,
m, ArH) and 7.32 (5 H, m, ArH); m/z 500 (Mϩ ϩ 18, 12%) and
351 (60).
(1R,4R)-3-Methylidene-1-phenyl-4-(tert-butyldimethylsilyl-
oxy)pentyl (S)-O-acetylmandelate 28. Eluted using ether–light
(1R,4R)-3-Methylidene-1-phenyl-4-(2-trimethylsilylethoxy-
methoxy)pentyl (S)-O-acetylmandelate 59. Eluted with ether–
light petroleum (4:6) (85%) (Found: Mϩ ϩ NH4, 516.2790.
C28H42NO6Si requires M, 516.2781); [α]D ϩ132.9 (c 0.9,
CH2Cl2); νmax/cmϪ1 1749, 1497, 1373, 1232, 1208, 1175, 1105,
1081, 1056, 1029, 860, 836, 754 and 697; δH Ϫ0.01 [9 H, s,
Si(CH3)3], 0.88 [2 H, m, CH2Si(CH3)3], 1.09 (3 H, d, J 6.5, 5-
H3), 2.13 (3 H, s, OCOCH3), 2.35 (1 H, dd, J 15.5, 4.5, 2-H),
2.51 (1 H, dd, J 15.5, 9, 2-HЈ), 3.44 and 3.63 [each 1 H, td, J 10,
7, OCHHCH2Si(CH3)3], 3.97 (1 H, q, J 6.5, 4-H), 4.31 and 4.42
(each 1 H, d, J 7, OCHHO), 4.52 and 4.75 (each 1 H, s, vinylic
H), 5.92 (1 H, m, 1-H), 5.93 (1 H, s, CHOCOCH3), 7.31 (5 H,
m, ArH), 7.35 (3 H, m, ArH) and 7.44 (2 H, m, ArH); δC Ϫ1.3,
18.2, 20.2, 20.8, 37.6, 65.1, 74.5, 74.8, 75.7, 92.0, 114.1, 126.2,
127.7, 128.0, 128.3, 128.6, 129.1, 133.7, 139.5, 143.8, 167.8 and
169.9; m/z 516 (Mϩ ϩ 18, 12%).
(1S,4R)-3-Methylidene-1-phenyl-4-(2-trimethylsilylethoxy-
methoxy)pentyl (R)-O-acetylmandelate 60. Eluted with ether–
light petroleum (4:6) (90%) (Found: Mϩ ϩ NH4, 516.2770.
C28H42NO6Si requires M, 516.2781); [α]D Ϫ48.1 (c 1.1, CH2Cl2);
νmax/cmϪ1 1750, 1455, 1373, 1232, 1208, 1175, 1102, 1081, 1055,
1028, 920, 860, 836, 754 and 697; δH Ϫ0.02 [9 H, s, Si(CH3)3],
0.86 [2 H, m, CH2Si(CH3)3], 1.09 (3 H, d, J 6.5, 5-H3), 2.13 (3 H,
s, OCOCH3), 2.41 (1 H, dd, J 15.5, 10.5, 2-H), 2.48 (1 H, dd, J
15.5, 9.0, 2-HЈ), 3.42 and 3.62 [each 1 H, td, J 10, 7, OCH-
HCH2Si(CH3)3], 4.02 (1 H, q, J 6.5, 4-H), 4.29 and 4.39 (each 1
H, d, J 7, OCHHO), 4.52 and 4.73 (each 1 H, s, vinylic H), 5.92
(1 H, m, 1-H), 5.93 (1 H, s, CHOCOCH3), 7.30 (5 H, m, ArH),
7.35 (3 H, m, ArH) and 7.43 (2 H, m, ArH); δC Ϫ1.3, 18.2, 19.9,
20.8, 37.7, 65.1, 74.5, 74.8, 75.6, 92.0, 114.5, 126.3, 127.7, 128.0,
128.3, 128.6, 129.1, 133.8, 139.6, 143.8, 167.9 and 169.9; m/z
516 (Mϩ ϩ 18, 12%).
petroleum (2:8) (76%) (Found:
M
ϩ ϩ NH4, 500.2837.
C28H42NO5Si requires M, 500.2832); [α]D ϩ97.9 (c 0.4, CH2Cl2);
νmax/cmϪ1 1752, 1372, 1231, 1175, 1117, 1084, 1056, 909 and
697; δH Ϫ0.09 and Ϫ0.06 (each 3 H, s, CH3Si), 0.82 [9 H, s,
SiC(CH3)3], 1.02 (3 H, d, J 5, 5-H3), 2.12 (3 H, s, OCOCH3),
2.37 (1 H, dd, J 11, 4, 2-H), 2.52 (1 H, dd, J 11, 6.5, 2-HЈ), 4.01
(1 H, q, J 5, 4-H), 4.40 and 4.76 (each 1 H, s, vinylic H), 5.87 (1
H, dd, J 6.5, 4, 1-H), 5.93 (1 H, s, CHOCOCH3) and 7.37 (10 H,
m, ArH); m/z 500 (Mϩ ϩ 18, 14%), 351 (70) and 157 (100).
(1S,4R)-3-Methylidene-1-phenyl-4-(tert-butyldimethylsilyl-
oxy)pentyl (R)-O-acetylmandelate 31. Eluted using ether–light
petroleum (2:8) (70%) (Found:
M
ϩ ϩ NH4, 500.2846.
C28H42NO5Si requires M, 500.2832); [α]D Ϫ180.0 (c 0.2,
CH2Cl2); νmax/cmϪ1 1752, 1371, 1232, 1055, 979, 836, 776, 745
and 697; δH 0.00 and 0.03 (each 3 H, s, CH3Si), 0.89 [9 H, s,
SiC(CH3)3], 1.11 (3 H, d, J 6.5, 5-H3), 2.19 (3 H, s, OCOCH3),
2.53 (2 H, d, J 6.5, 2-H2), 4.15 (1 H, q, J 6.5, 4-H), 4.40 and 4.73
(each 1 H, s, vinylic H), 5.97 (1 H, m, 1-H), 5.99 (1 H, s,
CHOCOCH3) and 7.44 (10 H, m, ArH); m/z 500 (Mϩ ϩ 18,
22%) and 351 (70).
(1S,4R)-3-Methylidene-1-phenyl-4-(tert-butyldimethylsilyl-
oxy)pentyl (S)-O-acetylmandelate 32. Eluted using ether–light
petroleum (2:8) (72%) (Found:
M
ϩ ϩ NH4, 500.2844.
C28H42NO5Si requires M, 500.2832); [α]D Ϫ6.9 (c 0.3, CH2Cl2);
νmax/cmϪ1 1750, 1371, 1231, 1175, 1083, 1056, 836, 776 and 697;
δH 0.00 and 0.03 (each 3 H, s, CH3Si), 0.87 [9 H, s, SiC(CH3)3],
1.20 (3 H, d, J 6.5, 5-H3), 2.16 (3 H, s, OCOCH3), 2.48 (2 H, m,
2-H2), 4.23 (1 H, q, J 6.5, 4-H), 4.78 and 5.06 (each 1 H, s,
vinylic H), 5.91 (1 H, dd, J 8, 5.5, 1-H), 5.97 (1 H, s, CHOC-
OCH3), 6.97 (2 H, m, ArH), 7.15 (3 H, m, ArH) and 7.32
(5 H, m, ArH); m/z 500 (Mϩ ϩ 18, 22%) and 351 (96).
(2R,5S)-3-Methylidene-5-phenyl-5-(tert-butyldimethylsilyl-
oxy)pentan-2-yl (R)-O-acetylmandelate 34. Eluted using ether–
light petroleum (2:8) (70%) (Found: Mϩ ϩ NH4, 500.2841.
C28H42NO5Si requires M, 500.2832); δH Ϫ0.31 and Ϫ0.12 (each
3 H, s, CH3Si), 0.79 [9 H, s, SiC(CH3)3], 1.32 (3 H, d, J 6.5, 1-
H3), 1.96 (1 H, dd, J 14, 4.5, 4-H), 2.17 (3 H, s, OCOCH3), 2.18
(1 H, dd, J 14, 7.5, 4-HЈ), 4.56 (1 H, dd, J 8.5, 4.5, 5-H), 4.72
and 4.84 (each 1 H, s, vinylic H), 5.34 (1 H, q, J 6.5, 2-H), 5.87
(1 H, s, CHOCOCH3), 7.08 (2 H, m, ArH), 7.2 (3 H, m, ArH),
7.28 (3 H, m, ArH) and 7.43 (2 H, m, ArH); m/z 500 (Mϩ ϩ 18,
5%), 368 (10) and 157 (100).
(1S,4R)-3-Methylidene-1-phenyl-4-(2-trimethylsilylethoxy-
methoxy)pentyl (S)-O-acetylmandelate 61. Eluted with ether–
light petroleum (4:6) (90%) (Found: Mϩ ϩ NH4, 516.2782.
C28H42NO6Si requires M, 516.2781); [α]D ϩ56.3 (c 1.4, CH2Cl2);
νmax/cmϪ1 1750, 1455, 1372, 1232, 1207, 1175, 1102, 1081, 1056,
1027, 919, 860, 836, 755 and 697; δH Ϫ0.02 [9 H, s, Si(CH3)3],
0.90 [2 H, m, CH2Si(CH3)3], 1.24 (3 H, d, J 6.5, 5-H3), 2.14 (3 H,
s, OCOCH3), 2.46 (1 H, dd, J 15.5, 5, 2-H), 2.55 (1 H, dd, J
15.5, 9, 2-HЈ), 3.46 and 3.67 [each 1 H, td, J 9, 8, OCH-
HCH2Si(CH3)3], 4.17 (1 H, q, J 6.5, 4-H), 4.44 and 4.46 (each 1
H, d, J 7, OCHHO), 4.93 and 5.09 (1 H, s, vinylic H), 5.9 (1 H,
m, 1-H), 5.95 (1 H, s, CHOCOCH3), 6.96 (2 H, m, ArH), 7.13 (3
H, m, ArH) and 7.33 (5 H, m, ArH); δC Ϫ1.3, 18.2, 20.2, 20.8,
37.6, 65.1, 74.4, 74.9, 76.3, 92.0, 114.6, 126.0, 127.8, 128.0,
128.5, 129.0, 129.1, 133.4, 139.5, 144.3, 167.6 and 169.9; m/z
516 (Mϩ ϩ 18, 55%) and 237 (50).
(2R,5S)-3-Methylidene-5-phenyl-5-(tert-butyldimethylsilyl-
oxy)pentan-2-yl (S)-O-acetylmandelate 35. Eluted using ether–
light petroleum (2:8) (70%) [α]D ϩ21.0 (c 0.8, CH2Cl2); νmax
/
cmϪ1 1746, 1454, 1372, 1232, 1178, 1084, 1068, 836, 777 and
699; δH Ϫ0.25 and Ϫ0.05 (each 3 H, s, CH3Si), 0.82 [9 H, s,
SiC(CH3)3], 1.16 (3 H, d, J 6.5, 1-H3), 2.18 (3 H, s, OCOCH3),
2.31 (1 H, dd, J 14.5, 4.5, 4-H), 2.35 (1 H, dd, J 14.5, 8, 4-HЈ),
4.74 (1 H, dd, J 8, 4.5, 5-H), 4.91 and 5.10 (each 1 H, s, vinylic
H), 5.40 (1 H, q, J 6.5, 2-H), 5.88 (1 H, s, CHOCOCH3), 7.24 (5
H, m, ArH), 7.35 (3 H, m, ArH) and 7.45 (2 H, m, ArH); m/z
500 (Mϩ ϩ 18, 10%), 368 (28) and 351 (100).
Tin(IV) halide promoted reactions between allylstannanes and
aldehydes
General procedure: preparation of 1-phenyl-3-methylidene-
pentane-1,4-diols 23 and 24. A cooled solution of tin() chlor-
ide (367 mg, 1.41 mmol) in dichloromethane (1.41 cm3) was
added dropwise to a stirred solution of the racemic hydroxy-
alkylstannane 9 (530 mg, 1.41 mmol) in dichloromethane (14.1
cm3) at Ϫ78 ЊC. After 5 min, a cooled solution of benzaldehyde
(1R,4R)-3-Methylidene-1-phenyl-4-(2-trimethylsilylethoxy-
methoxy)pentyl (R)-O-acetylmandelate 58. Eluted with ether–
light petroleum (4:6) (85%) (Found: Mϩ ϩ NH4, 516.2791.
J. Chem. Soc., Perkin Trans. 1, 1997
2555

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(1.41 mmol) in dichloromethane (0.4 cm3) was added and the
mixture stirred for 1 h at Ϫ78 ЊC. Saturated aqueous sodium
hydrogen carbonate (15 cm3) was added, and the mixture
allowed to warm to room temp., before being partitioned
between dichloromethane and water. The organic extract was
washed with brine, dried (MgSO4) and concentrated under
reduced pressure. Chromatography of the residue using light
petroleum–ethyl acetate as eluent gave a mixture of the diols 23
and 24 (55%) which were separated by HPLC. The less polar
product was identified as the (1RS,4RS)-diastereoisomer of the
title compound 23, a white solid, mp 66 ЊC (ethyl acetate–
hexane) (Found: Mϩ, 192.1148. C12H16O2 requires M,
192.1146); νmax/cmϪ1 3341, 1649, 1492, 1455, 1103, 1041, 915,
893, 766 and 702; δH 1.28 (3 H, d, J 6.5, 5-H3), 2.41 (1 H, dd, J
14.5, 3, 2-H), 2.56 (1 H, dd, J 14.5, 10, 2-HЈ), 3.04 and 3.37
(each 1 H, br s, OH), 4.37 (1 H, q, J 6.5, 4-H), 4.79 (1 H, dd, J
9.5, 3, 1-H), 4.99 and 5.17 (each 1 H, s, vinylic H) and 7.35 (5 H,
m, ArH); δC 22.4, 41.8, 70.9, 74.6, 113.8, 125.8, 127.5, 128.4,
144.4 and 149.6; m/z 210 (Mϩ ϩ 18, 20%) and 192 (Mϩ, 100).
The more polar product was identified as the (1RS,4SR)-
diastereoisomer of the title compound 24, a white solid, mp
47 ЊC (hexane) (Found: Mϩ, 192.1149. C12H16O2 requires M,
192.1146); νmax/cmϪ1 3344, 1646, 1494, 1453, 1040, 911, 756 and
700; δH 1.33 (3 H, d, J 6.5, 5-H3), 2.43 (1 H, dd, J 14.5, 9, 2-H),
2.63 (1 H, dd, J 14.5, 3.5, 2-HЈ), 2.65 and 3.65 (each 1 H, br s,
OH), 4.28 (1 H, q, J 6.5, 4-H), 4.91 (2 H, m, vinylic H and 1-H),
5.14 (1 H, s, vinylic H) and 7.40 (5 H, m, ArH); δC 21.8, 42.9,
70.7, 73.7, 113.6, 125.8, 127.4, 128.3, 144.2 and 148.8; m/z 210
(Mϩ ϩ NH4, 8%), 192 (Mϩ, 100) and 175 (42).
4-H), 4.98 (1 H, s, vinylic H), 5.15 (1 H, dd, J 9, 3.5, 1-H),
5.21 (1 H, s, vinylic H), 7.53 (3 H, m, ArH) and 7.87 (4 H, m,
ArH); m/z 260 (Mϩ ϩ 18, 10%), 243 (Mϩ ϩ 1, 20) and 242
(Mϩ, 100).
The following 1-substituted-4-alkoxy-3-methylidenepentan-
ols were prepared similarly. In some cases the (1RS,4SR)- and
(1SR,4RS)-diastereoisomers could not be separated. The
1H NMR peaks are given for the major isomer only (see
Table 1).
(1RS,4SR)-3-Methylidene-1-phenyl-4-(2-trimethylsilyl-
ethoxymethoxy)pentan-1-ol 47. Light petroleum–ethyl acetate
(10:1) as eluent (Found: Mϩ ϩ H, 323.2051. C18H31O3Si
requires M, 323.2043); νmax/cmϪ1 3443, 1647, 1494, 1453, 1375,
1249, 1105, 1024, 861, 836, 756 and 700; δH 0.06 [9 H, s,
Si(CH3)3], 0.97 [2 H, m, CH2Si(CH3)3], 1.36 (3 H, d, J 6.5, 5-
H3), 2.47 (1 H, dd, J 15, 8, 2-H), 2.64 (1 H, dd, J 15, 4, 2-HЈ),
3.00 (1 H, br s, OH), 3.70 [2 H, m, OCH2CH2Si(CH3)3], 4.27 (1
H, q, J 6.5, 4-H), 4.66 (2 H, s, OCHHO), 4.94 (1 H, dd, J 7, 4, 1-
H), 5.04 and 5.19 (each 1 H, m, vinylic H) and 7.40 (5 H, m,
aromatic H); δC Ϫ1.4, 18.1, 20.0, 42.1, 65.4, 72.8, 75.8, 92.6,
115.1, 125.8, 127.3, 128.3, 144.3 and 146.4; m/z 323 (Mϩ ϩ H,
2%), 277 (12) and 247 (40). The (1S,4R)-enantiomer 47
(Found: Mϩ ϩ NH4, 340.2298. C14H20O3 requires M, 340.2308)
had [α]D Ϫ2.0 (c 0.5, CH2Cl2).
(1RS,4SR)-3-Methylidene-1-phenyl-4-(methoxymethoxy)-
pentan-1-ol 48. Light petroleum–ethyl acetate (5:1) as eluent
(Found: Mϩ ϩ H, 237.1489. C14H21O3 requires M, 237.1491);
νmax/cmϪ1 3449, 1648, 1494, 1453, 1374, 1217, 1157, 1037, 917,
757 and 702; δH 1.37 (3 H, d, J 6.5, 5-H3), 2.45 (1 H, dd, J 14.5,
9, 2-H), 2.63 (1 H, dd, J 14.5, 4, 2-HЈ), 2.93 (1 H, br s, OH), 3.41
(3 H, s, OCH3), 4.26 (1 H, q, J 6.5, 4-H), 4.61 and 4.64 (each 1
H, d, J 7, OCHHO), 4.94 (1 H, dd, J 9, 4, 1-H), 5.08 and 5.22
(each 1 H, s, vinylic H) and 7.40 (5 H, m, ArH); δC 19.46, 41.96,
55.53, 72.75, 75.83, 94.28, 115.18, 125.82, 127.38, 128.36,
144.33 and 146.24; m/z 254 (Mϩ ϩ 18, 10%), 237 (Mϩ ϩ 1, 5),
219 (100) and 192 (42).
Following the above procedure, the stannane (R)-9 gave the
(1R,4R)-diol 23 (Found: Mϩ, 192.1148. C12H16O2 requires M,
192.1146); [α]D ϩ68.8 (c 0.2, CH2Cl2) and the (1S,4R)-diol 24
(Found: Mϩ, 192.1149. C12H16O2 requires M, 192.1146); [α]D
Ϫ52.0 (c 0.2, CH2Cl2).
The following 1-substituted-3-methylidenepentane-1,4-diols
were prepared using this procedure:
(1RS,4RS)- and (1SR,4RS)-3-Methylidene-1-(p-nitrophenyl)-
pentane-1,4-diols 36 and 38. The (1RS,4RS)-diol 36 (38%) was
a yellow solid, mp 118–120 ЊC (CH2Cl2–hexane) (Found:
(1RS,4SR)-4-Benzyloxy-3-methylidene-1-phenylpentan-1-ol
49. Light petroleum–ethyl acetate (10:1) as eluent (Found:
M
ϩ ϩ H, 283.1693. C19H23O2 requires M, 283.1698); νmax
/
M
ϩ ϩ NH4, 255.1341. C12H19N2O4 requires M, 255.1345); νmax
/
cmϪ1 3416, 3063, 3030, 1647, 1495, 1453, 1091, 912, 754 and
700; δH 1.41 (3 H, d, J 6.5, 5-H3), 2.50 (1 H, dd, J 15, 9, 2-H),
2.69 (1 H, dd, J 15, 4, 2-HЈ), 2.85 (1 H, br s, OH), 4.05 (1 H, q,
J 6.5, 4-H), 4.43 and 4.54 (each 1 H, d, J 12, PhCHHO),
4.98 (1 H, dd, J 8.5, 4, 1-H), 5.10 and 5.21 (each 1 H, s, vinylic
H) and 7.40 (10 H, m, ArH); δC 19.7, 41.6, 70.3, 72.7, 78.5,
115.3, 125.9, 127.4, 127.6, 127.7, 128.4, 128.5, 138.4, 144.4
and 146.2; m/z 300 (Mϩ ϩ 18, 5%), 283 (Mϩ ϩ 1, 4) and 265
(100).
cmϪ1 3341, 1604, 1519, 1347, 1106, 1071, 1038, 1015, 913 and
699; δH 1.39 (3 H, d, J 6.5, 5-H3), 2.39 (1 H, br s, OH), 2.54 (2 H,
d, J 6.5, 2-H2), 4.04 (1 H, br s, OH), 4.49 (1 H, q, J 6.5, 4-H),
4.94 (1 H, t, J 6.5, 1-H), 5.04 and 5.24 (each 1 H, s, vinylic H),
7.62 (2 H, d, J 9, ArH) and 8.25 (2 H, d, J 9, ArH); m/z 255
(Mϩ ϩ 18, 47%), 237 (Mϩ, 10) and 190 (100). The (1SR,4RS)-
diol 38 was an oil (53 mg, 22%) (Found: Mϩ ϩ NH4, 255.1355.
C12H19N2O4 requires M, 255.1345); νmax/cmϪ1 3343, 1604, 1519,
1347, 1106, 1070, 1037, 1013, 913 and 854; δH 1.43 (3 H, d, J
6.5, 5-H3), 2.11 (1 H, br s, OH), 2.44 (1 H, dd, J 14.5, 8.5, 2-H),
2.80 (1 H, dd, J 14.5, 3.5, 2-HЈ), 3.70 (1 H, br s, OH), 4.41 (1 H,
q, J 6.5, 4-H), 4.87 (1 H, s, vinylic H), 5.08 (1 H, m, 1-H), 5.19 (1
H, s, vinylic H), 7.59 (2 H, d, J 9, ArH) and 8.24 (2 H, d, J 9,
ArH); m/z 255 (Mϩ ϩ 18, 100%) and 237 (Mϩ, 10).
(3RS,6SR)-5-Methylidene-6-(2-trimethylsilylethoxy-
methoxy)hept-1-en-3-ol 50. Light petroleum–ethyl acetate (5:1)
as eluent (Found: Mϩ ϩ H, 273.1883. C14H29O3Si requires M,
273.1886); νmax/cmϪ1 3438, 1645, 1422, 1375, 1249, 1103, 1025,
920, 859 and 835; δH Ϫ0.01 [9 H, s, Si(CH3)3], 0.88 [2 H, m,
CH2Si(CH3)3], 1.25 (3 H, d, J 6.5, 7-H3), 2.15 (1 H, dd, J 14.5, 8,
4-H), 2.39 (1 H, dd, J 14.5, 4.5, 4-HЈ), 2.87 (1 H, d, J 4, OH),
3.52 and 3.62 [each 1 H, m, OCHHCH2Si(CH3)3], 4.17 (1 H, q,
J 6.5, 6-H), 4.26 (1 H, m, 3-H), 4.58 and 4.60 (each 1 H, d, J 6.5,
OCHHO), 4.96 (1 H, s, 1Ј-H), 5.04 (1 H, d, J 11, 1-H), 5.09 (1
H, s, 1Ј-HЈ), 5.21 (1 H, d, J 17.5, 1-HЈ) and 5.82 (1 H, ddd, J
17.5, 11, 6, 2-H); δC Ϫ1.4, 18.1, 19.9, 39.8, 65.3, 71.1, 75.5, 92.4,
114.3, 115.3, 140.6 and 145.9; m/z 290 (Mϩ ϩ 18, 8%) and 273
(Mϩ ϩ 1, 10).
(1RS,4RS)- and (1SR,4RS)-3-Methylidene-1-(2-naphthyl)-
pentane-1,4-diols 37 and 39. The (1RS,4RS)-diol 37 was an oil
(32%) (Found: Mϩ, 242.1302. C16H18O2 requires M, 242.1307);
νmax/cmϪ1 3300, 3055, 1645, 1602, 1509, 1451, 1434, 1368, 1320,
1270, 1122, 1106, 1069, 1038, 904, 859, 821 and 748; δH 1.39 (3
H, d, J 6.5, 5-H3), 2.58 (1 H, dd, J 14.5, 3.5, 2-H), 2.70 (1 H,
dd, J 14.5, 9.5, 2-HЈ), 2.81 and 3.3 (each 1 H, br s, OH), 4.46
(1 H, q, J 6.5, 4-H), 5.01 (1 H, dd, J 9.5, 3.5, 1-H), 5.08 and
5.24 (each 1 H, s, vinylic H), 7.55 (3 H, m, ArH) and 7.89 (4 H,
m, ArH); m/z 260 (Mϩ ϩ NH4, 8%), 243 (Mϩ ϩ 1, 18) and 242
(Mϩ, 100). The (1SR,4RS)-diol 39 was an oil (20%) (Found:
Mϩ, 242.1300. C16H18O2 requires M, 242.1307); νmax/cmϪ1 3307,
1644, 1602, 1509, 1453, 1435, 1368, 1270, 1121, 1102, 1071,
1039, 902, 859, 820 and 748; δH 1.42 (3 H, d, J 6.5, 5-H3),
2.29 (1 H, br s, OH), 2.58 (1 H, dd, J 14.5, 9, 2-H), 2.82 (1 H,
dd, J 14.5, 4, 2-HЈ), 3.02 (1 H, br s, OH), 4.39 (1 H, q, J 6.5,
(3RS,6RS)- and (3RS,6SR)-2-Methyl-5-methylidene-6-(2-
trimethylsilylethoxymethoxy)heptan-3-ols 44 and 51. In this case,
chromatography [light petroleum–ethyl acetate (10:1)] separ-
ated the (3RS,6RS)- and (3RS,6SR)-diastereoisomers. The
(3RS,6RS)-isomer of the title compound 44 was an oil (Found:
M
ϩ ϩ H, 289.2195. C15H33O3Si requires M, 289.2199); νmax
/
cmϪ1 3463, 1644, 1467, 1376, 1249, 1103, 1024, 860 and 836; δH
Ϫ0.02 [9 H, s, Si(CH3)3], 0.82 [2 H, m, CH2Si(CH3)3], 0.91 and
2556
J. Chem. Soc., Perkin Trans. 1, 1997

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0.93 (each 3 H, d, J 6, CH3), 1.25 (3 H, d, J 6.5, 7-H3), 1.67 (1 H,
m, 2-H), 2.07 (1 H, dd, J 14.5, 10, 4-H), 2.21 (1 H, d, J 14.5, 4-
HЈ), 2.85 (1 H, d, J 2.5, OH), 3.42 (1 H, m, 3-H), 3.55 and 3.64
[each 1 H, m, OCHHCH2Si(CH3)3], 4.18 (1 H, q, J 6.5, 6-H),
4.63 (2 H, m, OCH2O) and 4.96 and 5.09 (each 1 H, s, vinylic
H); δC Ϫ1.4, 17.7, 18.0, 18.7, 20.4, 33.7, 36.7, 65.4, 75.2, 75.5,
92.4, 114.5 and 147.8; m/z 306 (Mϩ ϩ 18, 8%), 289 (Mϩ ϩ 1,
10) and 243 (32). The (3RS,6SR)-isomer of the title compound
51 was also an oil (Found: Mϩ ϩ H, 289.2201. C15H33O3Si
requires M, 289.2199); νmax/cmϪ1 3474, 1645, 1467, 1375, 1249,
1103, 1027, 860 and 836; δH Ϫ0.02 [9 H, s, Si(CH3)3], 0.91
[8 H, m, CH(CH3)2 and CH2Si(CH3)3], 1.26 (3 H, d, J 6.5,
7-H3), 1.64 (1 H, m, 2-H), 2.00 (1 H, dd, J 14.5, 10, 4-H), 2.32
(1 H, d, J 14.5, 4-HЈ), 2.38 (1 H, d, J 3, OH), 3.49 (1 H, m, 3-H),
3.54 and 3.63 [each 1 H, m, OCHHCH2Si(CH3)3], 4.18 (1 H, q,
J 6.5, 6-H), 4.63 (2 H, m, OCH2O) and 4.97 and 5.10 (each 1 H,
s, vinylic H); δC Ϫ1.4, 17.5, 18.1, 18.8, 20.0, 33.6, 37.1, 65.4,
74.8, 75.8, 92.6, 114.3 and 147.5; m/z 306 (Mϩ ϩ 18, 6%) and
289 (Mϩ ϩ 1, 10).
(1RS,4SR)-3-Methylidene-1-phenyl-4-(2-trimethylsilylethoxy-
methoxy)-5-methylhexan-1-ol 52. Light petroleum–ethyl acetate
(10:1) as eluent (Found: Mϩ ϩ H, 351.2363. C20H35O3Si
requires M, 351.2355); νmax/cmϪ1 3443, 1644, 1493, 1454,
1384, 1250, 1132, 1026, 861, 836, 757 and 700; δH 0.06
[9 H, s, Si(CH3)3], 0.88 and 1.05 (each 3 H, d, J 6.5, CH3),
0.98 [2 H, m, CH2Si(CH3)3], 1.90 (1 H, m, 5-H), 2.41
(1 H, dd, J 15, 9, 2-H), 2.56 (1 H, dd, J 15, 4, 2-HЈ), 3.10
(1 H, br s, OH), 3.57 [1 H, m, OCHHCH2Si(CH3)3], 3.67
(1 H, d, J 8.5, 4-H), 3.77 [1 H, m, OCHHCH2Si(CH3)3], 4.55
and 4.61 (each 1 H, d, J 7, OCHHO), 4.95 (1 H, dd, J 8.5,
4, 1-H), 5.14 and 5.15 (each 1 H, s, vinylic H) and 7.40
(5 H, m, ArH); δC Ϫ1.4, 18.1, 19.0, 19.3, 30.8, 42.0, 65.5, 72.9,
86.9, 92.7, 117.3, 125.8, 127.3, 128.4, 144.1 and 144.4; m/z
368 (Mϩ ϩ 18, 10%), 351 (Mϩ ϩ 1, 12), 305 (100), 275 (70)
and 220 (67).
diethyl ether–light petroleum (8:2) as eluent gave the diol 23
(12.5 mg, 75%).
Following the above procedure, the SEM ether 47 gave the
diol 24 (12.5 mg, 75%).
(R)-1-Phenylpropane-1,3-diol 25
Ozonolysed air was bubbled through a solution of the diol 23
(20 mg, 0.10 mmol) in methanol (3 cm3) at Ϫ78 ЊC for 30 min.
Air was then blown through the solution for 10 min, and di-
methyl sulfide (65 mg, 1.0 mmol) was added. The reaction was
allowed to warm to room temperature and the solvent was
removed under reduced pressure. The residue was dissolved in
methanol (3 cm3), sodium borohydride (15 mg, 0.4 mmol) was
added at 0 ЊC and the mixture was stirred for 2 h at room tem-
perature. Aqueous hydrogen chloride (1 ; 1 cm3) was added at
0 ЊC, the layers were separated, and the aqueous layer was
extracted with ethyl acetate (3 × 3 cm3). The combined organic
extracts were dried (MgSO4), filtered and concentrated under
reduced pressure. Chromatography of the residue eluting with
light petroleum–ethyl acetate (9.8:0.2), gave (1R,3RS,4R)-
1-phenylpentane-1,3,4-triol (15.3 mg, 75%) (Found: Mϩ,
196.1099. C11H16O3 requires M, 196.1099); [α]D ϩ92.0 (c 0.4,
CH2Cl2); νmax/cmϪ1 3383, 3063, 3030, 1453, 1433, 1377, 1058,
760 and 701; δH 1.15 (3 H, d, J 7, 5-H3), 1.65 (1 H, br s, OH),
1.71–2.04 (2 H, m, 2-H2), 2.30 and 3.19 (each 1 H, br s, OH),
3.57–3.93 (2 H, m, 3-H and 4-H), 4.96 (0.6 H, dd, J 10, 4, 1-H),
5.07 (0.4 H, t, J 6, 1-H) and 7.32 (5 H, m, ArH); δC 17.1, 39.3,
70.2, 74.4, 75.3, 125.7, 127.6, 128.5 and 144.2; m/z 197 (Mϩ ϩ 1,
12%) and 196 (Mϩ, 100).
Saturated aqueous sodium hydrogen carbonate (15 µl) was
added to a solution of the triol (30 mg, 0.15 mmol), maintain-
ing the temperature below 25 ЊC. Solid sodium periodate (66
mg, 0.30 mmol) was added over a 10 min period with vigorous
stirring and the reaction was allowed to proceed for 2 h while
the temperature was maintained below 25 ЊC. The solid was
removed by filtration, the filtrate dried (MgSO4) and dichloro-
methane removed under reduced pressure. The crude product
was dissolved in methanol (5 cm3), sodium borohydride (46 mg,
1.22 mmol) was added at 0 ЊC and the mixture was stirred for 2
h at room temperature. Aqueous hydrogen chloride (1 ; 1 cm3)
was added at 0 ЊC, the layers were separated, and the aqueous
layer was extracted with ethyl acetate (3 × 3 cm3). The com-
bined organic extracts were dried (MgSO4), filtered and con-
centrated under reduced pressure. Chromatography of the
residue, eluting with ether–light petroleum (6:4), gave (R)-1-
phenylpropane-1,3-diol 25 (15.3 mg, 75%) (Found: Mϩ,
152.0841. C9H12O2 requires M, 152.0837); [α]D ϩ52.9 (c 1.2,
CHCl3) [lit.,12 ϩ69.0 (c 1.51, CHCl3)].
(1RS,4SR)-4-(Methoxymethoxy)-5-methyl-3-methylidene-1-
phenylhexan-1-ol 53. Light petroleum–ethyl acetate (8:1) as
eluent (Found: Mϩ ϩ H, 265.1809. C16H25O3 requires M,
265.1804); νmax/cmϪ1 3443, 1644, 1493, 1453, 1385, 1157, 1092,
1033, 915, 757 and 701; δH 0.88 and 1.06 (each 3 H, d, J 6.5,
CH3), 1.90 (1 H, m, 5-H), 2.42 (1 H, dd, J 14.5, 8, 2-H), 2.55 (1
H, dd, J 14.5, 4.5, 2-HЈ), 2.97 (1 H, br s, OH), 3.41 (3 H, s,
OCH3), 3.64 (1 H, d, J 8.5, 4-H), 4.45 and 4.58 (each 1 H, d, J 7,
OCHHO), 4.95 (1 H, dd, J 8, 4.5, 1-H), 5.13 and 5.16 (each 1 H,
s, vinylic H) and 7.40 (5 H, m, ArH); δC 19.1, 19.3, 30.6, 41.7,
55.8, 72.8, 86.9, 94.4, 117.5, 125.9, 127.4, 128.4, 143.8 and
144.4; m/z 282 (Mϩ ϩ 18, 8%), 265 (Mϩ ϩ 1, 7), 247 (100) and
220 (70).
Ethyl (2S,5R)-2-hydroxy-4-methylidene-5-(2-trimethylsilyl-
ethoxymethoxy)hexanoate 57. (71%) (Found:
M
ϩ ϩ NH4,
(1R,4R)-3-Methylidene-1-phenyl-4-(tert-butyldimethylsilyloxy)-
pentan-1-ol 26 and (2R,5R)-3-methylidene-5-phenyl-5-(tert-
butyldimethylsilyloxy)pentan-2-ol 29
336.2199. C15H34NO5Si requires M, 336.2206); [α]D ϩ35.2 (c 3,
CHCl3); νmax/cmϪ1 3448, 1738, 1372, 1249, 1197, 1102, 1025,
860 and 836; δH 0.05 [9 H, s, Si(CH3)3], 0.96 [2 H, m,
CH2Si(CH3)], 1.32 (6 H, m, 6-H3 and CH3CH2), 2.48 (1 H, dd, J
15, 7, 3-H), 2.6 (1 H, dd, J 15, 4, 3-HЈ), 3.39 (1 H, d, J 5.5, OH),
3.53–3.82 [2 H, m, OCH2CH2Si(CH3)3], 4.20–4.43 (4 H, m, 2-H,
CH3CH2 and 5-H), 4.67 and 4.68 (each 1 H, d, J 7, OCHHO)
and 5.09 and 5.19 (each 1 H, s, vinylic H); m/z 336 (Mϩ ϩ 18,
14%) and 243 (100).
tert-Butyldimethylsilyl trifluoromethanesulfonate (37 mg, 0.14
mmol) was added dropwise to a stirred solution of (1R,4R)-3-
methylidene-1-phenylpentane-1,4-diol 23 (25 mg, 0.13 mmol)
and 2,6-lutidine (28 mg, 0.26 mmol) in dichloromethane (1 cm3)
at 0 ЊC under argon. The reaction was allowed to warm to room
temperature and was stirred for 3 h. Water (1 cm3) and dichloro-
methane (5 cm3) were added. The organic extract was washed
with brine (1 cm3), dried (MgSO4) and concentrated under
reduced pressure. Chromatography of the residue eluting with
light petroleum–ether (8:2) gave the title compound 26 as a
colourless oil (21.5 mg, 54%) (Found: Mϩ Ϫ OH, 289.1985.
C18H29OSi requires M, 289.1988); [α]D ϩ11.1 (c 0.5, CH2Cl2);
νmax/cmϪ1 3450, 1643, 1471, 1255, 1197, 1116, 1087, 975, 836,
777 and 700; δH 0.17 and 0.18 (each 3 H, s, CH3Si), 0.97 [9 H, s,
SiC(CH3)3], 1.36 (3 H, d, J 6.5, 5-H3), 2.49 (1 H, dd, J 14.5, 3, 2-
H), 2.57 (1 H, dd, J 14.5, 9.5, 2-HЈ), 4.14 (1 H, s, OH), 4.44 (1
H, q, J 6.5, 4-H), 4.76 (1 H, br d, J 9.5, 1-H), 5.00 and 5.15
(each 1 H, s, vinylic H) and 7.30–7.48 (5 H, m, ArH); δC Ϫ4.7,
Deprotection of 2-trimethylsilylethoxymethyl ethers
Magnesium bromide–diethyl ether (359 mg, 1.39 mmol),
potassium carbonate (169 mg, 1.22 mmol) and butanethiol (75
µl, 0.70 mmol) were added to a stirred solution of the SEM ether
40 (28 mg, 0.087 mmol) in ether (3 cm3) at room temperature.
After 16 h the reaction mixture was partitioned between diethyl
ether and water. The aqueous phase was extracted with ether
(3 × 10 cm3) and the combined organic phases were washed
with brine (1 cm3), dried (MgSO4) and concentrated under
reduced pressure. Chromatography of the residue eluting with
J. Chem. Soc., Perkin Trans. 1, 1997
2557

View Article Online
18.2, 23.1, 25.9, 43.0, 72.9, 74.2, 114.4, 125.8, 127.3, 128.3,
144.7 and 149.8; m/z 289 (Mϩ Ϫ 17, 12%) and 157 (100). A
second fraction was isolated and identified as the title compound
29 (4.5 mg, 12%) (Found: Mϩ, 306.2019. C18H30O2Si requires
M, 306.2015); [α]D ϩ86.8 (c 0.4, CH2Cl2); νmax/cmϪ1 3432, 1644,
1471, 1454, 1363, 1256, 1085, 1065, 1026, 939, 855, 836, 777 and
700; δH Ϫ0.20 and Ϫ0.04 (each 3 H, s, CH3Si), 0.84 [9 H, s,
SiC(CH3)3], 1.20 (3 H, d, J 6.5, 1-H3), 2.31 (1 H, dd, J 14, 4, 4-
H), 2.59 (1 H, dd, J 14, 9, 4-HЈ), 3.37 (1 H, d, J 2, OH), 4.27 (1
H, q, J 6.5, 2-H), 4.74 (1 H, dd, J 9, 4, 5-H), 4.86 and 5.06 (each
1 H, s, vinylic H) and 7.30 (5 H, m, ArH); m/z 306 (Mϩ, 10%)
and 175 (100).
2.70 (1 H, d, J 4, OH), 3.46 and 3.77 [each 1 H, m, OCH-
HCH2Si(CH3)3], 4.32 (1 H, m, 2-H), 4.57 and 4.66 (each 1 H, d,
J 7, OCHHO), 4.88 (1 H, dd, J 8, 5.5, 5-H), 4.95 and 5.16 (each
1 H, s, vinylic H) and 7.35 (5 H, m, ArH); m/z 340 (Mϩ ϩ 18,
30%) and 323 (Mϩ ϩ 1, 20). Further elution gave unchanged
diol 24 (16%).
Asymmetric catalysis of reactions between (R)-2-[1-(2-trimethyl-
silylethoxymethoxy)ethyl]prop-2-enyl(tributyl)stannane 12 and
benzaldehyde
A solution of titanium() dibromide diisopropoxide (7.8 mg,
0.024 mmol) in toluene (0.12 cm3) was added dropwise to a
stirred solution of powdered 4 Å molecular sieves (50 mg) and
(R)-BINOL (3.4 mg, 0.012 mmoles) in dichloromethane (1 cm3)
at room temperature under argon. After stirring 2 h at room
temperature a solution of benzaldehyde (12 mg, 0.12 mmol) in
dichloromethane (50 cm3) was added to it. The reaction was
cooled at Ϫ78 ЊC and a solution of (R)-2-[1-(2-trimethylsilyl-
ethoxymethoxy)ethyl]prop-2-enyl(tributyl)stannane 12 (60 mg,
0.12 mmol) in dichloromethane (0.5 cm3) was added. The reac-
tion was stirred for 30 min at Ϫ78 ЊC and 3 days at Ϫ20 ЊC.
Saturated aqueous NaHCO3 (0.5 cm3) was added and the mix-
ture was filtered through a plug of Celite, dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the
residue eluting with diethyl ether–light petroleum (4:6) gave
(1R,4R)-3-methylidene-1-phenyl-4-(2-trimethylsilylethoxymeth-
(1S,4R)-3-Methylidene-1-phenyl-4-(tert-butyldimethylsilyloxy)-
pentan-1-ol 30 and (2R,5S)-3-methylidene-5-phenyl-5-(tert-
butyldimethylsilyloxy)pentan-2-ol 33
Following the above procedure, the (1S,4R)-diol 24 gave the
title compound 30 (10 mg, 25%) (Found: Mϩ, 306.2011.
C18H30O2Si requires M, 306.2015); [α]D Ϫ58.0 (c 1.0, CH2Cl2);
νmax/cmϪ1 3432, 1645, 1471, 1463, 1453, 1370, 1254, 1114, 1087,
1055, 907, 836 and 776; δH 0.07 and 0.8 (each 3 H, s, CH3Si),
0.90 [9 H, s, SiC(CH3)3], 1.28 (3 H, d, J 5, 5-H3), 2.38 (1 H, dd, J
11, 7, 2-H), 2.62 (1 H, dd, J 11, 2.5, 2-HЈ), 3.01 (1 H, d, J 2.5,
OH), 4.33 (1 H, q, J 5, 4-H), 4.83 and 5.08 (each 1 H, s, vinylic
H), 4.92 (1 H, m, 1-H) and 7.36 (5 H, m, ArH); m/z 306 (Mϩ,
4%), 305 (Mϩ Ϫ H, 5), 289 (20) and 157 (100). This was fol-
lowed by the title compound 33 (10 mg, 25%) (Found: Mϩ,
306.2018. C18H30O2Si requires M, 306.2015); [α]D Ϫ115.5 (c 0.1,
CH2Cl2); νmax/cmϪ1 3454, 1650, 1493, 1472, 1463, 1363, 1256,
1087, 1068, 940, 836, 770 and 770; δH Ϫ0.18 and Ϫ0.02 (each 3
H, s, CH3Si), 0.85 [9 H, s, SiC(CH3)3], 1.24 (3 H, d, J 5, 1-H3),
2.39 (1 H, dd, J 10.5, 5.5, 4-H), 2.54 (1 H, dd, J 10.5, 3.5, 4-HЈ),
2.70 (1 H, d, J 3, OH), 4.18 (1 H, m, 2-H), 4.67 and 5.03 (each 1
H, s, vinylic H), 4.84 (1 H, dd, J 5.5, 3.5, 5-H) and 7.24 (5 H, m,
ArH); m/z 306 (Mϩ, 6%) and 192 (100).
1
oxy)pentan-1-ol 40 (15.3 mg, 40%) containing ca. 8% (by H
NMR spectroscopy) of its epimer 47, [α]D ϩ83.1 (c 1.0, CH2Cl2)
(Found:
M
ϩ ϩ NH4, 340.2317. C18H34NO3Si requires M,
340.2308); νmax/cmϪ1 3443, 1493, 1453, 1375, 1248, 1023, 859,
836, 755 and 699; δH 0.06 [9 H, s, Si(CH3)3], 1.00 [2 H, m,
CH2Si(CH3)3], 1.35 (3 H, d, J 6.5, 5-H3), 2.45 (2 H, m, 2-H2),
3.46 (1 H, d, J 2.5, OH), 3.70 [2 H, m, OCH2CH2Si(CH3)3], 4.27
(1 H, q, J 6.5, 4-H), 4.73 (2 H, s, OCH2O), 4.85 (1 H, dd, J 7.5,
4.5, 1-H), 5.12 and 5.22 (each 1 H, s, vinylic H) and 7.40 (5 H,
m, ArH); δC Ϫ1.4, 18.1, 20.2, 42.4, 65.5, 73.3, 75.7, 92.5, 115.3,
125.8, 127.4, 128.4, 144.5 and 146.9; m/z 340 (Mϩ ϩ 18, 82%)
and 323 (Mϩ ϩ 1, 60).
(2RS,5RS)-3-Methylidene-5-phenyl-5-(2-trimethylsilylethoxy-
methoxy)pentan-2-ol 54
N,N-Diisopropylethylamine (267 mg, 2.07 mmol) was added to
the diol 23 (132 mg, 0.687 mmol) in dichloromethane (4 cm3).
The solution was cooled to 0 ЊC, 2-trimethylsilylethoxymethyl
chloride (122 mg, 0.734 mmol) was added, and the reaction
mixture stirred at room temperature for 12 h. The reaction was
diluted with dichloromethane (5 cm3) and washed with water (1
cm3) and brine (1 cm3). The organic layer was dried (MgSO4)
and concentrated under reduced pressure. Chromatography of
the residue using diethyl ether–light petroleum (3:7) as eluent
gave the SEM ether 40 (33 mg, 15%) followed by the title com-
This procedure using (S)-BINOL gave (1S,4R)-3-methyl-
idene-1-phenyl-4-(2-trimethylsilylethoxymethoxy)pentan-1-ol
1
47 (11.5 mg, 30%) containing ca. 12% (by H NMR spectro-
scopy) of its epimer 40 (Found: Mϩ ϩ NH4, 340.2298.
C18H34NO3Si requires M, 340.2308); [α]D Ϫ2.0 (c 0.5, CH2Cl2).
(R)-1-Phenyl-4-(2-trimethylsilylethoxymethoxy)pent-1-en-3-one
62
Ozonolysed air was bubbled through a solution of the alkene 47
(140 mg, 0.43 mmol) in methanol (5 cm3) at Ϫ78 ЊC for 30 min.
Air was then blown through the solution for 10 min, and di-
methyl sulfide (270 mg, 4.34 mmol) was added. The reaction
was allowed to warm to room temperature and the solvent was
removed under reduced pressure. Methanesulfonyl chloride (30
mg, 0.26 mmol) and triethylamine (66 mg, 0.65 mmol) were
added sequentially to the residue at 0 ЊC. The reaction mixture
was allowed to warm to room temperature and was stirred for
3 h, before being partitioned between dichloromethane and
water. The organic extract was washed with brine (1 cm3), dried
(MgSO4) and concentrated under reduced pressure. Chroma-
tography of the residue eluting with diethyl ether–light pet-
roleum (2:8), gave the title compound 62 (93 mg, 70%) (Found:
pound 54 (33 mg, 15%) (Found:
M
ϩ ϩ NH4, 340.2304.
C18H34NO3Si requires M, 340.2308); νmax/cmϪ1 3475, 1454,
1249, 1103, 1058, 1021, 916, 860, 836, 756 and 700; δH 0.04 [9 H,
s, Si(CH3)3], 0.88 [2 H, m, CH2Si(CH3)3], 1.29 (3 H, d, J 6.5, 1-
H3), 2.40 (1 H, dd, J 14.5, 4, 4-H), 2.71 (1 H, dd, J 14.5, 10, 4-
HЈ), 3.33 (1 H, d, J 2.5, OH), 3.45 and 3.77 [each 1 H, m,
OCHHCH2Si(CH3)3], 4.36 (1 H, m, 2-H), 4.54 and 4.63 (each 1
H, d, J 7, OCHHO), 4.77 (1 H, dd, J 10, 4, 5-H), 5.01 and 5.15
(each 1 H, s, vinylic H) and 7.36 (5 H, m, ArH); m/z 340
(Mϩ ϩ 18, 14%), 323 (Mϩ ϩ 1, 8) and 192 (100). Further elu-
tion gave recovered diol 23 (24 mg, 18%).
(2RS,5SR)-3-Methylidene-5-phenyl-5-(2-trimethylsilylethoxy-
methoxy)pentan-2-ol 55
M
ϩ ϩ H, 307.1731. C17H27O3Si requires M, 307.1729); [α]D
ϩ69.4 (c 3.0, CH2Cl2); νmax/cmϪ1 1692, 1609, 1576, 1450, 1373,
1331, 1249, 1202, 1109, 1060, 1031, 860, 836 and 761; δH 0.00 [9
H, s, Si(CH3)3], 0.93 [2 H, m, CH2Si(CH3)3], 1.44 (3 H, d, J 7, 5-
H3), 3.67 [2 H, m, OCH2CH2Si(CH3)3], 4.38 (1 H, q, J 7, 4-H),
4.75 and 4.82 (each 1 H, d, J 7, OCHHO), 7.13 (1 H, d, J 16, 2-
H), 7.42 (3 H, m, ArH), 7.61 (2 H, m, ArH) and 7.76 (1 H, d, J
16, 1-H); δC 1.6, 17.9, 65.8, 77.8, 94.2, 120.8, 128.4, 128.8, 128.9,
130.5, 134.5, 143.7 and 200.1; m/z 307 (Mϩ ϩ 1, 12%), 279 (20)
and 249 (100).
Chromatography of the products obtained by treatment of the
(1RS,4SR)-diol 24 with 2-trimethylsilylethoxymethyl chloride
following the above procedure gave the SEM ether 47 (35 mg,
16%) followed by the title compound 55 (33 mg, 15%) (Found:
M
ϩ ϩ NH4, 340.2299. C18H34NO3Si requires M, 340.2308);
νmax/cmϪ1 3451, 1454, 1249, 1152, 1102, 1057, 1023, 938, 916,
860, 836, 757 and 701; δH 0.04 [9 H, s, Si(CH3)3], 0.90 [2 H, m,
CH2Si(CH3)3], 1.34 (3 H, d, J 6.5, 1-H3), 2.58 (2 H, m, 4-H2),
2558
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
N,N-Diisopropylethylamine (3.9 g, 0.03 mol) was added to a
solution of isobutyl (R)-lactate 63 (1.5 g, 0.01 mol) in dichloro-
methane (10 cm3). The solution was cooled at 0 ЊC, then 2-
trimethylsilylethoxymethyl chloride (2.6 g, 0.015 mol) was
added and the reaction mixture was stirred at room temperature
for 12 h. The reaction mixture was washed with water and
brine, dried (MgSO4) and concentrated under reduced pressure.
Chromatography of the residue eluting with light petroleum–
ethyl acetate, gave isobutyl (R)-2-(2-trimethylsilylethoxy-
methoxy)propionate (2.41 g, 85%) (Found: Mϩ, 276.4467.
C13H28O4Si requires M, 276.4473); [α]D ϩ70.9 (c 3.2, CH2Cl2).
A solution of isobutyl (R)-2-(2-trimethylsilylethoxymeth-
oxy)propionate (750 mg, 2.71 mmol), lithium hydroxide (0.34 g,
8.15 mmol) in tetrahydrofuran (5 cm3) and water (0.5 cm3), was
stirred at room temperature for 12 h. After acidification using
aqueous hydrogen chloride (1 ; 20 cm3), extraction with ethyl
acetate (3 × 20 cm3) and drying of the organic extract (MgSO4)
gave the acid (598 mg, 80%) as a colourless liquid which was
used immediately. Triethylamine (186 mg, 1.83 mmol) and piv-
aloyl chloride (196 mg, 1.62 mmol) were added dropwise to a
solution of the crude acid (370 mg, 1.68 mmol) in tetrahydro-
furan (15 cm3) at Ϫ78 ЊC, and the resulting solution was
allowed to warm to 0 ЊC over 2 h, and then was maintained at
0 ЊC for 1 h. A solution of butyllithium (10  in hexane; 0.55
cm3, 5.5 mmol) was added slowly to a stirred suspension of
ethyltriphenylphosphonium bromide (1.96 g, 5.5 mmol) in
tetrahydrofuran (15 cm3) at 0 ЊC. After being stirred at 0 ЊC for
30 min, the ylide solution was added dropwise by syringe to
the crude mixed anhydride solution, which had been recooled
to Ϫ78 ЊC. The reaction was maintained at Ϫ78 ЊC for 1 h,
allowed to warm to room temperature for 2 h, and then
quenched by the addition of saturated aqueous ammonium
chloride (35 cm3). The organic phase was extracted with ethyl
acetate (3 × 20 cm3), washed sequentially with saturated aque-
ous sodium hydrogen carbonate (2 × 15 cm3) and brine (2 ×
15 cm3), dried (MgSO4) and concentrated under reduced
pressure. Chromatography of the residue eluting with light
petroleum–ethyl acetate (1:4), gave the ylide 64 (402 mg,
50%) (Found: Mϩ ϩ H, 479.2086. C28H36O3SiP requires M,
479.2172); [α]D ϩ39.6 (c 1.1, CH2Cl2); νmax/cmϪ1 3057, 1544,
1438, 1393, 1248, 1189, 1160, 1107, 1029, 861, 837, 749, 716
and 693; δH 0.00 [9 H, s, Si(CH3)3], 0.96 [2 H, m, CH2Si(CH3)3],
1.46 (3 H, d, J 6.5, 1-H3), 3.59–3.80 [2 H, m, OCH2CH2-
Si(CH3)3], 4.13 (2 H, m, 2-H and 4-H), 4.83 and 4.85 (each 1 H,
d, J 7, OCHHO) and 7.56 (15 H, m, ArH); m/z 479 (Mϩ ϩ 1,
100).
72.3, 78.8, 94.3 and 213.5; m/z 308 (Mϩ ϩ NH4, 98%) and 291
(Mϩ ϩ H, 30).
(2RS,3RS,5SR)-6-Methyl-2-(2-trimethylsilylethoxymethoxy)-
heptane-3,5-diol 69
Methoxydiethylborane (1  in THF; 0.2 cm3, 0.198 mmol) was
added dropwise to a solution of hydroxy ketone 68 (53 mg, 0.18
mmol) in tetrahydrofuran–methanol (5:1; 2.4 cm3) at Ϫ78 ЊC
and the mixture was stirred for 15 min. Sodium borohydride
(0.198 mmol) was added and the mixture was stirred at Ϫ78 ЊC
for 5 h before acetic acid (0.21 cm3) was added. The mixture was
then diluted with ethyl acetate, washed with aqueous sodium
hydrogen carbonate, dried (MgSO4), and concentrated under
reduced pressure. The residue was azeotroped with methanol
until hydrolysis of the borane was complete. Chromatography
using light petroleum–ethyl acetate (5:1) as eluent gave the title
compound 69 (32 mg, 60%) (Found: Mϩ ϩ H, 293.2150.
C14H33O4Si requires M, 293.2148); νmax/cmϪ1 3390, 1466, 1379,
1249, 1102, 1056, 1029, 858 and 836; δH Ϫ0.01 [9 H, s,
Si(CH3)3], 0.89 [8 H, m, 2 × CH3 and CH2Si(CH3)3], 1.14 (3 H,
d, J 6, 1-H3), 1.41 (1 H, dt, J 14, 10, 4-H), 1.55 (1 H, dt, J 14, 2,
4-HЈ), 1.66 (1 H, m, 6-H), 3.58 [5 H, m, 2-H, 3-H, 5-H and
OCH2CH2Si(CH3)3], 3.71 and 3.78 (each 1 H, br s, OH) and
4.71 (2 H, m, OCH2O); δC Ϫ1.4, 16.6, 17.5, 18.1, 18.4, 33.95,
35.3, 65.7, 76.4, 76.9, 78.8 and 94.3; m/z 310 (Mϩ ϩ NH4, 20%),
293 (Mϩ ϩ H, 75) and 247 (28).
(2RS,3SR,5SR)-6-Methyl-2-(2-trimethylsilylethoxymethoxy)-
heptane-3,5-diol 70
Anhydrous acetic acid (1.5 cm3) was added to a solution of
tetramethylammonium triacetoxyborohydride (700 mg, 2.68
mmol) in anhydrous acetonitrile (1.5 cm3) and the mixture
stirred at room temp. for 30 min. A solution of hydroxy ketone
68 (97 mg, 0.334 mmol) in anhydrous acetonitrile (0.7 cm3) was
added and the mixture stirred for 75 min at room temp. Water
was added, followed by ethyl acetate, and solid potassium car-
bonate until the pH reached 7. The aqueous solution was
extracted with ethyl acetate and the combined organic extracts
dried (MgSO4) and concentrated under reduced pressure.
Chromatography of the residue using light petroleum–ethyl
acetate (2:1) as eluent gave the title compound 70 (88 mg, 90%)
(Found: Mϩ ϩ H, 293.2151. C14H33O4Si requires M, 293.2148);
νmax/cmϪ1 3416, 1410, 1249, 1104, 1056, 1029, 859 and 836; δH
Ϫ0.01 [9 H, s, Si(CH3)3], 0.86 and 0.91 (each 3 H, d, J 7, CH3),
0.87 [2 H, m, CH2Si(CH3)3], 1.13 (3 H, d, J 6.5, 1-H3), 1.19 and
1.50 (each 1 H, m, 4-H), 1.66 [1 H, m, CH(CH3)2], 2.37 and 3.20
(each 1 H, br s, OH), 3.62 (4 H, m), 3.83 (1 H, m) and 4.67 and
4.70 (each 1 H, d, J 7, OCHHO); δC Ϫ1.4, 15.8, 17.9, 18.1, 18.8,
33.9, 34.8, 65.6, 70.8, 73.4, 78.6 and 94.2; m/z 310 (Mϩ ϩ NH4,
13%), 293 (Mϩ ϩ H, 70), 247 (38), 235 (30) and 192 (100).
A solution of the ylide 64 (250 mg, 0.52 mmol) and benzal-
dehyde (58 mg, 0.44 mmol) in benzene (5 cm3) was heated under
reflux for 60 h. The reaction mixture was concentrated under
reduced pressure. Chromatography of the residue eluting with
diethyl ether–light petroleum (2:8) gave the title compound 62
(128 mg, 80%) (Found: Mϩ ϩ H, 307.1726. C17H27O3Si requires
M, 307.1729); [α]D ϩ100.4 (c 2.5, CH2Cl2).
Crystal data for diol 36‡
C12H15NO4, M = 237.25, primitive orthorhombic cell, space
group Pbca (# 61), crystal dimensions 0.30 × 0.40 × 0.50 mm,
yellow crystal, a = 24.251(6), b = 14.837(9), c = 13.797(2) Å,
U = 4964(2) Å3 using the setting angles of 25 carefully centred
reflections in the range 30.21 < 2θ < 38.52Њ, Z = 16, Dc = 1.27 g
cmϪ1, F(000) = 2016.00. Rigaku AFC5R diffractometer, graph-
ite monochromated Mo-Kα radiation (λ = 0.710 69 Å) and a
rotating anode generator. The data were collected at a tem-
perature of 23 ± 1 ЊC using the ω scan technique to a maximum
of 2θ value of 50.1Њ. The weak reflections [I < 10.0σ(I)] were
rescanned (maximum of three scans) and the counts were
accumulated to ensure good counting statistics. A total of 4913
(2RS,5SR)-5-Hydroxy-6-methyl-2-(2-trimethylsilylethoxy-
methoxy)heptan-3-one 68
Ozonolysed air was bubbled through a solution of the alkenol
51 (540 mg, 1.875 mmol) in methanol (80 cm3) at Ϫ78 ЊC for 30
min. Air was then blown through the solution for 10 min, and
dimethyl sulfide (2.06 g, 18.75 mmol) was added. The mixture
was allowed to warm to room temp., and was concentrated
under reduced pressure. Chromatography of the residue using
light petroleum–ethyl acetate as eluent (10:1) gave the title
compound 68 (326 mg, 60%) (Found: Mϩ ϩ NH4, 308.2263.
C14H34NO4Si requires M, 308.2257); νmax/cmϪ1 3492, 1716,
1467, 1379, 1250, 1109, 1058, 1030, 861 and 836; δH Ϫ0.01 [9 H,
s, Si(CH3)3], 0.9 [8 H, m, 2 × CH3 and CH2Si(CH3)3], 1.29 (3 H,
d, J 6.5, 1-H3), 1.68 (1 H, m, 6-H), 2.63 (2 H, m, 4-H2), 2.97 (1
H, d, J 3, OH), 3.59 [2 H, m, OCH2CH2Si(CH3)3], 3.79 (1 H, m,
5-H), 4.10 (1 H, q, J 6.5, 2-H), 4.67 and 4.69 (each 1 H, d,
J 7, OCHHO); δC Ϫ1.4, 17.2, 17.8, 18.0, 18.4, 33.2, 41.8, 65.9,
‡ Atomic coordinates, thermal parameters and bond lengths and angles
have been deposited at the Cambridge Crystallographic Data Centre
(CCDC). See Instructions for Authors, J. Chem. Soc., Perkin Trans. 1,
1997, Issue 1. Any request to the CCDC for this material should quote
the full literature citation and the reference number 207/126.
J. Chem. Soc., Perkin Trans. 1, 1997
2559

View Article Online
Chem., 1993, 58, 6543; G. E. Keck and L. S. Geraci, Tetrahedron
reflections were collected. The intensities of three representative
reflections were measured after every 150 reflections. Over the
course of data collection, the standards decreased by 3.5%. A
linear correction factor was applied to the data to account for
this phenomenon. The linear absorption coefficient, µ, for Mo-
Kα radiation is 0.96 cmϪ1. An empirical absorption correction
based on azimuthal scans of several reflections was applied
which resulted in transmission factors ranging from 0.86 to
1.00. The data were corrected for Lorentz and polarisation
effects. The structure was solved by direct methods20 and
expanded using Fourier techniques.21 The asymmetric unit con-
tains two molecules, which are geometrically the same, within
experimental error. Fig. 1 shows molecule 1. The non-hydrogen
atoms were refined anisotropically. Hydrogen atoms bonded to
carbon were included in calculated positions. Those bonded to
oxygen were found by difference Fourier techniques. Some were
allowed to refine isotropically in early rounds of refinement, but
all were fixed in the final rounds. The final cycle of full-matrix
least-squares refinement on F was based on 2226 observed
reflections [I > 2.50σ(I)] and 307 variable parameters and con-
verged (largest parameter shift was 0.00 times its esd), with
R = 0.085, Rω = 0.069, weighting scheme ω = 1/[σ2Fo ϩ 0.000 01
|Fo|2]. The maximum and minimum peaks on the final difference
Fourier map corresponded to 0.55 and Ϫ0.36 e ÅϪ3, respect-
ively. Neutral atom scattering factors were taken from Cromer
and Waber.22 Anomalous dispersion effects were included in
Fcal;23 the values for ∆f Ј and ∆f Љ were those of Creagh and
McAuley.24 The values for the mass attenuation coefficients are
those of Creagh and Hubell.25 All calculations were performed
using the teXsan 26 crystallographic software package of
Molecular Structure Corporation.
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Acknowledgements
We thank the European Commission and the Spanish DGI-
CYT for fellowships (to M. G and P. A.).
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Received 2nd April 1997
Accepted 3rd June 1997
2560
J. Chem. Soc., Perkin Trans. 1, 1997