Stereocontrol in organic synthesis using silicon-containing compounds. Syntheses of (±)-2-deoxyribonolactone and (±)-arabonolactone

Article abstract of DOI:10.1039/a804282i

Samarium iodide reacts with methyl (Z)-3-dimethyl(4-methylphenyl)silylprop-2-enoate 5b to give dimethyl (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]hexane-1,6-dioate 8b with high stereoselectivity. This meso diester can be converted into (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]pentan-5-olide 16 by Dieckmann cyclisation, demethoxycarbonylation and Baeyer-Villiger reaction. Silyl-to-hydroxy conversion and relactonisation gave (±)-deoxyribonolactone, and anti-selective enolate hydroxylation followed by silyl-to-hydroxy conversion gave (±)-arabonolactone. An attempt to synthesise sugars with the relative configuration (3RS,4RS) was thwarted by an unprecedented retention of configuration at the migration origin in the cationic rearrangement of (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]-5-hydroxypentanoic acid 28 to (3RS,4SR)-3,5-bis[dimethyl(4-methylphenyl)silyl]pentan-1,4-olide 30.

Full text of DOI:10.1039/a804282i

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Stereocontrol in organic synthesis using silicon-containing
compounds. Syntheses of ( )-2-deoxyribonolactone and
( )-arabonolactone
Ian Fleming* and Sunil K. Ghosh
Department of Chemistry, Lensfield Road, Cambridge, UK CB2 1EW
Samarium iodide reacts with methyl (Z)-3-dimethyl(4-methylphenyl)silylprop-2-enoate 5b to give
dimethyl (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]hexane-1,6-dioate 8b with high stereo-
selectivity. This meso diester can be converted into (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]-
pentan-5-olide 16 by Dieckmann cyclisation, demethoxycarbonylation and Baeyer–Villiger reaction. Silyl-
to-hydroxyconversionandrelactonisationgave( )-deoxyribonolactone,andanti-selectiveenolatehydroxyl-
ation followed by silyl-to-hydroxy conversion gave ( )-arabonolactone. An attempt to synthesise sugars
with the relative configuration (3RS,4RS) was thwarted by an unprecedented retention of configuration
at the migration origin in the cationic rearrangement of (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]-
5-hydroxypentanoic acid 28 to (3RS,4SR)-3,5-bis[dimethyl(4-methylphenyl)silyl]pentan-1,4-olide 30.
the synthesis of compounds having the two silyl groups 1,2-
Introduction
related and providing suitably versatile functionality at both
ends of the chain. We prepared the trans acrylic esters 5 by
hydrosilylation of methyl acrylate using dicobalt octacarbonyl
as the catalyst,6 and the cis ester 7 by silylation of ethynylmag-
nesium bromide with tolyldimethylsilyl chloride followed by
methoxycarbonylation and catalytic hydrogenation (Scheme 2).
In order to extend the power of our silicon-based methods to
the synthesis of target molecules having more than the three or
four stereogenic centres present in the syntheses described so
far, we wanted to be able to set up starting materials possessing
two (or more) silicon-bearing centres related to each other. We
could also see that it would give us greater scope if the two
silicon-bearing centres were available in compounds having
them 1,2-related, 1,3-related and 1,4-related, and all these
molecules should also have terminal functionality, with which
to transfer stereochemical information out along each chain.
We have already reported a method for setting up 1,3-related,
silicon-bearing centres,1 and the following paper2 describes a
method for setting them up 1,4-related. We now describe in full
the synthesis of the diester 8b with the two centres 1,2-related,
enlarging on two preliminary communications.3 Having a com-
pound with 1,2-related silicon-bearing centres, and knowing
that both silyl groups could be converted into hydroxy groups,
we were naturally attracted to the possibility of using it to
synthesise sugars, which we did, not only to demonstrate this
capacity, but also to confirm the stereochemical relationship in
the diester 8b that we had prepared. In the last paper in this
series, we report a synthesis of nonactin from the same diester.
i
ArMe2Si
ArMe2SiH
+
CO2Me
CO2Me
68%
4a Ar = Ph
4b Ar = C6H4Me-p
5a
5b
77%
ii, iii
vi
TolMe2Si
CO2Me
TolMe2Si
CO2Me
iv, v
6
77%
7
92%
ArMe2Si
vii
ArMe2Si
ArMe2Si
CO2Me
CO2Me
CO2Me
CO2Me
+
5 or 7
or viii
ArMe2Si
Ar = Ph
Ar = C6H4Me-p
8a
8b
9a
9b
ArMe2Si
8
9
10
+
CO2Me
from 5a (vii)
from 5b (vii)
from 7 (viii)
48% 17%
54% 11%
25%
30%
24%
Results and discussion
10a
10b
Inanaga reported that samarium() iodide in THF–HMPA
containing one equivalent of tert-butyl alcohol induced the
reductive coupling of β-substituted acrylic acid derivatives like
1, giving 3,4-disubstituted adipic acid derivatives 2 and 3 in
favour (2:1) of the racemic diastereoisomer 2 (Scheme 1).4
72%
0%
Scheme 2 Reagents: i, Co2(CO)8 cat., ArSiMe2H; ii, EtMgBr; iii, Tol-
Me2SiCl; iv, BuLi; v, MeO2CCl; vi, H2, Pd/BaSO4, quinoline; vii, SmI2,
THF, HMPA, ButOH; viii, SmI2, THF, DMPU, dimethyl malonate
In agreement with Inanaga, we found that they gave the adipate
esters 8 and 9 by reductive coupling as the major pathway, and
in part agreement with Alper, there was also some apparently
R
R
R
i
CO2Me
CO2Me
CO2Me
CO2Me
R
+
CO2Me
R
unavoidable reduction of the C᎐C double bond giving the esters
᎐
1 R = Ph(CH2)2
70% 66:34
2
3
10 (Scheme 1). However, in contrast to Inanaga, the β-silylated
acrylic esters 5 and 7 favoured the meso diastereoisomers 8. The
phenyldimethylsilyl-containing product 8a was crystalline, but
low melting (mp 41–42 ЊC), and so we tried the tolyldimethyl-
silyl group. This group proved to have the advantage over the
phenyldimethylsilyl group of imparting a higher melting point
to the product 8b, and it should also prove to be somewhat
easier to remove in our silyl-to-hydroxy conversion. It has the
Scheme 1 Reagents: i, SmI2, THF, HMPA, ButOH
More recently, Alper has reported that he saw no reductive
coupling in HMPA alone, only reduction of the C᎐C double
᎐
bond.5
If the stereoselectivity could be improved, and if the reaction
would work for β-silylacrylic esters, this promised to be ideal for
J. Chem. Soc., Perkin Trans. 1, 1998
2711

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disadvantage that we have been unable to make the correspond-
ing silyllithium reagent from the chloride,7 but we did not need
a silyllithium or cuprate reagent for the preparation of either
the cis or the trans acrylic esters 7 or 5b. We tried several
combinations of solvent, geometry of starting material, and
conditions of coupling, and find that the best, at least for our
substrates, was to use the cis ester 7 in 6:1 THF–DMPU, which
was better than Inanaga’s THF–HMPA, with one equivalent
of freshly prepared samarium iodide at 20 ЊC, and with three
equivalents of dimethyl malonate as the proton source, which
was better than his tert-butyl alcohol. These conditions gave
the easily purified meso diester 8b, mp 96–97 ЊC, in 72% yield,
together with 24% of methyl 3-dimethyl(p-tolyl)silylpropano-
ate, but with no trace of the racemic diastereoisomer 9b, even in
the crude reaction mixture.
AcO
TolMe2Si
TolMe2Si
HO
HO
O
O
ii
iii
O
i
O
11
O
O
AcO
18 76%
16 100%
17 57%
iv, v, vi
OH
AcO
TolMe2Si
TolMe2Si
O
O
O
ii
O
vii, iii
O
HO
O
AcO
OTBDMS
OTBDMS
19 65%
OAc
21 71%
20 64%
AcO
We proved the relative stereochemistry of the major 8b and
minor 9b diastereoisomers by the sequence of reactions in
Scheme 3. Dieckmann cyclisation of the major product and
TolMe2Si
TolMe2Si
HO
HO
O
ii
O
O
O
iii
i
14
O
O
AcO
24 73%
TolMe2Si
22 75%
23 68%
OAc
Scheme 4 Reagents: i, MCPBA, Na2HPO4; ii, KBr, NaOAc, AcOOH;
iii, Ac2O, HClO4; iv, NaHMDS, THF; v, 2-phenylsulfonyl-3-phenyl-
oxaziridine; vi, TBDMSCl, imidazole; vii, TBAF, THF
TolMe2Si
12 83%
arabonolactone, as shown in Scheme 4. For this purpose, we
prepared the cyclopentanone 11 in a slightly better overall yield
(57%) by carrying out the samarium coupling on the E-acrylic
ester 5b in 6:1 THF–DMPU in the absence of a proton source,
but quenching with tert-butyl alcohol. This gave a mixture of
the Dieckmann cyclisation product and the diester 8b, directly
in 70% yield in a ratio of 8:2, which could no doubt have been
raised by longer treatment with butoxide ion. We submitted
the mixture to the conditions of the Krapcho reaction to get
the ketone 11, now easily separable from the diester. Baeyer–
Villiger reaction on the ketone 11 gave the lactone 16. Conver-
sion of the silyl to hydroxy groups using potassium bromide in
buffered peracetic acid10 gave the lactone alcohol 17, which
rearranged in acid to give the corresponding γ-lactone. Acetyl-
iii, iv
TolMe2Si
TolMe2Si
TolMe2Si
TolMe2Si
i, ii
CO2Me
CO2Me
O
11 79%
8b
iii, v
TolMe2Si
TolMe2Si
OAc
1
13 72%
ation gave the known acetate 18 with a H NMR spectrum
identical with that reported. Davis hydroxylation11 of the
lactone 16 followed by silylation gave the lactone 19, which we
converted to the arabonolactone acetate 21, with a 13C NMR
spectrum identical with that reported,12 by way of the γ-lactone
20. By a suitable combination of protection and Mitsunobu
or equivalent reactions, all the pentose lactones and 2-deoxy-
pentose lactones, and hence pentoses, are, in principle, available
from the diol 17 and the triol ether 20.
TolMe2Si
TolMe2Si
TolMe2Si
TolMe2Si
i, ii
CO2Me
CO2Me
O
14 51%
9b
iii, iv
or iii, v
However, it would avoid several of the Mitsunobu reactions,
and much complication, if we could make the racemic diester
9b, having the (3RS,4RS) relative configuration, as easily as we
can make the meso diester 8b, having the (3RS,4SR) relative
configuration. So far, we have been unable to find conditions in
which the liquid diastereoisomer 9b was the major product—
at best, using 6:1 THF–HMPA, and one equivalent of tert-
butyl alcohol as the proton source, we obtained 60% of the
adipic esters 8b and 9b in a ratio of 70:30, and isolated the
racemic adipate 9b from this mixture in only 14% overall
yield (Scheme 2). Nevertheless, we were able to show that this
compound could be a starting material for the synthesis of the
family of (3RS,4RS)-sugars. We repeated the same sequence of
Dieckmann and Krapcho reactions to give the cyclopentanone
14, Baeyer–Villiger reaction to give the lactone 22, silyl-to-
hydroxy conversion to give the diol lactone 23, and isomeris-
ation and acetylation to give acetate 24.13
TolMe2Si
OAc
TolMe2Si
15 80% and 71%
Scheme 3 Reagents: i, LDA; ii, NaCl, DMSO, H2O; iii, NaBH4; iv,
Ac2O; v, AcOH, DEAD, Ph3P
Krapcho demethoxycarbonylation8 gave the cyclopentanone
11, and we were able to make its diastereoisomer 14 from the
racemic diester isolated as the minor product in our exploratory
work on the reductive coupling. The cyclopentanone 11 gave
a 93:7 mixture of two acetates 12 and 13 on reduction with
sodium borohydride followed by acetylation. Alternatively,
reduction with sodium borohydride, followed by Mitsunobu
reaction9 using acetic acid, gave the acetates 12 and 13 in a
ratio of 7:93. In contrast, the cyclopentanone 14 gave a single
acetate 15 on reduction with sodium borohydride followed
by acetylation, and Mitsunobu reaction on the intermediate
alcohol returned the same acetate.
These three pentose syntheses are of course, of racemic sugar
derivatives. To make the first two 18 and 21 enantiomerically
enriched, we needed to find a method for desymmetrising the
meso ketone 11, and have done so14 using Simpkins’ chiral
base.15 The degree of the desymmetrisation was excellent, but
the sense in which it took place has not yet been established.
We used the cyclopentanone 11 to synthesise ( )-deoxy-
ribonolactone and its acetate 18, and the acetate 21 of ( )-
2712
J. Chem. Soc., Perkin Trans. 1, 1998

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Because we had not been able to prepare the diester 9b in
good yield, we sought an alternative route to the pentose lac-
tone 22 in the (3RS,4RS) series, avoiding the cyclopentanone
14. One way of overcoming this limitation might be to take
advantage of Hudrlik’s observation16 that lactones with an
embedded silylethylcarboxylate group sometimes undergo acid-
catalysed rearrangement, with inversion of configuration at
both sites, as in the example 25 → 26.
(typically 85:15) a γ-lactone in competition with a relactonis-
ation 28 → 16 that we could not completely suppress, but the
γ-lactone 30 that we obtained did not have the stereochemistry
27 that we had expected by analogy with Hudrlik’s work.
We proved the relative configuration in the lactone 30 by
converting the silyl groups to hydroxy groups, in a reaction
taking place reliably with retention of configuration,10 and
acetylating the product to give ( )-deoxyribonolactone di-
acetate 18, immediately recognisable, and distinguishable from
the diastereoisomer 24, which we expected and had already
prepared. To test whether we were observing simply the loss of
stereochemical integrity at C-4, which does have precedent,17 we
repeated this sequence of reactions using the diastereoisomeric
δ-lactone 22, and obtained, in addition to the usual product of
unavoidable (typically 16%) relactonisation 31 → 22, succes-
sively the γ-lactone 27 and ( )-deoxyxylonolactone diacetate
24. (In order to illustrate the connection between the lactones
22, 27 and 24, we have drawn the former in Scheme 5 as the
enantiomer of the drawing in Scheme 4.) We did not detect
O
O
H+
O
O
H
SiMe3
SiMe3
25
26
Not too surprisingly, we were not able to persuade the δ-
lactone 16, to rearrange to the γ-lactone 27, presumably
because the δ-lactone is thermodynamically the more stable
isomer, although we had hoped that steric repulsion between
the cis-disposed silyl groups in the lactone 16 might have dis-
turbed this pattern. To overcome this difficulty, we opened the
lactone to give the γ-hydroxy acid 28, and submitted it to
Mitsunobu conditions without an external nucleophile, hoping
that the kinetic preference for five-membered ring-formation
might set off the [1,2]-sigmatropic silyl shift, 29 arrows (Scheme
5). We found that the hydroxy acid 28 did indeed give largely
1
(TLC, H NMR) any cross contamination in the two series.
Clearly the rearrangement is strictly stereospecific, with reten-
tion of configuration at the migration origin, C-4, a remark-
able event that is, we believe, without precedent in cationic
rearrangements.
One possible explanation we raise only to dismiss. Hudrlik,
knowing the relative configuration in the lactone 25, had proved
the relative configuration in the lactone 26 by converting the
hydroxy acid derived from it into the corresponding trans
alkene with boron trifluoride–diethyl ether and into the cis
alkene with potassium hydride, in reactions known to be stereo-
specifically anti and syn, respectively. Strictly speaking, this is
compatible with double retention as well as with the double
inversion shown in 25 → 26. Dyotropic rearrangements of
this type with double retention or double inversion are forbid-
den to be concerted by the Woodward–Hoffmann rules,18 and
are most likely therefore stepwise ionic processes, as the need
for acid catalysis attests. Naturally Hudrlik chose to illustrate
his reaction as a double inversion, with which we concur,
because it seems extraordinarily unlikely that a nucleophilic
displacement of carboxylate at the migration terminus should
take place with retention of configuration.
TolMe2Si
TolMe2Si
4
O
O
O
TolMe2Si
O
3
TolMe2Si
16
i, ii
27
SiMe2Tol
:O
Ph3P+
TolMe2Si
TolMe2Si
4
3
O
OH
CO2H
We believe that the silyl groups in the intermediate 29 will
be disposed conformationally anti 32 at the time of rearrange-
ment, and that the cation 33 is an intermediate (Scheme 6).
This cation is highly stabilised, with silicon᎐carbon bonds over-
TolMe2Si
OH
28
iii
29
TolMe2Si
TolMe2Si
TolMe2Si
AcO
AcO
TolMe2Si
4
OH
O
4
3
4
O
O
iv, v
CO2H
O
TolMe2Si
O
O
3
TolMe2Si
3
28
30
18 49%
30 70%
4
TolMe2Si
TolMe2Si
O
TolMe2Si
SiMe2Tol
Ö
+
4
3
O
CO2H
4
H
3
Ph3P+
O
OH
3
22
i, ii
SiMe2Tol
SiMe2Tol
32
33
AcO
TolMe2Si
TolMe2Si
4
3
OH
CO2H
4
O
i, ii, iii
iv, v
O
27
71%
TolMe2Si
O
O
30
3
4
AcO
3
SiMe2Tol
24 44%
31
34
Scheme 5 Reagents: i, KOH, MeOH; ii, citric acid; iii, DEAD, Ph3P,
CH2Cl2; iv, KBr, AcOOH, AcOH; v, Ac2O, HClO4
Scheme 6
J. Chem. Soc., Perkin Trans. 1, 1998
2713

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lapping with the empty p-orbital on both surfaces of the
trigonal carbon, thus driving the rearrangement step without
any need for nucleophilic participation. Given that a nucleo-
phile could attack this cation anti to a silyl group on either
surface, it is not at first sight obvious why we observe a high
level of stereospecificity rather than a low level of stereoselectiv-
ity. We suggest that restricted rotation about the bond between
C-3 and C-4 ensures that the carboxylic acid group is held
above the plane of the trigonal carbon, as drawn, thus ensuring
the delivery of the nucleophile, 33 arrow, to the same surface
from which the silyl group had departed. The same argument,
applied to the hydroxy acid 31, leads to the lactone 27. One
other possibility is that the ionisation and rearrangement (32
arrows) are concerted with a shift of the C-3 silyl group, and the
capture of a C-3 ion by the carboxylate to give the β-lactone 34.
This attractive pathway takes place with a graceful sequence
of unexceptionable inversions of configuration at each centre.
We were unable to detect (IR) any β-lactone in our mixtures,
although we looked for it immediately after the reagents
had been mixed, by which time the reaction was effectively over.
Furthermore, it is hard to see how the β-lactone could re-
arrange to the γ-lactone 30, with a symmetry-forbidden inver-
sion at both centres, except by a stepwise pathway, by way of
the very cation 33 that is the basis for our earlier explanation.
The critical point here is that it is not obviously reasonable for
a reaction pathway to avoid the intermediate β-silyl cation 33
in going from the alcohol 28 to the β-lactone 34, only to use it
to get from the β-lactone to the γ-lactone 30. This pathway
remains a possibility, but it seems to us unlikely. The nearest
analogy to the event taking place at C-4 in our reaction is the
retention of configuration sometimes observed in SN1 reactions
of chiral halides and sulfonates in which nucleophilic par-
ticipation by a neighbouring group preserves stereochemical
information in the intermediate cation.19 Retention of con-
figuration at the migration terminus in a cationic rearrange-
ment, in which a β-silyl group preserves configuration, has also
been observed recently,20 complementing our results here, in
which the retention is at the migration origin. We prefer to
avoid bridged structures for the β-silyl cations—they are cer-
tainly unnecessary,21 except as transition structures for the 1,2-
shifts.
TolMe2Si
TolMe2Si
TolMe2Si
CO2Me
O
O
35
30
TolMe2Si
TolMe2Si
O
CO2Me
TolMe2Si
O
O
36
16
TolMe2Si
TolMe2Si
O
TolMe2Si
27
CO2Me
37
Starting material
Conditions
Yield
35:36:37
16
16
1. TBAF, THF; 2. MeI
1. BF3•OEt2; 2. CH2N2
94%
80%
0:100:0
49:14:37
16
30
30
1. RSO3H; 2. CH2N2
1. TBAF, THF; 2. MeI
1. BF3•OEt2; 2. CH2N2
60%
92%
85%
44:4:52
60:39:1
76:19:5
27
27
1. TBAF, THF; 2. MeI
1. BF3•OEt2; 2. CH2N2
83%
93%
8:51:41
4:6:90
Scheme 7
reduced pressure and the residue distilled to give the silane (39.1
g, 75%), bp 68–70 ЊC/30 mmHg; νmax(film)/cmϪ1 2140 (SiH),
1250 (SiMe) and 1110 (SiAr); δH(250 MHz; CDCl3) 7.45 (2 H,
d, J 7.8, Ar), 7.19 (2 H, d, J 7.8, Ar), 4.41 (1 H, septet, J 3.7,
SiH), 2.36 (3 H, s, 4-MeC6H4) and 0.33 (6 H, d, J 3.7, SiMe2);
m/z 150 (41, Mϩ), 149 (20, M Ϫ H) and 135 (100, M Ϫ Me)
(Found: Mϩ, 150.0868. C9H14Si requires M, 150.0865).
With two silyl groups β to the carboxylate group in the lac-
tones 30 and 27, we wondered which would be captured by
fluoride ion on treatment with tetrabutylammonium fluoride
(TBAF) or boron trifluoride–diethyl ether. Baldwin’s rules sug-
gest that endocyclic elimination ought not to be favoured, since
it is the reverse of a 5-endo-trig process.22 We find, however, that
the lactone 30 with TBAF gives more endocyclic elimination
30 → 35 than exocyclic 30 → 36, although the lactone 27
does give marginally more exocyclic elimination (Scheme 7).
However, both lactones give mainly endocyclic elimination with
boron trifluoride–diethyl ether. We suggest that these elimin-
ations, especially that catalysed by boron trifluoride, is an E1
reaction, with a cation like 33 as an intermediate, thus avoiding
the strictures of Baldwin’s rule. The formation of the more-
substituted alkenes 35 and 37 is then unexceptional.23 This
observation is further support for the explanation that we
suggest in Scheme 6. The lactone 16 also gave mixtures of the
esters 35 and 37 under acidic conditions, but treatment with
TBAF gave endocyclic elimination without rearrangement, and
provided us with a pure sample of the ester 36.
Chlorodimethyl(4-methylphenyl)silane
4-Methylphenylmagnesium bromide prepared from 4-bromo-
toluene (70.65 g, 0.413 mol) and magnesium turnings (10.5 g,
0.432 mol) in ether (250 cm3) was added dropwise to dichloro-
dimethylsilane (75 cm3, 0.619 mol) under nitrogen at 0 ЊC with
stirring. After 5 h at reflux, the mixture was filtered and the
filtrate was evaporated under reduced pressure. The residue was
distilled to give the silane (49.2 g, 65%); bp 89–93 ЊC/7 mmHg
(lit.,24 130–131 ЊC/40 mmHg); νmax(film)/cmϪ1 1260 (SiMe) and
1120 (SiAr); δH(250 MHz; CDCl3) 7.52 (2 H, d, J 7.8, Ar), 7.23
(2 H, d, J 7.8, Ar), 2.37 (3 H, s, 4-MeC6H4) and 0.67 (6 H,
s, SiMe2), contaminated with about 17% of bromodimethyl-
(4-methylphenyl)silane, δ 2.35 (4-MeC6H4) and 0.81 (SiMe2).
Methyl (E)-3-dimethyl(4-methylphenyl)silylprop-2-enoate 5b
Following the method of Sonoda,6 dimethyl(4-methylphenyl)-
silane 4b (9.0 g, 60 mmol) in benzene (10 cm3) was added drop-
wise with stirring to methyl acrylate (25.8 g, 27.0 cm3, 300
mmol) and dicobalt octacarbonyl (0.82 g, 2.4 mmol) in benzene
(50 cm3) under nitrogen at 25 ЊC and the mixture kept for 6 h.
The solvent was evaporated off under reduced pressure and the
residue was taken up in hexane (200 cm3), filtered through a
small pad of silica gel and the filtrate was evaporated under
reduced pressure. The residue was chromatographed (SiO2,
EtOAc–hexane, 5:95) to give the ester (10.8 g, 77%); Rf(EtOAc–
Experimental
Dimethyl(4-methylphenyl)silane 4b
Chlorodimethylsilane (38.0 cm3, 0.35 mol) was added slowly to
4-methylphenylmagnesium bromide prepared from 4-bromo-
toluene (60 g, 0.35 mol) and magnesium turnings (8.6 g, 0.354
mol) in ether (200 cm3) over 1 h and the mixture was refluxed
for 10 h. The mixture was filtered, the filtrate evaporated under
hexane, 5:95) 0.37; νmax(film)/cmϪ1 1735 (C᎐O), 1250 (SiMe)
and 1110 (SiAr); δH(250 MHz; CDCl3) 7.39 (2 H, d, J 7.8, Ar),
᎐
2714
J. Chem. Soc., Perkin Trans. 1, 1998

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7.35 (1 H, d, J 18.8, SiCH᎐CH), 7.18 (2 H, d, J 7.8, Ar), 6.25
dimethyl malonate (6 g, 45.5 mmol) in dry DMPU (30 cm3)
᎐
(1 H, d, J 18.8, CH᎐CHCO Me), 3.73 (3 H, s, OMe), 2.34 (3 H,
under nitrogen over 25 min at room temperature. After 1 min,
the mixture was quenched with aqueous sodium hydrogen
carbonate (saturated, 400 cm3) and extracted with ether
(3 × 200 cm3). The extracts were washed with water and brine,
dried (MgSO4) and evaporated under reduced pressure. The
residue was kept in methanol (120 cm3) overnight, and the
crystals collected to give the diester (1.55 g, 44%). The filtrate
was evaporated under reduced pressure, and the residue was
chromatographed (SiO2, EtOAc–hexane, 15:85) to give a
second crop (1.01 g, 28%, 72% overall), mp 96–97 ЊC (from
MeOH); Rf(EtOAc–hexane, 1:9) 0.2; νmax(CHCl3)/cmϪ1 1735
᎐
2
s, 4-MeC6H4) and 0.39 (6 H, s, SiMe2); m/z 234 (47%, Mϩ), 233
(39, M Ϫ H), 219 (100, M Ϫ Me), 203 (16, M Ϫ OMe) and
149 (42, 4-MeC6H4SiMe2) (Found: Mϩ, 234.1071. C13H18O2Si
requires M, 234.1076). The product 5b is contaminated with
methyl 3-dimethyl(4-methylphenyl)silylpropanoate 10b (8%, by
integration of the signals at δ 3.73 and 3.61) characterised
below.
Dimethyl(4-methylphenyl)silylethyne
Acetylene was bubbled through dry THF (100 cm3) while
ethylmagnesium bromide (165 cm3 of a 1 mol dmϪ3 solution in
THF) was added dropwise at 0 ЊC with stirring. After the add-
ition was over, acetylene was passed through the mixture over
1 h at room temperature. A solution of chlorodimethyl(4-methyl-
phenyl)silane (22.8 g, 123.5 mmol) in THF (20 cm3) was added
dropwise at 0 ЊC and the mixture was refluxed for 15 h. Satur-
ated aqueous ammonium chloride (100 cm3) was added to the
mixture at 0 ЊC, and the mixture extracted with hexane (3 × 100
cm3). The extract was washed with water and with brine, dried
(MgSO4) and evaporated under reduced pressure. The residue
was distilled to give the acetylene (18.3 g, 86%); bp 93–94 ЊC/13
(C᎐O), 1260 (SiMe) and 1110 (Si᎐Ar); δ (250 MHz; CDCl )
᎐
H
3
7.32 (4 H, d, J 7.8, Ar), 7.14 (4 H, d, J 7.8, Ar), 3.50 (6 H, s,
2 × OMe), 2.45 (2 H, dd, J 7.5 and 16.4, 2 × CHAHBCO2Me),
2.34 (2 H, dd, J 5.9 and 16.4, 2 × CHAHBCO2Me), 2.33 (6 H, s,
2 × 4-MeC6H4), 1.84–1.76 (2 H, m, 2 × SiCH), 0.26 (6 H, s,
2 × SiMe) and 0.21 (6 H, s, 2 × SiMe); m/z 455 (79%, M Ϫ Me),
439 (23, M Ϫ OMe), 397 (80, M Ϫ CH2CO2Me), 321 (47,
M Ϫ 4-MeC6H4SiMe2) and 149 (100, 4-MeC6H4SiMe2) (Found:
C, 66.27; H, 8.19. C26H38O4Si2 requires C, 66.33; H, 8.14%), and
methyl dimethyl(4-methylphenyl)silylpropanoate 10b (840 mg,
24%); Rf(EtOAc–hexane, 5:95) 0.37; νmax(film)/cmϪ1 1750
mmHg; Rf(hexane) 0.36; νmax(film)/cmϪ1 3280 (C᎐CH), 2050
(C᎐O), 1260 (SiMe) and 1110 (SiAr); δ (250 MHz; CDCl ) 7.38
᎐
᎐
᎐
H
3
᎐
(C᎐C), 1250 (SiMe) and 1110 (SiAr); δ (250 MHz; CDCl ) 7.53
(2 H, d, J 7.8, Ar), 7.21 (2 H, d, J 7.8, Ar), 2.50 (1 H, s, C᎐CH),
(2 H, d, J 7.8, Ar), 7.17 (2 H, d, J 7.8, Ar), 3.61 (3 H, s, OMe),
2.34 (3 H, s, 4-MeC6H4), 2.30–2.23 (2 H, m, CH2CO2Me), 1.1–
1.02 (2 H, m, SiCH2) and 0.26 (6 H, s, SiMe2); m/z 236
(0.2%, Mϩ), 221 (100, M Ϫ Me), 205 (12, M Ϫ OMe), 149 (59,
4-MeC6H4Me2Si) and 145 (70, M Ϫ 4-MeC6H4) (Found: Mϩ,
236.1227. C13H20O2Si requires M, 236.1232).
᎐
H
3
᎐
᎐
2.36 (3 H, s, 4-MeC6H4) and 0.43 (6 H, s, SiMe2); m/z 174 (30%,
Mϩ) and 159 (100, M Ϫ Me) (Found: Mϩ, 174.0876. C11H14Si
requires M, 174.0865).
Methyl 3-dimethyl(4-methylphenyl)silylprop-2-ynoate 6
Following the method of Solladié,25 n-butyllithium (1.5 mol
dmϪ3 in hexane, 50 cm3) was added dropwise to a stirred solu-
tion of the dimethyl(4-methylphenyl)silylethyne (8.5 g, 48.9
mmol) in dry THF (200 cm3) under nitrogen at Ϫ78 ЊC. After
15 min, methyl chloroformate (10 cm3, 12.23 g, 129 mmol) was
added dropwise over 10 min and the mixture was stirred for 2 h
at Ϫ78 ЊC. The temperature was allowed to rise slowly to 0 ЊC,
and the mixture poured into water and extracted with hexane
(3 × 125 cm3). The extract was washed with water and brine,
dried (MgSO4) and evaporated under reduced pressure. The
residue was chromatographed (SiO2, EtOAc–hexane, 1:9) to
give the ester (10.1 g, 89%); Rf(EtOAc–hexane, 1:9) 0.4;
Mixture of dimethyl (3RS,4SR)-3,4-bis[dimethyl(4-methyl-
phenyl)silyl]hexane-1,6-dioate 8b and dimethyl (3RS,4RS)-3,4-
bis[dimethyl(4-methylphenyl)silyl]hexane-1,6-dioate 9b
Following the method of Inanaga,4 freshly prepared samarium
diiodide (0.1 mol dmϪ3 in THF, 100 cm3) was added to the
(E)-acrylate 5b (2.55 g, 10 mmol based on unsaturated ester
present) and tert-butyl alcohol (740 mg, 10 mmol) in dry hexa-
methylphosphoric triamide (20 cm3) under nitrogen over 25
min at room temperature. After 1 min, the mixture was
quenched with aqueous sodium hydrogen carbonate (saturated,
400 cm3) and extracted with ether (3 × 200 cm3). The extracts
were washed with water and brine, dried (MgSO4) and evapor-
ated under reduced pressure. The residue was chromatographed
(SiO2, EtOAc–hexane, 15:85) to give the meso diester 8b (1.26
g, 54%), racemic diester 9b (265 mg, 11%); Rf(EtOAc–hexane,
νmax(film)/cmϪ1 2210 (C᎐C), 1730 (C᎐O), 1260 (SiMe) and 1120
᎐
᎐
᎐
(SiAr); δH(250 MHz; CDCl3) 7.49 (2 H, d, J 7.8, Ar), 7.21 (2 H,
d, J 7.8, Ar), 3.77 (3 H, s, OMe), 2.36 (3 H, s, 4-MeC6H4) and
0.47 (6 H, s, SiMe2); m/z 232 (20%, Mϩ), 217 (7, M Ϫ Me),
202 (19, M Ϫ 2 × Me) and 189 (100) (Found: Mϩ, 232.0922.
C13H16O2Si requires M, 232.0920).
1:9) 0.26; νmax(film)/cmϪ1 1745 (C᎐O), 1260 (SiMe) and 1110
᎐
(SiAr); δH(250 MHz; CDCl3) 7.34 (4 H, d, J 7.8, Ar), 7.12 (4 H,
d, J 7.8, Ar), 3.44 (6 H, s, 2 × OMe), 2.32 (6 H, s, 4-MeC6H4),
2.17 (2 H, dd, J 10.1 and 15.9, 2 × CHAHBCO2Me), 2.07 (2 H,
dd, J 3.8 and 15.9, 2 × CHAHBCO2Me), 1.75 (2 H, dd, J 3.8
and 10.1, 2 × SiCH), 0.24 (6 H, s, 2 × SiMe) and 0.22 (6 H,
s, 2 × SiMe); m/z 455 (10%, M Ϫ Me), 397 (13, M Ϫ CH2-
CO2Me), 321 (14, M Ϫ 4-MeC6H4Me2Si) and 149 (100, 4-Me-
C6H4Me2Si) (Found: C, 66.22; H, 8.16; M Ϫ Me, 455.2081.
C26H38O4Si2 requires C, 66.33; H, 8.14%; M Ϫ Me, 455.2074),
and the propanoate 10b (703 mg, 30%).
Methyl (Z)-3-dimethyl(4-methylphenyl)silylprop-2-enoate 7
The ester 6 (2.8 g, 12 mmol), quinoline (0.5 cm3, 546 mg, 4.24
mmol) and palladium (5% on BaSO4, 150 mg) were stirred in
toluene (25 cm3) under hydrogen for 3 h, by which time 270
cm3 of hydrogen had been absorbed. The mixture was filtered
through Celite and evaporated under reduced pressure. The
residue was chromatographed (SiO2, EtOAc–hexane, 1:9) to
give the acrylate (2.56 g, 92%); Rf(EtOAc–hexane, 1:9) 0.42;
νmax(film)/cmϪ1 1740 (C᎐O), 1260 (SiMe) and 1120 (SiAr);
Dimethyl (3RS,4SR)-3,4-bis[dimethyl(phenyl)silyl]hexane-1,6-
dioate 8a and dimethyl (3RS,4RS)-3,4-bis[dimethyl(phenyl)-
silyl]hexane-1,6-dioate 9a
᎐
δH(250 MHz; CDCl3) 7.45 (2 H, d, J 7.8, Ar), 7.17 (2 H, d, J 7.8,
Ar), 6.68 (1 H, d, J 14.5, CH᎐CHSi), 6.56 (1 H, d, J 14.5,
᎐
CH᎐CHCO Me), 3.64 (3 H, s, OMe), 2.34 (3 H, s, 4-MeC H )
Similarly, the (E)-acrylate 5a6 (630 mg, 2 mmol of unsaturated
ester) gave after chromatography (SiO2, EtOAc–hexane, 7:93)
the meso diester 8a (210 mg, 48%), mp 41–42 ЊC (from hexane);
᎐
2
6
4
and 0.45 (6 H, s, SiMe2); m/z 234 (2%, Mϩ), 219 (100, M Ϫ Me),
189 (49, M Ϫ 3 × Me) and 143 (83, M Ϫ 4-MeC6H4) (Found:
Mϩ, 234.1084. C13H18O2Si requires M, 234.1076).
Rf(EtOAc–hexane, 5:95) 0.23; νmax(film)/cmϪ1 1740 (C᎐O),
᎐
1260 (SiMe) and 1120 (SiAr); δH(250 MHz; CDCl3) 7.46–7.37
(4 H, m, Ph), 7.34–7.28 (6 H, m, Ph), 3.50 (6 H, s, 2 × OMe),
2.47 (2 H, dd, J 7.4 and 16.5, 2 × CHAHBCO2Me), 2.38 (2 H,
dd, J 6.2 and 16.5, 2 × CHAHBCO2Me), 1.88–1.80 (2 H, m,
2 × SiCH), 0.28 (6 H, s, 2 × SiMe) and 0.23 (6 H, s, 2 × SiMe);
Dimethyl (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]-
hexane-1,6-dioate 8b
Freshly prepared samarium diiodide26 (0.09 mol dmϪ3 in THF,
180 cm3) was added to the acrylate 7 (3.51 g, 15 mmol) and
J. Chem. Soc., Perkin Trans. 1, 1998
2715

View Article Online
m/z 427 (25.5%, M Ϫ Me) and 135 (100, PhMe2Si) (Found: C,
65.06; H, 7.78 C24H34O4Si2. requires C, 65.11; H, 7.74), racemic
diester 9a (74 mg, 17%), Rf(EtOAc–hexane, 5:95) 0.29;
SiMe-keto), 0.13 (3 H, s, SiMe-keto) and 0.11 (3 H, s, SiMe-
keto); m/z 438 (4.0%, Mϩ), 423 (5.3, M Ϫ Me) and 149 (100,
4-MeC6H4SiMe2) (Found: Mϩ, 438.2081. C25H34O3Si2 requires
M, 438.2046).
νmax(film)/cmϪ1 1740 (C᎐O), 1250 (SiMe) and 1110 (SiAr);
᎐
δH(250 MHz; CDCl3) 7.47–7.43 (4 H, m, Ph), 7.36–7.27
(6 H, m, Ph), 3.43 (6 H, s, 2 × OMe), 2.19 (2 H, dd, J 10.1
and 16, 2 × CHAHBCO2Me), 2.07 (2 H, dd, J 3.6 and 16, 2 ×
CHAHBCO2Me), 1.77 (2 H, dd, J 3.6 and 10.1, 2 × SiCH),
0.26 (6 H, s, 2 × SiMe) and 0.24 (6 H, s, 2 × SiMe); m/z
427 (5.8%, M Ϫ Me) and 135 (62.7, PhMe2Si) and 84 (100)
(Found: C, 65.29; H, 7.81. C24H34O4Si2 requires C, 65.11; H,
7.74%), and methyl dimethyl(phenyl)silylpropanoate27 (110 mg,
25% allowing for that in the starting material); Rf(EtOAc–
(3RS,4SR)-3,4-Bis[dimethyl(4-methylphenyl)silyl]cyclopentan-
1-one 11
Following the method of Krapcho and Lovey,28 the keto ester
prepared from 8b (2.19 g, 5 mmol), sodium chloride (590 mg,
10 mmol), water (0.2 cm3, 11 mmol) and dimethyl sulfoxide
(20 cm3) were heated under nitrogen at 130–150 ЊC for 3 h. The
mixture was poured into water and extracted with ether (3 × 40
cm3). The extracts were washed with water and with brine, dried
(MgSO4) and evaporated under reduced pressure. The residue
was chromatographed (SiO2, EtOAc–hexane, 1:9) to give the
ketone (1.635 g, 86%) as cubes, mp 80–81 ЊC (from hexane);
hexane, 5:95) 0.38; νmax(film)/cmϪ1 1740 (C᎐O), 1250 (SiMe)
᎐
and 1120 (SiAr); δH(250 MHz; CDCl3) 7.51–7.45 (2 H, m, Ph),
7.38–7.32 (3 H, m, Ph), 3.61 (3 H, s, OMe), 2.31–2.22 (2 H,
m, CH2CO2Me), 1.16–1.04 (2 H, m, SiCH2) and 0.28 (6 H, s,
SiMe2).
Rf(EtOAc–hexane, 1:9) 0.42; νmax(CHCl3)/cmϪ1 1745 (C᎐O),
᎐
1610 (Ar), 1260 (SiMe) and 1110 (SiAr); δH(250 MHz; CDCl3)
7.29 (4 H, d, J 7.7, Ar), 7.12 (4 H, d, J 7.7, Ar), 2.34 (6 H, s,
2 × 4-MeC6H4), 2.29 (2 H, dd, J 9.4 and 18.6, 2 × CHAHBCO),
2.14 (2 H, dd, J 7.3 and 18.6, 2 × CHAHBCO), 2.04–1.92 (2 H,
m, 2 × SiCH) and 0.24 (12 H, s, 2 × SiMe2); m/z 380 (2.6%, Mϩ)
and 149 (100, 4-MeC6H4SiMe2) (Found: C, 72.80; H, 8.59;
Mϩ, 380.1957. C23H32OSi2 requires C, 72.57; H, 8.47%; M,
380.1991).
(2RS,3RS,4SR)-2-Methoxycarbonyl-3,4-bis[dimethyl(4-methyl-
phenyl)silyl]cyclopentan-1-one
Method A. n-Butyllithium (1.5 mol dmϪ3 in hexane, 0.4 cm3)
was added dropwise to diisopropylamine (0.1 cm3, 0.65 mmol)
in dry THF (2 cm3) under nitrogen at Ϫ78 ЊC. After 20 min at
0 ЊC, the mixture was brought back to Ϫ78 ЊC and the diester
8b (235 mg, 0.5 mmol) in dry THF (2 cm3) was added dropwise
over 15 min. The mixture was stirred at Ϫ78 ЊC for 6 h,
quenched at 0 ЊC with hydrochloric acid (3 mol dmϪ3) and
extracted with ether (3 × 20 cm3). The extract was washed with
aqueous sodium hydrogen carbonate and with brine, dried
(MgSO4) and evaporated under reduced pressure. The residue
was chromatographed (SiO2, EtOAc–hexane, 1:9) to give the
keto ester (200 mg, 91%); Rf(EtOAc–hexane, 15:85) 0.31;
νmax(film)/cmϪ1 1760 (C᎐O), 1735 (C᎐O), 1610 (Ar), 1260
(3RS,4RS)-3,4-Bis[dimethyl(4-methylphenyl)silyl]cyclopentan-
1-one 14
Similarly,
(2RS,3RS,4RS)-2-methoxycarbonyl-3,4-bis[di-
methyl(4-methylphenyl)silyl]cyclopentanone (44 mg, 0.1 mmol)
gave the ketone (30 mg, 78%); Rf(EtOAc–hexane, 1:9) 0.24;
νmax(CDCl3)/cmϪ1 1740 (C᎐O), 1610 (Ar), 1260 (SiMe) and
᎐
1110 (SiAr); δH(250 MHz, CDCl3) 7.32 (4 H, d, J 7.8, Ar),
7.15 (4 H, d, J 7.8, Ar), 2.34 (6 H, s, 2 × 4-MeC6H4), 2.09
(4 H, d, J 7.4, 2 × CH2CO), 1.61 (2 H, t, J 7.4, 2 × SiCH),
0.21 (6 H, s, 2 × SiMe) and 0.20 (6 H, s, 2 × SiMe); m/z 380
(11.2%, Mϩ), 365 (1.4, M Ϫ Me) and 149 (100, 4-MeC6H4-
SiMe2) (Found: Mϩ, 380.1961. C23H32OSi2 requires M,
380.1991).
᎐
᎐
(SiMe) and 1110 (SiAr); δH(250 MHz, CDCl3) 7.31–7.26 (4 H,
m, Ar), 7.13 (4 H, d, J 7.8, Ar), 3.51 (3 H, s, OMe), 3.11 (1 H, d,
J 8.0, CHCO), 2.50–2.26 (3 H, m, CH2 and SiCH), 2.34 (6 H, s,
4-MeC6H4), 2.23–2.08 (1 H, m, SiCH), 0.25 (3 H, s, SiMe), 0.24
(3 H, s, SiMe), 0.23 (3 H, s, SiMe) and 0.22 (3 H, s, SiMe);
m/z 438 (0.7%, Mϩ), 379 (5.7, M Ϫ COOMe) and 149 (100,
4 Ϫ MeC6HMe2Si) (Found: Mϩ, 438.2056. C25H34O3Si2
requires M, 438.2046).
(1á,3á,4á)-3,4-Bis[dimethyl(4-methylphenyl)silyl]cyclopentan-
1-ol
Method B. Freshly prepared samarium diiodide (0.09 mol
dmϪ3 in THF, 230 cm3) was added with mechanical stirring
to the (E)-acrylate 5b (5.1 g, 20 mmol of unsaturated ester)
in dry DMPU (40 cm3) under nitrogen at room temperature
over 20–25 min, and stirred for 30 min. tert-Butyl alcohol
(1.85 g, 25 mmol) in dry THF (50 cm3) was added dropwise
over 1 h, and the mixture kept for 2 h at room temperature.
The mixture was quenched and worked up as before, with
chromatography (SiO2, EtOAc–hexane, 10:90) to give the keto
ester (3.11 g, 70%) contaminated with the meso diester 8b
(8:2, by integration of the signals at δ 3.50 and 3.11) Partial
removal of the diester 8b by crystallisation from methanol was
possible.
Sodium borohydride (3 mg, 0.08 mmol) and the ketone 11 (28
mg, 0.074 mmol) were stirred in propan-2-ol (1 cm3) at 0 ЊC for
1.5 h and at room temperature for 1 h. The solvent was removed
under reduced pressure. The residue was acidified with hydro-
chloric acid and extracted with ether (2 × 5 cm3). The extract
was washed with aqueous sodium hydrogen carbonate and with
brine, dried (MgSO4) and evaporated under reduced pressure to
give the alcohol (26 mg, 92%); Rf(EtOAc–hexane, 2:8) 0.33;
νmax(CDCl3)/cmϪ1 3630 (OH), 1610 (Ar), 1260 (SiMe) and 1110
(SiAr); δH(250 MHz; CDCl3) 7.32 (4 H, d, J 7.8, Ar), 7.11 (4 H,
d, J 7.8, Ar), 4.31–4.20 (1 H, m, CHOH), 2.33 (6 H, s, 2 ×
4-MeC6H4), 2.16–2.05 (2 H, m, 2 × SiCH), 1.63–1.40 (4 H, m,
2 × CH2), 0.24 (6 H, s, 2 × SiMe) and 0.19 (6 H, s, 2 × SiMe)
(Found: C, 71.99; H, 8.78. C23H34OSi2 requires C, 72.18; H,
8.95%).
(2RS,3RS,4RS)-2-Methoxycarbonyl-3,4-bis[dimethyl(4-methyl-
phenyl)silyl]cyclopentan-1-one
Similarly, using method A, the diester 9b (235 mg, 0.5 mmol)
gave, after chromatography (SiO2, EtOAc–hexane, 1:9), the
keto ester (143 mg, 65%) as a mixture of tautomers (keto:enol,
~6:4); Rf(EtOAc–hexane, 15:85) 0.47; νmax(CDCl3)/cmϪ1 3400
(OH), 1750 (C᎐O), 1730 (C᎐O), 1660 (C᎐C), 1610 (Ar), 1260
(SiMe) and 1110 (SiAr); δH(250 MHz; CDCl3) 10.35 (1 H, s,
OH-enol), 7.33–7.28 (8 H, m, Ar), 7.17–7.09 (8 H, m, Ar), 3.57
(3 H, s, OMe-enol), 3.52 (3 H, s, OMe-keto), 3.11 (1 H, d,
J 10.6, CHCO-keto), 2.34 (6 H, s, 2 × 4-MeC6H4), 2.33 (6 H, s,
2 × 4-MeC6H4), 2.54–2.12 (6 H, m, 2 × CH2 and 2 × SiCH),
1.60–1.40 (2 H, m, 2 × SiCH), 0.21 (6 H, s, 2 × SiMe-enol),
0.18 (9 H, s, SiMe-keto and 2 × SiMe-enol), 0.16 (3 H, s,
(1â,3â,4á)-3,4-Bis[dimethyl(4-methylphenyl)silyl]cyclopentan-
1-ol
Similarly, the ketone 14 (15 mg, 0.04 mmol) in ethanol (1 cm3)
gave the alcohol (14 mg, 94%); Rf(EtOAc–hexane, 2:8) 0.33;
νmax(CHCl3)/cmϪ1 3380 (OH), 1610 (Ar), 1260 (SiMe) and 1110
(SiAr); δH(250 MHz; CDCl3) 7.37 (2 H, d, J 7.8, Ar), 7.34 (2 H,
d, J 7.8, Ar), 7.15 (4 H, d, J 7.8, Ar), 3.96 (1 H, quintet, J 6.1,
CHOH), 2.34 (6 H, s, 2 × 4-MeC6H4), 2.00–1.89 (1 H, m,
SiCH), 1.82–1.73 (1 H, m, SiCH), 1.61–1.17 (4 H, m, 2 × CH2),
0.18 (3 H, s, SiMe), 0.17 (3 H, s, SiMe), 0.14 (3 H, s, SiMe)
and 0.13 (3 H, s, SiMe) (Found: C, 72.09; H, 8.90. C23H34OSi2
requires C, 72.18; H, 8.95%).
᎐
᎐
᎐
2716
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
(1á,3á,4á)-3,4-Bis[dimethyl(4-methylphenyl)silyl]cyclopent-1-yl
acetate 12
aqueous sodium thiosulfate and with aqueous sodium hydrogen
carbonate, dried (K2CO3) and evaporated under reduced pres-
sure to give the lactone (1.2 g, 99%) as cubes, mp 87–88 ЊC (from
MeOH); Rf(EtOAc–hexane, 2:8) 0.25; νmax(CHCl3)/cmϪ1 1730
(C᎐O), 1610 (Ar), 1260 (SiMe) and 1110 (SiAr); δ (250 MHz,
Acetic anhydride (0.01 cm3, 0.1 mmol), the (1α,3α,4α)-alcohol
(8 mg, 0.02 mmol) and 4-dimethylaminopyridine (1.2 mg, 0.01
mmol) were kept in pyridine (0.2 cm3) at room temperature for
15 h. Water (3 cm3) was added and the mixture was extracted
with ether (2 × 5 cm3). The extract was washed with aqueous
copper sulfate and with brine, dried (MgSO4) and evaporated
under reduced pressure. The residue was chromatographed
(SiO2, EtOAc–hexane, 1:9) to give the acetate (8 mg, 90%);
᎐
H
CDCl3) 7.31 (2 H, d, J 7.8, Ar), 7.27 (2 H, d, J 7.8, Ar), 7.16
(2 H, d, J 7.8, Ar), 7.14 (2 H, d, J 7.8, Ar), 4.39 (2 H, d, J 6.0,
CH2OCO), 2.64 (1 H, dd, J 7.3 and 18.5, CHAHBCO), 2.57
(1 H, dd, J 7 and 18.5, CHAHBCO), 2.36 (3 H, s, 4-MeC6H4),
2.35 (3 H, s, 4-MeC6H4), 1.75–1.58 (2 H, m, 2 × SiCH), 0.31
(3 H, s, SiMe), 0.29 (3 H, s, SiMe) and 0.28 (6 H, s, 2 × SiMe);
m/z 396 (45.8%, Mϩ) and 149 (100, 4-MeC6H4SiMe2) (Found:
C, 69.70; H, 8.22; Mϩ, 396.1944. C23H32O2Si2 requires C, 69.64;
H, 8.13%; M, 396.1941). This reaction was also carried out
without the orthophosphate, when the ketone 11 (0.5 mmol)
and m-chloroperoxybenzoic acid (1.5 mmol) in dichloro-
methane at room temperature for 15 h gave the same lactone
(185 mg, 95%).
Rf(EtOAc–hexane, 1:9) 0.30; νmax(CHCl3)/cmϪ1 1730 (C᎐O),
᎐
1610 (Ar), 1260 (SiMe) and 1110 (SiAr); δH(250 MHz; CDCl3)
7.30 (4 H, d, J 7.7, Ar), 7.11 (4 H, d, J 7.7, Ar), 5.14–4.94 (1 H,
m, CHOAc), 2.33 (6 H, s, 2 × 4-MeC6H4), 2.30–2.06 (2 H, m,
2 × SiCH), 2.02 (3 H, s, OAc), 1.62–1.50 (4 H, m, 2 × CH2),
0.22 (6 H, s, 2 × SiMe) and 0.19 (6 H, s, 2 × SiMe); m/z 409
(1.5%, M Ϫ Me) and 149 (100, 4-MeC6H4SiMe2) (Found: C,
70.89; H, 8.60. C25H36O2Si2 requires C, 70.69; H, 8.54%). The
acetate was contaminated with 7–8% of its diastereoisomer 13
as judged by the OAc peak at δ 1.93.
(3RS,4RS)-3,4-Bis[dimethyl(4-methylphenyl)silyl]pentan-5-
olide 22
(1â,3á,4á)-3,4-Bis[dimethyl(4-methylphenyl)silyl]cyclopent-1-yl
acetate 13
Similarly, the ketone 14 (0.38 g, 1 mmol) gave the lactone (300
mg, 75%) as needles, mp 95–96 ЊC (from hexane); Rf(EtOAc–
Diethyl azodicarboxylate (DEAD)9 (17.4 mg, 0.1 mmol) in
ether (0.2 cm3), the (1β,3α,4α)-alcohol (30 mg, 0.078 mmol),
triphenylphosphine (27 mg, 0.1 mmol) and acetic acid (0.006
cm3, 0.1 mmol) were stirred in ether (0.3 cm3) under argon at
room temperature for 5 h. Hexane (2 cm3) was added and the
mixture filtered. The filtrate was evaporated under reduced
pressure and the residue was purified by preparative thin layer
chromatography (SiO2, EtOAc–hexane, 1:9) to give the acetate
(26 mg, 78%); Rf(EtOAc–hexane, 1:9) 0.30; νmax(film)/cmϪ1
hexane, 2:8) 0.28; νmax(CHCl3)/cmϪ1 1730 (C᎐O), 1610 (Ar),
᎐
1260 (SiMe) and 1110 (SiAr); δH(250 MHz, CDCl3) 7.36 (2 H,
d, J 7.8, Ar), 7.35 (2 H, d, J 7.8, Ar), 7.19 (4 H, d, J 7.8, Ar),
4.10 (1 H, dd, J 5.5 and 11.5, CHAHBOCO), 4.0 (1 H, dd, J 4.5
and 11.5, CHAHBOCO), 2.4–2.33 (2 H, m, CH2CO), 2.35 (6 H,
s, 2 × 4-MeC6H4), 1.48–1.36 (2 H, m, 2 × SiCH), 0.27 (3 H, s,
SiMe), 0.22 (3 H, s, SiMe), 0.18 (3 H, s, SiMe) and 0.17 (3 H, s,
SiMe); m/z 396 (25.7%, Mϩ) and 149 (100, 4-MeC6H4SiMe2)
(Found: C, 69.76; H, 8.09; Mϩ, 396.1942. C23H32O2Si2 requires
C, 69.64; H, 8.13%; M, 396.1941).
1730 (C᎐O), 1610 (Ar), 1260 (SiMe) and 1110 (SiAr); δ (250
᎐
H
MHz; CDCl3) 7.30 (4 H, d, J 7.8, Ar), 7.11 (4 H, d, J 7.8, Ar),
5.17–5.04 (1 H, m, CHOAc), 2.33 (6 H, s, 2 × 4-MeC6H4), 2.10–
1.91 (1 H, m, SiCH), 1.93 (3 H, s, OAc), 1.86–1.74 (3 H, m, CH2
and SiCH), 0.19 (6 H, s, 2 × SiMe) and 0.17 (6 H, s, 2 × SiMe);
m/z 424 (0.2%, Mϩ), 409 (1.2, M Ϫ Me), 149 (100, 4-MeC6H4-
SiMe2) (Found: C, 70.23; H, 8.52; Mϩ, 424.2267. C25H36O2Si2
requires C, 70.69; H, 8.54%; M, 424.2253). The acetate was
contaminated with 7–8% of its diastereoisomer 12 as judged by
the OAc peak at δ 2.02.
2-Deoxyribonolactone
Peracetic acid (32–36% w/v in AcOH, 5 cm3) was stirred with
the lactone 16 (400 mg, 1 mmol), potassium bromide (285 mg,
2.4 mmol) and sodium acetate (1 g, 12.2 mmol) in acetic acid (5
cm3) at room temperature for 15 h. The solvent was azeotropi-
cally removed with toluene under vacuum. The residue was
triturated with MeOH–EtOAc (1:99), filtered and the filtrate
was evaporated under reduced pressure. IR spectra and TLC
showed that the product was
a mixture of γ-lactone
(1â,3â,4á)-3,4-Bis[dimethyl(4-methylphenyl)silyl]cyclopent-1-yl
acetate 15
Similarly, the (1β,3β,4α)-alcohol (20 mg, 0.05 mmol) gave the
[Rf(MeOH–EtOAc, 1:99) 0.26; νmax(CHCl3)/cmϪ1 1770] and
δ-lactone [Rf(MeOH–EtOAc, 1:99) 0.18; νmax(CHCl3)/cmϪ1
1740 cmϪ1]. The residue was kept in methanol (2 cm3) and
hydrochloric acid (3 mol dmϪ3 in H2O, 1 cm3) for 48 h. The
solvent was removed under vacuum and the residue was
chromatographed (SiO2, MeOH–EtOAc, 1:99) to give the
γ-lactone29 (76 mg, 58%); Rf(MeOH–EtOAc, 1:99) 0.26;
acetate (19 mg, 86%); Rf(EtOAc–hexane, 1:9) 0.33; νmax
-
(CDCl3)/cmϪ1 1735 (C᎐O), 1610 (Ar), 1260 (SiMe) and 1110
᎐
(SiAr); δH(250 MHz; CDCl3) 7.35 (2 H, d, J 7.8, Ar), 7.34 (2 H,
d, J 7.8, Ar), 7.14 (4 H, d, J 7.8, Ar), 4.90 (1 H, quintet, J 6.1,
CHOAc), 2.34 (6 H, s, 2 × 4-MeC6H4), 2.03 (1 H, ddd, J 6.4, 9.4
and 13.2, SiCH), 1.95 (3 H, s, OAc), 1.86 (1 H, ddd, J 6.4, 6.4
and 13.2, SiCH), 1.70 (1 H, ddd, J 6.1, 9.4 and 13.2, CHAHB-
CHO), 1.60–1.24 (3 H, m, CHAHBCHO and CH2), 0.18 (3 H, s,
SiMe), 0.15 (3 H, s, SiMe), 0.14 (3 H, s, SiMe) and 0.11 (3 H, s,
SiMe); m/z 424 (0.1%, Mϩ) and 149 (100, 4-MeC6H4SiMe2)
(Found: C, 70.81; H, 8.49; Mϩ, 424.2268. C25H36O2Si2 requires
C, 70.69; H, 8.54%; M, 424.2253). The same compound (10 mg,
75%) was prepared from the (1β,3β,4α)-alcohol (12 mg, 0.031
mmol) following the method for preparation of (1β,3α,4α)-3,4-
bis[dimethyl(4-methylphenyl)silyl]cyclopent-1-yl acetate 13.
νmax(film)/cmϪ1 3400 (OH), 1770 (C᎐O); δ (250 MHz, D O)
᎐
H
2
4.58–4.50 (2 H, m, CHOH and CHOCO), 3.86 (1 H, dd, J 2.9
and 13.0, CHAHBOH), 3.75 (1 H, dd, J 4.3 and 13.0, CHAHB-
OH), 3.04 (1 H, dd, J 6.8 and 18.5, CHAHBCO) and 2.57 (1 H,
dd, J 2.9 and 18.5, CHAHBCO); m/z 133 (1.5%, Mϩ ϩ H),
101 (72, M Ϫ CH2OH) and 44 (100, CO2) (Found: Mϩ ϩ H,
133.0506. C5H9O4 requires M ϩ H, 133.0500).
(3RS,4SR)-3,5-Diacetoxypentan-1,4-olide 18
Acetic anhydride (0.2 cm3 containing 1% v/v of 70% perchloric
acid) was stirred with the diol (20 mg, 0.15 mmol) at room
temperature for 0.5 h. The mixture was diluted with ice cold
water and extracted with dichloromethane (3 × 5 cm3). The
extract was washed with aqueous sodium hydrogen carbonate
and with brine, dried (MgSO4) and evaporated under reduced
pressure. The residue was chromatographed (SiO2, EtOAc–
hexane, 1:1) to give the diacetate13 (25 mg, 76%); Rf(EtOAc–
hexane, 1:1) 0.29; νmax(film)/cmϪ1 1790 (C᎐O) and 1740 (C᎐O);
(3RS,4SR)-3,4-Bis[dimethyl(4-methylphenyl)silyl]pentan-5-
olide 16
m-Chloroperoxybenzoic acid (50% w/w, 2.1 g, 6 mmol) in
dichloromethane (10 cm3) was dried (MgSO4) and then stirred
with the ketone 11 (1.14 g, 3 mmol) and disodium hydrogen
orthophosphate (3.5 g, 25 mmol) in dichloromethane (15 cm3)
at room temperature for 5 h. The mixture was filtered and
diluted with ether (100 cm3). The filtrate was washed with
᎐
᎐
δH(250 MHz, CDCl3) 5.26 (1 H, ddd, J 1.8, 1.8 and 7.4,
CHOAc), 4.67 (1 H, ddd, J 1.8, 3.5 and 3.5, CHOCO), 4.37
J. Chem. Soc., Perkin Trans. 1, 1998
2717

View Article Online
(1 H, dd, J 3.5 and 12.4, CHAHBOAc), 4.26 (1 H, dd, J 3.5 and
12.4, CHAHBOAc), 2.99 (1 H, dd, J 7.4 and 18.7, CHAHBCO),
2.61 (1 H, dd, J 1.8 and 18.7, CHAHBCO), 2.10 (3 H, s, OAc)
and 2.08 (3 H, s, OAc); m/z 217 (94%, Mϩ ϩ H), 143 (97,
M Ϫ CH2OAc), 128 (65, M Ϫ CH2OAc ϩ Me), 83 (100, M Ϫ
CH2OAc ϩ AcOH) (Found: Mϩ ϩ H, 217.0693. C9H13O6
requires M ϩ H, 217.0712).
vacuum. The residue was taken up in ethyl acetate (100 cm3),
filtered and the filtrate was evaporated under reduced pressure.
The residue was chromatographed (SiO2, EtOAc–hexane, 7:3)
to give the lactone (670 mg, 64%) as needles, mp 107–108 ЊC
(from hexane); Rf(EtOAc–hexane, 1:1) 0.21; νmax(CH2Cl2)/
cmϪ1 3600 (OH), 1800 (C᎐O) and 840 (SiO); δ (250 MHz,
᎐
H
CDCl3) 4.45–4.35 (2 H, m, CHOSi and CHOCO), 4.19–4.08 (1
H, m, CHOH), 3.98 (1 H, dd, J 3 and 12.8, CHAHBOH), 3.81 (1
H, dd, J 3.6 and 12.8, CHAHBOH), 0.93 (9 H, s, SiBut), 0.16 (3
H, s, SiMe) and 0.10 (3 H, s, SiMe); m/z 263 (0.6%, M ϩ H),
205 (53, M Ϫ But) and 75 (100, SiMe2OH) (Found: Mϩ ϩ H,
263.1322. C11H23O5Si requires M ϩ H, 263.1315).
(2RS,3SR,4RS)-3,4-Bis[dimethyl(4-methylphenyl)silyl]-2-
hydroxypentan-5-olide
Following Davis,30 the lactone 16 (2.39 g, 6 mmol) in THF
(10 cm3) was added to a stirred solution of sodium hexameth-
yldisilazide (1 mol dmϪ3 in THF, 10 cm3) in dry THF (10 cm3)
under nitrogen at Ϫ78 ЊC. After 30 min at Ϫ78 ЊC, 2-phenyl-
sulfonyl-3-phenyloxaziridine31 (3.13 g, 12 mmol) in dry THF
(12 cm3) was added dropwise over 10 min and the mixture was
stirred for 30 min. Camphorsulfonic acid (2.52 g, 10 mmol) in
dry THF (10 cm3) was added to the mixture, followed by satur-
ated aqueous ammonium chloride at Ϫ78 ЊC, and the mixture
extracted with ethyl acetate (3 × 100 cm3). The extract was
washed with 5% aqueous citric acid and with aqueous sodium
hydrogen carbonate, dried (MgSO4) and evaporated under
reduced pressure. The residue was left for 2 days to allow the
sulfonylimine to decompose to sulfonamide and benzaldehyde,
and chromatographed (SiO2, EtOAc–hexane, 15:85) to give
the lactone (1.73 g, 70%); Rf(EtOAc–hexane, 15:85) 0.16;
( )-Tri-O-acetylarabono-1,4-lactone 21
Tetrabutylammonium fluoride (1 mol dmϪ3 in THF, 0.8 cm3)
was stirred with the lactone 20 (96 mg, 0.37 mmol) in dry THF
(1 cm3) under nitrogen at room temperature for 30 min. The
solvent was evaporated off, and the residue was taken up in
EtOAc–MeOH (95:5), filtered through silica gel (8 cm) and the
filtrate was evaporated under reduced pressure. The residue was
treated with acetic anhydride (1 cm3, containing 1% v/v of 70%
perchloric acid) and stirred at room temperature for 30 min.
The mixture was poured onto crushed ice, stirred for 30 min and
extracted with dichloromethane (3 × 10 cm3). The extract was
washed with water and with brine, dried (MgSO4) and evapor-
ated under reduced pressure. The residue was chromatographed
(SiO2, EtOAc–hexane, 8:2) to give the triacetate12 (71 mg,
νmax(CDCl3)/cmϪ1 3440 (OH), 1720 (C᎐O), 1600 (Ar), 1250
᎐
(SiMe) and 1110 (SiAr); δH(250 MHz; CDCl3) 7.37 (2 H, d,
J 7.9, Ar), 7.18–7.10 (6 H, m, Ar), 4.40 (2 H, d, J 4.6,
CH2OCO), 4.27 (1 H, dd, J 1.5 and 9.3, CHOH), 2.97 (1 H, d,
J 1.5, OH), 2.37 (3 H, s, 4-MeC6H4), 2.34 (3 H, s, 4-MeC6H4),
1.92–1.80 (2 H, m, 2 × SiCH), 0.35 (3 H, s, SiMe), 0.33 (3 H, s,
SiMe), 0.26 (3 H, s, SiMe) and 0.23 (3 H, s, SiMe); m/z 395 (3%,
M Ϫ OH), 149 (100, 4-MeC6H4SiMe2) and 91 (38, 4-MeC6H4)
(Found: Mϩ Ϫ OH, 395.1841. C23H31O2Si2 requires M Ϫ OH,
395.1862).
71%); Rf(EtOAc) 0.58; νmax(CH2Cl2)/cmϪ1 1800 (C᎐O, lactone)
᎐
and 1750 (C᎐O, acetate); δ (250 MHz, CDCl ) 5.57 (1 H, d, J 7,
᎐
H
3
OCOCHOAc), 5.46 (1 H, dd, J 7 and 7, CHOAc), 4.55 (1 H,
ddd, J 3, 4.8 and 7, CHOCO), 4.48 (1 H, dd, J 3 and 12.5,
CHACHBOAc), 4.29 (1 H, dd, J 4.8 and 12.5, CHAHBOAc),
2.19 (3 H, s, OAc), 2.13 (3 H, s, OAc) and 2.12 (3 H, s, OAc);
δC(100 MHz, CDCl3) 170.27, 169.84, 169.47, 168.24, 77.39,
72.54, 72.17, 62.05, 20.57, 20.53 and 20.35; m/z 275 (3.2%,
M ϩ H), 274 (1.1, Mϩ), 232 (29, M Ϫ CH2CO), 214 (19, M Ϫ
AcOH), 201 (32, M Ϫ CH2OAc), 154 (80, M Ϫ 2 × AcOH),
128 (96, M Ϫ 2 × CH2OAc) and 115 (100) (Found: Mϩ,
274.0683. C11H14O8 requires M, 274.0689).
(2RS,3SR,4RS)-2-tert-Butyldimethylsilyloxy-3,4-bis[dimethyl-
(4-methylphenyl)silyl]pentan-5-olide 19
The hydroxylactone (412 mg, 1 mmol), imidazole (360 mg, 5
mmol) and tert-butylchlorodimethylsilane (375 mg, 2.5 mmol)
in dry DMF (1.5 cm3) were stirred at room temperature for 15
h. The mixture was poured into water and extracted with ether
(3 × 25 cm3). The extract was washed with aqueous sodium
hydrogen carbonate and with brine, dried (MgSO4) and evapor-
ated under reduced pressure. The residue was chromatographed
(SiO2, EtOAc–hexane, 1:9) to give the silyl ether (490 mg, 93%)
as needles, mp 93–94 ЊC (from hexane); Rf(EtOAc–hexane, 1:9)
2-Deoxyxylonolactone diacetate 24
Similarly to the preparation of the lactone 18 from the lactone
16, the lactone 22 (60 mg, 0.15 mmol) was converted to the diol
lactone 23 (13.5 mg, 68%), which was treated with aqueous
methanolic hydrochloric acid (1 mol dmϪ3 in MeOH᎐H2O, 2:1,
6 cm3) for 48 h at room temperature, worked up and chromato-
graphed (SiO2, EtOAc–hexane, 4:6) to give the diacetate13 (16
mg, 73%) (50% overall); Rf(EtOAc–hexane, 1:1) 0.20;
νmax(CHCl3)/cmϪ1 1790 (C᎐O) and 1740 (C᎐O); δ (250 MHz,
0.29; νmax(CHCl3)/cmϪ1 1740 (C᎐O), 1610 (Ar), 1260 (SiMe),
᎐
᎐
᎐
H
1110 (SiAr) and 1040 (SiO); δH(250 MHz; CDCl3) 7.32 (2 H, d,
J 7.9, Ar), 7.21 (2 H, d, J 7.9, Ar), 7.18 (2 H, d, J 7.9, Ar), 7.13
(2 H, d, J 7.9, Ar), 4.41 (1 H, ddd, J 1.5, 5.3 and 11.4, CHAHB-
OCO), 4.31 (1 H, dd, J 11.4 and 13.6, CHAHBOCO), 4.15 (1 H,
d, J 1.5, CHOSi), 2.68 (1 H, ddd, J 3, 5.3 and 13.6, SiCH), 2.37
(3 H, s, 4-MeC6H4), 2.33 (3 H, s, 4-MeC6H4), 1.55 (1 H, ddd,
J 1.5, 1.5 and 3, SiCH), 0.85 (9 H, s, SiBut), 0.3 (3 H, s, SiMe),
0.29 (3 H, s, SiMe), 0.25 (3 H, s, SiMe), 0.23 (3 H, s, SiMe),
Ϫ0.02 (3 H, s, SiMe) and Ϫ0.11 (3 H, s, SiMe); m/z 526 (1.3%,
Mϩ), 511 (1.8, M Ϫ Me), 469 (1.8, M Ϫ But), 435 (1.7, M Ϫ
4-MeC6H4), 395 (2, M Ϫ OSiMe2But) and 149 (100, 4-MeC6-
H4SiMe2) (Found: C, 66.18; H, 8.93; Mϩ, 526.2766. C29H46O3Si3
requires C, 66.10; H, 8.80%; M, 526.2755).
CDCl3) 5.55 (1 H, ddd, J 2.3, 4.9 and 7.0, CHOCO), 4.77 (1 H,
q, J 5, CHOAc), 4.38–4.28 (2 H, m, CH2OAc), 2.91 (1 H, dd, J
6.5 and 18.2, CHAHBCO), 2.62 (1 H, dd, J 2.3 and 18.2, CHAH-
BCO), 2.10 (3 H, s, OAc) and 2.09 (3 H, s, OAc).
(3RS,4SR)-3,5-Bis[dimethyl(4-methylphenyl)silyl]pentan-1,4-
olide 30
Potassium hydroxide (0.1 mol dmϪ3 in MeOH–H2O, 9:1, 75
cm3) and the lactone 16 (2 g, 5 mmol) were stirred in methanol
(5 cm3) at room temperature for 2 h. The solvent was removed
under reduced pressure and the residue was acidified with
aqueous citric acid, extracted with dichloromethane (2 × 25
cm3) and dried (MgSO4). A sample from an earlier run was
concentrated to identify the hydroxy acid 28; Rf(EtOAc–
hexane, 3:7) 0.17; νmax(CHCl3)/cmϪ1 3400–2500 (br, OH and
(2SR,3RS,4RS)-2-tert-Butyldimethylsilyloxy-3,5-dihydroxy-
valero-1,4-lactone 20
COOH), 1700 (C᎐O), 1600 (Ar), 1260 (SiMe) and 1100 (SiAr);
᎐
Peracetic acid (32–36% w/v in AcOH, 36 cm3), potassium brom-
ide (1.144 g, 9.6 mmol) and sodium acetate (10 g, 122 mmol)
were stirred with the lactone 19 (2.104 g, 4 mmol) in acetic acid
(25 cm3) at room temperature for 15 h. The solvent was azeo-
tropically removed with toluene at room temperature under
δH(250 MHz; CDCl3) 7.37 (4 H, d, J 7.8, Ar), 7.16 (2 H, d, J 7.8,
Ar), 7.13 (2 H, d, J 7.8, Ar), 3.73 (1 H, dd, J 4.9 and 11.2,
CHAHBOH), 3.67 (1 H, dd, J 7.2 and 11.2, CHAHBOH), 2.57
(1 H, dd, J 8.6 and 17.2, CHAHBCO), 2.44 (1 H, dd, J 4.9
and 17.2, CHAHBCO), 2.33 (3 H, s, 4-MeC6H4), 2.32 (3 H, s,
2718
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
4-MeC6H4), 1.84 (1 H, ddd, J 4.9. 4.9 and 8.6, SiCH), 1.47 (1 H,
ddd, J 4.9, 4.9 and 7.2, SiCH), 0.29 (3 H, s, SiMe), 0.28 (3 H, s,
SiMe), 0.25 (3 H, s, SiMe) and 0.24 (3 H, s, SiMe). Triphenyl-
phosphine (1.835 g, 7 mmol) was added, the mixture was cooled
to Ϫ20 ЊC and DEAD (1.22 g, 7 mmol) was added with stirring
under nitrogen at Ϫ20 ЊC. After 2.5 h at room temperature, the
solvent was removed under reduced pressure and the residue
was triturated with ether–hexane (1:1), filtered and the filtrate
was concentrated under reduced pressure. The residue was
chromatographed (SiO2, EtOAc–hexane, 15:85) to give the
lactone (1.4 g, 70%) as needles, mp 79–80 ЊC (from MeOH);
xylonolactone and its diacetate (14 mg, 44% overall) identical
(TLC, IR, 1H NMR) with the earlier sample.
Reaction of (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl-
pentan-5-olide 16 with camphorsulfonic acid
The lactone 16 (40 mg, 0.1 mmol) was stirred with camphor-
sulfonic acid (4 mg, 0.016 mmol) in dichloromethane (2 cm3) at
room temperature for 4 days. The solvent was removed under
reduced pressure and the residue was purified by preparative
layer chromatography (SiO2, EtOAc–hexane, 3:7) to give
mainly 5-[dimethyl(4-methylphenyl)silyl]pent-3-enoic acid (15
mg, 60%) (E:Z, 45:55); Rf(EtOAc–hexane, 30:70) 0.24; δH(250
MHz, CDCl3) 7.39 (2 H, d, J 7.8, Ar), 7.38 (2 H, d, J 7.8, Ar),
Rf(EtOAc–hexane, 15:85) 0.37; νmax(CHCl3)/cmϪ1 1760 (C᎐O),
᎐
1600 (Ar), 1250 (SiMe) and 1105 (SiAr); δH(250 MHz, CDCl3)
7.32 (2 H, d, J 7.8, Ar), 7.23 (2 H, d, J 7.8, Ar), 7.18 (2 H, d,
J 7.8, Ar), 7.15 (2 H, d, J 7.8, Ar), 4.38 (1 H, ddd, J 4.5, 9 and
9.8, CHOCO), 2.47 (1 H, dd, J 9 and 17.5, CHAHBCO), 2.37
(3 H, s, 4-MeC6H4), 2.36 (3 H, s, 4-MeC6H4), 2.26 (1 H, dd,
J 12.5 and 17.5, CHAHBCO), 1.57 (1 H, ddd, J 9.9 and 12.5,
SiCH), 1.09–0.93 (2 H, m, SiCH2), 0.30 (3 H, s, SiMe) and
0.28 (9 H, s, SiMe2 and SiMe); m/z 396 (2%, Mϩ) and 149 (100,
4-MeC6H4SiMe2) (Found: C, 69.70; H, 8.30; Mϩ, 396.1942.
C23H32O2Si2 requires C, 69.64; H, 8.13%; M, 396.1941), and
the lactone 16 (275 mg, 14%). The reaction was monitored
by IR, no absorption at around 1820 cmϪ1 for an intermediate
β-lactone was observed.
7.16 (4 H, d, J 7.8, Ar), 5.70–5.30 (4 H, m, CH᎐CH), 3.02 (2 H,
᎐
d, J 6.6, CH2CO of E), 2.97 (2 H, d, J 7.1, CH2CO of Z),
2.33 (6 H, s, 4-MeC6H4), 1.70 (4 H, d, J 8.2, SiCH2), 0.26 (6 H,
s, SiMe2 of Z) and 0.24 (6 H, s, SiMe2 of E), and recovered
lactone 16 (10 mg, 25%). The mixture of acids was treated with
ethereal diazomethane to give the mixture of esters; Rf(EtOAc–
hexane, 10:90) 0.39; GC (SGE BP-5, 0.32 mm id, 25 m, film
thickness 0.25 micron; 200 ЊC isothermal) 35 (44%, tR = 5.08
min), 37 (52%, tR = 5.36 min) and 36 (4%, tR = 4.35 min);
νmax(film)/cmϪ1 1730 (C᎐O), 1600 (Ar), 1250 (SiMe) and 1100
᎐
(SiAr); δH(250 MHz, CDCl3) 7.38 (2 H, d, J 7.9, Ar), 7.37 (2 H,
d, J 7.9, Ar), 7.16 (4 H, d, J 7.9, Ar), 5.70–5.330 (4 H, m,
CH᎐CH), 3.66 (3 H, s, OMe, E), 3.65 (3 H, s, OMe, Z), 2.99
᎐
(3RS,4RS)-3,5-Bis[dimethyl(4-methylphenyl)silyl]valero-1,4-
lactone 27
(2 H, d, J 6.5, CH2CO, E), 2.94 (2 H, d, J 6.8, CH2CO, Z), 2.34
(6 H, s, 4-MeC6H4), 1.68 (4 H, d, J 7.8, SiCH2), 0.25 (6 H, s,
SiMe2, Z), 0.24 (6 H, s, SiMe2, E).
Similarly, the lactone 22 (130 mg, 0.33 mmol) in methanol (2
cm3) with potassium hydroxide (0.5 mol dmϪ3 in MeOH–THF–
water, 8:1:14 cm3) was converted to a solution of the hydroxy
acid 31, which was treated with triphenylphosphine (173 mg,
0.66 mmol) and DEAD (116 mg, 0.66 mmol), worked up and
chromatographed (SiO2, Et2O–hexane, 30:70) to give the lac-
tone (92 mg, 71%) as needles, mp 109–110 ЊC (from MeOH);
Reactions of lactones with boron trifluoride–diethyl ether
Typically, boron trifluoride–diethyl ether (1.6 × 10Ϫ3 cm3,
0.013 mmol) was kept with the lactone (50 mg, 0.125 mmol) in
dichloromethane (1 cm3) under nitrogen at room temperature
for 1–3 days. The solvent was evaporated under reduced pres-
sure, the residue was esterified with ethereal diazomethane,
purified by preparative layer chromatography (SiO2, EtOAc–
hexane, 10:90) and analysed by GC (details above). The follow-
ing lactones were treated in this way.
The lactone 16 gave after 3 days the lactone 16 (10%) and a
mixture of esters (80%) in the ratios 35:37:36 49:37:14.
The lactone 30 gave after 40 h the mixture of esters (85%) in
the ratios 35:37:36 76:5:19.
Rf(Et2O–hexane, 30:70) 0.25; νmax(CHCl3)/cmϪ1 1760 (C᎐O),
᎐
1600 (Ar), 1250 (SiMe) and 1100 (SiAr); δH(250 MHz; CDCl3)
7.35 (2 H, d, J 7.8, Ar), 7.27 (2 H, d, J 7.8, Ar), 7.18 (2 H, d,
J 7.8, Ar), 7.14 (2 H, d, J 7.8, Ar), 4.74 (1 H, ddd, J 2.8, 7.2 and
10, CHOCO), 2.51 (1 H, dd, J 12.8 and 17.2, CHAHBCO), 2.42
(1 H, dd, J 3.6 and 17.2, CHAHBCO), 2.37 (3 H, s, 4-MeC6H4),
2.34 (3 H, s, 4-MeC6H4), 2.19–2.07 (1 H, m, SiCH), 1.05 (1 H,
dd, J 10 and 14.5, SiCHAHB), 0.90 (1 H, dd, J 2.8 and 14.5,
SiCHAHB), 0.35 (3 H, s, SiMe), 0.32 (3 H, s, SiMe), 0.29 (3 H,
s, SiMe) and 0.24 (3 H, s, SiMe); m/z 396 (32.3%, Mϩ) and
149 (100, 4-MeC6H4SiMe2) (Found: C, 69.65; H, 8.20; Mϩ,
396.1934. C23H32O2Si2 requires C, 69.64; H, 8.13%; M,
396.1941), and recovered lactone 22 (20 mg, 15%).
The lactone 27 gave after 28 h the mixture of esters (93%) in
the ratios 35:37:36 4:90:6. Data for methyl (Z)-5-dimethyl(4-
methylphenyl)silylpent-3-enoate 37 δH(250 MHz, CDCl3) 7.39
(2 H, d, J 7.9, Ar), 7.16 (2 H, d, J 7.9, Ar), 5.60 (1 H, ttd, J 1.5,
7.0 and 10.5, CH᎐CHCH CO), 5.45 (1 H, ttd, J 0.8, 8.3 and
᎐
2
10.5, CH᎐CHCH Si), 3.65 (3 H, s, OMe), 2.94 (2 H, dd, J 1.5
᎐
2
2-Deoxyribonolactone from the lactone 30
and 7.0, CH2CO), 2.34 (3 H, s, 4-MeC6H4), 1.69 (2 H, dd, J 0.8
and 8.3, SiCH2) and 0.26 (6 H, s, SiMe2).
The lactone 30 (400 mg, 1 mmol) was converted to deoxyri-
bonolactone (78 mg, 59%), identical (TLC, IR, 1H NMR) with
the earlier sample, using potassium bromide (300 mg, 2.4
mmol), sodium acetate (3 g, 36.6 mmol) and peracetic acid (10
cm3, of a 32% w/v solution in acetic acid) in acetic acid (16 cm3)
following the method for its preparation from the δ-lactone 16,
except that no acid treatment was needed to change lactone ring
size.
Reactions of lactones with tetrabutylammonium fluoride
Typically, tetrabutylammonium fluoride (1 mol dmϪ3 in THF,
0.4 cm3) was stirred with the lactone (80 mg, 0.2 mmol) in dry
THF (1 cm3) at room temperature for 0.5–1.5 h. Methyl iodide
(0.1 cm3, 1.6 mmol) was added and the mixture was stirred for
15 min, poured into water and extracted with ether (2 × 10
cm3). The extract was washed with water and with brine, dried
(MgSO4) and evaporated under reduced pressure. The residue
was chromatographed (SiO2, EtOAc–hexane, 1:9) and analysed
by GC (details above). The following lactones were treated in
this way.
(3RS,4SR)-2-Deoxyribonolactone diacetate [(3RS,4SR)-3,5-
diacetoxypentan-1,4-olide] 18
Acetic anhydride (0.2 cm3, containing 1% w/v of 70% perchloric
acid) was stirred with the lactone (20 mg, 0.15 mmol) at room
temperature for 0.5 h, and worked up as before to give the
diacetate (27 mg, 83%), identical (TLC, IR, 1H NMR) with the
earlier sample.
The lactone 16 gave after 30 min methyl 3-dimethyl(4-methyl-
phenyl)silylpent-4-enoate 36 (94%) isomerically pure; Rf-
(EtOAc–hexane, 10:90) 0.39; νmax(film)/cmϪ1 1735 (C᎐O), 1620
᎐
(C᎐C), 1600 (Ar), 1250 (SiMe) and 1100 (SiAr); δ (250 MHz,
᎐
H
2-Deoxyxylonolactone diacetate 24
Similar to the preparation of the lactone 18 from the lactone 30,
the lactone 27 (60 mg, 0.15 mmol) gave successively 2-deoxy-
CDCl3) 7.37 (2 H, d, J 7.8, Ar), 7.17 (2 H, d, J 7.8, Ar), 5.70
(1 H, ddd, J 7.5, 10.5 and 17.3, CH᎐CH ), 4.90 (1 H, d, J 10.5,
᎐
2
CH᎐CH H ), 4.81 (1 H, d, J 17.3, CH᎐CH H ), 3.58 (3 H, s,
᎐
᎐
A
B
A
B
J. Chem. Soc., Perkin Trans. 1, 1998
2719

View Article Online
12 K. Bock, I. Lundt and C. Pedersen, Acta Chem. Scand., Sect. B,
OMe), 2.46–2.23 (3 H, m, SiCH and CH2CO), 2.34 (3 H, s,
4-MeC6H4), 0.27 (3 H, s, SiMe) and 0.26 (3 H, s, SiMe); m/z 262
(52.5%, Mϩ) and 149 (100, 4-MeC6H4SiMe2) (Found: C, 68.83;
H, 8.63; Mϩ, 262.1371. C15H22O2Si requires C, 68.65; H, 8.45%;
M, 262.1389).
The lactone 30 gave after 1 h the mixture of esters (92%) in
the ratios 35:37:36 60:1:39. Data for methyl (E)-5-dimethyl(4-
methylphenyl)silylpent-3-enoate 35 δH(250 MHz, CDCl3) 7.39 (2
H, d, J 7.9, Ar), 7.17 (2 H, d, J 7.9, Ar), 5.53 (1 H, td, J 7.8 and
1981, 35, 155.
13 B. Rague, Y. Chapleur and B. Castro, J. Chem. Soc., Perkin Trans. 1,
1982, 2063.
14 B. J. Pradhan, PhD Thesis, Cambridge, 1996.
15 R. P. C. Cousins and N. S. Simpkins, Tetrahedron Lett., 1989, 30,
7241; C. M. Cain, R. P. C. Cousins, G. Coumbarides and N. S.
Simpkins, Tetrahedron, 1990, 46, 523; P. J. Cox and N. S. Simpkins,
Synlett, 1991, 321.
16 P. F. Hudrlik, A. M. Hudrlik, G. Nagendrappa, T. Yimenu, E. T.
Zellers and E. Chin, J. Am. Chem. Soc., 1980, 102, 6894 with a
correction J. Am. Chem. Soc., 1982, 104, 1157; P. F. Hudrlik, A. M.
Hudrlik, T. Yimenu, M. A. Waugh and G. Nagendrappa,
Tetrahedron, 1988, 44, 3791.
17 G. Procter, A. T. Russell, P. J. Murphy, T. S. Tan and A. N. Mather,
Tetrahedron, 1988, 44, 3953.
18 M. T. Reetz, Angew. Chem., Int. Ed. Engl., 1972, 11, 129.
19 B. Capon and S. P. McManus, Neighbouring Group Participation,
Vol. 1, Plenum, New York, 1976.
15.6, CH᎐CHCH CO), 5.34 (1 H, td, J 7.0 and 15.6, CH᎐
᎐
᎐
2
CHCH2Si), 3.66 (3 H, s, OMe), 2.98 (2 H, d, J 7.8, CH2CO),
2.34 (3 H, s, 4-MeC6H4), 1.69 (2 H, d, J 7.0, SiCH2) and 0.24
(6 H, s, SiMe2) (Found: C, 68.55; H, 8.30; M, 262.1375.
C15H22O2Si requires C, 68.65; H, 8.45%; M, 262.1389).
The lactone 27 gave after 1.5 h the mixture of esters (83%) in
the ratios 35:37:36 8:41:51.
20 M. Suginome, A. Takama and Y. Ito, J. Am. Chem. Soc., 1998, 120,
1930.
Acknowledgements
21 I. Fleming, Chemtracts, Org. Chem., 1993, 6, 113; J. B. Lambert,
J. Organomet. Chem., 1996, 521, 203; J. B. Lambert and Y. Zhao,
J. Am. Chem. Soc., 1996, 118, 7867.
22 J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976, 734.
23 N. Shimizu, S. Imazu, F. Shibata and Y. Tsuno, Bull. Chem. Soc.
Jpn., 1991, 64, 1122.
We thank the Commission of the European Communities
for a grant, B/CII*-913098, to S. K. G., and Professor Albert
Eschenmoser for a stimulating correspondence about the
mechanism of the rearrangement 28 → 30.
24 D. W. Lewis and G. C. Gainer, J. Am. Chem. Soc., 1952, 74, 2931.
25 G. Solladié and C. Hamdouchi, Synthesis, 1991, 979.
26 T. Imamoto and M. Ono, Chem. Lett., 1987, 501.
27 I. Ojima and M. Kumagai, J. Organomet. Chem. 1976, 111, 43.
28 A. P. Krapcho and A. J. Lovey, Tetrahedron Lett., 1973, 957.
29 Y. Kita, O. Tamura, F. Itoh, H. Yasuda, H. Kishino, Y. Y. Ke and
Y. Tamura, J. Org. Chem., 1988, 53, 554.
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Paper 8/04282I
Received 5th June 1998
Accepted 25th June 1998
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J. Chem. Soc., Perkin Trans. 1, 1998