Reactions of phenyldimethylsilyllithium with β-N,N- dimethylaminoenones: A convenient synthesis of β-dimethyl(phenyl) silylacrylic acid and its derivatives

Article abstract of DOI:10.1139/v03-194

Phenyldimethylsilyllithium reacted with 5,5-dimethyl-3-(N,N,-dimethylamino) cyclohex-2-enone (7), 3-(E)-N,N-dimethylaminopropenal (11), and 4-N,N-dimethylaminobut-3-en-2-one (13) to give the corresponding β-silyl-α,β-unsaturated carbonyl compounds 8, 12, and 14, in which the dimethylamino group has been displaced by the phenyldimethylsilyl group. Phenyldimethylsilyllithium reacted with ethyl β-N,N- dimethylaminopropenoate (15) by conjugate addition, but, in contrast to the ketones 7 and 13 and the aldehyde 11, the intermediate enolate 16 was C-protonated in the aqueous work-up to give ethyl 3-N,N-dimethylamino-3- dimethyl(phenyl)silylpropanoate (17). When the enolate 16 was instead given a mysteriously brief treatment with methyl iodide before work-up, the product was ethyl 3-(E)-dimethy(phenyl)silylpropenoate (18). Phenyllithium and methyllithium also added conjugatively to ethyl β-N,N-dimethylaminoacrylate (15) but, in contrast to the silyl case, the intermediate enolate 22 reacted unexceptionally with methyl iodide to give the products 25 and 26 of stereoselective C-methylation. This synthesis of the ester 18 was used to synthesize the Oppolzer sultam derivative 30.

Full text of DOI:10.1139/v03-194

325
Reactions of phenyldimethylsilyllithium with ␤-
N,N-dimethylaminoenones: A convenient synthesis
of ␤-dimethyl(phenyl)silylacrylic acid
and its derivatives1
Ian Fleming, Elena Marangon, Chiara Roni, Matthew G. Russell, and
Sandra Taliansky Chamudis
Abstract: Phenyldimethylsilyllithium reacted with 5,5-dimethyl-3-(N,N-dimethylamino)cyclohex-2-enone (7), 3-(E)-N,N-
dimethylaminopropenal (11), and 4-N,N-dimethylaminobut-3-en-2-one (13) to give the corresponding β-silyl-α,β-unsatu-
rated carbonyl compounds 8, 12, and 14, in which the dimethylamino group has been displaced by the
phenyldimethylsilyl group. Phenyldimethylsilyllithium reacted with ethyl β-N,N-dimethylaminopropenoate (15) by con-
jugate addition, but, in contrast to the ketones 7 and 13 and the aldehyde 11, the intermediate enolate 16 was C-
protonated in the aqueous work-up to give ethyl 3-N,N-dimethylamino-3-dimethyl(phenyl)silylpropanoate (17). When
the enolate 16 was instead given a mysteriously brief treatment with methyl iodide before work-up, the product was
ethyl 3-(E)-dimethy(phenyl)silylpropenoate (18). Phenyllithium and methyllithium also added conjugatively to ethyl β-
N,N-dimethylaminoacrylate (15) but, in contrast to the silyl case, the intermediate enolate 22 reacted unexceptionally
with methyl iodide to give the products 25 and 26 of stereoselective C-methylation. This synthesis of the ester 18 was
used to synthesize the Oppolzer sultam derivative 30.
Key words: conjugate addition, elimination, substitution, silyllithium, silylenone.
Résumé : Le phényldiméthylsilyllithium réagit avec la 5,5-diméthyl-3-(N,N-diméthylamino)cyclohex-2-énone (7), le 3-
(E)-N,N-diméthylaminopropénal (11) et la 4-N,N-diméthylaminobut-3-én-2-one (13) pour conduire à la formation des
composés carbonylés β-silyl-α,β-insaturés correspondants, 8, 12 et 14 dans lesquels le groupe diméthylamino a été rem-
placé par un groupe phényldiméthylsilyle. Avec le β-N,N-diméthylaminopropénoate d’éthyle (15), le phényldiméthylsi-
lyllithium donne une réaction d’addition conjuguée, mais, par opposition avec ce qui a été observé avec les cétones 7
et 13 et l’aldéhyde 11, l’intermédiaire énolique 16 la récupération aqueuse des produits provoque une C-alkylation qui
conduit au 3-N,N-diméthylamino-3-diméthyl(phényl)silylpropénoate (17). Toutefois, lorsque l’énolate 16 est soumis à un
mystérieusement court traitement par de l’iodure de méthyle avant la récupération des produits, le produit obtenu est
alors le 3-(E)-diméthyl(phényl)silylpropénoate d’éthyle (18). Le phényllithium et le méthyllithium s’ajoutent aussi de
façon conjugue au β-N,N-diméthylaminopropénoate d’éthyle (15) mais, par opposition à ce qui a été observé dans le
cas silylé, l’intermédiaire énolique 22 réagit sans surprise avec l’iodure de méthyle pour conduire aux produits 25 et 26
de C-méthylation stéréosélective. Cette synthèse de l’ester 18 a été utilisée pour réaliser la synthèse du dérivé sultame
d’Oppolzer 30.
Mots clés : addition conjugue, élimination, substitution, silyllithium, silylénone.
[Traduit par la Rédaction] Fleming et al. 332
Introduction
(4). More recently, we have been engaged in further studies
of the silyllithium reagent itself (5), and of its reactions with
a number of substrates, including aromatic esters (6), α-
silyloxy esters (7), saturated esters (8), amides (9, 10), thio-
amides (11), nitriles (12), sulfonamides (13), and acid chlo-
rides (14). Most notably, tertiary amides have been a source
of several remarkable reactions, which we have to a large
The phenyldimethylsilyllithium reagent (1) was first made
and, along with its triphenylsilyl analogue, quite extensively
studied by Gilman in the 1950s and 1960s (2), but it has
been relatively little used except as a source of the corre-
sponding cuprate reagent (3), which we introduced in 1978
Received 12 September 2003. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 13 February 2004.
Dedicated with affection to Professor Ed Piers.
I. Fleming,2 E. Marangon, C. Roni, M.G. Russell, and S. Taliansky Chamudis. Department of Chemistry, Lensfield Road,
Cambridge CB2 1EW, U.K.
1This article is part of a Special Issue dedicated to Professor Ed Piers.
2Corresponding author (e-mail: if10000@cam.ac.uk).
Can. J. Chem. 82: 325–332 (2004)
doi: 10.1139/V03-194
© 2004 NRC Canada

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Can. J. Chem. Vol. 82, 2004
Scheme 1.
extent unravelled (9, 10). Most strikingly, the simple N,N-
dimethylamide 1 could be induced to give in good yield any
one of three distinct products (2, 3, or 4), depending upon
the reaction conditions and (or) the stoichiometry
(Scheme 1) (8, 9).
Almost every change we made to the structure of the start-
ing amide led to other surprises, an experience Gilman was
not immune to either. Thus, the reaction of the acetylenic
amide 5 proved to be different from the saturated amide, not
only because conjugate addition was now both possible and
what occurred, but also because reduction took place as
well, at least in the products 6 that we could recognise
(Scheme 2). Conjugate addition is hardly surprising, since
silyllithium and stannyllithium reagents can easily react in
this way with unsaturated carbonyl compounds in THF (15),
although the cuprates are usually rather better, but reduction
to an aldehyde had not been a common outcome in our ear-
lier work. The yield, however, was unimpressive, and we did
not pursue this unpromising line. More interesting were the
results of reactions with vinylogous amide systems, which
we reported in a preliminary communication (16), and which
we report in full here.
Scheme 2.
Scheme 3.
Results and discussion
The reaction of phenyldimethylsilyllithium with the enone
7 was unexceptional in giving the β-silylenone 8 in which
the dimethylamino group has been replaced by the silyl
group (Scheme 3). Two pathways might have been followed.
In one, the silyllithium reagent attacked the carbonyl group
directly to give the enamine 9, hydrolysis of which, followed
by elimination of water, would give the enone 8. Alterna-
tively, conjugate attack took place to give the enolate 10,
which underwent elimination of the dimethylamino group. A
similar outcome was found for the enal 11 giving the enal
12, in a less clean reaction with the same two possible path-
ways. The conjugate addition–elimination pathway is cer-
tainly followed in the reaction between the silyllithium
reagent and the enone 13, which gave the β-silylenone 14 in
good yield. Furthermore, it is known that a β-amino group
encourages conjugate addition by organolithium reagents
(17), and trimethylsilyllithium is also known to give conju-
gate addition, rather than direct attack at the carbonyl group,
with cyclohexenones in THF (15). Finally, it is not obvious
why the pathway involving direct attack at the carbonyl
group should not enter the carbene-forming sequence that
we have seen is so accessible in the reactions described ear-
lier, and involved, for example, in the formation of the
enediamine 3 and the α-aminosilane 4 (9, 10). It seems
likely that the conjugate addition–elimination pathway is fol-
lowed in all of these reactions.
self, it raised the first question: why was the dimethylamino
group eliminated in the experiments in Scheme 3, and not
here? One possibility is that the ketone and aldehyde eno-
lates are kinetically protonated on oxygen. The resultant
enols might then live long enough to expel the dimethyla-
mino group in the aqueous medium before they underwent
tautomerism to the ketones or the aldehyde. In contrast, it is
possible that the ester enolate is protonated directly on car-
bon, and the dimethylamino group would not then be so eas-
ily lost.
However, this was not the most puzzling observation. If,
instead of the aqueous quench, we added methyl iodide, and
then worked up in the usual way, the major product was the
β-silylester 18. This was not the result that we expected, be-
cause the carbon atom of the enolate ion 16 ought to have
The products 8, 12, and 14 are easily made by other meth-
ods (18–20), and so we have not taken this investigation any
further. Instead, we investigated the corresponding reaction
with the vinylogous carbamate 15, which gave us a curious
result, and, incidentally, a better synthesis of the ester 18
than the one we had been using quite extensively hitherto in
our synthetic work.
When we added the silyllithium reagent to the ester 15,
the only product after an aqueous quench was that of conju-
gate addition 17 (Scheme 4). While this is unsurprising in it-
© 2004 NRC Canada

Fleming et al.
327
Scheme 4.
Scheme 5.
Scheme 6.
been more nucleophilic towards methyl iodide than the di-
methylamino group. The product of enolate methylation 19
was detectable on one occasion, and then only in a small
amount. Similarly, when we regenerated the enolate 16 from
the ester 17 using LDA, and treated that enolate with methyl
iodide, the same unsaturated ester 18 was formed.
Additionally remarkable is that the elimination of dime-
thylamine 16 → 18 achieved by the treatment with methyl
iodide took only a few minutes at –20 °C. In contrast, if we
treated the amine 17 with methyl iodide in THF, little N-
methylation took place over 18 h at room temperature — we
recovered the amine 17 in 86% yield. Evidently, the α-silyl
group does not on its own increase the nucleophilicity of the
nitrogen lone pair (21) enough to suggest an exceptionally
easy N-methylation. It seems improbable that coordination
by the enolate oxygen to the silyl group could make the ni-
trogen lone pair more nucleophilic than the carbon atom of
the enolate ion, and we have no convincing explanation for
the ease with which the elimination took place. It is not spe-
cific to using methyl iodide, since benzyl bromide and allyl
bromide had the same effect, although not in such good
yield. The most obvious explanation would have been that
the dimethylamide ion had already been expelled from the
enolate 16 before the aqueous quench, and had added back
during the aqueous quench giving the saturated ester 17. The
role of the methyl iodide in this scenario would have been to
quench the dimethylamide ion, and prevent it from adding
back. This is not the explanation, because the unsaturated es-
ter 18, which would have been the product of that elimina-
tion, reacted with lithium dimethylamide to give the amides
20 and 21 (Scheme 5). These products were not present in
the reaction mixtures from Scheme 3. Furthermore, quench-
ing the reaction mixture from the conjugate addition by in-
jecting it directly into aqueous hydrochloric acid, which can
be expected to protonate the amide ion rapidly, gave largely
the ester 17 (67%) and only a little (9%) of the product of
elimination 18.
the reaction with the ester 15 using phenyllithium instead of
phenyldimethylsilyllithium (Scheme 6). Conjugate addition
took place to give the enolate 22 (R = Ph); quenching with
ammonium chloride solution gave the amino ester 23, but
quenching with methyl iodide gave the expected enolate
methylation, with the expected (22) high degree of
diastereoselectivity in favour of the known (23) isomer 25.
Regeneration of the enolate 22 (R = Ph) from the ester 23
using LDA, followed by methylation with methyl iodide,
gave the same result: C-methylation, this time with a detect-
able but small amount of the diastereoisomer 27 formed as
well. In some rather lower yielding, but otherwise similar re-
actions, methyllithium also added in a conjugate manner,
and the enolate 22 (R = Me) could be trapped with either
protons or methyl iodide to give the esters 24 and 26, re-
spectively.
The ester 18 has usually been prepared most economically
by hydrosilylation–dehydrogenation of ethyl acrylate (24),
but in that otherwise excellent method it is always contami-
nated with the saturated analogue, no matter how much of an
excess of ethyl acrylate is used to limit the amount of hydro-
silylation. In our experience, the saturated analogue, al-
though harmless to what we were doing, has frequently been
difficult to remove, and we have found ourselves carrying it
through the next few steps of our synthetic work until we
found a stage at which it could be removed relatively easily.
The easy elimination induced by methyl iodide has some-
thing to do with the presence of the silyl group. We repeated
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Can. J. Chem. Vol. 82, 2004
Schcme 7.
167.2+, 142.9–, 137.5+, 133.6–, 128.3–, 15.9– and –0.9–
(1 signal missing). (Z)-isomer: H NMR (250 MHz, CDCl3)
1
δ: 9.7 (1H, d, J = 8.5, CHO), 7.5–7.4 (2H, m, Ph), 7.4–7.2
(3H, m, Ph), 6.5 (1H, dq, J = 8.5 and 1.4, C=CH), 2.1 (3H,
d, J = 1.4, CMe), and 0.5 (6H, s, SiMe2). 13C NMR
(100 MHz, CDCl3) δ: 190.2–, 163.9+, 137.8–, 135.4+,
134.0–, 129.7–, 128.1–, 26.8– and –0.4–.
5,5-Dimethyl-3-(dimethylphenylsilyl)cyclohex-2-enone (8)
Dimethyl(phenyl)silyllithium (2.4 mL, 1 mol dm–3 in
THF, 2.4 mmol) was added dropwise to 5,5-dimethyl-3-
(dimethylamino)cyclohex-2-enone (0.37 g, 2.20 mmol) in
THF (2 mL) at –78 °C, the mixture stirred at –78 °C for 1 h,
and then kept at –20 °C for 1 h. Saturated aqueous sodium
bicarbonate solution (5 mL) and diethyl ether (5 mL) were
added. The aqueous portion was removed and the basic
products removed from the organic fraction with dilute hy-
drochloric acid. The organic layers were dried (MgSO4) and
evaporated under reduced pressure to give the crude neutral
products (0.65 g) as a yellow oil. Chromatography (SiO2,
CH2Cl2) gave the ketone (18) (0.51 g, 90%) as an oil.
Rf(CH2Cl2) 0.44. IR νmax (film, cm–1): 1675 (C=O), 1589
1
(C=C), 1249 (SiC), and 1112 (SiC). H NMR (250 MHz,
CDCl3) δ: 7.5–7.45 (2H, m, Ph), 7.4–7.35 (3H, m, Ph), 6.30
(1H, t, J = 1.8, C=CH), 2.24 (2H, s, CH2CO), 2.19 (2H, d,
J = 1.8, CH2C=C), 0.95 (6H, s, CMe2), and 0.43 (6H, s,
SiMe2). 13C NMR (100 MHz, CDCl3) δ: 199.0+, 163.4+,
136.0–, 135.4–, 133.9–, 129.6–, 128.1–, 51.5+, 42.1+, 34.3+,
28.1– and –4.4–. MS m/z (EI): 259.1 (50%, MH+), 243.1
(90, M – Me), and 137.0 (100) (found: M+, 258.14402;
C16H22OSi requires M, 258.14398).
The synthesis reported here is free of this problem. For fur-
ther development, it was helpful to saponify the crude ester
18, to separate acidic products from the inevitable silicon-
containing by-products. The carboxylic acid was occasion-
ally crystalline, but recrystallization, either of the acid or of
various salts was not practical. Since we needed it attached
to Oppolzer’s sultam, as did he (25), we converted the acid
into its acid chloride and joined it onto the auxiliary
(Scheme 7), at which point we had a crystalline derivative
30 that could be purified by recrystallization. The overall
yield of this useful compound from the amino ester 15 was
41%.
3-(E)-Dimethyl(phenyl)silylpropenal (12)
3-(E)-N,N-Dimethylaminopropenal (90%, 0.5 mL,
4.5 mmol) in THF (4.5 mL) was added dropwise to a solu-
tion of dimethyl(phenyl)silyllithium (0.9 mol dm–3 in THF,
5.5 mL, 4.95 mmol) under argon at –78 °C. The mixture was
stirred for 1 h at this temperature and then at –15 °C for 1 h.
Saturated aqueous sodium bicarbonate solution (5 mL) was
added. The organic layer was washed with water (2 mL).
The combined aqueous layers were extracted with ether (3 ×
2 mL). The combined organic layers were washed with
aqueous hydrochloric acid (3 N, 2 mL), brine (2 mL), dried
(MgSO4), and the solvent evaporated under reduced pres-
sure. The residue was distilled to give the aldehyde (19)
(0.342 g, 40%), bp 91 °C at 0.9 mmHg (1 mmHg = 133.322
Pa). Rf(CH2Cl2) 0.84. IR νmax (film, cm–1): 1693 (C=O),
1428 (C=C), 1251 (SiC), and 1117 (SiC). 1H NMR
(400 MHz, CDCl3) δ: 9.53 (1H, d, J = 7.6, CHO) 7.52–7.50
(2H, m, Ph), 7.40–7.30 (4H, m, Ph and CHSi), 6.54 (1H, dd,
J = 18.7 and 7.6, CHCO), and 0.47 (6H, s, SiMe2). 13C
NMR (100 MHz, CDCl3) δ: 194.5–, 156.4–, 145.1–, 135.7+,
133.7–, 129.8–, 128.1– and –3.4–. MS m/z (EI): found: M+,
190.08271; C11H14OSi requires M, 190.08132.
Experimental
13C NMR data from attached proton tests (APT) are given
in the form 133.6– when the C atom has an odd number of
H atoms attached, and 167.2+ when it has an even number
of H atoms attached.
(E)- and (Z)-3-Dimethyl(phenyl)silybut-2-enal (6)
But-2-ynoic acid N,N-dimethylamide (26) (0.22 g,
2.00 mmol) in THF (2 mL) was added dropwise to dimethyl-
(phenyl)silyllithium (1, 7) (4.8 mL, 1 mol dm–3 in THF,
4.8 mmol) at –78 °C, and the mixture was kept at –20 °C for
1 h. Saturated aqueous sodium bicarbonate (5 mL) and
diethylether (5 mL) were added. The aqueous portion was
removed and the basic products extracted from the organic
fraction with dilute hydrochloric acid (3 N). The aqueous
layers were basified (10% NaOH) to pH 12 and then ex-
tracted with ether (3 × 20 mL), dried (MgSO4) and evapo-
rated under reduced pressure to give the crude products
(0.24 g). Chromatography (SiO2, CH2Cl2) gave the alde-
hydes (0.09 g, 22%) as an inseparable mixture (E:Z, 5:1).
4-(E)-[Dimethyl(phenyl)silyl]but-3-en-2-one (14)
Dimethyl(phenyl)silyllithium (0.9 mol dm–3 in THF,
5.25 mL, 4.7 mmol) was added dropwise to a solution of 4-
N,N-dimethylaminobut-3-en-2-one (0.5 mL, 4.3 mmol) in
THF (5 mL) at –78 °C under argon. The mixture was stirred
at this temperature for 1 h, and then at –10 °C for 1 h. Aque-
1
(E)-isomer: H NMR (250 MHz, CDCl3) δ: 10.1 (1H, d, J =
7.8, CHO), 7.5–7.4 (2H, m, Ph), 7.4–7.2 (3H, m, Ph), 6.3
(1H, dq, J = 7.8 and 1.7, C=CH), 2.2 (3H, d, J = 1.7, CMe),
and 0.4 (6H, s, SiMe2). 13C NMR (CDCl3) δ: 192.9–,
© 2004 NRC Canada

Fleming et al.
329
ous sodium bicarbonate (saturated, 5 mL) and ether (5 mL)
were added and the layers separated. The aqueous layer was
extracted with ether (2 × 3 mL). The combined organic lay-
ers were washed with dilute hydrochloric acid (3 N, 2 ×
3 mL), brine (2 mL), dried (MgSO4), and the solvent evapo-
rated off under reduced pressure. The residue was chroma-
tographed (SiO2, light petroleum (bp 40–60 °C)) to give the
ketone (20) (0.66 g, 76%). Rf(Et2O) 0.87. IR νmax
(Nujol, cm–1): 1678 (C=O), 1217 (SiMe2), 1115 (SiPh), 735
was stirred at room temperature for 20 min and quenched
with water (10 mL). The organic layer was washed with wa-
ter (2 × 10 mL) and the combined aqueous layers extracted
with ether (4 × 5 mL). The combined organic layers were
washed with aqueous hydrochloric acid (3 N, 7 mL). The
aqueous layer was then extracted with ether (4 × 2 mL). The
combined organic layers were washed with brine (10 mL),
dried (MgSO4), filtered and the solvent evaporated under re-
duced pressure to give the crude ester (27) (9.9 g, 96%).
Chromatography of an earlier run, with some losses, gave
pure ester (67%). Rf(Et2O:light petroleum (bp 40–60 °C),
50:50) 0.85. IR νmax (film, cm–1): 1727 (C=O), 732 (Ph), and
1
(Ph), and 700 (Ph). H NMR (400 MHz, CDCl3) δ: 7.52–
7.49 (2H, m, Ph), 7.40–7.36 (3H, m, Ph), 7.11 (1H, d, J =
19.2, SiCH), 6.48 (1H, d, J = 19.2, CHCO), 2.28 (3H, s,
COMe), and 0.43 (6H, s, SiMe2). 13C NMR (100 MHz,
CDCl3) δ: 198.6+, 145.6–, 144.0–, 136.3+, 133.8–, 129.6–,
127.9–, 26.3–, –3.2–. MS m/z (ESI): 227 (100%, M+Na)
(found: MNa+, 227.0871; C12H16OSi requires M + Na,
227.0868).
1
700 (Ph). H NMR (400 MHz, CDCl3) δ: 7.60–7.50 (2H, m,
Ph), 7.40–7.32 (3H, m, Ph), 7.28 (1H, d, J = 19, CH=), 6.28
(1H, d, J = 19, CH=), 4.21 (2H, q, J = 7.1, OCH2), 1.29 (3H,
t, J = 7.1, CH2Me), and 0.43 (6H, s, SiMe2). 1H NMR
(100 MHz, CDCl3) δ: 165.7+, 147.3–, 136.4+, 135.4–,
133.8–, 129.5–, 128.0–, 60.6+, 14.2– and –3.2–. MS m/z
(EI): found: M+, 234.1083; C13H18O2Si requires 234.1076).
MS m/z (ESI): 257 (100%, Mna+) (found: MNa+, 257.0971;
C13H18O2Si requires M + Na, 257.0974). In one run, the ba-
sic fraction gave ethyl 2-methyl-3-dimethylamino-3-
dimethyl(phenyl)silylpropanoate (19) (4%) as an inseparable
mixture of isomers (~3:1) characterized only by the defini-
Ethyl 3-N,N-dimethylamino-3-dimethyl(phenyl)silyl-
propanoate (17)
Dimethyl(phenyl)silyllithium (4.1 mL, 1 mol dm–3 in
THF, 4.1 mmol) was added dropwise to (E)-ethyl 3-
(dimethylamino)propenoate (0.53 g, 3.72 mmol) in THF
(5 mL) at –78 °C. The mixture was stirred at –78 °C for 1 h
then kept at –20 °C for 1 h. Saturated aqueous sodium bicar-
bonate (5 mL) and ether (5 mL) were added. The aqueous
portion was removed and the basic products extracted from
the organic fraction with dilute hydrochloric acid (3 N). The
aqueous extract was basified (10% NaOH) to pH 12 and
then extracted with ether (3 × 20 mL), dried (MgSO4) and
evaporated under reduced pressure to give the ester (1.17 g,
92%) as an oil. Rf(Et2O) 0.95. IR νmax (film, cm–1): 1732
(C=O), 1249 (SiC), and 1111 (SiC), 836 (SiC), 734 (Ph),
1
tive H NMR spectrum: (250 MHz, CDCl3) δ major isomer:
7.60–7.55 (2H, m, Ph), 7.35–7.30 (3H, m, Ph), 4.08 (2H, q,
J = 7.4, CO2CH2Me), 2.90–2.70 (2H, m, CHN and CHMe),
2.40 (6H, s, NMe2), 1.23 (3H, t, J = 7.1, CO2CH2Me), 0.97
(3H, d, J = 6.8, CHMe), and 0.42 (6H, s, SiMe2); minor iso-
mer: 7.60–7.55 (2H, m, Ph), 7.35–7.30 (3H, m, Ph), 3.91
(1H, q, J = 7.1, CO2CHAHBMe), 3.91 (1H, q, J = 7.1,
CO2CHAHBMe), 2.90–2.70 (2H, m, CHN and CHMe), 2.37
(6H, s, NMe2), 1.20 (3H, t, J = 7.1, CO2CH2Me), 0.97 (3H,
d, J = 6.8, CHMe), and 0.41 (6H, s, SiMe2).
1
and 701 (Ph). H NMR (250 MHz, CDCl3) δ: 7.57–7.53
(2H, m, Ph), 7.36–7.26 (3H, m, Ph), 4.03 (2H, q, J = 7.2,
OCH2Me), 2.92 (1H, dd, J = 8.7 and 5.2, CHSiN), 2.56 (1H,
dd, J = 15.2 and 8.8, CHAHBCO), 2.29 (6H, s, NMe2), 2.26
(1H, dd, J = 14.7 and 5.1, CHAHBCO), 1.20 (3H, t, J 7.2,
OCH2Me), 0.42 (3H, s, SiMeAMeB), and 0.37 (3H, s,
SiMeAMeB). 13C NMR (100 MHz, CDCl3) δ: 174.2+,
138.2+, 134.5–, 129.1–, 127.8–, 60.3+, 53.6–, 43.9–, 30.8+,
14.1–, 2.4– and –3.32–. LSI-MS m/z: found: MH+,
280.1750; C15H25NO2Si requires M + H, 280.1727. In vari-
ous runs, the neutral fraction gave small amounts of the con-
jugated ester 18 (typically 9%), identical (1H NMR, 13C
NMR) with the sample described below.
Method B
n-Butyllithium (1.45 mol dm–3 in hexanes, 5.4 mL,
7.9 mmol) was added slowly to a stirred solution of distilled
diisopropylamine (1.1 mL, 7.9 mmol) in dry THF (3.6 mL)
at 0 °C under nitrogen. After 15 min, the solution was
cooled to –78 °C and ethyl (E)-3-(N,N-dimethylamino)-3-
dimethyl(phenyl)silylpropanoate (1.0 g, 3.6 mmol) in dry
THF (4.5 mL) added by cannula, and the mixture was stirred
for 1 h. Methyl iodide (1.5 mL, 25 mmol) was added slowly,
and the mixture stirred for 1 h at –78 °C and warmed over
20 min to 0 °C. Saturated ammonium chloride solution was
added, the layers separated, and the aqueous layers extracted
with ether. The combined organic layers were washed with
brine, dried (MgSO4), and evaporated to give ethyl (E)-3-
dimethyl(phenyl)silylpropenoate (0.88 g, >100%), identical
A sample of the ester 17 was stirred overnight in iodo-
methane at room temperature. This gave, on work-up,
recovered starting material (86%) and ethyl (E)-3-(dimethyl-
phenylsilyl)-propenoate (14%).
1
(TLC, H NMR) with the earlier sample. Basification of the
aqueous layers (10% NaOH), and extraction with ether gave
the basic products (25 mg), which were a complex mixture
of several compounds (1H NMR).
Ethyl 3-(E)-dimethy(phenyl)silylpropenoate (18)
Method A
Ethyl 3-(E)-N,N-dimethylaminopropenoate (3 mL,
21 mmol) was added dropwise to a solution of dimethyl-
(phenyl)silyllithium (0.52 mol dm–3 in THF, 48 mL,
25 mmol) and toluene (25 mL) under argon at –15 °C keep-
ing the temperature below –10 °C, and then kept at –15 °C
for 15 min. Methyl iodide (3.9 mL, 63 mmol) was added
dropwise keeping the temperature below –5 °C. The mixture
Method C
The procedure of Method A was followed, but benzyl bro-
mide was used in place of methyl iodide. The products were
the unsaturated ester 18 (43%) and the conjugate addition
product 17 (38%). There was no sign of the product of C-
benzylation.
© 2004 NRC Canada

330
Can. J. Chem. Vol. 82, 2004
NMR (100 MHz, CDCl3) δ: 171.7+, 138.8+, 128.4–, 128–,
127.4–, 68.7–, 66.4+, 42.2–, 38.6+, 14.0–. MS m/z (EI): 222
(100%, MH+) (found: MH+, 222.1493; C13H19O2N requires
M + H, 222.1494); hydrochloride, mp 190 °C (from Me2CO)
(lit. (29) mp 192 °C).
Method D
The procedure of Method A was followed, but allyl bro-
mide was used in place of methyl iodide. The products were
the unsaturated ester 18 (67%) and the conjugate addition
product 17 (3%). There was no sign of the product of C-
allylation.
Ethyl (2SR,3RS)-3-dimethylamino-2-methyl-3- phenyl-
propionate (25)
(E)-N,N-Dimethyl-3-dimethyl(phenyl)silylpropenamide
(20) and N,N-dimethyl-3-dimethylamino-3-
dimethyl(phenyl)silylpropionamide (21)
Method A
n-Butyllithium (1.5 mL of a 1.7 mol dm–3 solution in hex-
anes, 2.55 mmol) was added to dimethylamine (2.2 mL of a
1.7 mol dm–3 solution in THF, 3.7 mmol) at –78 °C and
stirred at this temperature for 1 h to give a solution of lithium
dimethylamide. (E)-Ethyl 3-dimethyl(phenyl)silylpropenoate
(0.39 g, 1.68 mmol) in THF (2.0 mL) was added dropwise at
–78 °C and stirred at this temperature for 30 min and then
kept at –20 °C for 30 min. Saturated aqueous sodium bicar-
bonate (5 mL) and ether (5 mL) were added. The aqueous
portion was removed and the basic products extracted from
the organic fraction with hydrochloric acid (3 N). The organic
layer was dried (MgSO4) and evaporated under reduced pres-
sure to give (E)-N,N- dimethyl-3-dimethyl(phenyl)silylpro-
penamide (0.215 g, 55%). Rf(Et2O) 0.25. 1H NMR (250 MHz,
CDCl3) δ: 7.55–7.52 (2H, m, Ph), 7.39–7.29 (3H, m, Ph), 7.25
(1H, d, J = 18.4, SiCH=CH), 6.29 (1H, d, J = 18.4, CH=CH),
3.04 (6H, br s, CONMe2), and 0.39 (6H, s, SiMe2). The aque-
ous extract was basified (10% NaOH) to pH 12, and then ex-
tracted with ether (3 × 20 mL), dried (MgSO4), and
evaporated under reduced pressure to give N,N-dimethyl-3-
(dimethylamino)-3-dimethyl(phenyl)silylpropionamide (0.16 g,
Phenyllithium (12.5 mL, 1.8 mol dm–3, 22.4 mmol) was
added slowly to a solution of ethyl (E)-N,N-dimethylamino-
propenoate (2 g, 2 mL, 14 mmol) in dry ether (17 mL) under
Ar at –15 °C, keeping the temperature below 0 °C. The mix-
ture was stirred at –10 °C for 0.5 h and then kept at room
temperature for 1 h. Methyl iodide (2.2 mL, 35 mmol) was
added at –15 °C, and the solution kept at room temperature
for 15 h. The reaction was quenched with ammonium chlo-
ride solution (40 mL). The aqueous layer was extracted with
ether (3 × 10 mL). The combined organic layers were acidi-
fied with hydrochloric acid (3 N, 65 mL). The aqueous layer
was washed with ether (2 × 15 mL), basified with sodium
hydroxide solution (10%), and the basic product extracted
with ether (4 × 40 mL). The organic layer was washed with
brine, dried (MgSO4), and the solvent evaporated under re-
duced pressure to give the amine (23) (2.52 g, 80%).
Rf(Et2O–light petroleum (bp 40–60 °C), 1:1) 0.55. IR νmax
(film, cm–1): 1735 (C=O), 756 (Ph), and 705 (Ph). 13C NMR
(400 MHz, CDCl3) δ: 7.36–7.26 (3H, m, Ph), 7.13–7.12
(2H, m, Ph), 4.20 (2H, qd, J = 1.9 and 7.1, OCH2), 3.68
(1H, d, J 11.0, PhCH), 3.15 (1H, dq, J = 11.0 and 6.8,
CHMe), 2.10 (6H, s, NMe2), 1.28 (3H, t, J 7.1, CH2Me), and
0.93 (3H, d, J 6.8, CHMe). 13C NMR (100 MHz, CDCl3) δ:
175.6+, 134.0–, 129.3–, 127.9–, 127.3–, 72.3–, 60.0+, 42.1–,
41.2–, 14.6– and 14.2–. MS m/z (EI): 236 (2%, MH+), 191
(8, MH – OEt), and 160 (100, M – Ph) (found: M+,
236.1649; C14H22NO2 requires M, 236.1645).
1
34%). Rf(Et2O) 0.36. H NMR (250 MHz, CDCl3) δ: 7.62–
7.54 (2H, m, Ph), 7.36–7.32 (3H, m, Ph), 2.88 (3H, s,
CONMeAMeB), 2.82 (3H, s, CONMeAMeB), 2.60 (1H, dd, J =
13.2 and 5.4, CHNSi), 2.35 (6H, s, CHNMe2), 2.28–1.95
(2H, m, COCH2), 0.40 (3H, s, SiMeAMeB), and 0.38 (3H, s,
SiMeAMeB).
Method B
Ethyl 3-N,N-dimethylamino-3-phenylpropionate (23)
Phenyllithium (1.8 mol dm–3, 12.5 mL, 22.4 mmol) was
added slowly to a solution of ethyl (E)-3-N,N-dimethylami-
nopropenoate (1.84 g, 2 mL, 14 mmol) in dry ether (17 mL)
under argon at –15 °C, keeping the temperature below
−5 °C. The mixture was stirred at –10 °C for 0.5 h and at
room temperature for 2.5 h. The mixture was quenched with
aqueous ammonium chloride solution (25 mL, saturated).
The aqueous layer was extracted with ether (3 × 10 mL).
The combined organic layers were washed with aqueous hy-
drochloric acid (3 N, 65 mL). The aqueous layer was ex-
tracted with ether (3 × 10 mL), and then basified to pH 11
with sodium hydroxide solution (10%) using universal indi-
cator paper, and the aqueous layer was extracted with ether
(3 × 50 mL). The combined organic layers were washed
with brine (1 × 30 mL), dried (MgSO4), and evaporated un-
der reduced pressure to give the amine (28) as an oil (2.4 g,
76%). IR νmax(film, cm–1): 1735 (C=O), 1371 (CHCO) and
Butyllithium (1.47 mol dm–3 in hexane, 50 mL,
1.44 mmol) was added to a solution of diisopropylamine
(0.22 mL, 1.58 mmol) in dry THF (7.20 mL) under nitrogen
at –78 °C and stirred for 15 min. Ethyl 3-dimethylamino-3-
phenylpropionate (0.159 g, 0.718 mmol) was added at
–78 °C, and the temperature maintained for 1 h. Methyl io-
dide (0.11 mL, 1.8 mmol) was added, the mixture stirred at
–78 °C for 30 min and then allowed to come to room tem-
perature and kept for 1 h. The reaction was quenched with
ammonium chloride solution (10 mL). The aqueous layer
was extracted with ether (3 × 3 mL). The combined organic
layers were washed with brine, dried (MgSO4), and the sol-
vent was evaporated off under reduced pressure. The residue
was dissolved in ether (20 mL) and washed with hydrochlo-
ric acid (3 N, 20 mL). The aqueous layer was washed with
ether (3 × 6 mL) and basified with sodium hydroxide solu-
tion (10%), extracted with ether (4 × 10 mL), and the com-
bined organic layers washed with brine, dried (MgSO4), and
evaporated under reduced pressure to give a mixture of the
esters (0.117 g, 60%) in a ratio of 10:1. Rf(Et2O–light petro-
1
700 (Ph). H NMR (400 MHz, CDCl3) δ: 7.33 (2H, m, Ph),
7.27–7.23 (3H, m, Ph), 4.06 (2H, q, J = 7.1, OCH2), 3.86
(1H, dd, J = 6.9 and 8.2, CHPh), 2.95 (1H, dd, J = 14.8 and
6.9, CHACHB), 2.69 (1H, dd, J = 14.8 and 8.2, CHACHB),
2.18 (6H, s, NMe2), and 1.11 (3H, t, J = 7.1, CH2Me). 13C
1
leum (bp 40–60 °C), 1:1) 0.55. H NMR (400 MHz, CDCl3)
δ (signals from the major isomer, identical to those reported
© 2004 NRC Canada

Fleming et al.
331
above, together with signals from the minor isomer 27):
7.36–7.26 (3H, m, Ph), 7.13–7.12 (2H, m, Ph), 3.85 (2H, q,
J = 7.1, OCH2), 3.74 (1H, d, J = 11.0, PhCH), 3.10 (1H, dq,
J = 11.0 and 6.85, CHMe), 2.10 (6H, s, NMe2), 1.35 (3H, d,
J = 6.85, CHMe), and 0.91 (3H, t, J = 7.1, OCH2Me).
off under reduced pressure, and the residue was taken up in
distilled water (30 mL), washed with ether (4 × 10 mL),
acidified to pH 1 with aqueous hydrochloric acid (3 N,
~50 mL), and extracted with ether (4 × 15 mL). The com-
bined organic layers were washed with brine (15 mL), dried
(MgSO4), and the solvent evaporated off under reduced
pressure to give the acid (19) (3.2 g, 75% over two steps) as
an indeterminately low-melting solid. Rf(Et2O:light petro-
leum (bp 40–60 °C), 50:50) 0.43. IR νmax (film, cm–1): 1694
(C=O), 1593 (C=C), 840 (SiMe2), 732 (Ph), and 700 (Ph).
1H NMR (400 MHz, CDCl3) δ: 7.53–7.48 (2H, m, Ph), 7.51
(1H, d, J = 19, SiCH), 7.42–7.36 (3H, m, Ph), 6.29 (1H, d,
J = 19, CHCO), and 0.45 (6H, s, SiMe2). 13C NMR
(100 MHz, CDCl3) δ: 170.9+, 150.8–, 136.0+, 134.5–,
133.8–, 130.4–, 128.0–, and –3.6–. MS m/z (ESI): 229 (10%,
MNa+). Anal. calcd. for C11H14O2Si (%): C 64.0, H 6.8;
found: C 64.0 H 6.9. Benzylamine salt, mp 130 to 131 °C
(from MeOH). N.B. Upon addition of ether to the basic
aqueous solution, the formation of three layers was often ob-
served. The dark-coloured middle layer, presumably the
carboxylate salt, not completely soluble in the aqueous
layer, was combined with the lower aqueous layer, and car-
ried through in the acidification step. This problem was
worse when sodium hydroxide was used to hydrolyze the es-
ter, and largely avoided by using potassium hydroxide.
Ethyl 3-N,N-dimethylaminobutanoate (24)
Methyllithium (1.54 mol dm–3 in Et2O, 18.5 mL,
28.5 mmol) was added to 3-(E)-N,N-dimethylamino-
propenoate (2 g, 14 mmol) in dry ether (17 mL) at –15 °C
under nitrogen, maintaining the temperature below 0 °C. The
reaction was stirred at 0 °C for 30 min and then kept at room
temperature for 1 h. The reaction was quenched with ammo-
nium chloride solution (40 mL). The aqueous layer was ex-
tracted with ether (3 × 10 mL). The combined organic layers
were washed with brine, dried (MgSO4), and the solvent
evaporated under reduced pressure to give the amine (30)
1
(1.14g, 51%). IR νmax (film, cm–1): 1732 (C=O). H NMR
(400 MHz, CDCl3) δ: 4.13 (2H, q, J = 7.1, OCH2), 3.10 (1H,
ddq, J = 8.5, 5.7, and 6.6, CHMe), 2.53 (1H, dd, J = 14.4
and 5.7, CHACHBCO), 2.23 (6H, s, NMe2), 2.18 (1H, dd,
J = 14.4 and 8.5, CHACHBCO), 1.24 (3H, t, J 7.1,
OCH2Me), and 1.03 (3H, d, J = 6.6, CHMe).
Ethyl 3-N,N-dimethylamino-2-methylbutanoate (26)
Methyllithium (1.54 mol dm–3 in Et2O, 37 mL,
28.5 mmol)) was added to 3-(E)-N,N-dimethylamino-
propenoate (4 g, 28 mmol) in dry ether (34 mL) at –15 °C
under nitrogen, maintaining the temperature below 0 °C. The
reaction was stirred at –15 °C for 30 min and then kept at
room temperature for 16 h. The mixture was cooled to
–15 °C, methyl iodide (2.2 mL, 35 mmol) was added, and the
mixture kept at room temperature for 16 h. The reaction was
quenched with ammonium chloride solution (15 mL) and
water (10 mL). The aqueous layer was extracted with ether
(3 × 10 mL). The combined organic layers were washed
with brine and part of the solvent evaporated under reduced
pressure. The organic layer was washed with hydrochloric
acid solution (3 N), and the aqueous layer was washed with
ether (3 × 8 mL). The aqueous layer was basified with so-
dium hydroxide solution (10%), and extracted with ether (5
× 17 mL). The organic layer was washed with brine, dried
(MgSO4), and the solvent evaporated off to give the amine
(1.80 g, 37%) with only one diastereoisomer detectable, pre-
sumably the 2RS,3RS isomer by analogy with the formation
of the known compound 25. IR νmax (film, cm–1): 1735
N-{E-3-[Dimethyl(phenyl)silyl]propenoyl-(7R)-2,10-
camphorsultam (30)
Oxalyl chloride (2 mL, 23 mmol), was added to 3-(E)-
dimethyl(phenyl)silylpropenoic acid (3.2 g, 16 mmol) in di-
chloromethane (11 mL) under nitrogen at room temperature,
followed by N,N-dimethylformamide (0.55 mL), and the
mixture was stirred at this temperature until the bubbling
ceased (~1 h). The solvent and the excess oxalyl chloride
were evaporated off under reduced pressure at 50 °C and
then at 2 mmHg (1 mmHg = 133.322 Pa) for 2 h to give the
acid chloride 29. Meanwhile, n-butyllithium (1.6 mol L–1,
~10 mL) was added to (1R)-(+)-2,10-camphorsultam (31)
(3.23 g, 15 mmol) in THF (15 mL) under nitrogen at
−78 °C, using 1-pyreneacetic acid as the indicator. This so-
lution was added by cannula to the solution of the acid chlo-
ride 29 in THF (20 mL) at –78 °C, and the mixture stirred at
room temperature for 1 h. The mixture was filtered through
a silica pad, washing through with ether (50 mL). This fil-
trate was washed with sodium bicarbonate (30 mL), dried
(MgSO4), filtered and the solvent evaporated off under re-
duced pressure to give the crude product (5.694 g, 90%),
which was crystallized from ethanol (3.5 mL) to give a first
crop of the imide (2.23 g, 35% from the acid) as pale yellow
needles, mp 90 to 91 °C (from EtOH). The mother liquors
were then evaporated to give a second crop (0.14 g, 2%), mp
88.5–89.5 °C. The mother liquors were chromatographed
(SiO2, light petroleum (bp 40–60 °C) – Et2O, 9:1) to give a
third crop (0.765 g, 12%), mp 89.5–90 °C, making the total
1
(C=O) and 1155 (OC). H NMR (400 MHz, CDCl3) δ: 4.15
(2H, m, OCH2), 2.75 (1H, dq, J = 9.6 and 6.6, NCHMe),
2.51 (1H, dq, J = 9.6 and 6.9, COCHMe), 2.19 (6H, s,
NMe2), 1.09 (3H, d, J = 6.9, COCHMe), and 0.89 (3H, d,
J = 6.6, NCHMe). 13C NMR (100 MHz, CDCl3) δ: 176.1+,
61.8–, 59.8–, 44.6–, 40.6–, 14.2– and 8.5–. MS m/z (EI):
173 (30%, M+), 158 (20, M – Me), 128 (13, M – EtO), 73
(39, CO2Et), and 72 (100, Me2N=CHMe) (found: M+,
173.1411; C9H19NO2 requires M, 173.1416).
20
yield (3.13 g, 49%). [α]D +63.1 (c 1.04 in CHCl3).
Rf(Et2O–light petroleum (bp 40–60 °C), 50:50) 0.47. IR
3-(E)-Dimethyl(phenyl)silylpropenoic acid (28)
ν
max(Nujol, cm–1): 1672 (C=O), 1598 (C=C), 1166 (SO2N),
1
The crude ethyl 3-(E)-dimethy(phenyl)silylpropenoate
(15) (9.9 g) in methanol (40 mL) and potassium hydroxide
(10 g) in distilled water (9 mL) were stirred at room temper-
ature for 1.5 h. The methanol and ethanol were evaporated
and 1117 (SiPh). H NMR (250 MHz, CDCl3) δ: 7.52–7.50
(2H, m, Ph), 7.48 (1H, d, J = 18.2, SiCH), 7.36–7.35
(3H, m, Ph), 7.01 (1H, d, J = 18.2, CHCO), 3.93 (1H, dd,
J = 7.0 and 5.7, NCH), 3.50 (1H, d, J = 13.8, SO2CHAHB),
© 2004 NRC Canada

332
Can. J. Chem. Vol. 82, 2004
10. I. Fleming, S.R. Mack, and B.P. Clark. Chem. Commun. 715
(1998); I. Fleming and M.G. Russell. Chem. Commun. 198
(2003); M. Buswell and I. Fleming. Chem. Commun. 202
(2003).
11. M. Buswell and I. Fleming. ARKIVOC, vii, 46 (2002).
12. I. Fleming, M. Solay, and F. Stolwijk. J. Organomet. Chem.
521, 121 (1996).
3.44 (1H, d, J = 13.8, SO2CHAHB), 2.20–2.03 (2H, m),
2.00–1.84 (3H, m), 1.48–1.32 (2H, m), 1.18 (3H, s,
CMeAMeB), 0.98 (3H, s, CMeAMeB), and 0.44 (6H, s,
SiMe2). 13C NMR (100 MHz, CDCl3) δ: 163.5+, 148.7–,
136.4+, 134.2–, 133.9–, 129.5–, 128.0–, 65.2–. 53.1+, 48.6+,
47.8+, 44.7–, 38.5+, 32.9+, 26.5+, 20.9–, 19.9–, –3.2– and
–3.3–. MS m/z (EI): 403 (47%, M+), 267 (22, M –
PhMe2SiH), 189 (100, M – Me2N), and 135 (46, PhMe2Si+)
(found: M+ 403.1640; C21H29NO3SSi requires M, 403.1637).
Anal. calcd. for C21H29NO3SSi(%): C 62.5, H 7.2, N 3.5;
found: C 62.5, H 7.3, N 3.4. Although this compound has
been described before (25), no mp, and no spectroscopic or
analytical data were given.
13. I. Fleming, J. Frackenpohl, and H. Ila. J. Chem. Soc. Perkin
Trans. 1, 1229 (1998).
14. I. Fleming, A.J. Lawrence, R.D. Richardson, D.S. Surry, and
M.C. West. Helv. Chim. Acta, 85, 3349 (2002).
15. W.C. Still. J. Org. Chem. 41, 3063 (1976); W.C. Still. J. Am.
Chem. Soc. 99, 4836 (1977); W.C. Still and A. Mitra. Tetrahe-
dron Lett. 2659 (1978); E. Piers, H.E. Morton, and J.M. Chong.
Can. J. Chem. 65, 78 (1987).
Acknowledgements
16. I. Fleming, E. Marangon, C. Roni, M.G. Russell, and S.
Taliansky Chamudis. Chem. Commun. 200 (2003).
17. R.F. Abdulla and K.H. Fuhr. J. Org. Chem. 43, 4248 (1978); T.
Mukaiyama and T. Ohsumi. Chem. Lett. 875 (1983); C.
Fontenas, H. Aït-Haddou, E. Bejan, and G.G.A. Balavoine.
Synth. Commun. 28, 1743 (1998).
18. I. Fleming and D.A. Perry. Tetrahedron, 37, 4027 (1981).
19. I. Fleming and N.D. Kindon. J. Chem. Soc. Perkin Trans. 1,
303 (1995).
This work was supported by research grant (RG/M17013)
from the Engineering and Physical Sciences Research Coun-
cil (EPSRC) (for MGR), and by the ERASMUS scheme (for
ST), to both of which we are grateful. We also thank the De-
partment of Pharmaceutical Sciences, University of Padua
for arranging summer visits (for EM and CR). We thank
Professor Barry Trost for a helpful discussion about the dif-
ference between the aqueous work-up reactions in Schemes
3 and 4, and David Barden for the full characterization of
the sultam 30.
20. I. Fleming, T.W. Newton, V. Sabin, and F. Zammattio. Tetrahe-
dron, 48, 7793 (1992).
21. K.J. Shea, R. Gobeille, J. Braunblett, and E. Thompson. J.
Am. Chem. Soc. 100, 1611 (1978).
22. S.G. Davies and I.A.S. Walter. J. Chem. Soc. Perkin Trans. 1,
1129 (1994); S.G. Davies, O. Ichihara, and I.A.S. Walter. J.
Chem. Soc. Perkin Trans. 1, 1141 (1994).
23. E. Graf and M. Graser. Arch. Pharm. (Weinheim, Ger.), 302,
665 (1969).
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