Chiral silyl ketene acetals from thioesters: Reaction with acetals and peroxyacetals to form 3-alkoxy- and 3-peroxyalkanoates

Article abstract of DOI:10.1016/S0040-4020(00)00894-2

The Lewis acid-mediated reaction of chiral O- and S-silyl ketene acetals (SKAs) with peroxyacetals and acetals was investigated as an approach to the asymmetric synthesis of 3-peroxy- and 3-alkoxyalkanoates. SKAs derived from chiral O-acetates fail to react with peroxyacetals and provide little diastereoselection in reactions of nonperoxidic acetals. Reaction of thioacetate SKAs with peroxyacetals furnishes 3-peroxyalkanoate thioesters in good yield but with poor diastereoselection. In the case of silyl ketene acetals based upon a camphorsulfonamide chiral auxiliary the diastereomeric peroxyalkanoates are easily separated. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00894-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 9213±9220
Chiral Silyl Ketene Acetals from Thioesters: Reaction with
Acetals and Peroxyacetals to form 3-Alkoxy- and
3-Peroxyalkanoates
*
Patrick H. Dussault, Tony K. Trullinger and Su Cho-Shultz
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA
Received 5 July 2000; accepted 26 September 2000
AbstractÐThe Lewis acid-mediated reaction of chiral O- and S-silyl ketene acetals (SKAs) with peroxyacetals and acetals was investigated
as an approach to the asymmetric synthesis of 3-peroxy- and 3-alkoxyalkanoates. SKAs derived from chiral O-acetates fail to react with
peroxyacetals and provide little diastereoselection in reactions of nonperoxidic acetals. Reaction of thioacetate SKAs with peroxyacetals
furnishes 3-peroxyalkanoate thioesters in good yield but with poor diastereoselection. In the case of silyl ketene acetals based upon a
camphorsulfonamide chiral auxiliary the diastereomeric peroxyalkanoates are easily separated. q 2000 Elsevier Science Ltd. All rights
reserved.
Introduction
Lewis acid-mediated reactions of alkenes with peroxy-
acetals appears to involve intermediate peroxycarbenium
ion. Given this mechanistic assumption, neither the chirality
of the acetal, the Lewis acid, or the leaving group is likely to
exert a signi®cant in¯uence on product stereochemistry. We
were therefore drawn to the use of chiral nucleophiles, of
which chiral silyl ketene acetals (SKAs) appeared to be
ideal candidates. Several classes of chiral SKAs undergo
highly stereoselective Lewis acid-mediated aldol reactions
with prochiral aldehydes; in at least one example, reaction is
postulated to proceed via an open transition state.6±8 In
addition, the retention of the auxiliary chiral center in the
ester product provides a handle for resolution of stereo-
isomeric products. Finally, peroxyalkanoates are easily
saponi®ed or reduced without destruction of the peroxide.2,9
The 3-peroxycarbonyl and homoallyl peroxide motifs are
common substructures within peroxide natural products
and their synthetic precursors.1 Recent work in our group
has revealed an ef®cient approach to these subunits based
upon the Lewis acid-mediated reaction of peroxyacetals
with electron-rich alkenes (Fig. 1).2,3 In the course of
synthetic studies towards plakinic acids, we required a
method for synthesis of enantiomerically enriched 3-
peroxyalkanoates.4 We now report our investigations into
the reactions of chiral silyl ketene acetal nucleophiles with
prochiral peroxycarbenium ions.
Given the recent advances in methodology for enantio-
selective addition to prochiral aldehydes, control of stereo-
chemistry in corresponding reactions of peroxyacetals
might seem straightforward. However, in analogy to
the corresponding reactions of nonperoxidic acetals,5 the
Results and Discussion
Several substrates were employed for these studies (Fig. 2).
A monoperoxyacetal (1), prepared via transacetalization of
benzaldehyde dimethyl acetal, offered a model for additions
to secondary peroxycarbenium ions. Alkoxydioxolane 2,
prepared from 4-methyl-3-pentan-2-one according to a
Figure 1.
Keywords: thioester; chiral auxiliary; silyl ketene acetal; peroxide.
* Corresponding author. Tel.: 11-402-472-2732; fax: 11-402-472-9402;
e-mail: pdussault1@unl.edu
Figure 2.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00894-2

9214
P. H. Dussault et al. / Tetrahedron 56 (2000) 9213±9220
Table 1. Reaction of SKA derived from phenylcyclohexyl acetate
Substrate
R
X
T (8C)
Product
Yield (%)
Diast. ratio
1
2
3
Ph
Ph
Ph
OOt-Bu
OMe
OMe
220
278
0
6
7
7
18
37
42
54:46
56:43
52:48
Table 2. Reactions of SKA derived from ephedrine acetate
Substrate
X
Lewis acid
T (8C)
Product
Yield (%)
Diast. ratio
1
1
3
3
3
OOt-Bu
OOt-Bu
OMe
OMe
OMe
TMSOTf
TiCl4
SnCl4
TMSOTf
TiCl4
220
278
278
220
278
±
9
±
±
10
0
14
0
0
45
±
55:45
±
±
62:38
known procedure,10 provided a model for approaches to the
plakinic acids. Given the lack of data regarding reactions of
chiral SKAs with simple acetals we also investigated reac-
tions of benzaldehyde dimethyl acetal (3). Finally, benzal-
dehyde was included to allow direct comparison of the new
nucleophiles against more established reagents.
thioacetate SKAs are substantially easier to generate and
handle than the O-ester analogs.12
As illustrated in Table 3, the SKA of 1-phenylethanethiol
acetate underwent Lewis acid-mediated reaction with
peroxyacetals and acetal 3 to provide good yields of 3-
peroxy- and 3-alkoxyalkanoate thioesters. Unfortunately,
no diastereoselection was observed in either case.
Our initial efforts featured the t-butyl dimethyl silyl ketene
acetal 5 of trans-2-phenyl cyclohexyl acetate,11 reported to
undergo stereoselective addition to benzaldehyde. How-
ever, little product was observed for reaction with peroxy-
acetals, while reaction with benzaldehyde dimethyl acetal
proceeded with low chemical yield and minimal diastereo-
selection (Table 1).
We next investigated SKAs derived from camphorsulfona-
mide esters.6 The O-acetate SKAs have been reported to
achieve high stereoselection in acetate aldol reactions
through a transition state relevant to the peroxycarbenium
ion chemistry (Scheme 1).
A similar outcome was experienced with SKA 8, derived
from N-methyl ephedrine acetate (Table 2). The correspond-
ing E- or Z-propionate SKAs react with aldehydes to furnish
anti aldol products in high enantiomeric excess.8 However,
reaction of 8 with peroxyacetals 1 and 2 provided poor yield
and low diastereoselection (Table 2). Reaction with acetal 3
proceeded in moderate yield and low diastereoselection.
Given the low reactivity of O-acetate SKAs towards peroxy-
acetals, we elected to synthesize the thioacetate analog of
Oppolzer's camphorsulfonamide (Scheme 2). The known
camphorsulfonamide13 was converted to the corresponding
thione using Lawesson's reagent.14 Reduction with sodium
borohydride selectively produced the exo thiol, which was
easily converted to the corresponding thioacetate. Enoli-
zation, followed by trapping with trialkylsilyl chlorides,
furnished the TMS, TBS and TIPS silyl ketene acetals.
The crude SKAs obtained after extraction and concentration
were stable as refrigerated solutions in CH2Cl2 for periods
of up to several weeks.
At this point, unrelated work in our group with achiral esters
revealed the superiority of thioacetate SKAs as nucleophiles
towards peroxyacetals (Fig. 3).2 As an added bonus, the
Reaction of the trimethylsilyl SKA 17a with an acetal, the
two peroxyacetals, and benzaldehyde occurred in poor,
moderate, and good yield, respectively (Table 4). However,
diastereoselection was nonexistent. The bulkier triisopropyl
SKA 17c failed to react with peroxyacetal 1 but showed
high reactivity and moderate diastereoselection with benzal-
dehyde. The TBS SKA 17b provided good reactivity but no
Figure 3.

P. H. Dussault et al. / Tetrahedron 56 (2000) 9213±9220
Table 3. Reactions of SKAS from 1-phenethyl thioacetate
9215
Substrate
SKA
Lewis acid
X
T (8C)
Product
Yield (%)
Diast. ratio
1
1
3
3
3
12a
12b
12a
12b
12b
TMSOTf
TMSOTf
TMSOTf
TMSOTf
SnCl4
OOt-Bu
OOt-Bu
OMe
OMe
OMe
220
220
220
278
278
13
±
14
±
40
0
68
0
50:50
±
50:50
±
50:50
14
33
2a
2a
2b
TMSOTf
SnCl4
TiCl4
RˆMe
220
278
278
15
15
15
0
0
64
2
2
50:50
RˆMe
RˆMeOEt
Scheme 1.
Scheme 2.
Table 4. Reactions of SKAs from camphorsulfonamide thioacetate
SKA
Substrate
Lewis acid
T (8C)
220
220
220
278
278
278
220
Product
X
Yield (%)
Diast. ratio
17a
17c
17b
17a
17b
17c
17a
1
TMSOTf (0.1)
TMSOTf
TMSOTf
TiCl4
TiCl4
TiCl4
TMSOTf (0.1)
18
18
18
19
19
19
20
OOt-Bu
OOt-Bu
OOt-Bu
OH
54
0
50:50
±
1
1
4
4
4
3
50
70
58
52
28
50:50
50:50
37:63
29:71
50:50
OH
OH
OMe
17a
17c
17b
21
21
21
52
0
26
50:50
±
50:50

9216
P. H. Dussault et al. / Tetrahedron 56 (2000) 9213±9220
unless otherwise speci®ed; individual peaks are reported as
(multiplicity, number of hydrogens, coupling constant in
Hz). Unless otherwise indicated, IR spectra were recorded
as neat ®lms; only selected absorbances are reported.
Progress of reactions involving peroxides were monitored
by TLC, using an N,N0-dimethyl-p-phenylenediamine indi-
cator; hydroperoxides and peracids yield an immediate
reddish-pink spot while perketals or peresters exhibit a
pink or green-red color after mild charring.15 TLC plates
were also monitored with a handheld UV light source or
after staining/charring with a solution of 1% ceric sulfate/
2.5% ammonium molybdate in 10% sulfuric acid. Hydro-
peroxides were stabilized with a few drops of 1% solution of
BHT in CH2Cl2 prior to concentration. Much of the chroma-
tography was performed with ethyl acetate/hexane (EA/hex)
recycled and quantitated by a reported procedure.16 Elemen-
tal analyses were obtained from Desert Analytics in
(Tucson, Arizona, USA), or Quantitative Technologies,
Inc. (New Jersey, USA). Silyl ketene acetals of O- and
S-acetates were prepared using reported procedures.17
Figure 4.
diastereoselectivity in reaction with peroxyacetal 1; inter-
mediate diastereoselection (63:37) was achieved for reac-
tion with benzaldehyde. The correlation between aldol
diastereoselection and steric bulk of the silyl group
(TMS,TBS,TIPS) presumably re¯ects steric bias in the
transition state. The 3-hydroxyalkanoate thioester derived
from reactions of benzaldehyde product was easily separ-
able by ¯ash chromatography, while the 3-methoxyalkano-
ate thioesters from benzaldehyde dimethyl acetal were not
easily separated.
Safety: No problems were experienced in the course of these
studies. However, caution should always be observed in the
preparation and handling of peroxides.
General procedure for reaction of acetals and peroxyacetals
with silyl ketene acetals of trans-2-phenylcyclohexyl acetate
While no diastereoselection was seen with the peroxide
substrate, the 3-peroxyalkanoate thioester products were
easily separated by semipreparative HPLC. In the case of
the 1,2-dioxolane adduct 21, an X-ray structure was
obtained for the ®rst eluting isomer (Fig. 4).
To a 0.1 M solution of peroxyacetal (1 equiv.) in methylene
chloride was added the silyl ketene acetal11 (1.5 equiv.)
followed by TMSOTf (1 equiv.). The reaction mixture
was stirred until TLC indicated the reaction was complete.
The reaction mixture was then quenched with saturated
aqueous NaHCO3 solution and the aqueous layer was
extracted twice with methylene chloride. The combined
organic layers were washed with brine and water and
dried with anhydrous Na2SO4 prior to concentration. The
crude mixture was puri®ed by ¯ash chromatography (5%
EA/hex).
Conclusions
The SKA derived from N-methyl ephedrine furnishes low
yields and stereoselection in reactions with peroxyacetals,
and moderate yields and stereoselection with acetals. The
1-phenylethanethiol SKA provides moderate yields with
both acetals and peroxyacetals, but no stereoinduction.
The camphor-derived thioacetate displays good reactivity
with both peroxyacetals and acetals, but no stereoinduction.
The O-ester analog of 17b has been reported to react with
Lewis acid/aldehyde complexes through an open transition
state. However, the results obtained for reactions of 17b
suggest that, at least for the thioacetate SKA, the transition
states for reactions of aldehydes and acetals are quite differ-
ent. The ease of separation of the diastereomeric peroxy-
alkanoates, combined with the synthetic versatility of
thioesters, make the camphor thioacetate an excellent candi-
date for applications to peroxide natural product synthesis.
Further investigation of this methodology is under way and
will be reported in due course.
3-(t-Butyldioxy)benzenepropanoic acid, trans-2-phenyl-
1
cyclohexyl ester (6). Rf ˆ0.47 (10% EtOAc/hexanes); H
NMR d 7.20 (m, 5H), 5.17 (dd, 0.63H, Jˆ7.7, 6.0 Hz), 5.08
(apt. t, 0.37H, Jˆ6.9 Hz), 4.94 (td, 0.63H, Jˆ10.5, 4.4 Hz),
4.89 (td, 0.36, Jˆ10.9, 4.4 Hz), 2.78 (dd, 0.37H, Jˆ14.9,
6.9 Hz), 2.76 (dd, 0.63H, Jˆ15.7, 7.7 Hz), 2.64 (m, 1H),
2.41 (dd, 0.37H, Jˆ14.9, 7.3 Hz), 2.31 (dd, 0.63H,
Jˆ15.7, 6.0 Hz), 2.09 (m, 0.63H), 1.98 (m, 0.37H), 1.91
(m, 1H), 1.75±1.85 (m, 2H), 1.20±1.585 (m, 4H), 1.12
(s, 5.7H), 1.15 (s, 3.3H); 13C NMR (75 MHz) 170.0,
169.6, 143.1, 143.0, 139.4, 128.3, 128.2, 128.2, 128.0,
128.0, 127.5, 127.4, 127.1, 127.0, 126.4, 81.8, 81.8, 76.4,
76.2, 49.7, 49.5, 39.8, 33.8, 33.7, 32.2, 26.4, 25.8, 24.7,
24.7; IR 1733 cm21
.
3-Methoxy-3-phenyl propionic acid, trans-2-phenyl-
1
Experimental
cyclohexyl ester (7). Rfˆ0.47 (10% EtOAc/hexanes); H
NMR) d 7.23 (m, 10H), 5.03 (td, Jˆ10.5, 4.4 Hz), 5.00
(td, 0.55H, Jˆ10.9, 4.4 Hz), 4.37 (dd, 0.55H, Jˆ7.6,
6.0 Hz), 4.32 (dd, 0.45H, Jˆ9.7, 4.0 Hz), 3.08 (s, 1.65H),
2.98 (s, 1.35H), 2.71 (td, 0.45H, Jˆ11.3, 3.6 Hz), 2.69 (td,
0.55H, Jˆ11.3, 3.6 Hz), 2.57 (dd, 0.55H, Jˆ14.9. 8.0 Hz),
2.55 (dd, 0.45H, Jˆ15.3, 9.7 Hz), 2.37 (dd, 0.55H, Jˆ14.9,
All reagents and solvents were used as supplied commer-
cially, except THF and CH2Cl2, which were distilled from
Na/Ph2CO and CaH2, respectively. Compounds 1 and 24
were prepared using reported procedures. 1H and 13C spectra
were recorded at 300 and 75 MHz, respectively, in CDCl3

P. H. Dussault et al. / Tetrahedron 56 (2000) 9213±9220
9217
6.0 Hz), 2.26 (dd, 0.45H, Jˆ15.3, 4.0 Hz), 2.20 (m, 0.45H),
2.06 (m, 0.55H), 1.77±1.96 (m, 3.3H), 1.29±1.66 (m, 4.6H);
13C NMR 170.1, 169.9, 143.2, 143.1, 140.7, 140.6, 128.4,
128.3, 128.2, 128.16, 127.8, 127.5, 127.4, 126.5, 126.4,
126.35, 126.3, 79.9, 79.8, 76.1, 76.0, 56.5, 56.48, 49.6,
49.5, 43.6, 43.5, 34.0, 33.96, 32.3, 32.1, 25.8, 25.77, 24.7,
13C NMR 169.7, 139.8, 128.2, 127.6, 126.5, 84.2, 84.1, 76.0,
63.4, 56.5, 44.3, 41.2, 27.0, 25.7, 23.9, 9.3. Second eluting:
1
Rfˆ0.25 (2% MeOH/(50 % EtOAc/hexanes); H NMR d
7.31 (m, 5H), 5.94 (d, 1H, Jˆ4.5 Hz), 2.94 (apt. quintet,
1H, Jˆ6.4 Hz), 2.85 (d, 1H, Jˆ14.8 Hz), 2.70 (d, 1H,
Jˆ14.8 Hz), 2.54 (d, 1H, Jˆ12.6 Hz), 2.31 (s, 6H), 2.15
(d, 1H, Jˆ12.4 Hz), 1.38 (s, 3H), 1.37 (s, 3H), 1.34
(s, 3H), 1.09 (d, 3H, Jˆ6.7 Hz); 13C NMR 169.7, 139.7,
128.3, 127.6, 126.4, 84.3, 84.1, 75.9, 63.5, 56.6, 44.4,
41.3, 27.0, 25.7, 23.9, 9.3.
24.65; IR 1731 cm21
.
Reaction of acetals and peroxyacetals with silyl ketene
acetals derived from N-methyl ephedrine
Silyl ketene acetal of 1-phenylethanylthioacetate (12a).
Into a solution of thioacetate (16.6 mmol, 2.98 g) and
TMSOTf (16.6 mmol, 3.2 mL) in CH2Cl2 (20 mL) under
N2 in a dry 250 mL ¯ask at 08C was slowly added Et3N
(19.9 mmol, 2.8 mL). The reaction was stirred for 2 h and
then concentrated. The residue was dissolved in hexane and
®ltered though Celite. The crude product was used without
Silyl ketene acetals were prepared from N-methyl ephe-
drine18 using a reported procedure19 and were used without
puri®cation. To a 2788C 0.1 M solution of acetal or peroxy-
acetal (1 equiv.) in CH2Cl2 was added TiCl4 (1 equiv. of a
1 M solution in CH2Cl2), followed, after 3 min, by the silyl
ketene acetal (1.5 equiv.) The reaction mixture was stirred
until reaction was complete according to TLC. The reaction
was then quenched with 5% aqueous NaHCO3 and 1.5N
aqueous NaOH and ®ltered through Celite. The aqueous
layer was then extracted with CH2Cl2 (2£10 mL) and the
combined organic layers were dried over anhydrous Na2SO4
and concentrated. The crude product was puri®ed by
¯ash chromatography (49:49:2 EA/hexane/methanol).
The diastereomeric products were separated by semi-
preparative HPLC (20% ethanol/hexane, Rainin Dynamax
8 mm Si).
1
further puri®cation: H NMR d 7.34 (m, 5H), 4.76 (q, 1H,
Jˆ7.2 Hz), 4.42 (d, 1H, Jˆ1.6 Hz), 4.38 (d, 1H, Jˆ1.5 Hz),
4.33 (q, 1H, Jˆ7.2 Hz), 1.63 (d 3H, Jˆ7.2 Hz), 0.24 (s, 9H;
TMS); 13C NMR 152.5, 143.2, 128.4, 127.1, 127.0, 96.1,
44.2, 22.3, 20.1.
General procedure for reaction with thioacetate silyl
ketene acetals
To a 2208C 0.1 M solution of acetal or peroxyacetal
(1 equiv.) in CH2Cl2 was added the silyl ketene acetal
(1.5 equiv.) followed by TMSOTf (0.1 equiv.). The reaction
mixture was stirred until complete according to TLC. The
reaction mixture was then quenched with saturated aqueous
NaHCO3 and the aqueous layer extracted twice with CH2Cl2
and the organic layers were washed with brine and water,
dried with Na2SO4, concentrated and puri®ed by ¯ash
chromatography (5% EA/hex).
3-(t-Butyldioxy)-3-phenyl propionic acid, 2-(dimethyl-
amino)-1-phenylpropyl ester (9). First eluting: Rfˆ0.33
1
(49:49:2 EA/hexanes/MeOH); H NMR (500 MHz) d 7.34
(m, 10H), 6.04 (d, 1H, Jˆ4.9 Hz), 5.48 (apt. t, Jˆ7.0 Hz),
3.24 (dd, 1H, Jˆ15.7, 7.5 Hz), 2.99 (m, 1H), 2.88 (dd, 1H,
Jˆ15.5, 6.2 Hz), 2.39 (s, 6H), 1.29 (s, 9H), 1.13 (d, 3H,
Jˆ6.8 Hz); 13C NMR (125 MHz) 128.17, 127.15, 126.09,
81.74, 77.10. 75.58, 63.52, 57.06, 48.99, 42.44, 41.13,
40.19, 35.55, 27.68, 26.68, 26.20, 25.74, 24.61, 23.69,
9.25; IR (Neat) 1745 cm21
.
3-(t-Butyldioxy)-benzenepropanoic acid, 1-phenylethyl
1
thioester (13). Rfˆ0.20 (3% EtOAc/hexanes); H NMR d
Second eluting: 1H NMR (500 MHz) d 7.23 (m, 10H), 5.87
(d, 1H), 5.34 (apt. t, Jˆ7.0 Hz), 3.14 (dd, 1H, Jˆ15.7,
7.2 Hz), 2.87 (m, 1H), 2.77 (dd, 1H, Jˆ15.2, 6.8 Hz), 2.19
(s, 6H), 1.11 (s, 9H), 0.96 (d, 3H, Jˆ6.7 Hz); 13C NMR
(125 MHz) 128.26, 127.26, 126.47, 81.81, 75.71, 63.35,
7.29 (m, 10H), 5.39 (dd, 0.5H, Jˆ8.3, 5.5 Hz), 5.37 (dd,
0.5H, Jˆ8.1, 6.2 Hz), 4.74 (q, 0.5H, Jˆ7.2 Hz), 4.73
(q, 0.5H, Jˆ7.2 Hz), 3.19 (dd, 1H, Jˆ15.0, 8.3 Hz), 2.83
(dd, 0.5H, Jˆ14.5, 6.0 Hz), 2.81 (dd, 0.5H, Jˆ15.3, 5.7 Hz),
1.65 (d, 1.5H, Jˆ7.2 Hz), 1.21 (s, 4.5H1.13 (s, 4.5H); 13C
NMR 195.5, 142.4, 142.3, 139.1, 128.6, 128.5, 128.2, 128.1,
127.3, 127.2, 127.1, 126.9, 126.8, 82.1, 80.9, 80.8, 49.3,
49.2, 42.9, 42.8, 26.3, 26.2, 22.1, 21.9; IR (Neat)
40.95, 26.10, 9.10; (IR (Neat) 1742 cm21
.
3-Methoxy-3-phenyl propionic acid, 2-(dimethylamino)-
1-phenylpropyl ester (10). Rfˆ0.10 (2% MeOH/CH2Cl2);
1H NMR d 7.47 (m, 10H), 5.94 (d, 1H, Jˆ5.0 Hz), 4.61 (dd,
1H, Jˆ9.1, 4.8 Hz), 3.17 (s, 2H), 2.89 (dd, 1H, Jˆ15.3,
9.1 Hz), 2.88 (q, 1H, Jˆ6.7 Hz), 2.64 (dd, 1H, Jˆ15.3,
4.8 Hz), 2.24 (s, 6H), 1.00 (d, 3H, Jˆ6.7 Hz); 13C NMR
170.0, 140.5, 139.9, 128.6, 128.2, 128.16, 128.11, 128.06,
127.4, 80.1, 75.7, 63.6, 56.7, 43.8, 41.3, 9.3; IR (Neat)
1683 cm21
.
3-Methoxy-3-phenyl propanoic acid, 1-phenylethyl thio-
ester (14). Rfˆ0.39 (5% EtOAc/hexanes); 1H NMR d
7.31 (m, 10H), 4.78 (q, 0.5H, Jˆ7.2 Hz), 4.77 (q, 0.5H,
Jˆ7.2 Hz), 4.66 (dd, 0.5H, Jˆ9.1, 4.0 Hz), 4.65 (dd,
0.5H, Jˆ9.1, 5.0 Hz), 3.21 (s, 1.5H), 3.19 (s, 1.5H), 3.02
(dd, 0.5H, Jˆ14.8, 9.1 Hz), 3.01 (dd, 0.5H, 15.3, 9.3 Hz),
2.74 (dd, 0.5H, Jˆ14.5, 4.8 Hz), 2.69 (dd, 0.5H, Jˆ14.1,
5.0 Hz), 1.66 (d, 1.5H, Jˆ7.4 Hz), 1.61 (d, 1.5H, Jˆ7.2 Hz);
13C NMR 196.7, 141.0, 129.3, 129.2, 128.7, 127.9, 127.8,
127.2, 127.1, 80.7, 80.6, 57.6, 57.5, 52.8, 43.5, 22.8, 22.7;
1738 cm21
.
3,5,5-Trimethyl-1,2-dioxolane acetic acid, 2-(dimethyl-
amino)-1-phenypropylester (11). First eluting: Rfˆ0.25
1
(49:49:2 EA/hexanes/MeOH) H NMR d 7.30 (m, 5H),
5.92 (d, 1H, Jˆ5.5 Hz), 2.93 (apt. quintet, 1H, Jˆ6.2 Hz),
2.84 (d, 1H, Jˆ14.8 Hz), 2.71 (d, 1H, Jˆ14.8 Hz), 2.46 (d,
1H, Jˆ12.4 Hz), 2.28 (s, 6H), 2.14 (d, 1H, Jˆ12.8 Hz), 1.44
(s, 3H), 1.35 (s, 3H), 1.28 (s, 3H), 1.08 (d, 3H, Jˆ6.7 Hz);
IR (Neat) 1683 cm21
.
3,5,5-Trimethyl-1,2-dioxolane acetic acid, 1-phenylethyl
1
thioester (15). Rfˆ0.18 (3% EtOAc/hexanes); H NMR d

9218
P. H. Dussault et al. / Tetrahedron 56 (2000) 9213±9220
7.32 (m, 5H), 4.73 (q, 1H, Jˆ7.2 Hz), 2.97 (d, 0.5H,
Jˆ14.3 Hz), 2.94 (d, 0.5H, Jˆ14.3 Hz), 2.85 (d, 0.5H,
Jˆ14.3 Hz), 2.81 (d, 0.5H, Jˆ14.3 Hz), 2.57 (d, 0.5H,
Jˆ12.4 Hz), 2.50 (d, 0.5H, Jˆ12.4 Hz), 2.15 (d, 0.5H,
Jˆ12.4 Hz), 2.14 (d, 0.5H, Jˆ12.4 Hz), 1.65 (d, 3H,
Jˆ7.2 Hz), 1.44 (s, 1.5H), 1.39 (s, 1.5H), 1.36 (s, 1.5H),
1.35 (s, 1.5H), 1.34 (s, 1.5H), 1.29 (s, 1.5H); 13C NMR
195.8, 142.4, 142.3, 128.57, 127.3, 127.2, 84.4, 84.3, 84.2,
84.1, 56.4, 56.2, 52.5. 43.1, 27, 25.6, 24.1, 24.0, 22.2, 22.1;
CH2Cl2 (3.0 mL) was dropwise added of acetic anhydride
(0.19 mL, 2.4 mmol). The reaction was stirred for 2 h at 08C
and then allowed to warm to rt overnight. The residue
obtained upon concentration was directly subjected to
¯ash chromatography (5±15% EA/hex) to afford the thio-
acetate (0.423 g, 77.3%) as white powdery crystals: Rf 0.37
(10% EA/hex); [a]Dˆ179.18 (cˆ1.38, CHCl3); mp 172±
1
1758C; H NMR d 4.05 (dd, 1H, Jˆ8.2, 5.1 Hz), 3.25
(m, 2H), 3.21 (AB1, 1H, Jˆ13.6 Hz), 2.73 (AB2, 1H,
Jˆ13.8 Hz), 2.31 (s, 3H), 2.09 (m, 2H), 1.87±1.68 (15H),
1.65±1.57 (2H), 1.35±1.20 (5H), 1.11 (m, 3H), 0.89 (s, 3H)
0.87 (s, 3H) 13C NMR d 192.9, 57.3, 55.6, 50.5, 49.3, 48.0,
45.5, 40.8, 33.4, 33.2, 32.4, 30.4, 27.2, 26.5, 25.2, 20.4,
20.2; FT-IR 1738, 1694 cm2 1; HRMS calcd for
C24H41S2O3N (M1) 455.2528, found 455.2512.
IR (Neat) 1693 cm21
.
N,N-Dicyclohexyl-7,7-dimethyl bicyclo[2.2.1]heptane-1-
methanesulfonamide-2-thiol (16).A solution of 4-methoxy-
phenylthionophosphine sul®de, (12.28 g, 30.63 mmol) and
camphor-10-(N,N-dicyclohexyl)sulfonamide (10.1 g, 25.34
mmol) in anhydrous toluene (40 mL) was re¯uxed under
nitrogen. After 30 min pyridine (1.0 mL, 12.9 mmol) was
added, and the mixture was re¯uxed for an additional 2
days, at which time TLC indicated consumption of starting
material. The reaction was quenched with sat. aq. NaHCO3,
(200 mL), and diluted with ether (200 mL). The aqueous
layer was extracted with ether (2£150 mL). The combined
organic layers were washed with sat. aq. NaCl, dried over
sodium sulfate, ®ltered, concentrated, and puri®ed by ¯ash
chromatography (7±15% EA/hex). The residue was recrys-
tallized (50% EA/hex), to afford the thione (5.86 g, 55.6%),
as a bright orange solid: Rf 0.61 (10% EA/hex); mp 145±
1508C; [a]Dˆ194.18 (cˆ1.04, CHCl3); 1H NMR d 3.88 (d,
1H, Jˆ14.5 Hz), 3.33 (m, 2H), 2.90 (d, 1H, Jˆ14.5 Hz),
2.85±2.62 (m, 2H), 2.47 (d, 2H, Jˆ21.0 Hz), 2.23±2.05
(2H), 1.89±1.70 (12H), 1.62 (m, 2H), 1.46 (m, 2H), 1.40±
1.26 (3H), 1.25 (s, 3H), 1.13 (m, 2H), 1.00±0.94 (1H), 0.84
(s, 3H) 13C NMR 69.8, 57.6, 54.9, 49.7, 45.1, 33.1, 32.5,
General procedure for the formation of silyl ketene
acetals 17a±c
To a 2788C solution of NaHMDS (1.2 equiv., 0.5 M in
THF), in a oven dried ¯ask under nitrogen, was added drop-
wise a 2788C solution of camphor thioacetate (1 equiv.) in
THF (2.5 mL per mmol). After 10 min a 2788C solution of
trialkylsilyl chloride (5 equiv., 2.5 M in THF), was added
via cannula. (TMSCl was added directly as the supernatant
from centrifugation of 75% TMSCl and 25% triethylamine).
If after 30 min TLC still showed starting material additional
NaHMDS (0.5 equiv.) and trialkylsilyl chloride (0.5 equiv.)
were added by syringe to drive the reaction to completion.
After 4 h, the reaction was brought to rt and concentrated to
an oil. The residue was mixed with pentane. The pentane
solution was ®ltered through Celite, and concentrated to a
viscous yellow oil. The crude SKA was re-dissolved in
methylene chloride (1 M) and subsequently used without
further puri®cation.
29.7, 27.0, 26.5, 25.2, 19.8; FT-IR (KBr) 1733 cm21
;
HRMS calcd for C22H37S2O2N (M1) 411.2266, found
411.2275.
1
Trimethyl silyl ketene acetal (17a). 500 MHz H NMR d
To a stirred 08C solution of the thione (0.839 g, 2.04 mmol),
in THF (10 mL) and isopropanol (10 mL) was added NaBH4
(765 mg, 20.2 mmol. After 20 min the reaction was brought
to rt and stirred an additional 20 min at which time TLC
indicated consumption of thione. The reaction was slowly
diluted with H2O and 10% aq HCl was added until bubbling
subsided. The reaction was partitioned with ether (40 mL),
and the aqueous layer was extracted with ether (2£40 mL).
The combined organic layers were washed with sat. aq.
NaCl, H2O (2£), and then dried over MgSO4. The ®ltered
solution was concentrated, and puri®ed by ¯ash chromato-
graphy (5% EA/hex) to afford the thiol (0.70 g, 83.0%) as a
white ¯aky crystal: Rf 0.62 (10% EA/hex); mp 105±1108C;
4.35 (dd, 2H, Jˆ37.0, 1.4 Hz), 3.56 (t, 1H, Jˆ7.3 Hz), 3.47
(AB1, 1H, Jˆ13.8 Hz), 3.35 (2H), 2.76 (AB2, 1H,
Jˆ13.8 Hz), 2.24 (m, 1H), 2.00 (m, 2H), 1.90±1.64
(15H), 1.63±1.55 (4H), 1.42±1.21 (5H), 1.20±1.07
(m, 2H), 0.92 (s, 3H), 0.89 (s, 3H), 0.26 (s, 9H);
125 MHz; 13C NMR d 154.3, 91.6, 57.0, 55.7, 50.8, 50.7,
49.2, 45.6, 41.9, 33.6, 33.4, 32.1, 27.4, 26.4, 25.3, 20.8,
20.5.
1
t-Butyl dimethyl silyl ketene acetal (17b). 500 MHz H
NMR d 4.33 (dd, 2H, Jˆ33.9, 1.2 Hz), 3.60 (t, 1H,
Jˆ7.3 Hz), 3.46 (AB1, 1H, Jˆ13.8 Hz), 3.32 (2H), 2.75
(AB2, 1H, Jˆ13.8 Hz), 2.24 (m, 2H), 2.00 (m, 2H), 1.87±
1.65 (15H), 1.63±1.57 (3H), 1.40±1.20 (5H), 1.17±1.02
(2H), 0.94 (s, 9H), 0.91 (s, 3H), 0.88 (s, 3H), 0.23 (s, 3H),
0.21 (s, 3H); 125 MHz 13C NMR d 154.3, 91.2, 57.0, 55.5,
50.6, 50.3, 49.1, 45.5, 41.7, 33.5, 33.3, 32.1, 27.4, 26.4,
25.6, 25.6, 25.2, 20.7, 20.4, 18.1, 17.9.
1
[a]Dˆ231.48 (cˆ1.04, CHCl3); H NMR 3.72 (AB, 1H,
Jˆ13.4 Hz), 3.44 (m, 1H), 3.30 (m, 2H), 2.71 (AB2, 1H,
Jˆ13.4 Hz), 2.56 (d, 1H, SH), 2.02 (m, 2H), 1.87±1.69
(12H), 1.67±1.52 (4H), 1.39±1.2 (5H), 1.11 (m, 4H), 0.95
(s, 3H), 0.87 (s, 3H); 13C NMR 58.2, 56.1, 50.6, 50.3, 45.9,
44.8, 40.8, 34.2, 34.0, 33.0, 27.9, 27.2, 25.9, 21.7, 20.7; FT-
IR 2361, 2336 cm21; HRMS calcd for C22H39S2O2N (M1)
413.2422, found 413.2417.
Triisopropyl silyl ketene acetal (17c). 360 MHz 1H NMR
d 4.36 (dd, 1H, Jˆ8.3, 2.0 Hz), 3.66 (t, 1H, Jˆ7.8 Hz), 3.46
(AB1, 1H, Jˆ12.0 Hz), 3.36 (2H), 2.80 (AB2, 1H,
Jˆ12.5 Hz), 2.24 (m, 1H), 2.0 (m, 2H), 1.87±1.70 (15H),
1.65±1.55 (4H), 1.42±1.21 (5H), 1.13 (m, 23H), 0.95
(s, 3H), 0.91 (s, 3H).
N,N-Dicyclohexyl-7,7-dimethyl-bicyclo[2.2.1]heptane-1-
methanesulfonamide-2-thioacetate. Into a 08C solution
of the camphorsulfonamide thiol (0.504 g, 1.22 mmol),
pyridine (0.16 mL, 2.4 mmol), and DMAP (spatula tip) in

P. H. Dussault et al. / Tetrahedron 56 (2000) 9213±9220
9219
Procedure A: reaction of silyl ketene acetals with acetals
or peroxyacetals
Eluting: oil; Rf 0.37 (10% EA/hex); [a]Dˆ245.68 (cˆ1.25,
1
CHCl3); H NMR d 7.31 (5H), 5.25 (ABX, 1H, Jˆ10.0,
2.6 Hz), 4.13 (dd, 1H, Jˆ9.3, 5.0 Hz), 3.42 (br s, 1H,
OH), 3.23 (m1AB1, 3H, Jˆ13.6 Hz), 2.92 (ABX, 1H,
Jˆ15.1, 10.0 Hz), 2.88 (ABX, 1H, Jˆ15.1, 2.6 Hz), 2.68
(AB2, 1H, Jˆ13.8 Hz), 2.08 (m, 2H), 1.96±1.83 (14H),
1.82±1.78 (2H), 1.40±1.20 (6H), 1.12 (m, 2H), 0.94
(d, 1H, Jˆ6.7 Hz), 0.87 (s, 3H), 0.85 (s, 3H); 13C NMR) d
196.4, 142.5, 128.4, 127.5, 125.6, 70.7, 57.4, 55.6, 53.7,
50.7, 49.6, 47.3, 45.4, 40.7, 33.9, 33.2, 32.3, 27.3, 26.5,
25.1, 22.6, 20.4, 20.1.
To a 2208C solution of the acetal or peroxyacetal (1 equiv.)
in CH2Cl2 (0.1 M) was added the silyl ketene acetal
(1.5 equiv.) followed by TMSOTf (0.2 equiv.). The reaction
mixture was stirred until TLC indicated consumption of the
acetal. The reaction was quenched with sat. aq. NaHCO3
and the aqueous layer was extracted twice with CH2Cl2.
The combined organic layers were washed with brine and
water, dried with Na2SO4, concentrated and puri®ed by ¯ash
chromatography (5% EA/hex). The diastereomeric mixture
of peroxyacetals were separated by semipreparative HPLC
(10% EA/hex, Rainin Dynamax 8 mm Si).
2nd eluting: crystalline, mp 1208 C; Rf 0.37 (10% EA/hex);
[a]Dˆ138.48 (cˆ1.25, CHCl3); 1H NMR d 7.33 (5H), 5.25
(ABX, 1H, Jˆ10.1, 2.4 Hz), 4.11 (dd, 1H, Jˆ9.2, 5.1 Hz),
3.33 (br s, 1H, OH), 3.19 (m1AB1, 3H, Jˆ13.6 Hz), 2.95
(ABX, 1H, Jˆ15.4, 10.1 Hz), 2.92 (ABX, 1H, Jˆ15.4,
2.4 Hz), 2.70 (AB2, 1H, Jˆ13.6 Hz), 2.10 (m, 2H), 1.97±
1.62 (15H), 1.60±1.50 (2H), 1.40±1.15 (6H), 1.06 (m, 3H),
0.87 (s, 3H), 0.86 (s, 3H); 13C NMR d 196.1, 142.3, 128.5,
127.6, 125.5, 70.9, 57.5, 55.7, 53.0, 50.7, 49.6, 47.6, 45.5,
40.9, 33.9, 33.2, 32.4, 27.3, 26.6, 26.5, 25.1, 20.5, 20.2.
(Note: The chemical shifts and coupling constants for the
strongly coupled ABX spin systems were analyzed using
spin-simulation within Nuts software from Acorn NMR,
Inc.)
Procedure B: for reaction of benzaldehyde and 3-alkoxy-
1,2-dioxolane with silyl ketene acetals
To a 2788C solution of benzaldehyde or 3-alkoxy-1,2-
dioxolane (1 equiv.) in methylene chloride (0.1 M) was
added TiCl4 (1 equiv. of a 1 M solution), followed in
3 min by silyl ketene acetal (1.5 equiv. of a 1 M solution).
The reaction mixture was stirred until TLC indicated
completion and then quenched with saturated aqueous
NaHCO3. The aqueous layer was extracted twice with
methylene chloride, and the combined layers were washed
with brine and water, dried with MgSO4, ®ltered through
Celite, concentrated and puri®ed by ¯ash chromatography
(5% EA/hex). The diastereomeric alcohols or peroxides
could be separated by semipreparative HPLC (10% EA/
hex, Rainin Dynamax 8 mm Si).
3-Methoxy-3-phenyl propionic acid, N,N-dicyclohexyl-
7,7-dimethyl-bicyclo[2.2.1]heptane-1-methanesulfonamide-
1
2-thiyl ester (20). (mixture of diastereomers); H NMR d
7.31(5H), 4.75 (dd, 0.5H, Jˆ9.9, 2.9 Hz), 4.68 (dd, 0.5H,
Jˆ7.6, 6.0 Hz), 4.10 (dd, 0.5H, Jˆ9.2, 5.4 Hz), 4.02 (dd,
0.5H, Jˆ9.2, 5.1 Hz), 3.27 (m, 2H), 3.22 (s, 1.5H), 3.21
(s, 1.5H), 3.04 (m, 2H), 2.73 (m, 2H) 2.11 (m, 2H), 1.95±
1.67 (15H), 1.65±1.50 (3H), 1.40±1.20 (4H), 1.08 (m, 3H),
0.88 (s, 3H), 0.87 (s, 1.5H), 0.80 (s, 1.5H); 13C NMR
(300 MHz) d 194.1, 194.0, 140.8, 128.6, 128.5, 127.9,
127.8, 126.6, 126.3, 79.9, 79.6, 57.3, 57.27, 57.1, 56.9,
55.9, 55.6, 52.4, 52.3, 50.6, 50.3, 49.5, 49.4, 48.1, 48.05,
45.5, 40.9, 40.8, 33.6, 33.5, 33.4, 33.2, 32.4, 32.3, 27.3,
27.2, 26.6, 26.5, 26.47, 26.4, 25.2, 25.1, 20.5, 20.4, 20.3,
3-(t-Butyldioxy)-3-phenylpropionic acid, N,N-dicyclohexyl-
7,7-dimethyl-bicyclo[2.2.1]heptane-1-methanesulfonamide-
2-thiyl ester (18). FT-IR 1740, 1693 cm21; HRMS calcd for
C35H55S2O5N (M1) 633.3522, found 633.3499. 1st eluting:
oil, Rf 0.35 (10% EA/hex); [a]Dˆ183.38 (cˆ0.93, CHCl3);
1H NMR d 7.31 (5H), 5.40 (dd, 1H, Jˆ7.8, 6.3 Hz), 4.01
(dd, 1H, Jˆ9.2, 5.1 Hz), 3.33 (ABX1, 1H, Jˆ15.1, 6.3 Hz),
3.28 (m, 2H), 3.14 (AB1, 1H, Jˆ13.6 Hz), 2.91 (ABX1, 1H,
Jˆ15.1, 7.7 Hz), 2.72 (AB2, 1H, Jˆ13.8 Hz), 2.03 (m, 2H),
1.89±1.67 (15H), 1.62 (m, 3H), 1.38±1.25 (3H), 1.22 (s,
9H), 1.20±1.08 (4H), 0.86 (s, 3H), 0.80 (s, 3H); 13C NMR
d 193.3, 138.9, 128.3, 128.2, 127.1, 82.1, 80.8, 57.3, 55.8,
50.3, 49.5, 49.0, 48.0, 45.4, 40.8, 33.4, 33.3, 32.3, 27.2,
26.6, 26.5, 26.3, 25.2, 20.4, 20.2.
20.2; FT-IR 1743, 1694 cm21
;
HRMS calcd for
C32H49S2O4N (M1) 575.3103, found 575.3091.
3,5,5-Trimethyl-1,2-dioxolane-3-acetic acid, N,N-dicyclo-
hexyl-7,7-dimethyl-bicyclo [2.2.1]heptane-1-methane-
sulfonamide-2-thiyl ester (21). FT-IR 1738, 1692 cm21
;
HRMS calcd for C30H51S2O5N (M1) 569.3209, found
569.3183. 1st Eluting (crystalline); Rf 0.37 (10% EA/hex);
[a]Dˆ1155.68 (cˆ0.5, CHCl3); mp 119±1218C; 1H NMR d
4.03 (dd, 1H, Jˆ9.2, 5.1 Hz), 3.27 (m, 2H), 3.19 (AB1, 1H,
Jˆ13.8 Hz), 2.94 (dd, 2H, Jˆ34.1, 14.8 Hz), 2.71 (AB2, 1H,
Jˆ13.8 Hz), 2.66 (A0B1, 1H, Jˆ12.6 Hz), 2.20 (A0B2, 1H,
Jˆ12.4 Hz), 2.10 (m, 2H), 1.90±1.71 (15H), 1.70±1.55
(3H), 1.41 (s, 3H), 1.36 (s, 3H), 1.32 (s, 3H), 1.30±1.02
(7H), 0.88 (s, 6H); 13C NMR d 194.2, 84.5, 84.2, 57.4,
56.8, 55.6, 52.8, 50.6, 49.5, 48.0, 45.5, 41.0, 33.7, 33.3,
32.4, 27.3, 27.0, 26.6, 25.8, 25.2, 23.6, 20.5, 20.2.
2nd Eluting: crystalline; Rf 0.35 (10% EA/hex);
1
[a]Dˆ1158.78 (cˆ1.17, CHCl3); mp 1188 C; H NMR d
7.32 (5H), 5.49 (dd, 1H, Jˆ9.2, 3.9 Hz), 4.10 (dd, 1H,
Jˆ9.1, 5.3 Hz), 3.18 (AB1, 1H, Jˆ13.6 Hz), 3.18 (m, 2H),
3.10 (ABX1, 1H, Jˆ15.3, 9.1 Hz), 2.80 (ABX2, 1H, Jˆ15.3,
9.1 Hz), 2.73 (AB2, 1H, Jˆ13.6 Hz), 2.14 (m, 2H), 1.95±
1.55 (15H), 1.55±1.5 (3H), 1.38±1.25 (3H), 1.21 (s, 9H),
1.15±0.97 (4H), 0.902 (s, 3H), 0.895 (s, 3H); 13C NMR d
193.5, 139.6, 128.4, 128.0, 126.6, 81.9, 57.3, 55.7, 50.5,
49.6, 49.5, 48.1, 45.5, 40.9, 33.5, 33.2, 32.3, 27.2, 26.5,
26.47, 26.3, 25.2, 25.1, 20.5, 20.2.
2nd Eluting (oil); Rf 0.37 (10% EA/hex); [a]Dˆ134.38
(cˆ0.95, CHCl3); 1H NMR d 4.02 (dd, 1H, Jˆ8.8,
5.0 Hz), 3.25 (m, 2H), 3.15 (AB1, 1H, Jˆ13.6 Hz), 2.92
(dd, 2H, Jˆ53.8, 14.7 Hz), 2.70 (AB2, 1H, Jˆ13.6 Hz),
3-Hydroxy-3-phenyl propionic acid, N,N-dicyclohexyl-
7,7-dimethyl-bicyclo[2.2.1]heptane-1-methanesulfonamide-
2-thiyl ester (19). FT-IR 3508, 1738, 1689 cm21; HRMS
calcd for C31H47S2O4N (M1) 561.2946, found 561.2926. 1st

9220
P. H. Dussault et al. / Tetrahedron 56 (2000) 9213±9220
2.60 (A0B1, 1H, Jˆ12.4 Hz), 2.18 (A0B2, 1H, Jˆ12.4 Hz),
2.10 (m, 1H), 1.90±1.70 (16H), 1.68±1.57 (3H), 1.47 (s,
3H), 1.36 (s, 3H), 1.33 (s, 3H), 1.32±1.00 (7H), 0.89 (s,
6H, C(CH3)2); 13C NMR d 57.3, 56.1, 55.5, 52.8, 50.4,
49.6, 48.1, 45.8, 41.1, 33.9, 33.3, 32.3, 27.3, 27.1, 26.6,
26.5, 26.47, 25.7, 25.2, 24.3, 20.6, 20.2. Crystallographic
coordinates for this compound have been deposited with the
Cambridge Crystallographic Data Centre.
5. Sammakia, T.; Smith, R. S. J. Am. Chem. Soc. 1994, 116, 7915±
7916.
6. Oppolzer, W.; Marco-Contelles, J. Helv. Chim. Acta 1986, 69,
1699±1703.
7. Gennari, C.; Beretta, M. G.; Bernardi, A.; Moro, G.; Scolastico,
G.; Todeschini, R. Tetrahedron 1986, 42, 893±909.
8. Gennari, C. In Comprehensive Organic Synthesis, Trost, B. M.,
Fleming, I. Eds.; 1988; Vol. 2, pp 629±660.
9. Schultz, J. A. PhD Thesis, University of Nebraska, 1999.
10. Rieche, A.; Schmitz, E.; GruÈndemann, E. Chem. Ber. 1960, 93,
2443±2448.
Acknowledgements
È
11. Vasconcellos, M. L.; Desmaele, D.; Costa, P. R. R.; d'Angelo,
We thank the NIH for ®nancial support, Professor Richard
Shoemaker for assistance with NMR experiments, and Dr
John Desper for obtaining the crystal structure of the
dioxolane.
J. Tetrahedron Lett. 1992, 33, 4921±4924.
12. Fujita, Y.; Otera, J.; Fukuzumi, S. Tetrahedron 1996, 52, 9419.
13. Oppolzer, W. Tetrahedron 1987, 43, 1969±2004.
14. Lawesson, S. O.; Pedersen, B. S.; Scheibye, S.; Nilsson, N. H.
Bull. Soc. Chim. Belg. 1978, 87, 223±228.
References
15. Smith, L. L.; Hill, F. L. J. Chrom. 1972, 66, 101±109.
16. Dussault, P.; Woller, K. The Chem. Educator 1996, 1, 1±6.
17. Otera, J.; Fujita, Y.; Fukuzumi, S. Synlett 1994, 213±214.
18. Spasov, S.; Auramova, P.; Palamareva, M. J. Prakt Chem.
1981, 323, 793±800.
1. Casteel, D. A. Nat. Prod. Rep. 1999, 16, 55±73.
2. Dussault, P. H.; Lee, R. L.; Schultz, J. A.; Suh, Y. S.
Tetrahedron Lett. 2000, 41, 5457±5460.
3. Dussault, P. H.; Lee, I. Q. J. Am. Chem. Soc. 1993, 115, 6458±
6459.
4. Dussault, P. H.; Liu, X. Org. Lett. 1999, 1, 1391±1393.
19. Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc.
1986, 108, 6394±6395.