Double diastereoselective acetate aldol reactions with chiral N-acetyl thiazolidinethione reagents

Article abstract of DOI:10.1021/jo0605694

Double diastereoselective acetate aldol reactions using the N-acetyl thiazolidinethione-based chiral auxiliaries 1 and 2 and chiral aldehydes are described. Aldehydes that bear α-alkyl stereocenters exhibit moderate levels of double diastereoselection, wh

Full text of DOI:10.1021/jo0605694

SCHEME 1. Asymmetric Acetate Aldol Reactions with the
Pseudo-Enantiomeric Thiazolidinethione Reagents 1 and 2
Double Diastereoselective Acetate Aldol Reactions
with Chiral N-Acetyl Thiazolidinethione Reagents
Yingchao Zhang and Tarek Sammakia*
Department of Chemistry and Biochemistry, UniVersity of
Colorado, Boulder, Colorado 80309-0215
sammakia@colorado.edu
ReceiVed March 14, 2006
protecting groups which one might encounter in a polyacetate
synthesis are used.
Since the seminal work of Heathcock, double diastereo-
selection has been recognized as an important issue to be
addressed in the coupling of two chiral fragments via the aldol
reaction.4 In matched cases, useful increases in selectivities can
be observed, whereas mismatched cases can cause significant
erosions or reversals in selectivity. At times, subtle structural
features can influence the magnitude and sense of asymmetric
induction in aldol reactions with chiral aldehydes.5 For example,
in reactions of achiral propionate or ethyl ketone enolates with
Double diastereoselective acetate aldol reactions using the
N-acetyl thiazolidinethione-based chiral auxiliaries 1 and 2
and chiral aldehydes are described. Aldehydes that bear
R-alkyl stereocenters exhibit moderate levels of double
diastereoselection, while those that bear R- or â-alkoxy
substitution exhibit little to no double diastereoselection. In
all cases studied, the stereoselectivity of the reaction is
dictated by the reagent, not the substrate.
(2) For reviews of asymmetric acetate aldol reactions, see: (a) Masamune,
S.; Choy, W.; Petersen, J. S.; Sita, L. R. Angew. Chem., Int. Ed. Engl. 1985,
24, 1. (b) Braun, M. Angew. Chem., Int. Ed. Engl. 1987, 26, 24. For selected
examples of asymmetric acetate aldol reactions, see: (c) Iwasawa, N.;
Mukaiyama, T. Chem. Lett. 1983, 297. (d) Braun, M.; Devant, R.
Tetrahedron Lett. 1984, 25, 5031. (e) Nagao, Y.; Yamada, S.; Kumagai,
T.; Ochiai, M.; Fujita, E. J. Chem. Soc., Chem. Commun. 1985, 1418. (f)
Helmchen, G.; Leikauf, U.; Taufer-Kno¨pfel, I. Angew. Chem., Int. Ed. Engl.
1985, 24, 874. (g) Nagao, Y.; Hagiwara, Y.; Kumagai, T.; Ochiai, M.; Inoue,
T.; Hashimoto, K.; Fujita, E. J. Org. Chem. 1986, 51, 2391. (h) Masamune,
S.; Sato, T.; Kim, B. M.; Wollmann, T. A. J. Am. Chem. Soc. 1986, 108,
8279. (i) Devant, R.; Mahler, U.; Braun, M. Chem. Ber. 1988, 121, 397. (j)
Duthaler, R. O.; Herold, P.; Lottenbach, W.; Oertle, K.; Riediker, M. Angew.
Chem., Int. Ed. Engl. 1989, 28, 495. (k) Corey, E. J.; Imwinkelried, R.;
Pikul, S.; Xiang, Y. B. J. Am. Chem. Soc. 1989, 111, 5493. (l) Oppolzer,
W.; Starkemann, C. Tetrahedron Lett. 1992, 33, 2439. (m) Yan, T. H.;
Hung, H. C.; Hung, A. W.; Lee, H. C.; Chang, C. S. J. Org. Chem. 1994,
59, 8187. (n) Yan, T. H.; Hung, A. W.; Lee, H. C.; Chang, C. S.; Liu, W.
H. J. Org. Chem. 1995, 60, 3301. (o) Gonza´lez, AÄ .; Aiguade´, J.; Urp´ı, F.;
Vilarrasa, J. Tetrahedron Lett. 1996, 37, 8949. (p) Gabriel, T.; Wessjohan,
L. Tetrahedron Lett. 1997, 38, 4387. (q) Bond, S.; Perlmutter, P. J. Org.
Chem. 1997, 62, 6397. (r) Palomo, C.; Gonzalez, A.; Garcia, J. M.; Landa,
C.; Oliarbide, M.; Rodr´ıguez, S.; Linden, A. Angew. Chem., Int. Ed. 1998,
37, 180. (s) Saito, S.; Hatanaka, K.; Kano, T.; Yamamoto, H. Angew. Chem.,
Int. Ed. 1998, 37, 3378. (t) Fukuzawa, S.-i.; Matsuzawa, H.; Yoshimitsu,
S.-i. J. Org. Chem. 2000, 65, 1702. (u) Guz, N. R.; Phillips, A. J. Org.
Lett. 2002, 4, 2253. (v) Hodge, M. B.; Olivo, H. F. Tetrahedron 2004, 60,
9397.
We recently described a new chiral auxiliary-based method
for performing asymmetric acetate aldol reactions1,2 using the
N-acyl thiazolidinethione auxiliaries 1 and 2 (Scheme 1).3 Upon
enolization with PhBCl2 and sparteine, these pseudo-enantio-
meric reagents provide good yields and high diastereoselectivi-
ties in aldol reactions with a variety of achiral aldehydes,
including R- and â-oxygenated aliphatic aldehydes, and allow
for the synthesis of either stereochemistry at the hydroxyl group
of the aldol product. This note describes the use of these reagents
in reactions with chiral, nonracemic aldehydes and examines
the extent of double diastereoselection2a observed in these
reactions. Additionally, to assess the efficacy of this process
for the synthesis of polyacetate-derived natural products, alde-
hydes which are representative of the types of structures and
(3) (a) Zhang, Y.; Sammakia, T. Org Lett. 2004, 6, 3139. (b) Zhang, Y.;
Phillips, A. J.; Sammakia, T. Org Lett. 2004, 6, 23.
(1) For selected reviews on the aldol reaction, see: (a) Evans, D. A.;
Nelson, J. V.; Taber, T. R. Top. Stereochem. 1982, 13, 1. (b) Heathcock,
C. H. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: New York, 1991; Vol. 2, pp 181-238. (c) Arya, P.; Qin,
H. P. Tetrahedron 2000, 56, 917. (d) Kim, B.-M.; Williams, S. F.;
Masamune, S. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: New York, 1991; Vol. 2, pp 239-275. (e)
Cowden, C. J.; Paterson, I. Org. React. 1997, 51, 1. (f) Machajewski, T.
D.; Wong, C. H. Angew. Chem., Int. Ed. 2000, 39, 1353. (g) Carreira, E.
M. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley: New York, 2000.
For recent advances in asymmetric synthesis with chiral imide auxiliaries,
see: (h) Evans, D. A.; Shaw, J. T. Actual. Chim. 2003, 35. For a review
with examples of the use of the aldol reaction in total synthesis, see: (i)
Norcross, R. D.; Paterson, I. Chem. ReV. 1995, 95, 2041.
(4) (a) Heathcock, C. H.; White, C. T. J. Am. Chem. Soc. 1979, 101,
7076. (b) Heathcock, C. H.; Pirrung, M. C.; Buse, C. T.; Hagen, J. P.;
Young, S. D.; Sohn, J. E. J. Am. Chem. Soc. 1979, 101, 7077. (c) Heathcock,
C. H.; White, C. T.; Morrison, J. J.; VanDerver, D. J. Org. Chem. 1981,
46, 1296. (d) Heathcock, C. H.; Pirrung, M. C.; Lampe, J.; Buse, C. T.;
Young, S. D. J. Org. Chem. 1981, 46, 2290.
(5) For discussions of 1,2- and 1,3-asymmetric induction in aldol reactions
with chiral aldehydes, see: (a) Lodge, E. P.; Heathcock, C. H. J. Am. Chem.
Soc. 1987, 109, 3353. (b) Evans, D. A.; Duffy, J. L.; Dart, M. J. Tetrahedron
Lett. 1994 35, 8537. (c) Evans, D. A.; Dart, M. J.; Duffy, J. L.; Yang, M.;
Livingston, A. B. J. Am. Chem. Soc. 1995, 117, 6619. (d) Evans, D. A.;
Dart, M. J.; Duffy, J. L.; Yang, M. J. Am. Chem. Soc. 1996, 118, 4322. For
a review, see: (e) Mahrwald, R. Chem. ReV. 1999, 99, 1095. See also refs
6 and 7.
10.1021/jo0605694 CCC: $33.50 © 2006 American Chemical Society
Published on Web 07/13/2006
6262
J. Org. Chem. 2006, 71, 6262-6265

Table 1. All reactions were conducted under the optimized
reaction conditions previously described (enolization with 1.3
equiv of 1 or 2 and PhBCl2, and 2.6 equiv sparteine at 0 °C
followed by addition of 1 equiv of the aldehyde at -78 or 0
°C) and proceed in good to excellent yields. We find that the
extent of double diastereoselection varies according to the
position and nature of the stereocenter in the aldehyde. Thus,
reaction with the â-oxygenated aldehyde 3, which lacks a
stereocenter at the R-position, proceeds with little double
diastereoselection and provides good diastereoselectivity with
either reagent 1 or 2 (26:1 and 22:1, respectively, entries 1 and
2). Aldehyde 4, on the other hand, bears an R-stereocenter and
â-oxygenation and displays significant double diastereoselection;
the matched case provides excellent selectivity (>100:1) with
reagent 1, while the mismatched case provides lower selectivity
(12:1) with reagent 2 (entries 3 and 4, respectively). Similarly,
aldehydes 5 and 6, which also bear R-alkyl stereocenters, display
significant double diastereoselection with the matched cases
providing about 5 times higher levels of asymmetric induction
than that of the mismatched cases (compare entry 5 with entry
6, and entry 7 with entry 8). D-Glyceraldehyde acetonide9 (7),
which bears an R-oxygenated stereocenter, provides similar
selectivities with reagents 1 and 2 (13:1 and 12:1, entries 9 and
10, respectively). We also note that a variety of protecting
groups, including PMB, TBS, and TES ethers, and an acetonide
participate in this reaction.
We established that asymmetric induction is dictated by the
reagent rather than the aldehyde by reduction of the products
of entries 7-10 in Table 1 with NaBH4. The diols obtained
from the major products of entries 7 and 8 are diastereomeric,
as are those from the products of entries 9 and 10 (Scheme 2).
The sense of asymmetric induction was assigned in analogy
with our previous work with reagents 1 and 2.
In conclusion, we have shown that acetate aldol reactions
using thiazolidinethione reagents 1 and 2 are subject to modest
double diastereoselection in reactions with chiral aldehydes.
Aldehydes in which the chirality is due to the presence of an
alkyl group at the R-carbon show the greatest double diaste-
reoselection and difference in selectivity of the matched and
mismatched reaction pairs. When the chirality is due to R- or
â-oxygenation, little double diastereoselection is observed. In
all cases, the stereochemistry of the product is dictated by the
reagent, not the aldehyde. This study should enhance the
predictability of reactions using these reagents and thereby
facilitate the design of polyacetate synthesis.
FIGURE 1. Anti-Felkin and anti-Cornforth aldol additions.
chiral aldehydes, a reversal of the ordinary Felkin-Anh
selectivity can be observed when the aldehyde bears alkyl
branching at the R-position, and the enolate is of the Z-
configuration. This is thought to be due to a developing syn-
pentane interaction between the terminal methyl group of the
enolate and the methyl group at the R-position of the aldehyde
which is present in the Felkin, but not the anti-Felkin, transition
states (Figure 1).1a,6 Similarly, R-heteroatom-substituted alde-
hydes can provide unexpected selectivities when reacting with
achiral propionate or ethyl ketone enolates, though in these
cases, E-enolates are the offending reactants. This is also thought
to be due to developing syn-pentane-like interactions between
the terminal methyl group of the enolate and the R-heteroatom
group of the aldehyde which is present in the Cornforth, but
not the anti-Cornforth, transition states (Figure 1).7 Chiral
auxiliary-based propionate aldol reactions are highly selective,
and the stereochemical influence of the reagents usually
overrides that of a chiral aldehyde.1,2a While aldol additions of
acetate (rather than propionate) or methyl ketone (rather than
ethyl ketone) substrates to chiral aldehydes should be simpler
since the corresponding enolates bear a terminal methylene, the
levels of asymmetric induction displayed by chiral variants of
these reagents have traditionally been lower than those of
propionate or ethyl ketone substrates. We, therefore, wished to
explore this issue with the reagents we have developed in order
to determine if they can add in a stereochemically predictable
fashion to chiral aldehydes bearing R- or â-substituents.8
To study the levels of double diastereoselection in this
process, we prepared substituted aldehydes in nonracemic form
and subjected them to aldol reactions with our pseudo-
enantiomeric reagents. These aldehydes bear either â-alkoxy
substitution, R-alkyl substitution, or R-alkoxy substitution. These
are the most commonly encountered substitution patterns in the
synthesis of polyacetate fragments. Our results are shown in
Experimental Section
General Aldol Reaction Procedure: To a 10 mL round-bottom
flask were added N-acetyl thiazolidinethione (0.250 mmol, 1.30
equiv) and CH2Cl2 (1.25 mL). The flask was cooled in an ice bath,
and PhBCl2 (33.3 µL, 0.250 mmol, 1.30 equiv) was added dropwise
(8) While there are examples of asymmetric acetate additions to chiral
aldehydes, we know of no systematic study of double diastereoselectivity
with this class of reagents and a wide range of aldehydes. For selected
examples, see: (a) ref 4c. (b) Weiss, J. M.; Hofmann, H. M. R.
Tetrahedron: Asymmetry 1997, 8, 3913. (c) Crimmins, M. T.; Emmitte,
K. A. Org. Lett. 1999, 1, 2029. (d) Crimmins, M. T.; DeBaillie, A. C. Org.
Lett. 2003, 5, 3009. (e) Vicario, J. L.; Rodriguez, D.; Bad´ıa, D.; Carrillo,
L.; Reyes, E. Org. Lett. 2004, 6, 3171. (f) La Sann, C.; Mun˜oz, D. M.;
Saunders, N.; Simpson, T. J.; Smith, D. I.; Soulas, F.; Watts, P.; Willis, C.
L. Org. Biomol. Chem. 2005, 3, 1719.
(6) (a) Roush, W. R. J. Org. Chem. 1991, 56, 4151. For an exception to
this trend, see: (b) Evans, D. A.; Gage, J. R. Tetrahedron Lett. 1990, 31,
6129.
(7) In the case of the addition of propionate enolates to R-oxygenated
aldehydes, the groups of Evans and Marco have recently provided evidence
for the importance of the Cornforth model for asymmetric induction, which
is based on a dipole-minimized conformation of the aldehyde. See: (a)
Evans, D. A.; Siska, S. J.; Cee, V. J. Angew. Chem., Int. Ed. 2003, 42,
1761. (b) Marco, J. A.; Carda, M.; D´ıaz-Oltra, S.; Muraga, J.; Falomir, E.;
Roeper, H. J. Org. Chem. 2003, 68, 8577. (c) Cee, V. J.; Cramer, C. J.;
Evans, D. A. J. Am. Chem. Soc, 2006, 128, 2920.
(9) D-Glyceraldehyde acetonide was purchased and treated with 4 Å
molecular sieves in refluxing CHCl3 before use. As received, this material
was largely hydrated and was not suitable for use in the aldol reaction.
J. Org. Chem, Vol. 71, No. 16, 2006 6263

TABLE 1. Acetate Aldol Reactions of Thiazolidinethione Reagents 1 or 2 with Chiral Aldehydesa
1
a For a typical experimental procedure, see Supporting Information. b Ratios were determined by 500 MHz H NMR spectroscopic analysis of the crude
reaction mixtures. c Yield of the major diastereomer after purification.
SCHEME 2. Correlation of Stereochemistry of Products
The reaction mixture was then cooled to the temperature described
in Table 1, and the aldehyde (0.192 mmol, 1.0 equiv) in 0.8 mL of
CH2Cl2 was added dropwise via cannula over a period of about 5
min. The flask containing the aldehyde was rinsed with an additional
0.8 mL of CH2Cl2, which was also added to the reaction mixture
via cannula. For entries 1-4 of Table 1, the reaction mixture was
stirred for 6 h at -78 °C, and then slowly warmed to 0 °C over a
period of about 3 h by allowing the dry ice to evaporate. As the
temperature approached 0 °C, the reaction mixture was placed in
an ice bath and stirred for 30 min. As for entries 5-10 of Table 1,
the reaction mixture was stirred for 3 h at 0 °C. The reaction mixture
was then quenched by the addition of hexanes (3 mL) and H2O2
(30%, 1 mL) and stirred rapidly for 10 min at room temperature.
(Note that rapid stirring is required at this step. If the rate of stirring
is too slow, incomplete oxidation of the borane occurs, and boron
species remain in the product.) The solution was diluted with
hexanes/CH2Cl2 (4:1, 80 mL), and the layers were separated. The
organic layer was washed with distilled water and brine, dried over
anhydrous MgSO4, filtered, and concentrated at reduced pressure
1
to provide an orange oil. Analysis of this material by H NMR
provided the diastereomeric ratio values given in Table 1. The
products were purified by flash chromatography using neutral silica
gel (1:1 hexanes/CH2Cl2 to 1:4 hexanes/CH2Cl2 depending on
substrate; see general information in the Supporting Information
for details regarding the use of neutral silica gel) to provide the
aldol adducts as clear yellow oils. Note that N-acyl thiazolidineth-
iones are sensitiVe to hydrolysis, and that this workup has been
optimized to minimize hydrolysis and should be followed carefully
in order to obtain high yields and reproducible results.
to provide an orange colored solution. After stirring for 5 min, (-)-
sparteine (0.115 mL, 0.500 mmol, 2.6 equiv) was added dropwise,
at which point the solution turned yellow and cloudy. After stirring
for about a minute, the solution became homogeneous, but remained
yellow. The ice bath was then removed, and the reaction mixture
was allowed to warm to room temperature and stirred for 30 min.
Typical Aldol Reaction Procedure (Table 1, entry 1): To a
10 mL round-bottom flask were added N-acetyl thiazolidinethione
1 (54 mg, 0.250 mmol, 1.30 equiv) and CH2Cl2 (1.25 mL). The
6264 J. Org. Chem., Vol. 71, No. 16, 2006

flask was cooled in an ice bath, and PhBCl2 (33.3 µL, 0.250 mmol,
1.30 equiv) was added dropwise to provide an orange colored
solution. After stirring for 5 min, (-)-sparteine (0.115 mL, 0.500
mmol, 2.6 equiv) was added dropwise, at which point the solution
turned yellow and cloudy. After stirring for about a minute, the
solution became homogeneous, but remained yellow. The ice bath
was then removed, and the reaction mixture was allowed to warm
to room temperature and stirred for 30 min. The reaction mixture
was then cooled to the temperature described in Table 1, and
aldehyde 3 (48 mg, 0.192 mmol, 1.0 equiv) in 0.8 mL of CH2Cl2
was added dropwise via cannula over a period of about 5 min. The
flask containing the aldehyde was rinsed with an additional 0.8
mL of CH2Cl2, which was also added to the reaction mixture via
cannula. The reaction was cooled in a dry ice/acetone bath to -78
°C and stirred for 6 h and then slowly warmed to 0 °C over a period
of about 3 h by allowing the dry ice to evaporate. As the temperature
approached 0 °C, the reaction mixture was placed in an ice bath
and stirred for 30 min. The reaction mixture was then quenched
by the addition of hexanes (3 mL) and H2O2 (30%, 1 mL) and
stirred rapidly for 10 min at room temperature. The solution was
diluted with hexanes/CH2Cl2 (4:1, 80 mL), and the layers were
separated. The organic layer was washed with distilled water and
brine, dried over anhydrous MgSO4, filtered, and concentrated at
reduced pressure to an orange oil. Analysis of the 1H NMR spectrum
of the crude product revealed a diastereomeric ratio of 26:1. This
material was purified by flash chromatography using neutral silica
gel (1:1 hexanes/CH2Cl2; see general information in the Supporting
Information for details regarding the use of neutral silica gel) to
provide the product as a clear yellow oil (92 mg, 0.197 mmol, 79%).
1H NMR (500 MHz, CDCl3): δ 7.25 (m, 2H), 6.86 (m, 2H),
5.33 (X of ABX, 1H, J ) 0.73, 8.33 Hz), 4.48 (A of AB, J )
11.08 Hz), 4.40 (B of AB, J ) 11.08 Hz), 4.20 (m, 1H), 3.79 (s,
3H), 3.66 (m, 1H), 3.61 (d, OH, J ) 3.02 Hz), 3.55 (A of ABX,
1H, J ) 3.33, 11.80 Hz), 3.48 (A of ABX, 1H, J ) 8.33, 17.49
Hz), 3.32 (B of ABX, 1H, J ) 3.84, 17.49 Hz), 3.10 (B of ABX,
1H, J ) 0.73, 11.80 Hz), 1.83 (m, 1H), 1.68 (m, 2H), 1.55(m, 1H),
1.33 (m, 1H), 1.00 (s, 9H), 0.90 (d, 3H, J ) 3.94 Hz), 0.89 (d, 3H,
J ) 3.94 Hz). 13C NMR (400 MHz, CDCl3): δ 205.2, 172.6, 159.4,
130.8, 129.8, 114.0, 75.9, 72.3, 70.3, 66.8, 55.5, 45.6, 43.6, 41.0,
38.2, 30.7, 27.1, 24.9, 23.2, 23.1. IR (cm-1): 3452, 1685, 1607,
1507, 1460. [R]D ) 269° (c 1.26, EtOH). HRMS m/z calcd for
C24H37NO4S2Na+, 490.2056; found, 490.2075.
mmol, 2.6 equiv) was added dropwise, at which point the solution
turned yellow and cloudy. After stirring for about a minute, the
solution became homogeneous, but remained yellow. The ice bath
was then removed, and the reaction mixture was allowed to warm
to room temperature and stirred for 30 min. The reaction mixture
was then cooled back to 0 °C in an ice bath, and aldehyde 5 (50
mg, 0.192 mmol, 1.0 equiv) in 0.8 mL of CH2Cl2 was added
dropwise via cannula over a period of about 5 min. The flask
containing the aldehyde was rinsed with an additional 0.8 mL of
CH2Cl2, which was also added to the reaction mixture via cannula,
and the reaction was allowed to stir for 3 h at 0 °C. The reaction
was then quenched by the addition of hexanes (3 mL) and H2O2
(30%, 1 mL) and stirred rapidly for 10 min at room temperature.
The solution was diluted with hexanes/CH2Cl2 (4:1, 80 mL), and
the layers were separated. The organic layer was washed with water
and brine, dried over anhydrous MgSO4, filtered, and concentrated
1
at reduced pressure to provide an orange oil. Analysis of the H
NMR spectrum of the crude product revealed a diastereomeric ratio
of 4.5:1. This material was purified by flash chromatography using
neutral silica gel (1:1 hexanes/CH2Cl2; see general information for
details regarding the use of neutral silica gel) to provide the product
as clear yellow oil (89 mg, 0.15 mmol, 60%).
1H NMR (500 MHz, CDCl3): δ 5.35 (X of ABX, 1H, J ) 1.28,
8.05 Hz), 4.06 (m, 1H), 4.04 (m, 1H), 3.96 (d, OH, J ) 3.67 Hz),
3.51 (A of ABX, 1H, J ) 3.02, 16.94 Hz), 3.47 (A of ABX, 1H,
J ) 7.96, 11.35 Hz), 3.43 (B of ABX, 1H, J ) 8.97, 16.94 Hz),
3.41 (B of ABX, 1H, J ) 1.28, 11.35 Hz), 1.70 (m, 1H), 1.60 (m,
1H), 1.40 (m, 2H), 1.30 (s, 3H), 1.29 (s, 3H), 0.96 (t, 9H, J ) 8.05
Hz), 0.94 (t, 9H, J ) 7.78 Hz), 0.90 (d, 3H, J ) 6.59 Hz), 0.88 (d,
3H, J ) 6.59 Hz), 0.80 (d, 3H, J ) 7.05 Hz), 0.62 (q, 6H, J )
7.78 Hz), 0.60 (q, 6H, J ) 8.05 Hz). 13C NMR (400 MHz,
CDCl3): δ 205.7, 173.0, 77.0, 72.8, 72.4, 70.6, 44.3, 43.0, 42.4,
30.3, 28.6, 26.6, 24.9, 23.3, 23.2, 11.5, 7.5, 7.3, 7.0, 5.5. IR (cm-1):
3425, 1678. [R]D ) -216° (c 0.98, EtOH). HRMS m/z calcd for
C28H57NO4S2Si2Na+, 614.3159; found, 614.3154.
Acknowledgment. We wish to thank Professor Andrew
Phillips for helpful discussions. This work was supported by
the National Institutes of Health (GM48498). NMR instrumen-
tation used in this work was supported in part by the National
Science Foundation CRIF program (CHE-0131003).
Typical Aldol Reaction Procedure (Table 1, entry 6): To a
10 mL round-bottom flask were added N-acetyl thiazolidinethione
2 (83 mg, 0.250 mmol, 1.30 equiv) and CH2Cl2 (1.25 mL). The
flask was cooled in an ice bath, and PhBCl2 (33.3 µL, 0.250 mmol,
1.30 equiv) was added dropwise to provide an orange colored
solution. After stirring for 5 min, (-)-sparteine (0.115 mL, 0.500
Supporting Information Available: Experimental procedures
for the synthesis of aldehydes 3, 5, and 6, and for conducting aldol
reactions, and spectral data for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO0605694
J. Org. Chem, Vol. 71, No. 16, 2006 6265