Diastereoselective preparation of substituted δ-valerolactones. synthesis of (3R,4S)-And (3R,4R)-simplactones

Article abstract of DOI:10.1021/jo8025548

The syntheses of simplactones (3R,4S)-1 and (3R,4R)-2 were achieved in 5 steps from N-acyl thiazolidinethione chiral auxiliaries. The syntheses feature a double diastereoselective acetate aldol reaction solely controlled by the chirality of the auxiliary.

Full text of DOI:10.1021/jo8025548

in these double diastereoselective aldol reactions should increase
their use in the synthesis of natural products.7 In this Note, we
describe the acetate aldol reaction with enantiopure aldehydes
in the preparation of natural products simplactones A and B,
and other substituted δ-valerolactones that can find value for
the synthesis of polyketide natural products possessing a
hemiketal tetrahydropyran ring.8
Diastereoselective Preparation of Substituted
δ-Valerolactones. Synthesis of (3R,4S)- and
(3R,4R)-Simplactones
Antonio Osorio-Lozada and Horacio F. Olivo*
DiVision of Medicinal and Natural Products Chemistry, The
UniVersity of Iowa, Iowa City, Iowa 52242
horacio-oliVo@uiowa.edu
ReceiVed NoVember 18, 2008
Simplactones A and B were isolated in minute amount from
the Caribbean sponge Plakortis simplex by Fattorusso’s group
in 1999.9 One of these simplactones exhibited moderate
cytotoxicity against WEHI-164, murine fibrosarcoma cells.
Ogasawara prepared the (3R,4R)- and the (3R,4S)-simplactones
from enantiopure 4-cumyloxy-2-cyclopenten-1-one and revised
the structures initially reported.10 Ogasawara found that the
(3R,4R)-simplactone’s spectroscopic data (and sign, but not
value, of the optical rotation) matched the one reported for
simplactone A. The 1H but not the 13C NMR data of simplactone
(3R,4S) matched that of simplactone B. To avoid any confusion,
we refer to these lactones using their absolute configuration. A
second synthesis of (3R,4R)-simplactone was accomplished in
six steps featuring a boron enolate aldol reaction to create the
two stereogenic centers.11 The same simplactone was also
synthesized starting from (R)-glycidyl ether in nine steps and
featuring a Prins reaction.12
The syntheses of simplactones (3R,4S)-1 and (3R,4R)-2 were
achieved in 5 steps from N-acyl thiazolidinethione chiral
auxiliaries. The syntheses feature a double diastereoselective
acetate aldol reaction solely controlled by the chirality of
the auxiliary. Highly diastereoselective aldol reactions with
s-trioxane were also achieved with N-acyl thiazolidinethione
auxiliaries and the stereochemistry of an aldol product
confirmed by X-ray analysis.
SCHEME 1. Retrosynthetic Analyses of Simplactones
Recent advances in the acetate aldol reaction with chiral
auxiliaries have resulted in practical and efficient methods to
prepare R-unsubtituted aldol products with excellent diastereosel-
ectivities.1,2 Recently, we reported a conformationally rigid
indene-based thiazolidinethione chiral auxiliary and demon-
strated its utility in propionate and acetate aldol reactions with
a variety of simple aldehydes and in a formal synthesis of
aurisides.3,4 Sammakia5 and Crimmins6 have shown that more
sterically encumbered thiazolidinethione chiral auxiliaries deliver
aldol products with excellent stereocontrol when added to chiral
aldehydes. Titanium enolates derived from thiazolidinethiones
and oxazolidinethiones added to different types of chiral
aldehyde delivered products under the control of the chiral
auxiliary over-riding the facial control of the stereochemistry
of the aldehydes. The predictable stereoselectivity of products
Because of our interest in studying acetate aldol reactions
with nonracemic aldehydes using the new Indane-based thia-
zolidinethione, we envisioned syntheses of simplactones using
the double diastereoselective aldol products 3 and 4, Scheme
1. Acetate aldol reactions to chiral aldehydes 5 and ent-5 should
(7) Davies, S. G.; Nicholson, R. L.; Smith, A. D. Org. Biomol. Chem. 2004,
2, 3385–3400.
(1) Braun, M. Angew. Chem., Int. Ed. 1987, 26, 24–37.
(8) Rios, M. Y.; Velazquez, F.; Olivo, H. F. Tetrahedron 2003, 59, 6529–
6536.
(9) Cafieri, F.; Fattorusso, E.; Tagliatela-Scafati, O.; Di Rosa, M.; Ianaro,
A. Tetrahedron 1999, 55, 13831–13840.
(10) Sato, M.; Nakashima, H.; Hanada, K.; Hayashi, M.; Honzumi, M.;
Taniguchi, T.; Ogasawara, K. Tetrahedron Lett. 2001, 42, 2833–2837.
(11) Kumar, A. R.; Sudhakar, N.; Rao, B. V.; Raghunandan, N.; Venkatesh,
A.; Sarangapani, M. Bioorg. Med. Chem. Lett. 2005, 15, 2085–2086.
(12) Reddy, M. S.; Narender, M.; Rao, K. R. Tetrahedron 2007, 63, 11011–
11015.
(2) Kimball, D. B.; Silks, L. A. Curr. Org. Chem. 2006, 10, 1975–1992.
(3) (a) Osorio-Lozada, A.; Olivo, H. F. Org. Lett. 2008, 10, 617–620. (b)
For a comparison of other thiazolidinethione chiral auxiliaries in acetate aldol
reactions, see: Smith, T. E.; Kuo, W.-H.; Balskus, E. P.; Bock, V. D.; Roizen,
J. L.; Theberge, A. B.; Carroll, K. A.; Kurihara, T.; Wessler, J. D. J. Org. Chem.
2008, 73, 142–150.
(4) Tello-Aburto, R.; Olivo, H. F. Org. Lett. 2008, 10, 2191–2194.
(5) Zhang, Y.; Sammakia, T. J. Org. Chem. 2006, 71, 6262–6265.
(6) Crimmins, M. T.; Shamszad, M. Org. Lett. 2007, 9, 149–152.
1360 J. Org. Chem. 2009, 74, 1360–1363
10.1021/jo8025548 CCC: $40.75 2009 American Chemical Society
Published on Web 12/22/2008

SCHEME 2. Preparation of Enantiopure Aldehydes 9 and
ent-9
SCHEME 3. Double Diastereoselective Acetate Aldol
Reactions
give the desired aldol products when the chiral auxiliary is a
thiazolidinethione that directs the stereochemistry of the prochiral
center.
We prepared the two enantiomeric aldehydes 9 and ent-9 via
aldol reaction using a thiazolidinethione auxiliary derived from
phenylalanine and an indene-based thiazolidinethione prepared
from (1R,2R)-amino-2-indanol, Scheme 2. The corresponding
N-butanoyl thiazolidinethiones 6 and 10 were prepared by
addition of the acid chloride to the corresponding thiazolidi-
nethione with triethylamine and dichloromethane at 0 °C in high
yields. Aldol reaction of N-acyl thiazolidinethiones with trioxane
was carried out following Evans protocol for similar reactions
with oxazolidinone chiral auxiliaries.13 The aldol reaction with
trioxane delivered the aldol products in very good yields and
high diastereoselectivities. An X-ray crystallographic analysis
of aldol product 7 confirmed its stereochemistry unambiguously.
Protection of the aldol products 7 and 11 as their silyl ethers
and partial reduction with dibal-H afforded the corresponding
aldehydes 9 and ent-9 in excellent yields.
SCHEME 4. Tandem Deprotection and Cyclization
Acetate aldol reactions with enantiopure aldehydes were
carried out with Crimmins optimized conditions, Scheme 3.14
A solution of Ti(IV) chloride (1 equiv) and (-)-sparteine (1
equiv) was added to the N-acetyl thiazolidinethione 13 to form
the metal enolate. Aldehyde (0.9 equiv) was added to the
reaction mixture at - 78 °C. N-Acetyl thiazolidinethione 13
was reacted with aldehyde 9 and also with its enantiomer
delivering aldol products 14 and 15, respectively, in high yields
and diastereoselectivities. Similarly, enantipure aldehyde 16,
prepared in three steps via acetate aldol reaction, was reacted
with N-acetyl thiazolidinethione 13 and also with its antipode
ent-13 delivering aldol products 17 and 18 in very good yields
and excellent diastereoselectivities. Aldol products 14 and 15
were utilized for the syntheses of simplactones, which proved
their stereochemistry. We observed that only the chirality of
the chiral auxiliary played a role in the stereochemical outcome
of the aldol products with enantipure aldehydes.
SCHEME 5. Preparation of Acetonides
Treatment of aldol products 14 and 15 with trifluoroacetic
acid in dichloromethane at room temperature removed the silyl
protecting groups and sparked cyclization to furnish the corre-
sponding simplactones (3R,4S) and (3R,4R), respectively, in
good yields, Scheme 4. Both the spectroscopic data of sim-
plactones and their optical rotation were in agreement with those
reported by Ogasawara.10 The syntheses of these two simplac-
tones confirmed the stereochemistry of the aldol products.
The other two aldol products 17 and 18 were transformed
into their acetonides 19 and 20, respectively, to confirm their
relative stereochemistry, using Rychnovsky‘s method, Scheme
5.15 Indeed, the 1,3-syn acetonide’s methyl groups showed 13
NMR peaks with very different chemical shifts, while the 1,3-
anti acetonide’s methyl group chemical shift peaks were very
similar.
C
(13) Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J. S.; Bilodeau, M. T.
J. Am. Chem. Soc. 1990, 112, 8215–8219.
(14) Crimmins, M. T.; She, J. Synlett 2004, 1371–1374.
(15) Rychnovsky, S. D.; Rogers, B.; Yang, G. J. Org. Chem. 1993, 58, 3511–
3515.
J. Org. Chem. Vol. 74, No. 3, 2009 1361

m), 1.35-1.27 (6H, m), 0.97 (9H, t, J ) 8.1 Hz), 0.90 (3H, t, J )
7.1 Hz), 0.64 (6H, q, J ) 8.1 Hz); 13C NMR (CDCl3) δ 201.4
(CS), 173.5 (CO), 139.1 (C), 138.9 (C), 129.6 (CH), 128.3 (CH),
126.1 (CH), 125.3 (CH), 75.7 (CH), 72.4 (CH), 67.3 (CH), 47.3
(CH), 46.3 (CH2), 42.7 (CH2), 37.9 (CH2), 36.4 (CH2), 32.2 (CH2),
24.8 (CH2), 14.2 (CH3), 7.1 (3CH3), 5.3 (3CH2).
In summary, we have shown that the stereochemical outcome
of the acetate aldol reactions mediated by the indene-based
thiazolidienthione chiral auxiliary is driven solely by the chirality
of the auxiliary and not by the chirality of the chiral aldehyde.
The double diastereoselective acetate aldol reactions were
valuable for very short syntheses of both (3R,4S)- and (3R,4R)-
simplactones.
syn-Acetate Aldol Product 18. Yellow oil; Rf 0.30 (75:25,
1
petroleum ether-ethyl acetate); [R]22 +385.3 (c 1.0, CHCl3). H
D
NMR (CDCl3) δ 7.41-7.28 (4H, m), 6.60 (1H, d, J ) 7.0 Hz),
4.57 (1H, dd, J ) 7.0, 6.1 Hz), 4.32 (1H, m), 3.98 (1H, m), 3.73
(1H, d, J ) 2.6 Hz), 3.58 (1H, dd, J ) 17.1, 7.5 Hz), 3.49 (1H, dd,
J ) 17.1, 4.7 Hz), 3.40 (1H, dd, J ) 17.0, 6.1 Hz), 3.15 (1H, d, J
) 17.0 Hz), 1.75-1.70 (2H, m), 1.55-1.47 (2H, m), 1.37-1.25
(6H, m), 0.98 (9H, t, J ) 8.0 Hz), 0.89 (3H, t, J ) 7.1 Hz), 0.64
(6H, q, J ) 8.0 Hz); 13C NMR (CDCl3) δ 201.4 (CS), 174.0 (CO),
139.1 (C), 138.8 (C), 129.7 (CH), 128.4 (CH), 126.1 (CH), 125.3
(CH), 75.7 (CH), 71.9 (CH), 67.5 (CH), 47.2 (CH), 45.9 (CH2),
43.1 (CH2), 37.7 (CH2), 36.4 (CH2), 32.2 (CH2), 24.8 (CH2), 22.8
(CH2), 14.2 (CH3), 7.1 (3CH3), 5.3 (3CH2).
(3R,4S)-Simplactone 1. To a stirred yellow solution of acetate
aldol product 14 (232 mg, 0.5 mmol) in CH2Cl2 (10 mL) at room
temperature was added TFA (3 drops). The reaction mixture was
stirred at room temperature for 5 h. The reaction mixture was
washed with NaHCO3 sat. soln. (5 mL). The organic layer was
collected and the aqueous layer was extracted with CH2Cl2 (5 mL).
The combined organic layers were dried over anhydrous Na2SO4
and evaporated to give a white solid. The residue was purified by
flash column chromatography on a (2 cm × 12 cm) silica gel
column (petroleum ether-ethyl acetate, 3:7) to give simplactone
as a colorless oil: 60 mg, 84% yield; Rf 0.28 (3:7, petroleum
ether-ethyl acetate); [R]22D +23.3 (c 1.0, CHCl3). 1H NMR (CDCl3)
δ 4.36 (1H, dd, J ) 11.1, 10.8 Hz), 4.24 (1H, dd, J ) 11.1, 5.4
Hz), 4.20 (1H, bd, J ) 2.8 Hz), 2.80 (1H, bs), 2.74 (1H, dd, J )
18.2, 3.1 Hz), 2.65 (1H, dd, J ) 18.2, 3.9 Hz), 1.84 (1H, m), 1.47
(1H, ddq, J ) 13.7, 7.4, 2.3 Hz), 1.35 (1H, ddq, J ) 13.7, 7.4, 2.8
Hz), 0.98 (3H, t, J ) 7.4 Hz). 13C NMR (CDCl3) δ 170.9 (CO),
69.2 (CH2), 64.5 (CH), 39.4 (CH), 39.3 (CH2), 19.7 (CH2), 11.4
(CH3).
(3R,4R)-Simplactone 2. To a stirred yellow solution of acetate
aldol product 15 (70 mg, 0.15 mmol) in CH2Cl2 (15 mL) at room
temperature was added trifluoroacetic acid (2 drops). The reaction
mixture was stirred at room temperature for 1 h. The reaction
mixture was treated with NaHCO3 sat. soln. (5 mL) and stirred at
room temperature for 5 min. The organic layer was collected and
the aqueous layer was extracted with CH2Cl2 (2 × 5 mL). The
combined organic layers were dried over anhydrous Na2SO4 and
evaporated to give a light yellow oil. The residue was purified by
flash column chromatography on a (2 cm × 10 cm) silica gel
column (petroleum ether-ethyl acetate, 3:7) to give simplactone
as a colorless oil: 17.9 mg, 85% yield. Rf 0.34 (3:7, petroleum
ether-ethyl acetate); [R]22D -25.4 (c 1.0, CHCl3). 1H NMR (CDCl3)
δ 4.49 (1H, dd, J ) 11.5, 4.5 Hz), 3.97 (1H, dd, J ) 11.5, 7.8 Hz),
3.96 (1H, overlapped), 2.86 (1H, dd, J ) 17.4, 5.6 Hz), 2.61 (1H,
bs), 2.55 (1H, dd, J ) 17.4, 5.8 Hz), 1.78 (1H, m), 1.63 (1H, ddq,
J ) 14.0, 7.4, 5.4 Hz), 1.35 (1H, ddq, J ) 14.0, 8.5, 7.4 Hz), 1.01
(3H, t, J ) 7.4 Hz). 13C NMR (CDCl3) δ 171.0 (CO), 69.3 (CH2),
68.1 (CH), 42.6 (CH), 38.3 (CH2), 21.8 (CH2), 11.4 (CH3).
General Procedure for Preparation of Acetonides. Trifluo-
roacetic acid (0.2 mL) was added to a stirred yellow solution of
aldol product 17 (111 mg, 0.22 mmol) in 5 mL of CH2Cl2 at 0 °C.
The reaction mixture was stirred at 0 °C for 90 min. The volatiles
were evaporated and the residue was dissolved in CH2Cl2 (5 mL).
2,2-Dimethoxypropane (0.2 mL) and one crystal of camphor
sulfonic acid were successively added over the solution. The
reaction mixture was stirred overnight. The reaction mixture was
treated with 5 mL of sat. NaHCO3 soln. and stirred for 5 min. The
organic layer was collected, dried over anhydrous Na2SO4 and
evaporated. The residue was purified by flash column chromatog-
raphy on a (2 cm × 10 cm) silica gel column (petroleum
Experimental Section
General Procedure for Acetate Aldol Reaction with Chiral
Aldehydes. To a stirred yellow solution of N-acetate thiazolidi-
nethione 13 (498 mg, 2 mmol) in CH2Cl2 (15 mL) at -78 °C was
added a solution of TiCl4 (2 mL, 2 mmol, 1 M CH2Cl2 soln.)
dropwise over 5 min under argon atmosphere. The yellow slurry
was stirred at -78 °C for 10 min. A solution of (-)-sparteine (469
mg, 0.5 mmol) in CH2Cl2 (1 mL) was added dropwise over 5 min
to the reaction mixture. The deep-red reaction mixture was stirred
at -78 °C for 30 min. A solution of aldehyde 9 (389 mg, 1.8 mmol)
in CH2Cl2 (0.5 mL) was added dropwise over 10 min to the reaction
mixture. The reaction mixture was stirred at -78 °C for 2.5 h. The
reaction was quenched by addition of NaHCO3 sat. soln. (0.5 mL)
at -78 °C and stirred while reaching room temperature for 5 min.
More NaHCO3 sat. soln. (10 mL) was added. The organic layer
was collected. The aqueous layer was extracted with CH2Cl2 (3 ×
10 mL). The combined organic layers were dried over anhydrous
Na2SO4, filtered, and evaporated to give a yellow thick oil. 1H NMR
analysis on the crude reaction indicated 96:4 dr (δH 4.41 major
diastereomer and δH 4.51 minor diastereomer). The residue was
purified by flash column chromatography on a (3 cm × 14 cm)
silica gel column (petroleum ether-ethyl acetate, 75:25) to give
the aldol product 14 as yellow foam: 719 mg, 86% yield.
syn-Acetate Aldol 14. Yellow foam; Rf 0.38 (75:25, petroleum
ether-ethyl acetate); [R]22 +433.1 (c 1.0, CHCl3). 1H NMR
D
(CDCl3) δ 7.43 (1H, m), 7.37-7.27 (3H, m), 6.61 (1H, d, J ) 7.0
Hz), 4.57 (1H, dd, J ) 7.0, 6.1 Hz), 4.42 (1H, dddd, J ) 9.1, 8.8,
5.7, 3.2 Hz), 3.93 (1H, dd, J ) 10.2, 3.3 Hz), 3.76 (1H, d, J ) 5.7
Hz), 3.74 (1H, dd, J ) 10.2, 4.8 Hz), 3.62 (1H, dd, J ) 17.0, 9.1
Hz), 3.52 (1H, dd, J ) 17.0, 3.2 Hz), 3.39 (1H, dd, J ) 17.0, 6.1
Hz), 3.14 (1H, d, J ) 17.0 Hz), 1.65-1.40 (3H, m), 0.98 (3H, t, J
) 7.4 Hz), 0.97 (9H, t, J ) 7.7 Hz), 0.62 (6H, q, J ) 7.7 Hz). 13
C
NMR (CDCl3) δ 201.5 (CS), 173.9 (CO), 139.2 (C), 139.0 (C),
129.6 (CH), 128.3 (CH), 126.2 (CH), 125.3 (CH), 75.9 (CH), 70.8
(CH), 63.9 (CH2), 47.4 (CH), 46.1 (CH), 44.6 (CH2), 36.3 (CH2),
21.3 (CH2), 12.0 (CH3), 6.9 (3CH3), 4.4 (3CH2). HRMS (EI) calcd
for (C23H35NO3S2Si) m/z 465.1828, found m/z 465.1833.
syn-Acetate Aldol Product 15. Yellow oil; Rf 0.33 (75:25,
petroleum ether-ethyl acetate); [R]22 +401.2 (c 1.0, CHCl3). H
1
D
NMR (CDCl3) δ 7.43 (1H, m), 7.38-7.28 (3H, m), 6.61 (1H, d, J
) 7.0 Hz), 4.58 (1H, dd, J ) 7.0, 6.0 Hz), 4.52 (1H, ddd, J )
10.0, 3.8, 2.5 Hz), 3.82 (1H, dd, J ) 10.3, 4.1 Hz), 3.75 (1H, dd,
J ) 10.3, 6.8 Hz), 3.69 (1H, d, J ) 4.9 Hz), 3.61 (1H, dd, J )
17.2, 10.0 Hz), 3.40 (1H, dd, J ) 17.0, 6.0 Hz), 3.38 (1H, dd, J )
17.2, 3.8 Hz), 3.14 (1H, d, J ) 17.0 Hz), 1.70 (1H, m), 1.46-1.38
(2H, m), 0.97 (9H, t, J ) 8.0 Hz), 0.97 (3H, t, overlapped), 0.62
(6H, q, J ) 8.0 Hz). 13C NMR (CDCl3) δ 201.5 (CS), 174.0 (CO),
139.2 (C), 139.1 (C), 129.6 (CH), 128.3 (CH), 126.2 (CH), 125.3
(CH), 75.9 (CH), 70.9 (CH), 64.4 (CH2), 47.4 (CH), 46.4 (CH),
42.9 (CH2), 36.4 (CH2), 19.2 (CH2), 12.5 (CH3), 6.9 (3CH3), 4.4
(3CH2). HRMS (ESI) calcd for (C23H35NO3S2Si) m/z 465.1828,
found m/z 465.1837.
syn-Acetate Aldol Product 17. Yellow solid; mp 99-100 °C;
Rf 0.36 (6:4, petroleum ether-ethyl acetate); [R]22D -428.4 (c 1.0,
CHCl3). 1H NMR (CDCl3) δ 7.42-7.27 (4H, m), 6.61 (1H, d, J )
7.0 Hz), 4.57 (1H, dd, J ) 7.0, 6.1 Hz), 4.43 (1H, m), 3.99 (1H,
dd, m), 3.62 (1H, d, J ) 2.1 Hz), 3.59 (1H, dd, J ) 17.5, 3.1 Hz),
3.39 (1H, dd, J ) 17.0, 6.1 Hz), 3.34 (1H, dd, J ) 17.5, 8.8 Hz),
3.14 (1H, d, J ) 17.0 Hz), 1.74-1.70 (2H, m), 1.56-1.49 (2H,
1362 J. Org. Chem. Vol. 74, No. 3, 2009

ether-ethyl acetate, 8:2) to give the title acetonide as a yellow
solid: 75 mg, 79% yield.
6.1 Hz), 3.14 (1H, d, J ) 17.0 Hz), 1.76-1.71 (2H, m), 1.56-1.43
(2H, m), 1.40 (3H, s), 1.35 (3H, s), 1.32-1.25 (6H, m), 0.89 (3H,
t, J ) 6.8 Hz). 13C NMR (CDCl3) δ 201.4 (CS), 172.1 (CO), 139.2
(C), 138.9 (C), 129.6 (CH), 128.3 (CH), 126.2 (CH), 125.3 (CH),
100.8 (C), 75.9 (CH), 66.8 (CH), 63.3 (CH), 47.4 (CH), 44.7 (CH2),
38.3 (CH2), 36.4 (CH2), 36.0 (CH2), 31.9 (CH2), 25.2 (CH2), 24.9
(CH3), 24.8 (CH3), 22.8 (CH2), 14.3 (CH3).
syn-Acetonide 19. Rf 0.33 (8:2, petroleum ether-ethyl acetate);
[R]22D -414.2 (c 1.0, CHCl3). Mp 56-57 °C. 1H NMR (CDCl3) δ
7.41-7.37 (4H, m), 6.57 (1H, d, J ) 7.0 Hz), 4.60-4.52 (2H, m),
3.86 (1H, m), 3.50 (1H, dd, J ) 17.2, 3.8 Hz), 3.41 (1H, dd, J )
17.0, 6.0 Hz), 3.40 (1H, dd, J ) 17.2, 7.7 Hz), 3.15 (1H, d, J )
17.0 Hz), 1.64 (1H, m), 1.43-1.36 (2H, m), 1.47 (3H, s), 1.39
(3H, s), 1.33-1.25 (6H, m), 0.89 (3H, t, J ) 7.0 Hz). 13C NMR
(CDCl3) δ 201.3 (CS), 172.2 (CO), 139.2 (C), 138.9 (C), 129.6
(CH), 128.3 (CH), 126.2 (CH), 125.3 (CH), 98.9 (C), 75.9 (CH),
69.2 (CH), 65.9 (CH), 47.3 (CH), 45.4 (CH2), 36.7 (CH2), 36.5
(CH2), 36.4 (CH2), 31.9 (CH2), 30.4 (CH3), 24.8 (CH2), 22.8 (CH2),
19.9 (CH3), 14.2 (CH3).
Acknowledgment. We thank Dr. Dale Swanson for obtaining
the X-ray crystal analysis of aldol product 7.
1
Supporting Information Available: Copies of H and 13C
spectra for compounds 1, 2, 6-20, an ortep drawing and CIF
file for the X-ray structure of aldol product 7, and expermental
details for compounds 6-9, 11, 12, and 16. This material is
available free of charge via the Internet at http://pubs.acs.org.
anti-Acetonide 20. Yellow oil; Rf 0.35 (8:2, petroleum ether-ethyl
acetate); [R]22 +419.8 (c 1.0, CHCl3). 1H NMR (CDCl3) δ
D
7.41-7.27 (4H, m), 6.55 (1H, d, J ) 7.1 Hz), 4.57 (1H, dd, J )
7.1, 6.1 Hz), 4.52 (1H, m), 3.80 (1H, m), 3.50 (1H, dd, J ) 17.5,
7.7 Hz), 3.44 (1H, dd, J ) 17.5, 4.6 Hz), 3.39 (1H, dd, J ) 17.0,
JO8025548
J. Org. Chem. Vol. 74, No. 3, 2009 1363