circumvent recombination of 1,3-propanedithiol with the
carbonyl function in 11 to diol 10 during workup, the reaction
mixture was quenched with additional acetaldehyde. In this
fashion the dithiol component (entry 6, footnote a) was
scavenged via tranthioacetalization. The use of two flanking
MEM groups in the aldol pattern 9 was not helpful (entry
7). Some decomposition was observed, presumably due to
overactivation. The BOM group could be used as a further
chelation group (entry 8).
although other 1,3-diols did not. We assume that the
â-hydroxyester part of dithiane 13 serves as a bidentate
ligand and is complexed first of all (cf. ii), before a second
molecule of Lewis acid removes the S,S-acetal.
As a test substrate, vinylogous â-hydroxyester 15 was
prepared and unlike diol 13 was found to be stable to the
deprotection conditions. The deprotection-cyclizing protec-
tion failed on diol 16 and triols 17 and 18, as expected.
Starting materials were recovered (Scheme 5), and in the
We have also applied the deprotection protocol to terminal
S,S-acetals (Scheme 4). Because of the high reactivity of
Scheme 5
Scheme 4
case of acetonide 16 deprotection to the corresponding tetrol
was observed in 99% yield.
The superiority of the MEM chelator is demonstrated in
Scheme 6. MEM-protected dithiane 19 afforded a mixture
Scheme 6
aldehydes toward liberated 1,3-propanedithiol under the
reaction conditions, we chose a free hydroxy group in a 1,5-
functionality distance hoping to obtain a methoxy acetal. In
fact, SEM-protected dithiane 12 afforded masked lactol 14
in excellent yield: The double deprotection-cyclization
involves at least three steps and is of interest in the synthesis
of natural products.8,9
To our surprise, diol 13 without any hydroxy protecting
group at all also cyclized to 14 under these conditions,
(8) Representive Experimental Procedure. Synthesis of 14. Anhydrous
ZnBr2 (230 mg, 1.02 mmol) was added to a solution of dithiane 12 (21
mg, 0.051 mmol) in 0.5 mL of CH2Cl2 and MeOH (83 µL, 2.04 mmol).
The resulting solution was stirred for 20 h at room temperature and then
diluted with MTB ether and washed with 1 N HCl (10 mL). The organic
layer was washed with 2 N NaOH (2 × 10 mL), the aqueous layer was
extracted with EtOAc (2 × 20 mL), the combined organic layers were
washed with brine (2 × 20 mL) and dried (Na2SO4), and the solvent was
removed. The crude product was purified by column chromatography (SiO2;
MTB/PE, 3:1 f MTB) to afford 14 (10 mg, 95%), colorless oil, [R]20
)
D
-14.5° (c 0.25, CHCl3): IR (neat) ν 3668, 2933, 1718, 1438, 1387, 1264,
1196, 1154, 1120, 1042, 972 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.83 (d,
3J ) 3.2 Hz, 1 H, CHOMe), 4.23-4.06 (m, 2 H, CH(OH)CH2CHCH2),
3.70 (s, 3 H, CO2CH3), 3.33 (s, 3 H, OCH3), 2.57 (dd, 2J ) 15.5 Hz, 3J )
2
3
8.9 Hz, 1 H, CH2CO2), 2.46 (dd, J ) 15.5 Hz, J ) 4.4 Hz, 1 H, CH2-
CO2), 2.10-1.96 (m, 3 H, CH2CH(OH)CH2), 1.54-1.45 (m, 1 H, CH2-
CH(OH)CH2), 1.28 (q, 1 H, 2/3J ) 11.7 Hz, 1 H, CH2CH(OH)CH2); 13C
NMR (100 MHz, CDCl3) δ 171.49 (4°, CO2), 98.93 (3°, CHOMe), 64.40
(3°, CHCH2CO2), 63.38 (3°, CHOH), 54.57 (1°, OCH3), 51.64 (1°,
CO2CH3), 40.54 (2°, CH2CO2), 40.18/38.85 (2°, CH2CH(OH)CH2); MS
(170 °C) m/z 204 (M+, 8), 187 (5), 159 (11), 155 (80), 133 (12), 123 (21),
107 (12), 85 (21), 81 (100), 69 (13).
of O,S-acetal 22 and a small amount of formaldehyde-derived
unstable hemiacetal 22′, which results from incomplete
deprotection of the MeOCH2CH2OCH2 group.
On slow isolation, hemiacetal 22′ was converted into 22.
Presumably the gem-dimethyl group prevents further reaction
to the methoxy acetal which was observed for the parent
system (Scheme 4). SEM-protected dithiane 20 and alcohol
(9) See also: Vakalopoulos, A.; Hoffmann, H. M. R. Org. Lett. 2001,
3, 177.
Org. Lett., Vol. 3, No. 14, 2001
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