Stereoselective synthesis of substituted 5-hydroxy-1,3-dioxanes

Article abstract of DOI:10.1055/s-1998-2090

A series of 5-hydroxy-1,3-dioxanes has been synthesized using a practical three-step strategy beginning with acetal/ketal formation of tris(hydroxymethyl)aminomethane followed by oxidative cleavage of the amino alcohol. After the ketone was revealed, stereoselective reduction with common hydride reagents, LiAlH₄ for the trans isomers and L-Selectride for the cis analogues, gave the target compounds in high yield.

Full text of DOI:10.1055/s-1998-2090

June 1998
SYNTHESIS
879
Stereoselective Synthesis of Substituted 5-Hydroxy-1,3-dioxanes
David C. Forbes,* Doina G. Ene, Michael P. Doyle1
Department of Chemistry, Trinity University, San Antonio, Texas 78212, USA
E-mail: dforbes@u.arizona.edu
Received 1 September 1997
Abstract: A series of 5-hydroxy-1,3-dioxanes has been synthe-
sized using a practical three-step strategy beginning with acetal/
ketal formation of tris(hydroxymethyl)aminomethane followed by
oxidative cleavage of the amino alcohol. After the ketone was
revealed, stereoselective reduction with common hydride
reagents, LiAlH4 for the trans isomers and L-Selectride for the cis
analogues, gave the target compounds in high yield.
Key words: 5-hydroxy-1,3-dioxanes, synthesis, cyclization, so-
dium periodate oxidation, stereoselective reduction
The synthesis of 2-substituted 5-hydroxy-1,3-dioxanes
has been achieved by a laborious process initiated with the
acetalization of glycerol.2 Four isomeric products are
formed upon treatment of glycerol with aldehydes: cis-
and trans-2-alkyl-4-hydroxymethyl-1,3-dioxolanes 1 to-
gether with cis- and trans-2-alkyl-5-hydroxy-1,3-diox-
anes 2. Ketalization of glycerol leads to 4-hydroxymethyl-
id in 86% yield after neutralization of the reaction mixture
with triethylamine and removal of the excess DMF. When
the dimethyl acetal derived from benzaldehyde was em-
ployed under the same reaction conditions, cyclization af-
forded the desired phenyl acetal 3b in 90% yield.
1,3-dioxolanes 1 virtually exclusively.
Although there is considerable interest in their properties
and uses as synthetic intermediates,2, 3 5-hydroxy-1,3-diox-
anes have required labor-intensive separation schemes for
their isolation4 that, even with recently reported transacetal-
ization/recrystallization5 and chemoselective derivatization6
methodologies, result in low isolated product yields (17–
40%). We wish to report a new synthetic methodology for
theconstructionof2-substituted5-oxo-1,3-dioxaneswhich
is a considerable improvement to the current technology7, 8
that also incorporates, for the first time, the synthesis of 2,2-
disubstituted 5-hydroxy-1,3-dioxanes.
Because all attempts to prepare the corresponding tert-bu-
tyl acetal from tris(hydroxymethyl)aminomethane in re-
producibly high yields failed, we examined modifications
to the existing protocol. Thus we replaced tris(hydroxy-
methyl)aminomethane with the corresponding nitro deriv-
ative. Although ketal/acetal formation with this nitro
compound, a process previously reported in the litera-
ture,7 adds one step to the synthetic route described to give
5, it does permit the incorporation of sterically demanding
residues at C-2. Treatment of pivaldehyde with tris(hy-
droxymethyl)nitromethane in refluxing benzene using a
Soxlet apparatus for the extraction of water afforded the
desired cyclized product in 98% yield. Reduction of the
nitro moiety using catalytic Raney nickel under 1400 psi
of hydrogen at 85 °C afforded the desired tert-butyl acetal
3c quantitatively.
Recognizing the general limitations of glycerol as the
starting material for the synthesis of 2, we selected com-
mercially available tris(hydroxymethyl)aminomethane
which as the hydrochloride salt is readily converted by
transacetalization or transketalization to 3. Periodate oxi-
dation of 3 forms the corresponding 1,3-dioxan-5-ones 4
which undergo stereoselective reduction or alkylation.
The major advantages of this approach are: (1) the exclu-
sive formation of the dioxane and not the dioxolane, a
complication noted in previously reported syntheses,5, 6
(2) a stereoselective reduction of the ketonic moiety to
provide either the cis or trans diastereomer, and (3) com-
plete control of substitution at positions C-2 and C-5.
Sodium periodate cleavage of amino alcohols 3a–c gave
the desired ketones 4 in 85–98% yield as either clear and
colorless oils or solids after purification. Using THF, ei-
Using 2,2-dimethoxypropane as the starting ketal, the de-
sired amino alcohol 3a was obtained as a low melting sol-

880
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SYNTHESIS
tuted acetal 4b was reduced to afford cis-5b in 94% yield
as a 92:8 mixture of diastereomers favoring the desired cis
analogue (50% isolated yield) whereas with the tert-butyl
acetal 4c, the cis diastereomer 5c was formed exclusively
(75% isolated yield).9
ther as a cosolvent or exclusively, greatly improved the
yields with the more lipophilic amino alcohols. This two-
step sequence has been used on a multigram scale in high
yields for the production of the desired ketones 4a–c, be-
ginning with commercially available triol, which is a
substantial advancement to the previously reported
approach.6–8 Overall yields from the triol increased from
35% to 73% (4a), 23% to 66% (4b), and 45% to 98%
(4c).7
Application of this synthetic protocol allows for the prep-
aration of both secondary and tertiary 5-hydroxy-1,3-di-
oxanes by way of organometallic additions to the ketone
moiety. Accordingly, methyl-substituted alcohol 7 was
prepared using anhydrous cerium trichloride and methyl-
lithium in 70% yield. This process was found to be opti-
mal when compared to other classical methodologies such
as Grignard-based additions.
Synthesis of the target molecules was completed with the
stereoselective reduction of each symmetrical ketone 4.
For the dimethyl ketal 4a, LiAlH4 was found to be effec-
tive in providing the desired hydroxydioxane 5a in 97%
yield. Since the requisite hydroxydioxanes 5b and 5c are
diastereomeric, stereoselective reductions were per-
formed. Upon treatment of either the phenyl- 4b or tert-
butyl- 4c substituted ketone with LiAlH4, a mixture of
diastereomers (GC analysis) in 87% and 90% yield, re-
spectively, favoring the desired isomer (86:14 and 87:13,
trans/cis) was obtained. The pure diastereomer was isolat-
ed after silica gel chromatography in 50% yield for trans-
5b and 83% yield for trans-5c.9
The most attractive features of this three-step strategy, as
illustrated, are the relative ease of preparation and exclu-
sive formation of the hydroxy-1,3-dioxane template in
high yield, which has been problematic in previous meth-
odologies. Substitution at both C-2 and C-5 has been
achieved providing novel 2,2-disubstituted 5-hydroxy-
1,3-dioxanes both stereoselectively and, again, in high
yields.
1H NMR (300 or 400 MHz) and 13C NMR (75 or 100 MHz) spectra
were obtained as solutions in CDCl3, and chemical shifts are reported
in parts per million (ppm, d) downfield from internal TMS. MS were
obtained using electron ionization (70 eV) on a quadrupole instru-
ment. IR were recorded as a thin film on NaCl plates or in a KBr pellet
as indicated, and absorptions are reported in wavenumbers (cm–1).
Mps are uncorrected. Anhyd THF was distilled from Na/benzophe-
none under N2. Anhyd CH2Cl2 was dried over CaH2 for 24 h and then
distilled prior to use. CeCl3·7 H2O was dried prior to use (150°C/30
Torr) for 12 h. Both tris(hydroxymethyl)aminomethane hydrochlo-
ride and tris(hydroxymethyl)nitromethane were purchased from Ald-
rich. Analytical data listed for amino alcohols 3, ketones 4 and
hydroxydioxanes 5 and 7 are in agreement with those previously re-
ported.7, 8, 10
The diastereomeric counterparts cis-5b and cis-5c man-
date an equatorial addition of hydride to the ketonic moi-
ety at C-5. The bulky reductant L-Selectride was chosen
and found to yield, in very high levels of stereoselectivity,
5-Amino-5-hydroxymethyl-2,2-dimethyl-1,3-dioxane (3a); Typi-
cal Procedure:
A general procedure7, 8 was followed for the preparation of 3a and 3b.
The preparation of 3a is representative. To a solution of tris(hy-
the cis isomers based on GC analysis. The phenyl-substi- droxymethyl)aminomethane hydrochloride (20.0 g, 125 mmol) in an-

June 1998
SYNTHESIS
881
hyd DMF (140 mL) was added PTSA (1.8 g, 6.0 mmol, 0.050 equiv) was added. The mixture was fitted into the setup, charged with 1400 psi
followed by 2,2-dimethoxypropane (16.9 mL, 138 mmol, 1.1 equiv) of H2 and allowed warm to 85°C for a period of 4 h with stirring.
in one portion. The resulting clear and colorless solution was allowed Upon cooling the mixture, the slurry was filtered through a cotton
to stir overnight (12 h) at which time Et3N (1.0 mL, 7.0 mmol, plug, and concentrated in vacuo to afford 5.4 g (29 mmol, 98% yield)
0.060 equiv) was added and allowed to stir for an additional 10 min. of amino alcohol 3c as a white solid that required no further purifica-
The mixture was next concentrated in vacuo and treated with Et3N tion.
(13.7 mL, 98.0 mmol) and EtOAc (500 mL). The white precipitate 1H NMR (400 MHz, CDCl3): d = 0.93 (s, 9 H), 2.29 (br s, 3 H), 3.41
which was formed upon addition of the base was removed via (s, 2 H), 3.61 (d, J = 11.3 Hz, 2 H), 3.88 (d, J = 11.3 Hz, 2 H), 4.06
filtration and the filtrate was purified by bulb-to-bulb distillation (s, 1 H).
[85°C/0.7 Torr (air-bath temp)] to afford 17.4g (108 mmol, 86%
yield) of 3a as a white solid.
1H NMR (400 MHz, CDCl3): d = 1.41 (s, 3 H), 1.44 (s, 3 H), 2.36 (br
2,2-Dimethyl-5-oxo-1,3-dioxane (4a); Typical Procedure:
A general procedure7, 8 was followed for the preparation of 4a–c. The
s, 3 H), 3.49 (s, 2 H), 3.53 (d, J = 11.8 Hz, 2 H), 3.78 (d, J = 11.9 Hz,
2 H).
preparation of 4a is representative. To a cold (5°C) solution contain-
ing 5-amino-5-hydroxymethyl-2,2-dimethyl-1,3-dioxane (9.7 g, 60
mmol) and KH2PO4 (8.2 g, 60 mmol, 1.0 equiv) in water (200 mL)
was added dropwise via addition funnel a solution of NaIO4 (12.8 g,
60.0 mmol, 1.00 equiv) in water (175 mL). Upon completion, ca. 3 h,
the mixture was allowed to stir for an additional hour at 5°C and then
5 h at r.t. Na2S2O3 (14.8 g, 60.0 mmol, 1.00 equiv) was next added,
and the resulting solution was allowed to stir for approximately
13C NMR (100 MHz, CDCl3): d = 22(q), 25(q), 50(t), 64(t), 67(t),
98(s).
5-Amino-5-hydroxymethyl-2-phenyl-1,3-dioxane (3b):
From the combination of tris(hydroxymethyl)aminomethane hydro-
chloride (20.0 g, 127 mmol), PTSA (1.1 g, 6.0 mmol), benzaldehyde
dimethyl acetal (22.3 g, 139 mmol), and Et3N (13.9 mL, 99.0 mmol),
acetal 3b was obtained after purification by bulb-to-bulb distillation 15 min at which time it was extracted with CH2Cl2 (15 ´ 50 mL). The
[70°C/0.3 Torr (air-bath temp)] in 19.5 g (93 mmol, 90% yield) as a
white solid.
combined organic phases were dried (MgSO4), filtered, concentrated
in vacuo, and purified by bulb-to-bulb distillation [85°C/20 Torr (air-
bath temp)] to afford 6.6 g (51 mmol, 85% yield) of 4a as a clear and
colorless oil.
1H NMR (400 MHz, CDCl3): d = 3.03 (s, br, 3 H), 3.93 (s, 2 H), 3.84
(d, J = 11.4 Hz, 2 H), 3.93 (d, J = 11.4 Hz, 2 H), 5.41 (s, 1 H), 7.33–
7.51 (m, 5 H).
IR (CHCl3): n = 1755 (C=O) cm–1.
13C NMR (100 MHz, CDCl3): d = 51(t), 64(s), 74(t), 101(d), 125(d),
128(d), 129(d), 137(s).
1H NMR (400 MHz, CDCl3): d = 1.45 (s, 6 H), 4.15 (s, 4 H).
5-Oxo-2-phenyl-1,3-dioxane (4b):
From the combination of amino alcohol 3b (4.6 g, 21.8 mmol),
KH2PO4 (3.0 g, 22 mmol), NaIO4 (4.6 g, 22 mmol), and Na2S2O3
(5.4 g, 22 mmol), ketone 4b was obtained in 3.5 g (20 mmol, 90%
yield) as a white solid that required no further purification.
IR(CHCl3): n = 2864, 1745 (C=O) cm–1.
1H NMR (300 MHz, C6D6): d = 4.03 (d, J = 17.3 Hz, 2 H), 5.28 (s, 1
H), 7.10–7.49 (m, 5 H).
13C NMR (100 MHz, C6D6): d = 72(t), 99(d), 127(d), 128(d), 129(d),
134(s), 138(s).
5-Amino-2-tert-butyl-5-hydroxymethyl-1,3-dioxane (3c):
2-tert-Butyl-5-hydroxymethyl-5-nitro-1,3-dioxane (6):
2-tert-Butyl-5-oxo-1,3-dioxane (4c):
From the combination of amino alcohol 3c (4.7 g, 25 mmol), KH2PO4
(4.1 g, 30 mmol, 1.2 equiv), NaIO4 (6.4 g, 30 mmol, 1.2 equiv), and
Na2S2O3 (7.4 g, 30 mmol) while using THF as solvent (120 mL), ke-
tone 4c was obtained in 4.2 g (26 mmol, quantitative yield) as a pale
yellow solid that required no further purification.
From the combination of tris(hydroxymethyl)nitromethane (7.6 g,
50 mmol), PTSA (0.9 g, 5 mmol), and pivaldehyde (6.6 g, 50 mmol)
in benzene (150 mL) using the typical procedure for 3a, acetal 6 was
obtained in 11.0 g (50 mmol, quantitative yield) as a white solid that
required no further purification.
1H NMR (400 MHz, CDCl3): d = 0.96 (s, 9 H), 4.25 (dd, J = 18.0,
0.9 Hz, 2 H), 4.41 (s, 1 H), 4.42 (dd, J = 18.0, 0.9 Hz, 2 H).
1H NMR (400 MHz, CDCl3) minor: d = 0.92 (s, 9 H), 1.85 (br s, 1
H), 4.00 (d, J = 11.5 Hz, 2 H), 4.11 (s, 1 H), 4.28 (s, 2 H), 4.28 (d, J
= 11.5 Hz, 2 H); major: d = 0.88 (s, 9 H), 1.26 (t, J = 4.2 Hz, 1 H),
3.81 (s, 2 H), 3.82 (d, J = 12.7 Hz, 2 H), 4.13 (s, 1 H), 4.86 (d, J =
12.9 Hz, 2 H).
5-Hydroxy-2,2-dimethyl-1,3-dioxane (5a); Typica1 Procedure:
A general procedure was followed for the preparation of 5a–c. The
preparation of 5a is representative. To a cold (0°C) solution of 2,2-
dimethyl-5-oxo-1,3-dioxane (6.0 g, 46 mmol) in THF (120 mL) was
added via syringe 1.0 M LiAlH4 in THF (46 mL, 46 mmol, 1.0 equiv)
dropwise. The resulting solution was allowed to warm to r.t. and stir
for 1 h at which time the mixture was diluted with Et2O (300 mL).
Quenching the mixture began with a cautious addition of water
(1.8 mL) followed by 10% aq NaOH (1.8 mL) and finally water (5.3
mL). The precipitate was removed via gravity filtration, and the
filtrate was concentrated in vacuo to afford, after purification by
chromatography (silica gel, hexanes/EtOAc 1:1), 5.9 g (45 mmol,
97% yield) of 5a as a clear and colorless oil. Spectral data are in
agreement with those previously reported.7
IR (neat): n = 3445 (OH), 2993, 2874, 1647 cm–1.
5-Amino-2-tert-butyl-5-hydroxymethyl-1,3-dioxane (3c):
1H NMR (300 MHz, CDCl3): d = 1.44 (d, J = 0.6 Hz, 3 H), 1.46 (d,
J = 0.6 Hz, 3 H), 2.89–2.92 (m, 1 H), 3.53 (br s, OH), 3.73–3.75 (m,
The following procedure7 required the use of a Parr reactor, a high
pressure autoclave which allows for both external heating and stirr-
ing. Acetal 6 (6.5 g, 30 mmol) was dissolved in EtOH (75 mL) at 1 H), 3.77–3.79 (m, 1 H), 4.05–4.06 (m, 1 H), 4.09–4.10 (m, 1 H).
which time a solution of Raney nickel11 (8 mL, 0.6 g/mL in EtOH)
13C NMR (100.6 MHz, CDCl3): d = 20.6, 25.9, 62.9, 64.9, 98.0.

882
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SYNTHESIS
trans-5-Hydroxy-2-phenyl-1,3-dioxane (trans-5b):
5-Hydroxy-2,2,5-trimethyl-1,3-dioxane (7):
From the combination of ketone 4b (5.0 g, 28 mmol) and 1.0 M
LiAlH4 in THF (28 mL, 28 mmol), alcohol 5b was obtained in 87%
yield as a mixture of diastereomers. The cis/trans mixture (14:86) was
separated by chromatography (deactivated silica gel, hexanes/EtOAc
1:1) to afford 2.5 g (14 mmol, 50% yield) of trans-5b as a white solid.
Spectral data are in agreement with those previously reported.5c
1H NMR (400 MHz, CDCl3): d = 1.82 (d, J = 5.8 Hz, 1 H), 3.58–3.63
(m, 2 H), 3.96–4.05 (m, 1 H), 4.32 (dd, J = 11.3, 4.9 Hz, 1 H), 5.43
(s, 1 H), 7.35–7.49 (m, 5 H).
To a cold (–78°C) solution consisting of anhyd CeCl3 (26 g, 60 mmol,
2.0 equiv) in anhyd THF (20 mL) was added 1.5 M MeLi in THF (40
mL, 60 mmol, 2.0 equiv) dropwise. As the MeLi was added to the
mixture, the initially white CeCl3 solution turned black over a period
of 30 min. At this time, 2,2-dimethyl-5-oxo-1,3-dioxane (4a) (4.0 g,
30 mmol, 1.0 equiv) was added neat. The mixture was stirred for an
additional 4 h at –78°C. During this time, a white/beige precipitate
was observed. The mixture was warmed to r.t., quenched with water
(10 mL) and extracted with Et2O (3 ´ 50 mL). The combined organic
phase was dried (anhyd MgSO4), filtered and concentrated in vacuo
to afford 2.5 g of 7 as a clear and colorless oil that required no further
purification. An additional 0.55 g of 7 (21 mmol, 70% combined
yield) was obtained via continuous extraction (Et2O). Spectral data
are in agreement with those previously reported.10
13C NMR (CDCl3, 100 MHz): d = 61(d), 71(t), 71(t), 100(d), 126(d),
128(d), 129(d), 137(s).
trans-2-tert-Butyl-5-hydroxy-1,3-dioxane (trans-5c):
From the combination of ketone 4c (3.6 g, 23 mmol) and 1.0 M
LiAlH4 in THF (23 mL, 23 mmol), alcohol 5c was obtained in 90%
yield as a mixture of diastereomers. The reaction was quenched by
the cautious addition of 10% aq NaOH. This addition proceeded until
the formation of a white precipitate was observed. The cis/trans mix-
ture (13:87) was separated by chromatography (silica gel, hexanes/
EtOAc 1:1) to afford 3.0 g (19 mmol, 83% yield) of trans-5c as a
white solid. Spectral data are in agreement with those previously re-
ported.7
1H NMR (400 MHz, CDCl3): d = 1.05 (s, 3 H), 1.44 (s, 6 H), 3.30 (br
s, 1 H), 3.53 (d, J = 11.7 Hz, 2 H), 3.79 (d, J = 11.7 Hz, 2 H).
We are grateful to the National Institutes of Health (GM 46503), the
National Science Foundation and the Robert A. Welch Foundation
for financial support.
1H NMR (400 MHz, CDCl3): d = 0.90 (s, 9 H), 1.56 (d, J = 5.6 Hz,
1 H), 3.33 (t, J = 10.1 Hz, 1 H), 3.84 (ddd, J = 15.4, 10.5, 5.3 Hz, l
H), 3.99 (s, 1 H), 4.19 (dd, J = 5.2, 1.4 Hz, 1 H).
(1) Current address: The University of Arizona, Department of
Chemistry, Chemistry Building, P. O. Box 210041, Tucson, AZ
85721-0041, USA
(2) Showler, A. J.; Darley, P. A. Chem. Rev. 1967, 67, 442.
(3) (a) Eliel, E. L.; Nader, F. W. J. Am. Chem. Soc. 1970, 92, 584.
(b) Sokoloski, A.; Burczyk, B. J. Prakt. Chem. 1981, 323, 63.
(c) Lunkenheimer, K.; Burcyk, B.; Piasecki, A.; Hirte, R. Lang-
muir 1991, 7, 1765.
(4) (a) Baumann, W. J. J. Org. Chem. 1971, 36, 2743.
(b) Barker, S. A.; Brimacombe, J. S.; Foster, A. B.; Whiffen, D.
H.; Zweifel, G. Tetrahedron 1959, 7, 10.
(c) Baggett, N.; Bakhari, M. A.; Foster, A. B.; Lehmann, J.;
Webber, J. M. J. Chem. Soc. 1963, 4157.
(5) (a) Piasecki, A.; Burczyk, B.; Sokolowski, A.; Kotlewska, U.
Synth. Commun. 1996, 26, 4145.
cis-5-Hydroxy-2-phenyl-1,3-dioxane (cis-5b); Typical Procedure:
To a cold (–78°C) solution of 1.0 M L-Selectride in THF (56 mL,
56 mmol) was added 5-oxo-2-phenyl-1,3-dioxane (4b) (5.0 g,
28 mmol) as a solution in THF (14 mL) dropwise. The mixture was
allowed to stir for 3 h at which time it was quenched with water (2.0 mL)
and extracted with Et2O (3 ´ 30 mL). The combined organic phase was
dried (MgSO4), filtered and concentrated in vacuo. Analysis of the
crude product revealed a 92:8 (cis/trans) mixture of diastereomers in
94% yield. Purification by chromatography (silica gel, hexanes/EtOAc
1:1) afforded 2.6 g (14 mmol, 50% yield) of cis-5b as a white solid.
Spectral data are in agreement with those previously reported.5c
1H NMR (400 MHz, CDCl3): d = 3.06 (d, J = 11.1 Hz, 1 H), 3.63 (d,
J = 11.0 Hz, 1 H), 4.11–4.20 (m, 4 H), 5.56 (s, 1 H), 7.35–7.51 (m, 5
H).
(b) Juaristi, E.; Antúnez, S. Tetrahedron 1992, 48, 5941.
(c) Kobayashi, Y. M.; Lambrecht, J.; Jochims, J. C.; Burkert, U.
Chem. Ber. 1978, 111, 3442.
(d) Senda, Y.; Terasawa, T.; Ishiyamma, J. Bull. Chem. Soc.
Jpn. 1989, 62, 2948.
13C NMR (100.6 MHz, CDCl3): d = 65(s), 72(d), 101(d), 125(d),
128(d), 129(d), 137(s).
(e) Schmidt, U.; Riedl, B. Synthesis 1993, 815.
(6) Gras, J.-L.; Dulphy, H.; Marot, C.; Rollin, P. Tetrahedron Lett.
1993, 34, 4335.
(7) Majewski, M.; Gleave, D. M.; Nowak, P. Can. J. Chem. 1995,
73, 1616 and references cited therein.
(8) Hoppe, D.; Schmincke, H.; Kleemann, H.-W. Tetrahedron
1989, 45, 687.
(9) Isolation of alcohols 5b and 5c required extensive chromatogra-
phic separation which is reflected in the isolated yield.
(10)Wirz, B.; Barner, R.; Hübsher, J. J. Org. Chem. 1993, 58, 3980.
(11)Vogel, A. In Vogel,s Textbook of Practical Organic Chemistry;
Furniss, B. S.; Hannaford, A. J.; Rogers, V.; Smith, P. W. G.;
Tatchell, A. R, Eds.; Longman: London, 1978; Chapter 2.
cis-2-tert-Butyl-5-hydroxy-1,3-dioxane (cis-5c):
From the combination of ketone 4c (2.0 g, 13 mmol) and 1.0 M L-Se-
lectride in THF (22 mL, 22 mmol), alcohol 5c was purified by chro-
matography (silica gel, hexanes/EtOAc 1:1) to afford 1.6 g
(9.4 mmol, 75% yield) of cis-5c as a white solid. Spectral data are in
agreement with those previously reported.5d
1H NMR (300 MHz, CDCl3): d = 0.93 (s, 9 H), 2.87 (d, J = 11.5 Hz,
1 H), 3.35 (d, J = 10.5 Hz, 1 H), 3.85 (d, J = 10.5 Hz, 2 H), 4.17 (d,
J = 10.5 Hz, 2 H), 4.15 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 24(q), 35(s), 64(d), 72(t), 72(t), 107
(d).