Osmium catalyzed dihydroxylation of 1,2-dioxines: A new entry for stereoselective sugar synthesis

Article abstract of DOI:10.1021/jo060949p

A series of 3,6-substituted 3,6-dihydro-1,2-dioxines were dihydroxylated with osmium tetroxide to furnish 1,2-dioxane-4,5-diols (peroxy diols) in yields ranging from 33% to 98% and with de values not less than 90%. The peroxy diols were then reduced to generate a stereospecific tetraol core with R,R,S,S or "allitol" stereochemistry. The peroxy diols and their acetonide derivatives were also ring-opened with Co(II) salen complexes to give novel hydroxy ketones in 77-100% yield, including the natural sugar psicose. Importantly, preliminary work on the catalytic asymmetric ring-opening of meso-peroxy diols using the Co(II) Jacobsens's catalyst indicates that asymmetric sugar synthesis from 1,2-dioxines is possible.

Full text of DOI:10.1021/jo060949p

Osmium Catalyzed Dihydroxylation of 1,2-Dioxines: A New Entry
for Stereoselective Sugar Synthesis
Tony V. Robinson,† Dennis K. Taylor,*,† and Edward R. T. Tiekink‡
Department of Chemistry, The UniVersity of Adelaide, South Australia 5005, Australia, and Department of
Chemistry, The UniVersity of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-0698
dennis.taylor@adelaide.edu.au
ReceiVed May 7, 2006
A series of 3,6-substituted 3,6-dihydro-1,2-dioxines were dihydroxylated with osmium tetroxide to furnish
1,2-dioxane-4,5-diols (peroxy diols) in yields ranging from 33% to 98% and with de values not less than
90%. The peroxy diols were then reduced to generate a stereospecific tetraol core with R,R,S,S or “allitol”
stereochemistry. The peroxy diols and their acetonide derivatives were also ring-opened with Co(II)
salen complexes to give novel hydroxy ketones in 77-100% yield, including the natural sugar psicose.
Importantly, preliminary work on the catalytic asymmetric ring-opening of meso-peroxy diols using the
Co(II) Jacobsens’s catalyst indicates that asymmetric sugar synthesis from 1,2-dioxines is possible.
SCHEME 1
Introduction
The stereospecific synthesis of sugars and other polyhydroxy-
lated compounds remains a challenge to the modern synthetic
chemist. The Sharpless dihydroxylation of olefins has made the
assembly of such compounds substantially easier, however, this
method does not readily allow access to all stereoisomers
because of the inherent stereochemical control defined by the
Sharpless dihydroxylation procedure.1 In a study by Sharpless,
it was shown that one-pot dihydroxylation of 1,3-dienes and
1,3,5-trienes could be used to generate tetraols and hexaols with
a fair degree of selectivity (Scheme 1).2 Thus four to six
contiguous stereogenic centers could be assembled in one step.
Sharpless found dihydroxylation of E,E 1,3-dienes gave a tetraol
core with R,S,R,S or ‘galactitol’ stereochemistry as the major
product, with varying amounts of R,S,S,R or ‘iditol’ tetraol
forming as the minor product depending on the R groups
(Scheme 1). The preference for galactitol over iditol stereo-
chemistry dramatically decreased when the R groups were small
or when E,Z 1,3-dienes were used. This methodology has
recently been extended by the stepwise asymmetric dihydroxy-
lation of dienoates, providing a convenient route to galacto-
and talo-lactones.3,4
Our group is largely concerned with the chemistry of 1,2-
dioxines, and so it was proposed that singlet oxygen addition
to 1,3-butadienes could accomplish stereoselective addition of
* To whom correspondence should be addressed. Phone: (+61) 8 8303 5494.
Fax: (+61) 8 83034358.
† The University of Adelaide.
‡ The University of Texas at San Antonio.
(1) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. ReV.
1994, 94, 2483.
(2) Park, C. Y.; Kim, B. M.; Sharpless, K. B. Tetrahedron. Lett. 1991,
32, 1003.
(3) Ahmed, Md. M.; O’Doherty, G. A. J. Org. Chem. 2005, 70, 10576.
(4) Ahmed, Md. M.; Berry, B. P.; Hunter, D. J.; Tomcik, D. J.;
O’Doherty, G. A. Org. Lett. 2005, 7, 745.
10.1021/jo060949p CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/17/2006
7236
J. Org. Chem. 2006, 71, 7236-7244

Osmium Catalyzed Dihydroxylation of 1,2-Dioxines
TABLE 1. Osmium Catalyzed Dihydroxylation of Dihydro
2 hydroxyl groups, which would be masked as the cyclic
peroxide. This would leave only a solitary double bond as part
of a cis fused heterocycle, which if dihydroxylated would allow
for improved selectivity, and also a different stereochemistry
than is available from direct dihydroxylation of the precursor
1,3-dienes. Thus dihydroxylation would allow for the stereospe-
cific generation of a tetraol core with allitol stereochemistry
(Scheme 1). Moreover, 1,2-dioxines may also be homolytically
cleaved by metal catalysts,5 therefore dihydroxylation of dihydro
dioxines could also be a viable route to polyhydroxylated keto
compounds such as the natural sugar psicose.
Previous studies have shown that both unsaturated acyclic
peroxides6 and 1,2,4-trioxane antimalarial compounds7 can be
dihydroxylated using osmium tetroxide with no disruption to
the peroxide linkage. However, osmium(II) complexes have
been previously shown to homolytically ring-open 1,2-dioxines
to give bisepoxides and hydroxy ketones.8 To the best of our
knowledge, there have been no previous reports of the dihy-
droxylation of dihydro dioxines.We therefore report herein the
first examples of the osmium catalyzed cis-1,2-dihydroxyaltion
of 3,6-dihydro-1,2-dioxines and demonstrate the utility of this
transformation by the stereospecific generation of polyhydroxy-
lated products.
Dioxines 1a-k
dihydro
dioxine
product
(% yield)
entry
methoda
time (d)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1f
1f
1f
A
A
A
A
D
A
B
C
D
D
D
A
D
C
D
E
1
5
1
6
1
3
5
5
1
1
1
5
1
1
1
14
b
2b (80)
2c (33)
2d (98)
2e (73)
2f (93)
2f (65)c
d
2f (94)
2g (95)
2h (89)
2i (98)
2j (96)
d
9
10
11
12
13
14
15
16
1g
1h
1i
1j
1k
1k
1k
e
2k (77)
a See Experimental Section for reaction conditions. b Product decomposed
during isolation. c Remainder of yield was recovered starting material.
d Major product isolated was 1,4-diketone.9 e Major product isolated was
furan.
accelerating effects of amine ligands with OsO4 dihydroxyl-
ation.12 With this in mind, the Upjohn process (method C) was
employed;13 however, the presence of excess NMO resulted only
in the formation of diketone which occurs readily with 1,2-
dioxines when exposed to amine bases via the Kornblum-De
La Mare rearrangement.14
In a recent report, Sharpless found that the standard Upjohn
conditions could be modified by buffering with citric acid, which
made dihydroxylation possible under mildly acidic conditions,
and was found to also dramatically increase the reaction rate
for many sluggish substrates.15 These conditions (method D)
were found to work remarkably well for the dihydroxylation of
most dihydro dioxines, decreasing the reaction rate over standard
AD mix conditions as well as avoiding the complications of
excess amine bases.
Dihydroxylation of substrate 1k was initially complicated by
diketone formation under basic conditions (entry 14) and furan
formation under mildly acidic conditions (entry 15). This can
be attributed to the two phenyl groups R to the peroxide linkage
which dramatically increase the acidity of the protons R to the
peroxide linkage, thus making decomposition of the peroxide
relatively facile under acidic and basic conditions. To avoid these
problems, diol 2k was prepared using neutral conditions based
upon KClO3 as the reoxidant (method E);16 the diol was
unobtainable using any other method.
Results and Discussion
3,6-Dihydro-1,2-dioxines 1a-k were prepared by photooxi-
dation of the requisite 1,3-butadienes in the presence of rose
bengal bis(triethylammonium) salt or 5,10,15,20-tetraphenyl-
21H,23H-porphine as previously reported.9 Because of conven-
ience, dihydroxylation of the dihydro dioxines was initially
carried out with commercially available AD mix (method A)
which generally gave good yields; however, the reaction times
were somewhat slow (Table 1). The slow dihydroxylation turn-
over of the cyclic cis fused olefin is consistent with the general
sluggishness exhibited by cis olefins.10,11
When the substrate contained an additional free alcohol, it
was found that protection with TBDMS prior to dihydroxylation
dramatically increased the yield and aided in the ease of isolation
(compare entries 1, 2 and 3, 4 in Table 1). Given that the model
dihydro dioxines were either meso or racemic, employing chiral
AD mixes seemed wasteful, so a mix without the chiral ligand
was prepared (method B) and used on substrate 1f (entry 7). It
was found that without the chiral ligand, the reaction time
slowed dramatically and did not go to completion, which is in
agreement with the findings of Sharpless in regards to the rate
(5) (a) Herz, W.; Ligon, R. C.; Turner, J. A.; Blount, J. F. J. Org. Chem.
1977, 42, 1885. (b) Boyd, J. D.; Foote, C. S.; Imagawa, D. K. J. Am. Chem.
Soc. 1980, 102, 3641. (c) Suzuki, M.; Noyori, R.; Hamanaka, N. J. Am.
Chem. Soc. 1981, 103, 5606. (d) Balci, M.; Sutbeyaz, Y. Tetrahedron Lett.
1983, 24, 4135. (e) Harter, R.; Weymuth, C.; Scheffold, R.; Engel, P.;
Linden, A. HelV. Chim. Acta 1993, 76, 353. (f) Avery, T. D.; Jenkins, N.
F.; Kimber, M. C.; Lupton, D. W.; Taylor, D. K. Chem. Commun. 2002,
28.
The addition of the cis-1,2-diol unit was found to occur with
high diastereoselectivity. Not surprisingly the diastereomeric
excess was lowest for the monosubstituted dihydro dioxine 1e
at 90%, with all other de values being greater than 95% as
determined by yields and 1H NMR integration. It was found in
all cases that the major diastereomer occurred by anti addition
of the 1,2-diol unit with respect to the substituents R to the
(6) Schulz, M.; Kluge, R.; Liebsch, S.; Lessig, J.; Halik, M.; Gadissa,
F. Tetrahedron 1996, 52, 13151.
(7) Jefford, C. W.; Misra, D.; Dishington, A. P.; Timari, G.; Rossier, J.;
Bernardinelli, G. Tetrahedron Lett. 1994, 35, 6275.
(8) Suzuki, M.; Ohtake, H.; Kameya, Y.; Hamanaka, N.; Noyori, R. J.
Org. Chem. 1989, 54, 5292.
(9) Matsumoto, M.; Dobashi, S.; Kuroda, K,; Kondo, K. Tetrahedron
1985, 41, 2147.
(12) Jacobsen, E. N.; Marko, I.; France, M. B.; Svendsen, J. S.; Sharpless,
K. B. J. Am. Chem. Soc. 1989, 111, 737.
(13) (a) Schneider, W. P.; McIntosh, A. V. U.S. Patent 2, 769,824, Nov.
6, 1956. (b) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett.
1976, 17, 1973.
(10) Wang, Z.; Kakiuchi, K.; Sharpless, K. B. J. Org. Chem. 1994, 59,
6895.
(11) Andersson, P. G.; Sharpless, K. B. J. Am. Chem. Soc. 1993, 115,
7047.
(14) Kornblum, N.; DeLaMare, H. E. J. Am. Chem. Soc. 1951, 73, 880.
(15) Dupau, P.; Epple, R.; Thomas, A. A.; Fokin, V. V.; Sharpless, K.
B. AdV. Synth. Catal. 2002, 344, 421.
(16) Hoffman, K. A.; Chem. Ber. 1912, 45, 3329.
J. Org. Chem, Vol. 71, No. 19, 2006 7237

Robinson et al.
SCHEME 2
TABLE 2. Reduction of the Peroxide Bond of 2 To Give Tetraols
and Polyols 3
TABLE 3. Ring-Opening of 1,2-Dioxanes 2 Using Co(II) Salen
product,
isolated
yield (%)
product
entrya
dioxane
anomeric ratiob
entry
dioxane
methoda
(% yield)b
1
2
3
4
5
2f
c
91
c
92
c
1
2
3
4
5
6
7
8
9
10
11
12
13
2b
2d
2e
2f
2f
2f
2f
2f
2g
2h
2i
A
A
A
A
B
C
D
E
A
A
A
B
B
3b (75)
3d (69)
3e (62)
3f (72)
3f (84)
3f (69)
3f (77)
3f (66)
3g (66)
3h (73)
3i (90)
3j (84)
3k (77)
2g
2h
2j
4g, 16:(45:39)
4j, 0:(51:49)
2k
a Reactions were performed in THF using 5 mol % of N,N′-bis(sali-
cylidene)ethylenediaminocobalt(II). b Ratio was determined by 1H NMR by
dissolving the sample in deuterated solvent and allowing the mixture to
equilibrate for 1 h before integrating the peak height. The individual anomers
could not be unambiguously assigned. Furanose forms are in parentheses.
c No isolable product was recovered.
2j
2k
SCHEME 3
a See Experimental Section for reaction conditions. b Isolated yield after
recrystallization.
peroxide linkage (Scheme 2). This is the expected stereochem-
istry given the preference for OsO4 to add from the least
hindered face,17 and was verified by 1H NMR coupling constants
and through the synthesis of allitol and psicose. Surprisingly
the peroxy diols were found to be moderately unstable at room
temperature with decomposition evident after only a few days
in some instances. The stability could be improved by keeping
the diols in solvent or by storage below 0 °C with minimal
evidence of decomposition in the neat samples after several
weeks.
We next examined reduction of the peroxide linkage to
generate stereospecific tetraol core structures (Table 2). There
are several methods in the literature for peroxide reduction,
including hydrogenation with metal catalysts,18,19 LiAlH4,20 Zn/
AcOH,21 Mg/MeOH,22 and thiourea. The latter has become a
popular choice as a mild reductant for bicyclic peroxides.23 Of
these methods, reduction with Pd/C in the presence of H2
(method A) proved to be the most convenient owing to the small
amount of catalyst required, good yields, and ease of purifica-
tion. It was also found that by using Pd/C in methanol both
peroxide reduction and removal of the TBDMS group for
compounds 2b,d, and i could be accomplished in one pot,
consistent with the literature.24
The exceptionally mild reducing conditions of zinc dust in
acetic acid (method B) proved to be a useful alternative where
incompatibilities with Pd/C arose, such as with the dibromo
compound 2j (entry 12). This allowed for the convenient
synthesis of the previously unknown dibromo allitol, which
could potentially be a potent anticancer agent, given the clinical
use of the mannitol and galactitol versions.25,26 The tetraols and
polyols afforded by reduction were all crystalline and thus
readily purified by recrystallization from methanol and ether
(17) Schroder, M. Chem. ReV. 1980, 80, 187.
(18) Endo, K.; Seya, K.; Hikino, H. Tetrahedron 1987, 43, 2681.
(19) Adam, W.; Klug, G.; Peters, E. M.; Peters, K.; Von Schnerring, H.
G. Tetrahedron 1985, 41, 2045.
(20) Campagnole, M.; Bourgeois, M. J.; Montaudon, E. Tetrahedron
2002, 58, 1165.
(21) Kropf, H. In Houben-Weyl Methoden der Organischen Chemie,
Peroxo-Verbindungen (Houben-Weyl Methods of Organic Chemistry, Per-
oxo-Connections); Kropf, H., Ed.; Thieme: Stuttgart, Germany, 1988; pp
1102-1116.
(22) Dai, P.; Dussault, P. H.; Trullinger, T. K. J. Org. Chem. 2004, 69,
2851.
(24) Ikawa, T.; Sajiki, H.; Hirota, K. Tetrahedron 2004, 60, 6189.
(25) Weisburger, J. H.; Griswold, D. P.; Prejean, J. D.; Casey, A. E.;
Wood, H. B.; Weisburger, E. K. Recent Results Cancer Res. 1975, 52, 1.
(26) Chiuten, D. F.; Rozencweig, M.; Von Hoff, D. D.; Muggia, F, M.
Cancer 1981, 47, 442.
(23) Kara, Y.; Balci, M. Tetrahedron 2003, 59, 2063.
7238 J. Org. Chem., Vol. 71, No. 19, 2006

Osmium Catalyzed Dihydroxylation of 1,2-Dioxines
SCHEME 4a
TABLE 4. Acetonide Protection of Diols 2 To Give 1,2-Dioxane
Acetonides 6, Followed by Co(II) Salen Ring-Opening To Give
Furanoses 7
product
1,2-dioxane
acetonideb
product
(% yield)
anomeric
ratioc
entry 1,2-dioxanea (% yield) entry
1
2
3
4
5
2f
6f (91)
6g (87)
6h (98)
6j (93)
6k (94)
6
7
8
9
6f
7f (100)
7g (91)
7h (100)
7j (91)
70:30
53:47
75:25
95:5
2g
2h
2j
6g
6h
6j
2k
10
6k
7k (80)
80:20
a Reactions were typically performed on a 200 mg scale with 3 equiv of
2,2-DMP and 10 mol % TsOH in CH2Cl2. b Reactions were performed in
THF using 5 mol % of N,N′-bis(salicylidene)ethylenediaminocobalt(II).
c Ratio was determined by 1H NMR by dissolving the sample in deuterated
solvent and allowing the mixture to equilibrate for 1 h before integrating
the peak height. The individual anomers could not be unambiguously
assigned.
a Reagents and conditions: (i) N,N′-carbonyldiimidazole, benzene, 1 h;
(ii) (CH3)2C(OCH3)2, p-TSA, CH2Cl2, 1 h; (iii) Co(II)[SALEN]2, THF, 3-12
h; C6H6CH(OCH3)2, p-TSA, CH2Cl2; 1 h.
Given the moderate instability of the peroxy diols and the
mixed results of the Co(II) ring-opening of them, it was decided
to investigate whether acetal protection of the 1,2-diols would
have any effect on stability (Scheme 4). Acetonide protection
was found to occur rapidly and in high yield (Table 4) with no
apparent decomposition of the peroxide linkage. Interestingly,
the addition of the acetonide group was also found to dramati-
cally increase stability over the free diols, with the neat protected
1,2-dioxanes being stable at room temperature for months with
no evidence of decomposition. Both carbonate and benzylidene
acetals were also found to form rapidly in good yield to give 5
and 8; however, the benzylidene acetal was found to be labile
over a period of days.
or chloroform. The stereochemistry of the tetraol core formed
by the dihydroxylation/reduction sequence was determined by
assigning the structure of the meso hexitol 3i as allitol by
comparison with the 13C NMR’s of the hexitols and their
hexaacetates.27 Unambiguous determination was also afforded
by X-ray analysis of the tetraol 3f clearly showing the R,R,S,S
stereochemistry (see Supporting Information).
A previous study by Taylor et al. showed that epoxy-1,2-
dioxines can be homolytically ring-opened with Co(II) salen
complexes to give stabilized 1,4-hydroxy ketones.28 It was
therefore of interest to extend this methodology to the peroxy
diols described thus far. Initial attempts at ring-opening the free
hydroxy compounds using 5 mol % of N,N′-bis(salicylidene)-
ethylenediaminocobalt(II) gave mixed results (Table 3, Scheme
3). Compounds 2g,j gave good yields of the hydroxy ketones
which existed predominantly in the ring-closed furanose forms.
The reactions of compounds 2f,h,k showed complete consump-
tion of starting material; however, no major products were
recovered upon workup.
Co(II) ring-opening of the acetonide protected dioxanes 6
gave the desired hydroxy ketones 7 in excellent yields (Table
4). As with the 1,2-dioxanes, acetonide protection of the hydroxy
ketones resulted in a dramatic increase in stability, with all of
products being stable at room temperature for months with no
detectable decomposition. All of the hydroxy ketones 7 formed
were found to exist solely in their cyclic furanose forms, both
in solution as indicated by NMR (Table 4), and in their neat
form as indicated by an absence of a carbonyl stretch in the IR
spectra.
SCHEME 5a
a Reagents and conditions: (i) Co(II)[SALEN]2, THF, 3-12 h; (ii) 3:2 AcOH/H2O, 16 h.
J. Org. Chem, Vol. 71, No. 19, 2006 7239

Robinson et al.
TABLE 5. Asymmetric Ring-Opening of meso-1,2-Dioxanes 6k and
by 1,2-dioxine (1 mmol). The mixture was stirred rapidly until
complete by TLC. The reaction mixture was extracted with CH2Cl2
or ethyl acetate (4 × 50 mL), dried (Na2SO4), concentrated in vacuo,
and the product was subjected to flash chromatography to yield
the product peroxy diol.
Method B. To a stirred solution of t-BuOH (5 mL) and water
(5 mL) was added K2OsO4 (0.5 mol %), K3Fe(CN)6 (3 mmol),
K2CO3 (3 mmol), and methane sulfonamide (1 mmol), followed
by 1,2-dioxine (1 mmol), The mixture was stirred rapidly until
complete by TLC. The workup was as per method A.
2i
entrya
1,2-dioxane
eed
1
2
3
4
6kb
6kc
2ib
20
20
26
26
2ic
a Reactions were performed in THF (2 mL) on a 30 mg scale using 5
mol % of Co(II) catalyst. b Catalyst used was (R,R)-(-)-N,N′-bis(3,5-di-
tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt(II). c Catalyst used was
(S,S)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminoco-
balt(II). d Ratio was determined by chiral shift NMR using europium tris[3-
(heptafluoropropylhydroxymethylene)]-(+)-camphorate in CDCl3.
Method C. To a stirred solution of K2OsO4 (0.5 mol %) and
NMO (1 mmol) in acetone (10 mL) was added 1,2-dioxine (1
mmol). The mixture was stirred rapidly until complete by TLC.
The workup was as per method A.
By utilizing the osmium tetroxide catalyzed dihydroxylation
of 1,2-dioxines, it was envisaged that the rare sugar psicose as
well as 1-deoxypsicose could be readily made from the Co(II)
ring-opening of the peroxy diols. It was initially decided to try
Co(II) ring-opening on the free diols for efficiency which yielded
the TBDMS protected hydroxy ketones (Scheme 5). Silyl
deprotection with aqueous acetic acid afforded the racemic keto
sugars in good yields which showed NMR spectra identical to
those found in the literature.29-31
Taylor and others have previously established that 1,2-
dioxines could be asymmetrically ring opened using chiral Co(II)
catalysts to give optically enriched hydroxy ketones.3,24 It
therefore follows that the peroxy diols described herein should
also be amenable to asymmetric ring-opening with the same
catalysts. Preliminary results using the commercially available
Co(II) Jacobsen catalyst are tabulated in Table 5. It was found
that both acetonide protected 6k and free diol 2i derivatives
showed moderate selectivity with the Jacobsen catalyst, which
should be improved using the previously described catalysts that
are customed to 1,2-dioxine ring-opening.5,28 The ring-opening
of 2i to give optically enriched D- and L-psicose shows that
the synthesis of optically enriched sugars from 1,2-dioxines is
possible.
Method D. To a stirred solution of 1,2-dioxine (1 mmol) in
t-BuOH or CH3CN (5 mL) and water (5 mL) was added K2OsO4
(0.5 mol %) and citric acid (2 mmol), followed by NMO (1.1
mmol). The mixture was stirred rapidly until complete by TLC.
The workup was as per method A.
Method E. To a stirred solution of 1,2-dioxine (1 mmol) in
CH3CN (5 mL) and water (5 mL) was added K2OsO4 (0.5 mol %)
and KClO3 (3 mmol). The mixture was stirred rapidly until complete
by TLC. The workup was as per method A.
(()-(3S,4R,5S,6R)-3-([1-(tert-Butyl)-1,1-dimethylsilyl]oxy-
methyl)-6-methyl-1,2-dioxane-4,5-diol (2b). Colorless solid (458
mg); mp 69-70 °C; Rf ) 0.25 (2:3 ethyl acetate/hexane). IR
1
(neat): 3401, 1472, 1255, 1123, 838, 779 cm-1. H NMR (600
MHz, CDCl3): δ 0.09 (s, 6H), 0.90 (s, 9H), 1.36 (d, J ) 6.6 Hz,
3H), 2.53 (br s, 1H), 2.76 (br s, 1H), 3.69 (dd, J ) 4.8, 4.2 Hz,
1H), 3.82 (dd, J ) 11.1, 6.6 Hz, 1H), 3.95 (dd, J ) 11.1, 5.4 Hz,
1H), 4.01 (dd, J ) 6.0, 4.2 Hz, 1H), 4.24 (ddd, J ) 6.6, 6.0, 5.4
Hz, 1H), 4.31 (dq, J ) 6.6, 4.8 Hz, 1H). 13C NMR (75 MHz,
CDCl3): δ -5.6, -5.5, 15.2, 18.2, 25.8, 61.6, 65.4, 69.1, 80.1,
82.9. MS m/z (+EI): 279 (M+ + H, 100), 261 (61), 243 (12), 173
(12), 159 (14), 117 (13). HRMS calcd for (M+ + Na) C12H26O5-
SiNa, 301.1447; found, 301.1439.
(()-(3S,4R,5S,6R)-3-(3-Hydroxypropyl)-6-methyl-1,2-dioxane-
4,5-diol (2c). Colorless solid (80 mg); mp 76.5-78.5 °C (ethyl
acetate); Rf ) 0.28 (19:1 ethyl acetate/methanol). IR (Nujol) 3392,
3342, 1419, 1363, 1074, 1049, 923 cm-1. 1H NMR (600 MHz, d6
DMSO): δ 1.13 (d, J ) 6.6 Hz, 3H), 1.37-1.44 (m, 1H), 1.49-
1.59 (m, 2H), 1.60-1.67 (m, 1H), 3.36-3.38 (m, 2H), 3.40 (ddd,
J ) 6.6, 6.0, 3.6 Hz, 1H), 3.50 (ddd, J ) 5.4, 4.8, 3.6 Hz, 1H),
3.96 (dddd, J ) 4.8, 4.8, 4.2, 4.2 Hz, 1H), 4.14 (dq, J ) 6.6, 6.6
Hz, 1H), 4.37 (t, J ) 5.4 Hz, OH), 4.70 (d, J ) 5.4 Hz, OH), 4.71
(d, J ) 6.0 Hz, OH). 13C NMR (150 MHz, d6 DMSO): δ 15.2,
26.6, 28.8, 60.5, 67.2, 68.4, 78.8, 84.0. MS m/z (+EI): 193 (M+
+ H, 18), 175 (64), 87 (50), 71 (90), 60 (85), 43 (100). HRMS
calcd for (M+ + Na) C8H16O5Na, 215.0895; found, 215.0899.
(()-(3S,4R,5S,6R)-3-(3-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-
propyl)-6-methyl-1,2-dioxane-4,5-diol (2d). Colorless oil (301
mg); Rf ) 0.27 (2:3 ethyl acetate/hexane). IR (neat) 3401, 1472,
1256, 1100, 1061, 837, 776 cm-1. 1H NMR (300 MHz, CDCl3): δ
0.05 (s, 6H), 0.90 (s, 9H), 1.33 (d, J ) 6.6 Hz, 3H), 1.52-1.68
(m, 1H), 1.70-1.83 (m, 3H), 2.40 (br s, 2H), 3.60-3.70 (m, 3H),
3.75 (dd, J ) 4.8, 3.6 Hz, 1H), 4.14 (dd, J ) 11.7, 6.3 Hz, 1H),
4.27 (dq, J ) 6.6, 6.3 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ
-5.3, 15.2, 18.3, 25.8, 25.9, 28.7, 62.6, 68.3, 69.2, 79.5, 84.3. MS
m/z (+EI): 307 (M+ + H, 82), 271 (13), 203 (7), 187 (18), 157
(14), 145 (100). HRMS calcd for (M+ + Na) C14H30O5SiNa,
329.1760; found, 329.1753.
Conclusion
In summary, peroxy diols 2 can be readily prepared from
3,6-dihydro-1,2-dioxines 1 in high yield and excellent de. Facile
reduction of the peroxide bond under a range of conditions
allows for a synthetically viable route to stereospecific tetraols
without the use of protecting groups. Ring-opening of the peroxy
diols, and their considerably more stable acetonide derivatives,
afforded novel hydroxy ketones in excellent yields, providing
a useful pathway to keto-sugars such as psicose and its
derivatives. Preliminary work applying chiral Co(II) Jacobsen
complexes to the ring-opening of meso-peroxy diols gave some
asymmetric induction, meaning with appropriate chiral Co(II)
complexes highly enantioselective synthesis of sugar type
hydroxy ketones is feasible.
Experimental Section
General Methods for Dihydroxylation of 1,2-Dioxines. Method
A. To a stirred solution of t-BuOH (5 mL) and water (5 mL) was
added AD mix (2.8 g) and methane sulfonamide (1 mmol), followed
(()-(3R,4S,5S)-3-Cyclohexyl-1,2-dioxane-4,5-diol (2e). Color-
less solid (183 mg); mp 78-80 °C; Rf ) 0.27 (1:1 ethyl acetate/
hexane). IR (Nujol) 3459, 3299, 1078, 1060, 1044, 988, 890 cm-1
.
(27) Angyal, S. J.; Le Fur, R. Carbohydr. Res. 1980, 84, 201.
(28) Greatrex, B. W.; Jenkins, N. F.; Taylor, D. K.; Tiekink, E. R. T. J.
Org. Chem. 2003, 68, 5205.
(29) Angyal, S. J.; Bethell, G. S. Aust. J. Chem. 1976, 29, 1249.
(30) Angyal, S. J.; Bethell, G. S.; Cowley, D. E. Aust. J. Chem. 1976,
29, 1239.
1H NMR (600 MHz, CDCl3): δ 1.04-1.40 (m, 5H), 1.63-1.83
(m, 6H), 2.36 (br s, 2H), 3.82 (dd, J ) 8.4, 3.6 Hz, 1H), 3.96 (ddd,
J ) 3.6, 3.6, 1.8 Hz, 1H), 4.00 (dd, J ) 8.4, 3.6 Hz, 1H), 4.21 (dd,
J ) 13.2, 3.6 Hz, 1H), 4.36 (dd, J ) 13.2, 1.8 Hz, 1H). 13C NMR
(75 MHz, CDCl3): δ 26.3, 26.3, 26.4, 26.5, 30.1, 37.3, 66.0, 66.3,
(31) Kaufmann, H.; Reichstein, T. HelV. Chim. Acta 1967, 50, 2280.
7240 J. Org. Chem., Vol. 71, No. 19, 2006

Osmium Catalyzed Dihydroxylation of 1,2-Dioxines
75.8, 86.1. MS m/z (+EI): 202 (M+, 2), 186 (8), 150 (7), 95 (95),
83 (100), 60 (79). Anal. Calcd for C10H18O4: C, 59.39; H, 8.97.
Found: C, 59.06; H, 8.87.
Method C. As per method A except 10% platinum on carbon
was used.
Method D. To a stirred solution of 1,2-dioxine (1 mmol) in
methanol (5 mL) was added magnesium turnings (5 mmol) and
catalytic iodine. The reaction mixture was heated gently until the
iodine color faded and then stirred rapidly for 24 h. The solvent
was removed in vacuo, and the solids triturated with THF. The
triturate was then recrystallized as per method A.
Method E. To a stirred solution of 1,2-dioxine (1 mmol) in
methanol (5 mL) was added thiourea (5 mmol), and the mixture
rapidly stirred until complete by TLC (ca. 3-5 days). The solvent
was removed in vacuo, and the residue purified by flash chroma-
tography to give the polyol product.
(()-(3R,4S,5R,6S)-3,6-Dipropyl-1,2-dioxane-4,5-diol (2f). Amor-
phous solid (223 mg); mp 76 °C; Rf ) 0.28 (2:3 ethyl acetate/
hexane). IR (Nujol): 3351, 1300, 1277, 1085, 1068, 1037, 1028
1
cm-1. H NMR (600 MHz, CDCl3): δ 0.95 (t, J ) 7.2 Hz, 6H),
1.36-1.45 (m, 2H), 1.51-1.60 (m, 2H), 1.62-1.72 (m, 4H), 2.19
(br s, 2H), 3.66-3.69 (m, 2H), 4.09-4.13 (m, 2H). 13C NMR (75
MHz, CDCl3): δ 13.9, 18.9, 31.4, 68.2, 83.8. MS m/z (+EI): 205
(M+ + H, 2), 187 (9), 171 (7), 145 (14), 115 (42), 60 (80), 43
(100). Anal. Calcd for C10H20O4: C, 58.80; H, 9.87. Found: C,
58.90; H, 9.88.
(()-(3R,4S,5R,6S)-3,6-Dimethyl-1,2-dioxane-4,5-diol (2g). Col-
orless oil (616 mg); Rf ) 0.39 (7:3 ethyl acetate/hexane). IR
(()-1-Deoxyallitol (3b). Colorless needles (58 mg); mp 106-
108 °C; Rf ) 0.40 (7:3 dichloromethane/methanol). IR (Nujol) 3306,
3188, 1333, 1118, 1068, 997 cm-1. 1H NMR (300 MHz, CD3OD):
δ 1.21 (d, J ) 6.3 Hz, 3H), 3.55 (dd, J ) 6.6, 5.4 Hz, 1H), 3.60-
3.68 (m, 2H), 3.74-3.84 (m, 2H), 3.93 (dq, J ) 6.3, 5.4 Hz, 1H).
13C NMR (75 MHz, CD3OD): δ 18.4, 64.3, 69.9, 74.6, 74.6, 77.3.
MS m/z (+EI): 167 (M+ + H, 5), 131 (8), 117 (20), 103 (14), 73
(100). Anal. Calcd for C6H14O5: C, 43.37; H, 8.49. Found: C,
43.07; H, 8.68.
(()-(4S,5S,6R,7R)Octane-1,4,5,6,7-pentaol (3d). Colorless solid
(80 mg); mp 108.5-109.5 °C; Rf ) 0.19 (4:1 CH2Cl2/methanol).
IR (Nujol) 3249, 1338, 1057, 1048, 998, 974 cm-1. 1H NMR (600
MHz, CD3OD): δ 1.19 (d, J ) 6.6 Hz, 3H), 1.45-1.52 (m, 1H),
1.56-1.64 (m, 1H), 1.71-1.81 (m, 2H), 3.46 (dd, J ) 7.5, 5.1 Hz,
1H), 3.49 (dd, J ) 7.5, 4.8 Hz, 1H), 3.59 (dd, J ) 6.6, 6.0 Hz,
2H), 3.74 (ddd, J ) 9.5, 5.1, 2.4 Hz, 1H), 3.93 (dq, J ) 6.6, 4.8
Hz, 1H). 13C NMR (75 MHz, CD3OD): δ 18.0, 29.3, 30.1, 63.3,
70.0, 74.2, 76.7, 77.2. MS m/z (+EI): 194 (M+, 8), 191 (11), 147
(29), 124 (15), 68 (100). Anal. Calcd for C8H18O5: C, 49.47; H,
9.34. Found: C, 49.25; H, 9.27.
(()-(1R,2R,3S)-1-Cyclohexylbutane-1,2,3,4-tetraol (3e). Amor-
phous solid (75 mg); mp 133-134 °C; Rf 0.36 (17:3 CH2Cl2/
methanol). IR (Nujol): 3369, 3227, 1089, 1070, 1050, 1015, 947
cm-1. 1H NMR (600 MHz, CD3OD): δ 1.12-1.38 (m, 5H), 1.54-
1.58 (m, 1H), 1.64-1.72 (m, 2H), 1.74-1.81 (m, 3H), 3.40 (dd, J
) 8.4, 3.6 Hz, 1H), 3.59 (dd, J 8.4, 5.4 Hz, 1H), 3.63 (dd, J )
12.6, 7.2 Hz, 1H), 3.75-3.78 (m, 2H). 13C NMR (75 MHz,
CD3OD): δ 27.0, 27.6, 27.9, 28.0, 31.6, 40.8, 64.3, 72.9, 75.3,
78.6. MS m/z (+EI): 205 (M+ + H, 45), 187 (49), 169 (52), 151
(36), 113 (34), 95 (100). Anal. Calcd for C10H20O4: C, 58.80; H,
9.87. Found: C, 58.85; H, 9.69.
1
(neat): 3418, 1378, 1241, 1087, 1014, 972 cm-1. H NMR (300
MHz, CDCl3): δ 1.37 (d, J ) 6.6 Hz, 6H), 2.44 (br s, 2H), 3.67
(d, J ) 5.1 Hz, 2H), 4.29 (dq, J ) 6.6, 5.1 Hz, 2H). 13C NMR (75
MHz, CDCl3): δ 15.2, 69.1, 80.0. MS m/z (+EI): 149 (M+ + H,
6), 131 (12), 117 (18), 85 (33), 60 (100). HRMS calcd for (M+
Na) C6H12O4Na, 171.0633; found, 171.0631.
+
(()-(3R,4S,5R,6S)-3,6-Dicyclopentyl-1,2-dioxane-4,5-diol (2h).
White solid (616 mg); mp 117-118 °C; Rf ) 0.39 (2:3 ethyl acetate/
hexane). IR (Nujol): 3307, 1337, 1077, 1050, 1007 cm-1. 1H NMR
(300 MHz, CDCl3): δ 1.32-1.46 (m, 4H), 1.50-1.71 (m, 8H),
1.73-1.90 (m, 4H), 2.31 (sext, J ) 8.4 Hz, 2H), 2.38 (d, J ) 8.4
Hz, 2H), 3.79-3.93 (m, 4H). 13C NMR (75 MHz, CDCl3): δ 25.2,
25.6, 28.3, 29.2, 39.3, 67.7, 87.3. MS m/z (+EI): 257 (M+ + H,
2), 189 (28), 158 (23), 145 (56), 131 (50), 108 (100). Anal. Calcd
for C14H24O4: C, 65.60; H, 9.44. Found: C, 65.60; H, 9.42.
(()-(3R,4S,5R,6S)-3,6-Di([1-(tert-butyl)-1,1-dimethylsilyl]oxy-
methyl)-1,2-dioxane-4,5-diol (2i). Colorless oil (533 mg); Rf )
0.38 (3:7 ethyl acetate/hexane). IR (neat): 3403, 1472, 1361, 1256,
1
1128, 1005, 838 cm-1. H NMR (600 MHz, CDCl3): δ 0.079 (s,
6H), 0.082 (s, 6H), 0.90 (s, 18H), 2.45 (br s, 2H), 3.81 (dd, J )
11.0, 6.0 Hz, 2H), 3.95 (dd, J ) 11.0, 5.4 Hz, 2H), 4.03-4.05 m
(2H), 4.23-4.26 (m, 2H). 13C NMR (75 MHz, CDCl3): δ -5.6,
-5.5, 18.2, 25.8, 61.3, 65.3, 83.3. MS m/z (+EI): 409 (M+ + H,
2), 315 (31), 299 (23), 201 (48), 117 (69), 89 (93), 73 (100). HRMS
calcd for (M+ + Na) C18H40O6Si2Na, 431.2261; found, 431.2254.
(()-(3R,4R,5S,6S)-3,6-Di(bromomethyl)-1,2-dioxane-4,5-di-
ol (2j). White solid (710 mg); mp 115-118 °C (dec); Rf ) 0.33
(1:1 ethyl acetate/hexane). IR (Nujol): 3495, 3360, 1418, 1336,
1232, 1048 cm-1. 1H NMR (300 MHz, CDCl3/d6 DMSO): δ 3.65
(d, J ) 5.7 Hz, 4H), 3.78 (br s, 2H), 3.97-4.02 (m, 2H). 13C NMR
(75 MHz, CDCl3/d6 DMSO): δ 28.9, 65.3, 82.7. MS m/z (+EI):
307 (M+ + H, 3), 200 (8), 179 (27), 156 (45), 72 (100). Anal.
Calcd for C6H10O4Br2: C, 23.55; H, 3.29. Found: C, 23.66; H,
3.44.
(()-(4R,5R,6S,7S)Decane-4,5,6,7-tetraol (3f). Colorless crystals
(62 mg); mp 176 °C. IR (Nujol): 3370, 1325, 1211, 1064, 1026,
1
980 cm-1. H NMR (300 MHz, CD3OD): δ 0.94 (t, J ) 7.2 Hz,
6H), 1.30-1.68 (m, 8H), 3.46-3.52 (m, 2H), 3.70-3.76 (m, 2H).
13C NMR (75 MHz, CD3OD): δ 14.7, 20.0, 32.2, 74.0, 76.8. MS
m/z (+EI): 207 (M+ + H, 17), 189 (5), 99 (21), 70 (100), 57 (45),
44 (66). Anal. Calcd for C10H22O4: C, 58.23; H, 10.75. Found: C,
57.94; H, 10.51.
(()-(3R,4S,5R,6S)-3,6-Diphenyl-1,2-dioxane-4,5-diol (2k). White
solid (320 mg); Rf ) 0.22 (2:3 ethyl acetate/hexane). IR (Nujol)
1
3345, 1495, 1341, 1098, 1048, 949 cm-1. H NMR (300 MHz,
(()-1,6-Dideoxyallitol (3g). Colorless needles (100 mg); mp
177-178 °C (lit32 178 °C); Rf ) 0.20 (17:3 CH2Cl2/methanol). IR
(Nujol): 3294, 3207, 1341, 1125, 1056, 999 cm-1. 1H NMR (300
MHz, CD3OD): δ 1.19 (d, J ) 6.3 Hz, 6H), 3.40-3.46 (m, 2H),
3.90-3.99 (m, 2H). 13C NMR (75 MHz, CD3OD): δ 17.6, 69.9,
77.0. MS m/z (+EI): 155 (M+ + H, 100), 133 (73), 115 (97), 97
(85), 57 (88).
(()-(1R,2R,3S,4S)-1,4-Dicyclopentylbutane-1,2,3,4-tetraol (3h).
Colorless flakes (110 mg); mp 203-205 °C; Rf ) 0.56 (17:3
CH2Cl2/methanol). IR (Nujol): 3398, 3260, 1329, 1284, 1055, 1021
cm-1. 1H NMR (300 MHz, CD3OD): δ 1.38-1.80 (m, 16H), 2.19-
2.32 (m, 2H), 3.61-3.71 (m, 4H). 13C NMR (75 MHz, CD3OD):
δ 26.6, 26.7, 27.6, 30.1, 43.1, 76.1, 76.5. MS m/z (+EI): 259 (M+
CDCl3): δ 2.56 (br s, 2H), 4.28 (d, J ) 5.4 Hz, 2H), 5.39 (d, J )
5.4 Hz, 2H), 7.34-7.44 (m, 10H). 13C NMR (300 MHz, CDCl3):
δ 68.5, 84.6, 127.2, 128.6, 128.7, 135.7. HRMS calcd for (M+
Na) C16H16O4Na, 295.0946; found, 295.0940.
+
General Methods for Peroxide Reduction. Method A. To a
stirred solution of 1,2-dioxine (1 mmol) in methanol (5 mL) was
added 10% w/w of 5% palladium on carbon, and the mixture stirred
overnight under a hydrogen atmosphere. The suspension was then
filtered through kenite washing with methanol, and the solvent was
removed in vacuo giving the crude polyol, which was readily
recrystallized from methanol/ether or methanol/chloroform.
Method B. To a stirred solution of 1,2-dioxine (1 mmol) in acetic
acid (5 mL) was added zinc dust (5 mmol), and the mixture was
rapidly stirred for 24 h. The acetic acid was removed in vacuo,
and the solids triturated with THF. The triturate was then recrystal-
lized as per method A.
(32) Lett, R.; Bory, S.; Moreau, B.; Marquet, A. Bull. Soc. Chim. Fr.
1972, 6, 2299.
J. Org. Chem, Vol. 71, No. 19, 2006 7241

Robinson et al.
+ H, 20), 223 (100), 205 (57), 111 (41), 81 (40), 73 (56). Anal.
Calcd for C14H26O4: C, 65.09; H, 10.14. Found: C, 65.10; H,
10.26.
atmosphere until complete by TLC (∼1 h). The reaction mixture
was diluted with ether (50 mL), washed with water (4 × 20 mL),
dried (Na2SO4), and concentrated in vacuo, and the product was
subjected to flash chromatography to yield the title compound (112
mg) as a colorless oil; Rf ) 0.22 (3:2 CH2Cl2/hexane). IR (neat)
(()-Allitol (3i). Colorless crystals (78 mg); mp 149-150.5 °C
(lit 150 °C33). 13C NMR (75 MHz, D2O): δ 65.0, 74.9, 75.0.
(()-1,6-Dibromo-1,6-dideoxyallitol (3j). Colorless cubes (170
mg); mp 119-121 °C; Rf ) 0.26 (9:1 CH2Cl2/methanol). IR
(Nujol): 3344, 1338, 1290, 1056, 1016 cm-1. 1H NMR (300 MHz,
CD3OD): δ 3.55 (dd, J ) 10.8, 7.2 Hz, 2H), 3.72 (dd, J ) 10.8,
3.0 Hz, 2H), 3.71-3.77 (m, 2H), 3.93-4.00 (m, 2H), 4.63 (br s,
4H). 13C NMR (75 MHz, CD3OD): δ 37.7, 73.4, 75.0. MS m/z
(+EI): 308 (M+, 10), 208 (21), 123 (22), 103 (81), 73 (90), 57
(100). Anal. Calcd for C6H12O4Br2: C, 23.40; H, 3.93. Found: C,
23.60; H, 3.92.
1
1808, 1466, 1381, 1303, 1173, 1135, 1056 cm-1. H NMR (300
MHz, CDCl3): δ 0.96 (t, J ) 7.2 Hz, 6H), 1.38-1.78 (m, 8H),
4.24-4.30 (m, 2H), 4.48-4.54 (m, 2H). 13C NMR (75 MHz,
CDCl3): δ 13.6, 18.4, 32.6, 74.3, 79.7, 153.7. MS m/z (+EI): 231
(M+ + H, 69), 97 (37), 87 (59), 71 (94), 55 (100). Anal. Calcd for
C11H18O5: C, 57.38; H, 7.88. Found: C, 57.65; H, 7.92.
General Procedure for the Acetonide Protection of Diols 2f-
h, j,k. To a stirred solution of 1,2-dioxine (1 mmol) in dry CH2Cl2
(5 mL) was added 2,2-dimethoxypropane (3 mmol) followed by
p-toluenesulfonic acid (10 mol %), and the solution was stirred
under nitrogen until complete by TLC (∼1 h). The reaction mixture
was diluted with CH2Cl2 (20 mL), washed with saturated NaHCO3
(20 mL), and dried (Na2SO4), and the solvent was removed in
vacuo. The residue was then purified by flash chromatography.
(()-(3aR,4S,7R,7aS)-2,2-Dimethyl-4,7-dipropylperhydro[1,3]-
dioxolo[4,5-d][1,2]dioxine (6f). Colorless oil (271 mg); Rf ) 0.30
(1:1 CH2Cl2/hexane). IR (neat) 1460, 1382, 1247, 1220, 1066, 869
(()-(1R,2R,3S,4S)-1,4-Diphenylbutane-1,2,3,4-tetraol (3k). Col-
orless needles (96 mg); mp 175-176.5 °C. IR (Nujol): 3321, 1496,
1
1338, 1309, 1075, 1040 cm-1. H NMR (300 MHz, CD3OD): δ
3.59-3.65 (m, 2H), 4.84 (dd, J ) 3.3, 1.5 Hz, 2H), 7.22-7.35 (m,
6H), 7.41-7.46 (m, 4H). 13C NMR (75 MHz, CD3OD): δ 76.4,
76.8, 128.6, 129.0, 129.2, 142.6. MS m/z (+EI): no molecular ion,
150 (19), 132 (68), 131 (47), 107 (68), 79 (100), 77 (47). Anal.
Calcd for C16H18O4: C, 70.06; H, 6.61. Found: C, 70.23; H, 6.57.
General Procedure for the Ring-Opening of 1,2-Dioxines
using Co(II) Salen. To a stirred solution of N,N′-bis(salicylidene)-
ethylenediaminocobalt(II) in THF (5 mL) at ambient temperature
was added 1,2-dioxine (1 mmol), and the reaction mixture was left
to stir until complete by TLC (∼16 h). All volatiles were then
removed in vacuo, and the product was purified by flash chroma-
tography.
1
cm-1. H NMR (300 MHz, CDCl3): δ 0.94 (t, J ) 7.2 Hz, 6H),
1.37 (s, 3H), 1.39-1.70 (m, 8H), 1.53 (s, 3H), 3.95-4.00 (m, 2H),
4.13-4.19 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 13.8, 18.8,
26.3, 28.1, 33.1, 73.8, 81.0, 109.2. MS m/z (+EI): 245 (M+ + H,
15), 229 (65), 143 (68), 129 (61), 101 (90), 55 (100). Anal. Calcd.
for C13H24O4: C, 63.91; H, 9.90. Found: C, 63.61; H, 9.72.
(()-(3aR,4S,7R,7aS)-2,2,4,7-Tetramethylperhydro[1,3]dioxolo-
[4,5-d][1,2]dioxine (6g). Colorless solid (331 mg); mp 47-48 °C;
(()-1,6-Dideoxy psicose (4g). Keto Anomer. Colorless oil (56
Rf ) 0.33 (CH2Cl2). IR (Nujol): 1248, 1220, 1153, 1069, 864 cm-1
.
mg); Rf ) 0.27 (ethyl acetate). IR (neat): 3388, 1713, 1455, 1380,
1H NMR (300 MHz, CDCl3): δ 1.34 (d, J ) 6.6 Hz, 6H), 1.37 (s,
3H), 1.52 (s, 3H), 3.94-3.99 (m, 2H), 4.27-4.36 (m, 2H). 13C
NMR (75 MHz, CDCl3): δ 16.7, 26.3, 28.1, 74.5, 77.6, 109.4. MS
m/z (+EI): 189 (M+ + H, 29), 173 (68), 129 (32), 100 (31), 85
(100). Anal. Calcd for C9H16O4: C, 57.43; H, 8.57. Found: C,
57.49; H, 8.65.
1
1130, 1072, 921 cm-1. H NMR (600 MHz, CD3OD): δ 1.21 (d,
J ) 6.6 Hz, 3H), 2.22 (s, 3H), 3.63 (dd, J ) 7.2, 4.8, 1H), 3.83
(dq, J ) 7.2, 6.6 Hz, 1H), 4.12 (d, J ) 4.8 Hz, 1H). 13C NMR
(150 MHz, CD3OD): δ 20.3, 27.6, 68.4, 78.9, 80.8, 212.3. MS
m/z (+EI): 149 (M+ + H, 11), 131 (100), 113 (15), 87 (27), 74
(36), 71 (68). HRMS calcd for (M+ + Na) C6H12O4Na, 171.0633;
found, 171.0632.
(()-(3aR,4S,7R,7aS)-4,7-Dicyclopentyl-2,2-dimethylperhydro-
[1,3]dioxolo[4,5-d][1,2]dioxine (6h). Colorless solid (340 mg); mp
73-74 °C; Rf ) 0.33 (1:1 CH2Cl2/hexane). IR (Nujol): 1245, 1221,
Major Anomer. 1H NMR (600 MHz, CD3OD): δ 1.20 (d, J )
6.6 Hz, 3H), 1.38 (s, 3H), 3.64 (dd, J ) 6.0, 4.8 Hz, 1H), 3.96 (dq,
J ) 6.6, 4.8 Hz, 1H), 3.74 (d, J ) 6.0 Hz, 1H). 13C NMR (150
MHz, CD3OD): δ 19.8, 26.2, 76.2, 77.6, 79.9, 103.9.
1
1156, 1063, 1023 cm-1. H NMR (300 MHz, CDCl3): δ 1.38 (s,
3H), 1.40-1.50 (m, 4H), 1.51-1.70 (m, 8H), 1.53 (s, 3H), 1.73-
1.90 (m, 4H), 2.11 (sext, J ) 8.4 Hz, 2H), 3.87-3.94 (m, 2H),
4.09-4.14 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 25.1, 25.5,
26.4, 28.1, 29.1, 29.2, 41.2, 73.2, 85.1, 109.0. MS m/z (+EI): 297
(M+ + H, 23), 279 (39), 239 (28), 132 (60), 92 (77), 41 (100).
Anal. Calcd for C17H28O4: C, 68.89; H, 9.52. Found: C, 68.88; H,
9.59.
1
Minor Anomer. H NMR (600 MHz, CD3OD): δ1.29 (d, J )
6.0 Hz, 1H), 1.40 (s, 3H), 3.70 (d, J ) 4.8 Hz, 1H), 3.88 (dq, J )
7.8, 6.0 Hz, 1H), 4.03 (dd, J ) 7.8, 4.8 Hz, 1H). 13C NMR (150
MHz, CD3OD): δ 21.2, 23.3, 78.7, 78.8, 79.9, 107.3.
(()-1,6-Dibromo-1,6-dideoxy Psicose (4j). Major Anomer.
Colorless solid (92 mg); mp 59-60 °C (dec); Rf ) 0.23 (1:1 ethyl
acetate/hexane). IR (Nujol): 3343, 1237, 1193, 1129, 1065, 1008
cm-1. 1H NMR (600 MHz, CD3OD): δ 3.45 (d, J ) 10.2 Hz, 1H),
3.49 (dd, J ) 10.5, 7.2 Hz, 1H), 3.61 (dd, J ) 10.5, 4.2 Hz, 1H),
3.70 (d, J ) 10.2 Hz, 1H), 3.94 (d, J ) 4.2 Hz, 1H), 4.08 (ddd, J
) 7.2, 7.2, 4.2 Hz, 1H), 4.26 (dd, J ) 7.2, 4.2 Hz, 1H). 13C NMR
(75 MHz, CD3OD): δ 33.7, 35.5, 72.9, 75.7, 84.2, 106.3. MS m/z
(+EI): 306 (M+, 4), 269 (8), 254 (33), 191 (10), 149 (17), 80 (100).
HRMS calcd for (M+ + Na) C6H10O4Br2Na, 326.8844; found,
326.8836.
(()-(3aR,4R,7S,7aS)-4,7-Di(bromomethyl)-2,2-dimethyl-
perhydro[1,3]dioxolo[4,5-d][1,2]dioxine (6j). Colorless needles
(220 mg); mp 79-80 °C; Rf ) 0.31 (1:1 CH2Cl2/hexane). IR
(Nujol): 1421, 1251, 1220, 1153, 1071, 1044 cm-1. 1H NMR (300
MHz, CDCl3): δ 1.40 (s, 3H), 1.54 (s, 3H), 3.54-3.65 (m, 4H),
4.37-4.43 (m, 4H). 13C NMR (75 MHz, CDCl3): δ 26.1, 27.9,
29.3, 70.7, 80.8, 110.4. MS m/z (+EI): 346 (M+, 4), 330 (17),
127 (19), 85 (46), 59 (42), 43 (100). Anal. Calcd. for C9H14O4Br2:
C, 31.24; H, 4.08. Found: C, 31.45; H, 4.26.
(()-(3aR,4S,7R,7aS)-2,2-Dimethyl-4,7-diphenylperhydro[1,3]-
dioxolo[4,5-d][1,2]dioxine (6k). Colorless solid (113 mg); mp 126-
127 °C; Rf ) 0.45 (3:2 CH2Cl2/hexane). IR (Nujol) 1496, 1244,
1221, 1071, 880, 750 cm-1. 1H NMR (300 MHz, CDCl3): δ 1.45
(s, 3H), 1.69 (s, 3H), 4.57-4.62 (m, 2H), 5.34-5.39 (m, 2H), 7.31-
7.47 (m, 10H). 13C NMR (75 MHz, CDCl3): δ 26.4, 28.3, 74.3,
83.1, 109.6, 127.3, 128.5, 128.6, 137.0. MS m/z (+EI): 313 (M+
+ H, 11), 296 (43), 237 (15), 219 (26), 100 (100), 85 (97). Anal.
Calcd. for C19H20O4: C, 73.06; H, 6.45. Found: C, 73.27; H, 6.42.
(()-(3aS,6S,6aS)-2,2-Dimethyl-4,6-dipropylperhydrofuro[3,4-
d][1,3]dioxol-4-ol (7f). Major Anomer. White solid (75 mg); mp
57.5-58.5 °C; Rf ) 0.22 (1:9 ethyl acetate/hexane). IR (neat) 3462,
Minor Anomer. 1H NMR (600 MHz, CD3OD): δ 3.49 (s, 2H),
3.50 (dd, J ) 10.8, 5.4 Hz, 1H), 3.58 (dd, J ) 10.8, 4.8 Hz, 1H),
4.01 (dd, J ) 6.0, 5.4 Hz, 1H), 4.11-4.14 (m, 2H). 13C NMR (150
MHz, CD3OD): δ 35.1, 35.8, 74.1, 76.6, 83.1, 103.2.
(()-(3aR,4S,7R,7aS)-4,7-Dipropylperhydro[1,3]dioxolo[4,5-d]-
[1,2]dioxin-2-one (5). To a stirred solution of 2f (110 mg, 0.73
mmol) in dry benzene (5 mL) was added N,N-carbonyldiimidazole
(175 mg, 1.08 mmol), and the mixture was stirred under a nitrogen
(33) Coffey, S. Rodd’s Chemistry of Carbon Compounds, 2nd ed.;
Elsevier Publishing Company: Amsterdam, The Netherlands, 1967; Vol.
1F, p 19.
7242 J. Org. Chem., Vol. 71, No. 19, 2006

Osmium Catalyzed Dihydroxylation of 1,2-Dioxines
1
1
1463, 1374, 1210, 1072, 878 cm-1. H NMR (600 MHz, CDCl3):
Minor Anomer. H NMR (600 MHz, CDCl3): δ 1.29 (s, 3H),
δ 0.92 (m, 6H), 1.38 (s, 3H), 1.39-1.71 (m, 7H), 1.59 (s, 3H),
1.75 (ddd, J ) 13.4, 11.4, 4.8 Hz, 1H), 3.95 (br s, 1H), 3.99 (ddd,
J ) 7.2, 6.6, 5.4 Hz, 1H), 4.33 (dd, J ) 7.2, 5.4 Hz, 1H), 4.43 (d,
J ) 7.2 Hz, 1H). 13C NMR (150 MHz, CDCl3): δ 14.0, 14.2, 16.9,
18.7, 25.1, 26.6, 35.4, 41.3, 80.7, 83.2, 84.6, 102.1, 112.3. MS m/z
(+EI): 245 (M+ + H, 1), 227 (82), 187 (50), 141 (21), 98 (25), 86
(100). Anal. Calcd for C13H24O4: C, 63.91; H, 9.90. Found: C,
64.17; H, 9.90.
1.46 (s, 3H), 2.71 (br s, 1H), 4.76 (d, J ) 5.4 Hz, 1H), 5.17 (dd,
J ) 5.4, 2.4 Hz, 1H), 5.44 (d, J ) 2.4 Hz, 1H), 7.26-7.41 (m,
6H), 7.49-7.52 (m, 2H), 7.65-7.68 (m, 2H). 13C NMR (150 MHz,
CDCl3): δ 25.3, 26.8, 86.9, 87.3, 88.3, 108.0, 113.3, 126.0, 127.0,
127.4, 127.9, 128.4, 128.7, 139.9, 141.4.
(()-(3aR,4S,7R,7aS)-2-Phenyl-4,7-dipropylperhydro[1,3]-
dioxolo[4,5-d][1,2]dioxine (8). To a stirred solution of 2f (90 mg,
0.44 mmol) in dry CH2Cl2 (5 mL) was added R,R-dimethoxytoluene
(201 mg, 1.32 mmol) followed by p-toluenesulfonic acid (7 mg,
0.04 mmol), and the mixture was stirred under a nitrogen
atmosphere until complete by TLC (∼1 h). The reaction mixture
was diluted with CH2Cl2 (50 mL), washed with saturated NaHCO3
(20 mL), dried (Na2SO4), and concentrated in vacuo, and the product
was purified by flash chromatography to yield the title compound
(110 mg) as a colorless oil; Rf ) 0.50 (1:1 CH2Cl2/hexane). IR
1
Minor Anomer. H NMR (600 MHz, CDCl3): δ 0.92-0.98
(m, 6H), 1.33 (s, 3H), 1.39-1.71 (m, 7H), 1.49 (s, 3H), 1.85 (ddd,
J ) 13.7, 10.5, 5.4 Hz, 1H), 2.0 (br s, 1H), 4.06 (ddd, J ) 7.8, 7.2,
1.8 Hz, 1H), 4.49 (d, J ) 6.0 Hz, 1H), 4.60 (dd, J ) 6.0, 1.8 Hz,
1H). 13C NMR (150 MHz, CDCl3): δ 13.8, 14.3, 16.7, 19.3, 25.1,
26.7, 38.0, 38.4, 85.3, 85.6, 86.3, 108.3, 112.3.
(()-1,6-Dideoxy-3,4-O-(1-methylethylidene) Psicose (7g).34
Major Anomer. Colorless oil (91 mg); Rf ) 0.34 (3:7 ethyl acetate/
1
(neat) 3366, 1461, 1406, 1220, 1094, 1070, 1028 cm-1. H NMR
1
hexane). H NMR (600 MHz, CDCl3): δ 1.30 (d, J ) 6.6 Hz,
(300 MHz, CDCl3): δ 0.93 (t, J ) 7.2 Hz, 6H), 1.38-1.77 (m,
8H), 4.06-4.11 (m, 2H), 4.25-4.32 (m, 2H), 5.91 (s, 1H), 7.38-
7.44 (m, 3H), 7.49-7.54 (m, 2H). 13C NMR (75 MHz, CDCl3): δ
13.8, 18.7, 33.2, 74.7, 81.2, 104.1, 126.6, 128.5, 129.5, 137.1. MS
m/z (+EI): 292 (M+, 8), 191 (9), 177 (21), 105 (100), 77 (31).
HRMS calcd for (M+ + Na) C17H24O4Na, 315.1572; found,
315.1562.
3H), 1.39 (s, 3H), 1.49 (s, 3H), 1.60 (s, 3H), 4.03 (br s, 1H), 4.10
(dq, J ) 6.6, 4.8 Hz, 1H), 4.33 (dd, J ) 7.2, 4.8 Hz, 1H), 4.46 (d,
J ) 7.2 Hz, 1H). 13C NMR (150 MHz, CDCl3): δ 18.6, 25.1, 26.2,
26.7, 77.2, 85.9, 84.5, 100.7, 116.2.
1
Minor Anomer. H NMR (600 MHz, CDCl3): δ 1.33 (s, 3H),
1.36 (d, J ) 6.6 Hz, 3H), 1.49 (s, 3H), 1.51 (s, 3H), 2.32 (br s,
1H), 4.27 (dq, J ) 6.6, 1.2 Hz, 1H), 4.53 (d, J ) 5.4 Hz, 1H), 4.60
(dd, J ) 5.4, 1.2 Hz, 1H); 21.8, 23.6, 25.1, 26.6, 82.3, 86.4, 86.5,
107.1, 112.4.
(()-1,6-Bis-O-[1,1-dimethylethyl)dimethylsilyl] Psicose (9).
Major Anomer. Colorless oil (153 mg); Rf ) (0.19) (3:7 ethyl
acetate/hexane). IR (neat): 3391, 1472, 1362, 1256, 1104, 837
(()-(3aS,6S,6aS)-4,6-Dicyclopentyl-2,2-dimethylperhydrofuro-
[3,4-d][1,3]dioxol-4-ol (7h). Major Anomer. Colorless oil (120
mg); Rf ) 0.33 (1:9 ethyl acetate/hexane). IR (neat): 3506, 1455,
1372, 1210, 1078, 868 cm-1. 1H NMR (600 MHz, d6-benzene): δ
1.13 (s, 3H), 1.33 (s, 3H), 1.40-1.90 (m, 16H), 1.95-2.03 (m,
1H), 2.28 (quint, J ) 8.4 Hz, 1H), 4.05 (dd, J ) 8.4, 5.4 Hz, 1H),
4.05 (br s, 1H), 4.14 (dd, J ) 7.8, 5.4 Hz, 1H), 4.22 (d, J ) 7.8
Hz, 1H). 13C NMR (150 MHz, d6-benzene): δ 25.1, 25.8, 25.9,
26.5, 26.6, 26.7, 27.4, 27.7, 28.5, 29.6, 42.9, 47.8, 83.4, 84.2, 84.7,
103.8, 115.9. MS m/z (+EI): 297 (M+ + H, 5), 279 (100), 239
(17), 140 (66), 124 (65), 97 (80). HRMS calcd for (M+ + Na)
C17H28O4Na, 319.1885; found, 319.1881.
cm-1 13C NMR (75 MHz, d6-benzene): δ -5.0, -5.0, -5.0, -4.9,
.
18.8, 19.0, 26.4, 26.4, 64.4, 66.9, 72.9, 73.1, 84.6, 103.7. MS m/z
(+EI): 409 (M+ + H, 3), 391 (32), 315 (27), 201 (45), 159 (44),
117 (93), 75 (100). HRMS calcd for (M+ + Na) C18H40O6Si2Na,
431.2261; found, 431.2259.
Minor Anomer. 13C NMR (75 MHz, d6-benzene): δ -5.3, -5.2,
-5.1, -5.0, 18.8, 18.8, 26.2, 26.3, 64.2, 67.2, 73.3, 76.4, 85.7,
104.6.
(()-Psicose (10). To a solution of acetic acid (3 mL) and water
(2 mL) was added 9 (153 mg, 0.37 mmol), and the mixture was
stirred overnight. The solvent was removed in vacuo, and the residue
was dried at reduced pressure to give psicose (67.4 mg) as a viscous
oil. 13C NMR (75 MHz, D2O): δ 60.7, 64.1, 65.1, 65.6, 65.8, 66.0,
66.7, 66.9, 67.8, 68.2, 68.6, 71.7, 73.0, 73.0, 73.1, 73.7, 74.5, 77.4,
85.4, 85.4, 100.4, 101.2, 106.0, 108.3.
1
Minor Anomer. H NMR (600 MHz, d6-benzene): δ 0.56 (br
s, 1H), 1.22 (s, 3H), 1.40-1.90 (m, 16H), 1.50 (s, 3H), 2.15-2.21
(m, 1H), 2.69 (quint, J ) 8.4 Hz, 1H), 3.94 (dd, J ) 11.1, 1.8 Hz,
1H), 4.57-4.60 (m, 2H). 13C NMR (150 MHz, d6-benzene): δ 25.4,
25.6, 25.6, 26.2, 26.3, 26.5, 27.0, 28.0, 29.0, 30.6, 44.6, 45.1, 85.3,
86.6, 91.6, 109.5, 112.4.
(()-1-Deoxy-6-O-[1,1-dimethylethyl)dimethylsilyl] Psicose (11).
Colorless oil (70 mg); Rf ) 0.23 (1:1 ethyl acetate/hexane). IR
(()-1,6-Dibromo-1,6-dideoxy-3,4-O-(1-methylethylidene) Psi-
cose (7j). Major Anomer. Colorless planks (123 mg); mp 72-73
°C (dec); Rf ) 0.18 (1:9 ethyl acetate/hexane). IR (Nujol): 3459,
(neat): 3401, 1716, 1472, 1255, 1119, 837 cm-1 13C NMR (75
.
MHz, CDCl3): δ -5.7, -5.6, -5.6, -5.5, -5.5, -5.4, 18.2, 18.2,
18.3, 21.0, 24.1, 25.8, 25.8, 25.8, 26.6, 62.6, 63.4, 64.4, 70.3, 71.3,
72.5, 73.3, 75.2, 77.3, 79.0, 83.9, 83.9, 103.2, 105.7, 207.7. MS
m/z (+EI): 278 (M+, 1), 261 (41), 243 (27), 203 (17), 117 (22),
85 (100). HRMS calcd for (M+ + Na) C12H26O5SiNa, 301.1447;
found, 301.1446.
1
1274, 1215, 1061, 1011, 873 cm-1. H NMR (300 MHz, CDCl3):
δ 1.35 (s, 3H), 1.50 (s, 3H), 3.30 (br s, 1H), 3.45-3.54 (m, 2H),
3.62 (d, J ) 10.8 Hz, 1H), 3.73 (d, J ) 10.8 Hz, 1H), 4.39 (ddd,
J ) 90., 6.9, 1.2 Hz, 1H), 4.66 (d, J ) 6.0 Hz, 1H), 4.95 (dd, J )
6.0, 1.2 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 25.0, 26.4, 32.5,
37.7, 84.1, 85.1, 86.0, 104.9, 113.5. MS m/z (+EI): 347 (M+
+
(()-1-O-[1,1-Dimethylethyl)dimethylsilyl]-6-deoxypsicose (12).
Colorless oil (30 mg); Rf ) 0.34 (1:1 ethyl acetate/hexane). IR (neat)
H, 6), 329 (100), 289 (17), 271 (21), 251 (9). Anal. Calcd for
C9H14O4Br2: C, 31.24; H, 4.08. Found: C,31.42; H, 4.19.
(()-(3aS,6S,6aS)-2,2-Dimethyl-4,6-diphenylperhydrofuro[3,4-
d][1,3]dioxol-4-ol (7k). Major Anomer. Colorless oil (59 mg); Rf
) 0.19 (1:9 ethyl acetate/hexane). IR (neat) 3401, 1496, 1211, 1066,
1
3402, 1472, 1390, 1255, 1104, 839 cm-1. H NMR (300 MHz,
CDCl3): δ 0.09 (s, 3H), 0.10 (s, 3H), 0.91 (s, 9H), 1.26 (d, J )
6.6 Hz, 3H), 2.82 (d, J ) 6.9 Hz, 1H), 3.13 (d, J ) 6.9 Hz, 1H),
3.65 (s, 2H), 3.71-3.78 (m, 1H), 3.97 (ddd, J ) 6.9, 6.0, 5.7 Hz,
1H), 4.04 (br s, 1H), 4.11 (dq, J ) 6.6, 4.4 Hz, 1H). 13C NMR (75
MHz, CDCl3): δ -5.4, 18.3, 18.9, 25.8, 65.9, 71.6, 76.0, 79.1,
102.4. MS m/z (+EI): 278 (M+, 1), 261 (100), 243 (63), 159 (18),
131 (25), 75 (54). HRMS calcd for (M+ + Na) C12H26O5SiNa,
301.1447; found, 301.1446.
(()-1-Deoxypsicose (13). Deprotection Procedure as per 10.
Colorless oil (37 mg). 13C NMR (75 MHz, D2O): δ 23.9, 26.4,
26.4, 26.9, 29.1, 60.9, 64.1, 65.6, 65.6, 66.8, 67.8, 68.8, 71.2, 72.5,
73.1, 73.9, 74.1, 74.1, 74.9, 75.9, 76.9, 78.7, 81.7, 85.1, 85.9, 100.7,
101.2, 105.7, 108.7, 215.0.
1
1049, 1027 cm-1. H NMR (600 MHz, CDCl3): δ 1.37 (s, 3H),
1.74 (s, 3H), 4.69 (dd, J ) 7.2, 5.4 Hz, 1H), 4.71 (br s, 1H), 4.74
(d, J ) 7.2 Hz, 1H), 5.23 (d, J ) 5.4 Hz, 1H), 7.30-7.41 (m, 6H),
7.47-7.49 (m, 2H), 7.63-7.65 (m, 2H). 13C NMR (150 MHz,
CDCl3): δ 25.2, 26.7, 82.9, 86.3, 86.6, 101.5, 117.2, 125.6, 125.9,
128.0, 128.3, 128.4, 128.6, 139.0, 142.0. MS m/z (+EI): 312 (M+,
3), 299 (67), 238 (26), 206 (100), 175 (43), 165 (85). HRMS calcd
for (M+ + Na) C19H20O4Na, 335.1259; found, 335.1250.
(34) Suh, H.; Wilcox, C. S. J. Am. Chem. Soc. 1988, 110, 470.
J. Org. Chem, Vol. 71, No. 19, 2006 7243

Robinson et al.
(()-6-Deoxypsicose (14). Deprotection Procedure as per 10.
Colorless oil (19 mg). 13C NMR (75 MHz, D2O): δ 20.3, 22.0,
65.1, 66.1, 73.0. 77.8, 77.9, 78.7, 80.6, 81.2, 105.6, 107.9.
Supporting Information Available: Experimental details for
compounds 1a-k and crystallographic data for 3f; 13C NMR spectra
for compounds 1d, 2b-d,i,k, 3b,g,i,j, 4 g,j, 5, 6f,j, 7f,h,j,k, and
9-14, and 1H NMR spectra for compounds 1,b,i,j, 2f,g,j, 3d,f,i,k,
6k, and 8. This material is available free of charge via the Internet
at http://pubs.acs.org.
Acknowledgment. We thank the Australian Research Coun-
cil for financial support. T. V. Robinson thanks the Common-
wealth government of Australia, for support in the form of a
scholarship.
JO060949P
7244 J. Org. Chem., Vol. 71, No. 19, 2006