Syntheses of D- and L-mannose, gulose, and talose via diastereoselective and enantioselective dihydroxylation reactions

Full text of DOI:10.1021/jo990410+

2982
J . Org. Chem. 1999, 64, 2982-2983
Sch em e 1
Syn th eses of D- a n d L-Ma n n ose, Gu lose, a n d
Ta lose via Dia ster eoselective a n d
En a n tioselective Dih yd r oxyla tion Rea ction s
J oel M. Harris, Mark D. Keranen, and
George A. O’Doherty*
Sch em e 2
Department of Chemistry, University of Minnesota,
Minneapolis, Minnesota 55455
Received March 8, 1999
The de novo enantioselective synthesis of the hexoses
stands as a challenge to asymmetric catalysis.1 Despite
some germinal efforts toward the hexoses, notably by
Masamune/Sharpless (epoxidation),2 Danishefsky (Diels-
Alder),3 J ohnson/Hudlicky (enzymatic desymmetrization),4
and Wong/Sharpless (osmium/enzyme),5 there still does not
exist a practical, nonenzymatic route to the hexoses.6 As part
of our program aimed at investigating the biological role of
oligosaccharides, we are interested in the synthesis of
analogues of the anti-HIV agent kakelokelose (Scheme 1).
Kakelokelose is a polysulfated â-oligomannosugar, isolated
as an oligomer from the Pacific tunicate Didemnum molle.
It has been proposed that the biologically active form is an
oligosaccharide.7 We are particularly interested in studying
oligosaccharide analogues of the all D-, all L-, and mixed D,L-
oligosugar structures. Consequently, we required an efficient
approach to both D- and L-mannose. The ideal route would
allow for the synthesis of other mixed D- and L-oligosaccha-
rides, such as the D-mannose-L-gulose portion of bleomycin.8
Herein, we would like to present our discovery of an
expeditious route to mannose, gulose, or talose using Sharp-
less’s dihydroxylation reaction to set the D- or L-configuration
depending on the ligand used.
We have targeted differentially protected D- and L-
mannose 1 as building blocks for the assembly of analogues
of kakelokelose (Scheme 1). We desired a route in which the
synthetic efficiency is better than traditional protection/
deprotection strategies from mannose and is amenable to
both D- and L-mannose. The ideal synthesis should also start
from a commercially available starting material that is even
cheaper than D-mannose.9,10 The strategy outlined below has
led to a highly stereocontrolled synthesis of D- or L-mannose
in only five steps and in approximately 39% yield from
furfural (Scheme 2). Our approach relies upon the use of
catalytic asymmetric osmium chemistry on vinylfuran 3
developed by Ogasawara11 and augments the earlier work
of Achmatowicz.12
To accomplish this goal we, as have others, recognized
that substituted furyl alcohols possess the proper C-5
stereochemistry for the hexopyranoses.13 Crucial to this
approach is a simple three-step route toward pyranone 6b
(Scheme 3). We envision 6b as the linchpin molecule that
will be amenable for the synthesis of all the possible
stereoisomers of the hexoses. A key part of this sequence is
our ability to convert furfural into an ether solution of
vinylfuran.14 This one-step in situ process for the generation
of vinylfuran constitutes a significant improvement in terms
of overall efficiency. A 2 M solution of vinylfuran can be used
directly in the t-BuOH/H2O AD-mix reaction mixture de-
veloped by Sharpless.12,15 The (DHQ)2Phal ligand gave an
85% yield of (R) diol 2(R) from furfural in 90% ee.16 The
(DHQD)2Phal ligand afforded (S) diol 2(S) in an 85% yield
with a 92% ee.17 The absolute configuration is based upon
the Sharpless mnemonic15 and Mosher ester analysis.18 Diol
2 can be selectively protected with TBSCl (90%) to give furan
5, which smoothly rearranges to hemiacetal 6a when
oxidized with NBS.19 Hemiacetal 6a exists as an equilibrat-
ing mixture of anomers, diastereomerically enriched mix-
tures of 6a equilibrate to a (1:1) mixture of anomers in
deuterated chloroform. Our hopes of taking advantage of the
difference in reactivities of axial versus equatorial anomeric
alcohols were realized when hemiacetal 6a was treated with
benzoyl chloride at -78 °C to produce pyranone 6b (>20:1
ratio of diastereomers). This result appears to be general
for acid chlorides as pivaloyl chloride (>10:1) showed similar
selectivity, whereas TBSCl gave approximately a 1:1 mixture
(11) (a) Achmatowicz, O.; Bielski, R. Carbohydr. Res. 1977, 55, 165. (b)
Grapsas, I.; K.; Couladouros, E. A.; Georgiadis, M. P. Pol. J . Chem. 1990,
64, 823.
(1) For a good review: Zamoiski, A.; Banaszek, A.; Grynkiewicz, G. Adv.
Carbohydr. Chem. Biochem. 1982, 40, 1.
(2) Sharpless, K. B.; Masamune, S. Science 1983, 220, 949.
(3) For a review, see: (a) Danishefsky, S. J . Chemtracts 1989, 273. For
improved catalysis, see: (b) Schaus, S. E.; Branalt, J .; J acobsen, E. N. J .
Org. Chem. 1998, 63, 403-405.
(4) (a) J ohnson, C. R.; Golebiowski, A.; Steensma, D. H.; Scialdone, M.
A. J . Org. Chem. 1993, 58, 7185-7194. (b) Hudlicky, T.; Pitzer, K. K.;
Stabile, M. R.; Thorpe, A. J .; Whited, G. M. J . Org. Chem. 1996, 61, 4151-
4153.
(12) Ogasawara has previously demonstrated the asymmetric dihydroxy-
lation of vinylfuran and applied it toward the synthesis of D- and L-
levoglucosenone: (a) Taniguchi, T.; Nakamura, K.; Ogasawara, K. Synlett
1996, 971. (b) Taniguchi, T.; Ohnishi, H.; Ogasawara, K. Chem. Commun.
1996, 1477-1478.
(13) For a good review, see: Hudlicky, T.; Entwistle, D. A.; Thorpe, A. J .
Chem. Rev. 1996, 96, 1195.
(14) This in situ use of vinylfuran allows for much higher yields of diol
7. Wittig technology provides vinylfuran in yields on the order of 10%.
Previous practical approaches to vinylfuran involve a four-step sequence
from furfural that involves a stoichiometric Cu-promoted decarboxylation
of 3-furylpropanoic acid, see: Schmidt, U.; Werner, J . Synthesis 1986, 986.
(15) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483-2547.
(16) Although we were concerned about an adverse solvent effect caused
by the presence of ether, Ogasawara has observed identical ee’s in t-BuOH/
H2O; see ref 12a.
(5) Henderson, I.; Sharpless, K. B.; Wong, C.-H. J . Am. Chem. Soc. 1994,
116, 558-561.
(6) Recently Wong has developed a route to a mixture of glucose and
fructose using an enzymatic process: Gijsen, H. J . M.; Qiao, L.; Fitz, W.;
Wong, C.-H. Chem. Rev. 1996, 96, 443-73.
(7) Riccio, R.; Kinnel, R. B.; Bifulco, G.; Scheur, P. J . Tetrahedron Lett.
1996, 37, 1979.
(8) For a recent total synthesis of bleomycin, see: (a) Boger, D. L.; Honda,
T. J . Am. Chem. Soc. 1994, 116, 5647-5656. (b) Boger, D. L.; Honda, T.;
Menezes, R. F.; Colletti, S. L. J . Am. Chem. Soc. 1994, 116, 5631-5646. (c)
Boger, D. L.; Teramoto, S.; Zhou, J . C. J . Am. Chem. Soc. 1995, 117, 7344-
7356.
(17) The (R) diol 7 has been prepared on a half mole scale with no
reduction of enantioselectivity. Similarly the (S) diol 7 has been prepared
on a quarter mole scale.
(9) According to the Aldrich catalog, on a per gram basis D-mannose cost
35 times more than furfural and for L-mannose the cost ratio is 4000.
(10) Furfural is commercially produced by Great Lakes Chemical. For a
convenient laboratory procedure, see: Adams, R.; Voorhees, V. Organic
Syntheses; Wiley: New York, 1921; Collect. Vol. I, p 280.
(18) (a) Sullivan, G. R.; Dale, J . A.; Mosher, H. S. J . Org. Chem. 1975,
38, 2143. (b) Yamaguchi, S.; Yasuhara, F.; Kabuto, K. T. Tetrahedron 1976,
32, 1363.
(19) Georgiadis, M. P.; Couladoures, E. A. J . Org. Chem. 1986, 51, 2725
and ref 11b.
10.1021/jo990410+ CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/08/1999

Communications
J . Org. Chem., Vol. 64, No. 9, 1999 2983
Sch em e 3
Sch em e 4
Sch em e 5
of anomers.20 Pyranone 6b was easily purified by filtering
through silica gel and isolated as a single diastereomer in a
56% yield from 2. With the two stereocenters of 6b intro-
duced, the molecule was poised for introduction of the
remaining functionality of the hexoses (Scheme 3).
Pyranone 6b was stereoselectively reduced under the
Luche conditions (NaBH4/CeCl3, -78 °C)21 to give alcohol
7a 22 as the only observable stereoisomer (>95%), which can
be protected without purification to give ethyl carbonate 7b
or benzyl carbonate 7c, each in 80% yield. Three partially
protected mannosugars were produced via a completely
diastereoselective dihydroxylation reaction of 7a , 7b, or 7c
in ∼90% yield in each case (Scheme 3).23 A differentially
protected mannose was easily achieved upon treatment of
diol 1b with trimethyl orthoacetate to form a cyclic ortho
ester in situ, which was hydrolyzed to the axial acetate 1d .
The differentiated mannosugar 1d was formed in a 62% yield
with a regioselectivity greater than 25:1.24
The C-4 isomer of 7d , allylic alcohol 8, can also be easily
produced by performing a Mitsunobu reaction on 7d (Scheme
4). Key to this transformation is the selective hydrolysis of
a p-nitrobenzoyl ester in the presence of the anomeric ester.
Although this operation can be performed on benzoate 6b,
more reproducible results are observed when pivolate 6c is
used. Reduction of pyranone 6c under the Luche conditions
yielded allylic alcohol 7d as a single diastereomer in 95%
yield. Exposure of 7d to the Mitsunobu reaction conditions
(PPh3, DEAD, p-nitrobenzoic acid (PNBOH)) yielded a
p-nitrobenzoic ester (65%) which was selectively hydrolyzed
with Et3N in MeOH to yield the axial alcohol 8 (90%).25
Finally, access to 8 extends this versatile synthetic
strategy to other hexoses, as illustrated by the synthesis of
protected talose 9 and gulose 10 (Scheme 5). Treatment of
allylic alcohol 8 with OsO4/NMO in t-BuOH/H2O afforded
an 80% yield of the protected gulose isomer 10.26 Amazingly,
the protected talose isomer 9 can be selectively produced
upon treatment of 8 with the TMEDA adduct of OsO4
(80%).27 Unfortunately for this system, the hydroxy-directed
delivery of a cis diol requires an axial alcohol; exposure of
7a to the identical conditions only yielded the mannose
isomer 1a . The relative configurations of 1a , 9, and 10 were
determined by examining relevant coupling constants and
1
NOE’s from a series of 1H NMR, 1H,1H-COSY, and H NOE
experiments. The relative and absolute configurations of the
gulose sugar 10 were confirmed by single-crystal X-ray
analysis (see Supporting Information).
In summary, we have developed a practical five-step
synthesis of both D- and L-mannose from furfural (39% yield).
This route is amenable to multigram scale preparation.
Similarly we have also extended this methodology to D- and
L-gulose and D- and L-talose in comparable yields (19%). We
are currently investigating an epoxide ring opening approach
to the other isomers of the hexoses. We feel this new route
to L-sugars will be very beneficial for the synthesis of natural
and unnatural oligosaccharides.
Ack n ow led gm en t. We thank the University of Min-
nesota (grant in aid program), the ACS for an Institutional
Research Grant (IRG-58-001-40-IRG-19), and the National
Science Foundation for their generous support of our
program. We would also like to thank Dr. Dirk Friedrich
(Hoechst Marion Roussel) for his help in the structure
determination of 1a , 9, and 10 and Dr. Victor G. Young
for the X-ray analysis of 10.
(20) The selective benzoylation allows for the simple purification of 6b
without resorting to tedious chromatographic separation. BzCl at room
temperature with excess Et3N gave a 4:1 mixture of isomers, whereas 1
equiv of Et3N gave a 1:1 mixture. Achmatowicz has previously shown that
molecules related to 6a gave a 1:1 mixture of methoxy anomers with MeOH/
acid; see ref 11a.
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic and ana-
lytical data for all new compounds as well as experimental
procedures. This material is available free of charge via the
Internet at http://pubs.acs.org.
(21) Luche, J .-L. J . Am. Chem. Soc. 1978, 110, 2226.
(22) Mosher ester analysis of 7a showed that recrystallized enone 6b
had significantly increased enantioexcess (>96% ee).
J O990410+
(23) For a review of diastereoselection in the osmium-catalyzed dihy-
droxylation reaction, see: Cha, J . K.; Kim, N.-S. Chem. Rev. 1995, 95, 1761.
(24) A mixture of axial and equitorial acetates was produced upon
treatment of 1c with 1 equiv of Ac2O which allowed for easy detection of
the > 25:1 mixture by 1H NMR.
(25) (a) Martin, S. P.; Dodge, J . A.Tetrahedron Lett. 1991, 32, 3017. (b)
Grynkiewicz, G. Pol. J . Chem. 1979, 53, 2501. (c) Mitsunobu, O. Compr.
Org. Synth. 1991, 6, 1.
(26) For
a recent eight-step synthesis of gulose from L-xylose, see:
Dondoni, A.; Marra, A.; Massi, A. J . Org. Chem. 1997, 62, 6261. Dondoni
appraises L-gulose at $2000/g.
(27) Less than 5% of the gulose isomer was formed. These conditions
were chosen for the hydroxy-directed delivery of a cis diol. See: Donohoe,
T. J .; Moore, P. R.; Waring, M. J .; Newcombe, N. J . Tetrahedron Lett. 1997,
38, 5027.