Stereoselective synthesis of β-Phenylselenoglycosides from glycals and rationalization of the selenoglycosylation processes

Article abstract of DOI:10.1021/jo100145s

β-Phenylselenoglycosides have been efficiently and stereoselectively synthesized by direct oxidative glycosylation of benzenselenolate (PhSe ^-) with glycals. A rationalization of the presently described β-selectivity and the opposite α-selectivity reported by Danishefsky in the ring-opening of epoxy glycals with benzeneselenol (PhSeH) is proposed.

Full text of DOI:10.1021/jo100145s

pubs.acs.org/joc
routes to selenoglycosides involve the treatment of orthoester5a
Stereoselective Synthesis
of β-Phenylselenoglycosides from Glycals and
Rationalization of the Selenoglycosylation Processes
or 1-O-acetyl sugars5b,c with phenylselenol, treatment of glyco-
syl halides with diphenyl diselenide under reduction conditions,6
or in a convenient odorless methodology with selenides
derived from a zinc-dust/ZnCl2 or indium(I) iodide-mediated
cleavage of diselenide.7 In a recent procedure used for the
stereospecific synthesis of R- and β-selelenoglycosides and
selenodisaccharides, p-methylbenzoyl selenoglycosides as the
glycosyl donors are coupled with various electrophiles.8
Moreover, only R-phenylselenoglycosides such as 3 can be
efficiently synthesized starting from 3,4,6-tri-O-benzyl-D-glu-
cal (1), via 1,2-anhydro derivative 2, as reported by Danishefs-
ky (Scheme 1).9-11 Actually, in a single exception reported by
Shuto,12 β-phenylselenoglycoside 5 is obtained, via corres-
ponding epoxide, from 3,4-di-O-tert-butyldimethylsilyl-6-O-
trityl-D-glucal (4), but the β-stereoselective reaction is not
generalized and seems to be limited only to this conforma-
tionally restricted substrate (Scheme 1). To date there have
been no more reports of the synthesis of β-selenoglycosides
starting from glycals.
Valeria Di Bussolo,*,† Annalisa Fiasella,†
Federica Balzano,‡ Gloria Uccello Barretta,‡ and
Paolo Crotti*,†
†Dipartimento di Scienze Farmaceutiche, sede Chimica
Biorganica e Biofarmacia, Universitaꢀdi Pisa,Via Bonanno 33,
56126 Pisa, Italy, and ‡Dipartimento di Chimica e Chimica
Industriale, Universitaꢀ di Pisa, Via Risorgimento 35, 56126
Pisa, Italy
valeriadb@farm.unipi.it
Received January 29, 2010
SCHEME 1. r- and β-Phenylselenoglycosides from Glycals
β-Phenylselenoglycosides have been efficiently and stereo-
selectively synthesized by direct oxidative glycosylation of
benzenselenolate (PhSe-) with glycals. A rationalization
of the presently described β-selectivity and the opposite R-
selectivity reported by Danishefsky in the ring-opening of
epoxy glycals with benzeneselenol (PhSeH) is proposed.
(5) (a) Aloui, M.; Chambers, D. J.; Cumpstey, I.; Fairbanks, A. J.;
Redgrave, A. J.; Seward, C. M. P. Chem.;Eur. J. 2002, 8, 2608. (b) Mehta,
S.; Pinto, B. M. Tetrahedron Lett. 1991, 32, 4435. (c) Stork, G.; Suh, H. S.;
Kim, G. J. Am .Chem. Soc. 1991, 113, 7054.
(6) Crich, D.; Suk, D.-H.; Sun, S. Tetrahedron: Asymmetry 2003, 14,
2861.
In the past few years, considerable attention has been
focused on selenoglycosides as useful and stable glycosyl
donors for the preparation of oligosaccharides, C-glycosides,
and glycoconjugates.1 They are also interesting when used in
an iterative glycosylation process for the construction of
oligosaccharide libraries,2 and for the preparation of C(2)-
functionalized glycals.3 Presently,4 the most common synthetic
(7) (a) Mukherjee, C.; Tiwari, P.; Misra, A. K. Tetrahedron Lett. 2006, 47,
441. (b) Tiwari, P.; Misra, A. K. Tetrahedron Lett. 2006, 47, 2345.
(8) (a) Kawai, Y.; Ando, H.; Ozeki, H.; Koketsu, M.; Ishihara, H. Org.
Lett. 2005, 7, 4653. (b) Nanami, M.; Ando, H.; Kawai, Y.; Koketsu, M.;
Ishihara, H. Tetrahedron Lett. 2007, 48, 1113.
(9) (a) Gordon, D. M.; Danishefsky, S. J. Carbohydr. Res. 1990, 206, 361.
In this procedure, contrary to the protocol originally employed with other
nucleophiles, ZnCl2 is not used as the promoting Lewis acid to open epoxide
2 synthetized with Murray’s reagent DMDO (for DMDO preparation see:
Murray, R.W.; Singh, M. Org. Synth. 1997, 74, 91). (b) Danishefsky, S. J.;
Bilodeau, M. T. Angew. Chem., Int. Ed. Engl. 1996, 35, 1380.
(10) For pioneering studies on ring opening of 1,2-anhydropyranoside
(Brigl anhydride) with benzeneselenol, see: Frenzel, H.; Nuhn, P.; Wagner,
G. Arch. Pharm. 1962, 302, 62 and ref 1h.
(1) (a) Mehta, S.; Pinto, B. M. J. Org. Chem. 1993, 58, 3269. (b) Randell,
K. D.; Johnston, B. D.; Brown, P. N.; Pinto, B. M. Carbohydr. Res. 2000, 325,
253. (c) Jiaang, W.-T.; Chang, M.-Y.; Tseng, P.-H.; Chen, S.-T. Tetrahedron
Lett. 2000, 41, 3127. (d) Grant, L.; Liu, Y.; Walsh, K. E.; Walter, D. S.;
Gallagher, T. Org. Lett. 2002, 4, 4623. (e) Mallet, A.; Mallet, J.-M.; Sinay, P.
Tetrahedron: Asymmetry 1994, 5, 2593. (f) van Well, R. M.; Karkkainem,
T. S.; Kartha, K. P. R.; Field, R. A. Carbohydr. Res. 2006, 341, 1391.
(11) For electrophilic seleno activations of glycals see: (a) Jaurand, G.;
Beau, J.-M.; Sinay, P. J. Chem. Soc., Chem. Commun. 1981, 572. (b) Kaye,
A.; Neidle, S.; Reese, C. B. Tetrahedron Lett. 1988, 29, 2711. (c) Santoyo-
ꢀ
ꢁ
ꢁ
´
Gonzales, F.; Calvo-Flores, F. G.; Garcıa-Mendoza, P.; Hernandez-Mateo,
F.; Isac-Garcıa, J.; Robles-Dıaz, R. J. Org. Chem. 1993, 58, 6122.
(g) Valeria, S.; Iadonisi, A.; Adinolfi, M.; Ravida, A. J. Org. Chem. 2007, 72,
6097. (h) For a comprehensive review on selenium-containing sugars see:
Witczak, Z. J.; Czernecki, S. Adv. Carbohydr. Chem. Biochem. 1998, 53, 143.
(2) Yamago, S.; Yamada, T.; Ito, H.; Hara, O.; Mino, Y.; Yoshida, J.-i.
Chem.;Eur. J. 2005, 11, 6159.
(3) Chambers, D. J.; Evans, G. R.; Fairbanks, A. J. Tetrahedron 2004, 60,
8411.
(4) For early synthetic approaches to selenoglycosides see: (a) Schneider,
W.; Wrede, F. Ber. Dtsch. Chem. Ges. 1917, 50, 793. (b) Wrede, F. Ber. Dtsch.
Chem. Ges. 1919, 52, 2153. (c) Bonner, W. A.; Robinson, A. J. Am. Chem.
Soc. 1950, 72, 354.
´
´
(d) Czernecki, S.; Ayadi, E.; Randriamandimby, D. J. Org. Chem. 1994,
59, 8256.
(12) (a) Shuto, S.; Terauchi, M.; Yahiro, Y.; Abe, H.; Ichikawa, S.;
Matsuda, A. Tetrahedron Lett. 2000, 41, 4151. (b) Terauchi, M.; Yahiro,
Y.; Abe, H.; Ichikawa, S.; Tovey, S. C.; Dedos, S. G.; Taylor, C. W.; Potter,
B. V. L.; Matsuda, A.; Shuto, S. Tetrahedron 2005, 61, 3697 and references
cited therein. Except for 5 and conformationally similar 3,4-di-O-TBDS- or
3,4-di-O-TIPS-D-glucal, other β-phenylselenoglycosides were prepared by
the authors in a different way.
4284 J. Org. Chem. 2010, 75, 4284–4287
Published on Web 05/17/2010
DOI: 10.1021/jo100145s
r
2010 American Chemical Society

Di Bussolo et al.
JOCNote
Furthermore, no rationalization was provided in order to
justify the R-selectivity found by Danishefsky in the opening
reaction of epoxide 2 by PhSeH, a result that differs from the
usual β-selectivity obtained by the same author in the classic
“glycal assembly” strategy with many other nucleophiles.9b
The β-selectivity obtained by Shuto was not rationalized,
either.
In this paper, we report a general protocol for the com-
pletely stereoselective synthesis of β-selenoglycosides start-
ing from glycals, and we focus on the rationalization of the
present results, as well as of previously reported data refer-
ring to the same matter.
In the framework of studies dealing with the synthesis of
new glycosyl donors, we needed β-phenylselenoglycoside 7,
bearing appropriate protecting groups on C(3), C(4), and
C(6), as shown (Scheme 2). The use of glucal 6 as the
precursor of 7 appeared to be particularly attractive for this
purpose, provided that a 1,2-trans functionalization of the
endocyclic π-system of 6 was possible (Scheme 2).
An additional interest in this reaction derived from the
observation that the β-selectivity obtained in the direct
oxidative glycosidic coupling with PhSeH is not substrate
dependent. In fact when other glycals such as glucal 1, 3,4,6-
tri-O-benzyl-D-galactal (10) and hexa-O-benzyl lactal (11)16
are used, the corresponding β-phenylselenoglycosides 12,5a
13,1e and 14 are obtained, respectively, as the only glycosyla-
tion products (Scheme 5). It should be observed that in the
glycosylation of PhSeH with galactal 10, the formate deri-
vative 15, isomer of β- phenylselenoglycoside 13, was also
isolated (32%) as a byproduct of the reaction.
SCHEME 5. β-Selenoglycosylation of Glycals 1, 10, and 11
SCHEME 2. 1,2-Trans Functionalization of the Endocyclic
π-System of Glucal 6
On the basis of the mechanism of Gin’s direct oxidative
glycosylation,14b a likely reaction pathway for the formation
of formate 15 involves an initial R-approach17 of the acti-
vated electrophilic diphenyl sulfoxide ([Ph2SOTf]þ[TfO]-)
onto the C(2) position of galactal 10, due to the steric
hindrance to the usual β-approach14b by the C(4) axial
substituent, to produce, with an excess of Ph2SO, intermedi-
ate 16 (Scheme 6).
The subsequent addition of MeOH and Et3N leads to the
formation of β-epoxy galactal 17, which in the presence of
selenolate nucleophile allows the generation of R-selenogly-
coside 18. The diaxial disposition of the C(1) and C(2) substi-
tuents and the C(2)-OH activation by the Ph2SOMeþTfO-
favors the intramolecular cyclization of 18 to R-episeleno-
nium ion intermediate 19. Final aqueous workup of 19 leads
to the regioisomeric trans addition product 20, which spon-
taneusly rearranges to formate 15, as tentatively shown in
Scheme 6.18
As expected, the nucleophilic addition of PhSeH, under
Danishefsky’s conditions,9a to a THF solution of 1,2-anhy-
dropyranoside 8, easily prepared from 6 by Dondoni’s
protocol,13 afforded only the corresponding R-phenylsele-
noglycoside 9, resulting from a completely stereoselective
1,2-cis functionalization of the π system of the starting glucal
6 (Scheme 3).
SCHEME 3. r-Selenoglycosylation of Glucal 6
This result prompted us to verify whether a corresponding
diastereoselective 1,2-trans functionalization of the π system
of glucal 6 was feasible by a new application of Gin’s direct
oxidative glycosylation protocol14 with PhSeH as the glyco-
syl acceptor. Much to our delight, as reported with most of
the nucleophiles used in the original procedure, the desired
1,2-trans functionalization of 6 was obtained with a com-
pletely diastereoselective construction of the corresponding
C(2)-R-hydroxy-β-phenylselenoglycoside 7, needed for our
synthetic purposes (Scheme 4).15
(14) (a) Di Bussolo, V.; Kim, Y.-J.; Gin, D. Y. J. Am. Chem. Soc. 1998,
120, 13515. (b) Honda, E.; Gin, D. Y. J. Am. Chem. Soc. 2002, 124, 7343.
(15) We found that when using PhSeH as the nucleophile in the direct
oxidative glycosylation with glucal 6, Lewis acid is not necessary for coupling
to proceed.
(16) Upreti, M.; Ruhela, D.; Vishwakarma, R. A. Tetrahedron 2000, 56,
6577.
(17) For examples of R-approach of electrophilic reagents onto the C(2)
position of protected glycals see: (a) Grewal, G.; Kaila, N.; Franck, R. W.
J. Org. Chem. 1992, 57, 2084. (b) Roush, W. R.; Sebesta, D. P.; James, R. A.
Tetrahedron 1997, 53, 8837.
(18) Traces (less than 5%) of the corresponding formate, inseparable
from the glycosylation product, are also obtained in the β-phenylselenogly-
cosylation of glucal 6. Control reaction carried out on β-phenylselenoglyco-
side 13 and R-phenylselenoglycoside 22, independently synthetized by ring
opening of epoxy galactal 21 (see ref 13) with PhSeH, showed the stability of
both glycosides to the Gin’s reaction conditions with no evident isomeriza-
tion to formate 15.
SCHEME 4. β-Selenoglycosylation of Glucal 6
Investigations into the validity of the proposed reaction pathway proposed
for the formation of 15 are currently underway.
(13) Cheshev, P.; Marra, A.; Dondoni, A. Carbohydr. Res. 2006, 341,
2714.
J. Org. Chem. Vol. 75, No. 12, 2010 4285

Di Bussolo et al.
JOCNote
SCHEME 6. Proposed Mechanism for the Formation of
Formate 15
ion-dipole pair 25.21 Subsequent nucleophilic attack on C(1)
of 25 would preferentially occur by the internal nucleophile,
from the same side as the coordination, with complete
retention of the configuration, to afford the syn adduct, the
R-anomer 9 (route a, Scheme 7), as experimentally found. In
this framework the attack of the nucleophile internal to the
ion-dipole pair25appears tobe so entropicallyfavored thata
corresponding attack by an external nucleophile, which would
lead to the correspondinganti adduct, the β-anomer 7 (route b,
Scheme 7), can reasonably be excluded.22
SCHEME 7. Rationalization of r- and β-Selenoglycosylation of
Epoxide 8
At this point an attractive challenge was to find an explana-
tion for the different diastereoselective results observed in the
glycosylation of PhSeH by means of two apparently very
similar protocols: the R-selectivity observed in the oxirane
ring-opening of epoxide 8 generated via DMDO oxidation of
the corresponding glucal 6, and the β-selectivity obtained by
applying the direct oxidative glycosylation of PhSeH with
glucal donor 6. The following observations revealed some key
aspects crucial for the formulation of an appropriate rationa-
lization: (i) in both glycosylation procedures (Schemes 3 and
4), the glycosyldonoris an intermediate epoxide such as8, and
the glycosyl acceptor (the nucleophile) is PhSeH; (ii) when
glycosylation is carried out with the epoxide generated by
DMDO oxidation, the reaction mixture is neutral, whereas it
is somewhat alkaline when modified Gin’s direct oxidative
glycosylation is applied, due to the presence of an excess of
Et3N; and (iii) when PhSeH (pKa = 5.9) is mixed with Et3N
following Gin’s protocol, a complete, or almost complete,
proton transfer occurs, with the formation of the triethylam-
monium selenolate salt (eq 1).19
On the other hand, when direct oxidative glycosylation is
employed (Gin’s protocol) (Scheme 7, reaction conditions
B), the nucleophile (PhSeH) is mostly present, in the reaction
mixture, in its corresponding deprotonated form (PhSe-)
due to the presence of an excess (4 equiv) of Et3N. The
phenylselenolate is such a strong nucleophile that it is able to
open directly, in an SN2-like fashion, the oxirane ring of 8,
with a complete inversion of configuration on C(1) affording
the anti adduct, the β anomer 7, as the only reaction product,
through a completely anti stereoselective process.
To check the validity of the proposed rationalization, the
ring-opening reaction of epoxy glucal 8, obtained by oxida-
tion of glucal 6 with in situ generated DMDO,13 was
performed with PhSe-Et3NHþ, independently prepared by
reaction of PhSeH (3 equiv) and Et3N (4 equiv) (Scheme 7,
reaction conditions C). In these conditions, the nucleophile
actually present in the reaction mixture (PhSe-) cannot
obviously “protonate” the oxirane oxygen of 8 and generate
the intermediate species 25 (Scheme 7): it can only attack
directly epoxide 8 in an SN2-like process, affording the
corresponding anti adduct, the β-phenylselenoglycoside 7,
as experimentally found.23
PhSeH þ Et3NuPhSe- Et3NHþ
ð1Þ
On this basis, we think that the above-described opposite
stereoselective results simply depend on the different nature
of the nucleophile present in the reaction mixture and
involved in the ring-opening of the intermediate epoxide 8.
Under Danishefsky’s conditions (Scheme 7, reaction condi-
tions A), the nucleophile PhSeH is present in the undisso-
ciated form, which is acidic enough to protonate the oxirane
oxygen and to determine the ring-opening of epoxide 8 under
acid conditions, following the ion-dipole pair mechanism,
as admitted in the case of 2-aryloxiranes.20 In this way, the
protonated epoxide 23 leads to an intramolecular intimate
ion-dipole pair 24, in which there is an extended oxirane
oxygen-C(1) bond. By an internal rearrangement, 24 can
evolve to the more carbocationic nucleophile-separated
(19) Reich, H. J.; Cohen, M. L. J. Org. Chem. 1979, 44, 3148.
(20) (a) Crotti, P.; Di Bussolo, V.; Macchia, F.; Favero, L.; Pineschi, M.;
Lucarelli, L.; Roselli, G.; Renzi, G. J. Phys. Org. Chem. 2005, 18, 321.
(b) Crotti, P.; Dell’Omodarme, G.; Ferretti, M.; Macchia, F. J. Am. Chem.
Soc. 1987, 109, 1463.
(21) The isomerization from the less carbocationic 24 to the more
carbocationic intermediate 25 is favored by the ability of the endocyclic
oxygen to stabilize, by conjugative electron-donating effect, the developing
of an adjacent carbocationic center.
(22) For examples of cis opening of glycal epoxides metal-catalyzed see:
(a) Rainier, J. D.; Cox, J. M. Org. Lett. 2000, 2, 2707. (b) Xue, S.; Han, K.-Z.;
He, L.; Guo, Q.-X. Synlett 2003, 870. (c) Wipf, P.; Pierce, J. G.; Zhuang, N.
Org. Lett. 2005, 7, 483. (d) Sing, I.; Seitz, O. Org. Lett. 2006, 8, 4319.
ꢁ
(e) Castilla, J.; Marın, I.; Matheu, M. I.; Dıaz, Y.; Castillon, S. J. Org. Chem.
´ ´
2010, 75, 514.
(23) The ring-opening reaþction of epoxy galactal 21 (see ref 18) and epoxy
glucal 2 with PhSe-Et3NH also affords only β-selenoglycoside 13 and
β-selenoglycoside 12, respectively.
4286 J. Org. Chem. Vol. 75, No. 12, 2010

Di Bussolo et al.
JOCNote
As further confirmation of our rationalization, when the
ring-opening of epoxy glucal 2, synthesized by DMDO oxida-
tion of glucal 1,13 was carried out with PhSeH (3 equiv) in the
presence of ZnCl2 (2 equiv), a very significant 60:40 mixture of
corresponding R-3 and β-phenylselenoglycoside 12 was ob-
tained (Scheme 8). Under these conditions, due to the con-
temporary presence of PhSeH and ZnCl2, two different reac-
tion pathways are reasonably possible. The coordination of
PhSeH with the oxirane oxygen of 2 determines the occurrence
of the ion-dipole pair mechanism which, through correspond-
ing species 26, leadsto R-anomer 3 (route c, Scheme 8), whereas
the competitive coordination of ZnCl2 with 2 and subsequent
formation of the corresponding species 27 necessarily leads to
β-anomer 12 (route d, Scheme 8). Actually, in the coordinated
species 27, the C(1)-oxirane oxygen bond is not completely
broken24 and, as a consequence, the nucleophilic attack by
PhSeH can occur only from the β-face, affording the anti
adduct 12. Analogously, when the same reaction was per-
formed on epoxide 8 a corresponding 55:45 R-9/β-phenylsele-
noglycoside 7 mixture was obtained.25
-78 °C. The reaction mixture was stirred at this temperature for
10 min then a solution of 4-O-acetyl-6-O-benzyl-3-O-(tert-
butyldimethylsilyl)-D-glucal (6) (750 mg, 1.92 mmol, 1 equiv)
in anhydrous CH2Cl2 (6 mL) was added and the mixture was
stirred at this temperature for 30 min and then at -40 °C for
1 h. Methyl alcohol (78 μL, 1.92 mmol, 1 equiv) and triethyla-
mine (1.02 mL, 7.68 mmol, 4 equiv) were added sequentially at
-40 °C. The solution was stirred at this temperature for 30 min,
at 0 °C for 2 h, then benzeneselenol (0.61 mL, 5.76 mmol,
3 equiv) was added. The mixture was stirred at 0 °C for 1 h
and at 23 °C for 12 h. The reaction was diluted with CH2Cl2
(80 mL) and washed sequentially with sat aq NaHCO3 (2 ꢀ
40 mL) and sat aq NaCl (40 mL). The organic layer was dried
(Na2SO4) and concentrated, and the residue was purified by
silica gel flash chromatography (10% EtOAc in hexane) to afford
phenyl 4-O-acetyl-6-O-benzyl-3-O-(tert-butyldimethylsilyl)-1-seleno-
β-D-glucopyranoside (7) as light yellow liquid (845 mg, 1.50 mmol,
78% yield): Rf (10% EtOAc in hexane) 0.25; [R]20 -17.1 (c
D
1.00, CHCl3); IR (neat film) νmax 3481, 2928, 1743, 1579, 1473,
1373, 1234, 1128 cm-1 1H NMR (250 MHz, CDCl3) δ
;
7.59-7.68 (m, 2H), 7.18-7.39 (m, 8H), 4.83 (t, 1H, J = 9.3
Hz), 4.74 (d, 1H, J = 10.3 Hz, H-1), 4.54 (d, 1H, J = 12.4 Hz),
4.49 (1H, J = 12.4 Hz), 3.65 (t, 1H, J = 8.7 Hz), 3.49-3.60 (m,
3H), 3.36 (ddd, 1H, J = 9.9, 8.5, and 2.5 Hz), 2.32 (d, 1H, J =
SCHEME 8. Selenoglycosylation of Epoxide 2 whit PhSeH and
ZnCl2
2.3 Hz), 1.96 (s, 3H), 0.84 (s, 9H), 0.10 (s, 3H), 0.05 (s, 3H); 13
C
NMR (250 MHz, CDCl3) δ 170.1, 138.1, 135.1, 133.5, 129.4,
128.7, 128.1, 127.8, 127.1, 85.1, 79.1, 76.3, 73.7, 73.5, 72.3, 70.2,
25.8, 21.5, 18.3, -3.9, -4.8. Anal. Calcd for C27H38O6SeSi: C,
57.33; H, 6.77. Found: C, 57.54; H, 6.49.
Typical Procedure for r-Phenylselenoglycosylation of Glycals
by Danishefsky’s Protocol. Compound 9: To a 0 °C vigorously
stirred, biphasic solution of 4-O-acetyl-6-O-benzyl-3-O-(tert-
butyldimethylsilyl)-D-glucal (6) (120 mg, 0.306 mmol, 1 equiv)
in CH2Cl2 (1.5 mL), acetone (0.15 mL), and satd aq NaHCO3
(2.5 mL) was added a solution of Oxone (377 mg, 0.612 mmol, 2
equiv) in H2O (1.8 mL) dropwise over 10 min. The mixture was
vigorously stirred at 0 °C for 30 min and then at rt for an
additional 15 h. The reaction was diluted with CH2Cl2 and the
organic phase was separated, dried (Na2SO3), and concentrated.
The residue was immediatly dissolved in anhydrous THF (6 mL)
and benzeneselenol (0.162 mL, 1.53 mmol, 5 equiv) was added.
The mixture was stirred at 23 °C for 12 h then concentrated in
vacuo. The residue was purified by silica gel flash chromatog-
raphy (10% EtOAc in hexane) to afford phenyl 4-O-acetyl-6-O-
benzyl-3-O-(tert-butyldimethylsilyl)-1-seleno-R-D-glucopyrano-
side (9) as light yellow liquid (140 mg, 0.25 mmol, 81%): Rf (10%
EtOAc in hexane) 0.16; [R]20D þ117.8 (c 1.31, CHCl3); IR (neat
In conclusion, the use of PhSe- (from PhSeH and Et3N)
allows a new synthetic access to β-phenylselenoglycosides
from glycals. The completely opposite stereoselective results
obtained in the glycosylation of PhSeH with glycals by
Danishefsky’s protocol (R-selenoglycosylation) and Gin’s
modified direct oxidative protocol (β-selenoglycosylation)
are simply due to the nature of the nucleophile (PhSeH or
PhSe-) actually present in the reaction mixture. In our opinion,
the different nucleophile determines a different ring-opening
process (retention with PhSeH and inversion with PhSe-) of the
intermediate R-epoxy glycal and, as a consequence, the obtained
opposite stereoselectivity. In this way, a completely stereodiver-
gent selenoglycosylation process can be nicely obtained.
film) νmax 3475, 2918,1740, 1568, 1465, 1370, 1227, 1120 cm-1
;
1H NMR (250 MHz, CDCl3) δ 7.58-7.68 (m, 2H), 7.14-7.40
(m, 8H), 5.91 (d, 1H, J = 5.1 Hz, H-1), 4.98 (t, 1H, J = 5.1 Hz),
4.52 (d, 1H, J = 11.8 Hz), 4.45 (d, 1H, J = 11.8 Hz), 4.28-4.39
(m, 1H), 3.62-3.84 (m, 2H), 3.50-3.58 (m, 2H), 2.24 (d, 1H, J =
6.3 Hz), 2.00 (s, 3H), 0.88 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H); 13
C
Experimental Section
NMR (250 MHz, CDCl3) δ 169.8, 137.9, 134.5, 129.3, 128.9,
128.5, 128.1, 127.8, 89.6, 75.1, 73.6, 73.2, 72.3, 71.4, 69.3, 25.8,
21.4, 18.2, -4.0, -4.5. Anal. Calcd for C27H38O6SeSi: C, 57.33;
H, 6.77. Found: C, 57.59; H, 6.41.
Typical Procedure for β-Phenylselenoglycosylation of Glycals
by Gin’s Modified Direct Oxidative Protocol. Compound 7:
Trifluoromethanesulfonic anhydride (0.48 mL, 2.88 mmol, 1.5
equiv) was added to a solution of diphenyl sulfoxide (1.165 g,
5.76 mmol, 3.0 equiv) and 2,4,6-tri-tert-butylpyridine (TTBP)
(1.65 g, 6.72 mmol 3.5 equiv) in anhydrous CH2Cl2 (80 mL) at
Acknowledgment. This work was supported by the Uni-
ꢀ
versita di Pisa and MIUR, Roma. P.C. gratefully acknowl-
edges Merck Research Laboratories for the financial support
deriving from the 2005 ADP Chemistry Award.
(24) Anomeric selectivity in the opening of 1,2-anhydropyranosides with
nucleophiles has been demostrated to be dependent on the nature of the
Lewis acid and ZnCl2 was found to be not able to determine the formation of
a fully developed carbocationic species. See refs 9 and 14, as well as the
^ ꢁ
following: Evans, D. A.; Trotter, B. W.; Cote, B. Tetrahedron Lett. 1998, 39,
1709.
(25) Control reactions carried out on phenylselenoglycosides 7 and 9
separately treated in THF solution with ZnCl2 (2 equiv) did not lead to
anomeric epimerization after 24 h at 23 °C.
Supporting Information Available: Experimental proce-
dures, full characterization data for new compounds, and copies
of NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 12, 2010 4287