Ulose formation by selenoxide elimination

Article abstract of DOI:10.1016/S0008-6215(98)00044-5

Ring opening of methyl 2,3-anhydro-(R)-4,6-O-benzylidene-α-D- mannopyranoside with phenyl selenide gives (R)-4,6-O-benzylidene-3-Se- phenyl-3-seleno-α-D-altropyranoside (2). Oxidation of (2) with H₂O₂ followed by thermolysis gives methyl (R)-4,6-O-benzylidene-3-deoxy-α-D- erythrohexopyranosid-2-ulose via syn-elimination and ketoenol tautomerization.

Full text of DOI:10.1016/S0008-6215(98)00044-5

Carbohydrate Research 307 (1998) 371±373
Note
Ulose formation by selenoxide elimination
Christine E. Heath, Maria C. Gillam, Carrie S. Callis, Robert R. Patto,
Christopher J. Abelt *
Department of Chemistry, College of William and Mary, Williamsburg, VA 23187-8795, USA
Received 24 October 1997; accepted 26 January 1998
Abstract
Ring opening of methyl 2,3-anhydro-(R)-4,6-O-benzylidene-ꢀ-d-mannopyranoside with phenyl
selenide gives (R)-4,6-O-benzylidene-3-Se-phenyl-3-seleno-ꢀ-d-altropyranoside (2). Oxidation of
(2) with H2O2 followed by thermolysis gives methyl (R)-4,6-O-benzylidene-3-deoxy-ꢀ-d-erythro-
hexopyranosid-2-ulose via syn-elimination and ketoenol tautomerization. # 1998 Elsevier Science
Ltd. All rights reserved
Keywords: Selenoxide elimination; Enol formation; Epoxide ring opening; phenyl selenide; Methyl 2,3-anhy-
dro-(R)-4,6-O-benzylidene-ꢀ-d-mannopyranoside
In connection with our interest in cyclomalto-
heptaose, we sought an ecient method for con-
verting a trans-vicinal diol to a methylene ketone
without the necessity of protecting groups. Scheme
1 illustrates a possible sequence of reactions for
this transformation. The related epoxide is a
potentially useful intermediate because its forma-
tion and subsequent ring opening can be per-
formed with selectivity and in the presence of
hydroxyl groups. Nucleophilic ring opening of the
epoxide creates a hydroxyl group that is anti-
periplanar to the nucleophile. Syn-elimination of
the nucleophile or derivative and an adjacent
hydrogen atom gives an enol that tautomerizes to a
ketone. Of the numerous potential nucleophiles,
phenyl selenide seemed an ideal choice for this
transformation.
when complexed with borohydride [1]. With
fused, six-membered rings a trans-diaxial ꢁ-
hydroxyselenide is formed initially. The selenide
can be converted to the corresponding selenoxide
with a variety of oxidizing agents, most commonly
H2O2. The thermal syn-elimination of phenyl sele-
nenic acid to form an alkene is a useful synthetic
method because elimination is so facile, often
occurring at or below room temperature [2].
Sharpless and Lauer studied epoxide ring open-
ing with phenyl selenide and found that the selen-
oxides generated from subsequent oxidation
undergo regioselective elimination to form allylic
alcohols and not enols [3]. Many other examples of
the formation of allylic alcohols from ꢁ-hydro-
xyselenoxides have been reported [4]. The pre-
ference for allylic alcohol formation is supported
by a theoretical study, but the magnitude of the
observed speci®city was not reproduced by the
calculations [5].
Phenyl selenide anion is an extremely potent
nucleophile. It reacts smoothly with epoxides even
In spite of overwhelming literature precedent, we
felt that ꢁ-hydroxyselenoxides should react to form
* Corresponding author. Fax: 001 757 221 2715.
0008-6215/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00044-5

372
C.E. Heath et al./Carbohydrate Research 307 (1998) 371±373
acetal. Ultimately, this procedure gave a 50% yield
of the 2-ulose 3 after puri®cation by silica gel
chromatography (to remove remaining diphenyl
diselenide) and sublimation. The identity of 3 was
con®rmed by independent synthesis from the reac-
tion of 1 with LiAlH4 followed by Cr(VI) oxida-
tion [8]. We suggest that several factors may lead to
the unusual reactivity of the selenoxide: the axial
orientation of the selenoxide group (and the
resulting strain), the conformational rigidity of the
ring, and the fact that only H-2 is accessible to the
selenoxide.
Since Martin et al. have shown that epoxide ring
opening with phenyl selenide can be accomplished
with unprotected carbohydrates, this synthetic
sequence could have wider application [4]. Further
study will de®ne the limits of this unusual mode of
selenoxide reactivity. We are hoping to apply this
method to cyclomaltoheptaose chemistry.
Scheme 1. Conversion of a vicinal trans-diol to a methylene
ketone.
enols under appropriate conditions, such as when
enol formation is the only option. We report here
the use of a phenyl selenide ring opening of the
manno epoxide of a protected glucopyranose and
subsequent oxidation±elimination as a route into
the 2-ulose derivative.
The manno epoxide 1 is available from the reac-
tion of the benzylidene acetal of methyl± ꢀ-d-glu-
coside with tosylimidazole [6]. The epoxide reacts
smoothly with phenyl selenide generated from
diphenyl diselenide and NaBH4. Addition is com-
plete within several hours, and TLC conveniently
monitors the progress of the reaction. The resulting
ꢁ-hydroxy selenide 2 is assigned as the 3-seleno
altro isomer shown in Scheme 2. The nucleophilic
attack of the manno epoxide occurs at the C-3
position, and it results in trans diaxial ring opening
according to the Furst±Plattner rule [7]. The small
1. Experimental
General methods.ÐThin-layer chromatography
was performed on Analtech silica gel HLF plates
(250 ꢂm, UV 254) using 1:3 v/v EtOAc±hexanes.
NMR spectra were obtained using a GE QE-300
spectrometer. Combustion analysis was performed
by Desert Analytics. Methyl 2,3-anhydro-(R)-4,6-
O-benzylidene-ꢀ-d-mannopyranoside was pre-
pared according to a literature method [6] and was
puri®ed by recrystallization, followed by sublima-
tion (Rf 0.57).
Methyl (R)-4,6-O-benzylidene-3-Se-phenyl-3-
seleno-a-d-altropyranoside (2).ÐDiphenyl diselenide
(4.73 g, 15.1 mmol) was dissolved in absolute etha-
nol (100 mL), and NaBH4 (1.64 g, 43.3 mmol) was
added in several portions. After the solution
became colorless, methyl 2,3-anhydro-(R)-4,6-O-
1
coupling constants observed in the H NMR spec-
trum indicate the equatorial orientations of H-1-
H-3. The oxidation of 2 to the selenoxide with 30%
aq H2O2 was allowed to run overnight to ensure
complete reaction. Two equivalents of H2O2 were
employed. The excess (second) equivalent helps
minimize the production of diphenyl diselenide
from the disproportionation of phenyl selenenic
acid formed during thermolysis. The selenoxide is
relatively stable in contrast to many other selen-
oxides that su€er elimination even at room tem-
perature. Heating the reaction at re¯ux for several
hours induces elimination. The addition of pyr-
idine prevents decomposition of the benzylidene
benzylidene-ꢀ-d-mannopyranoside
(1,
2.00 g,
7.57 mmol) was added, and the mixture was
heated at re¯ux for 2.5 h. The reaction was
poured into cold aq NaCl. The resulting solid
Scheme 2. Formation of a 2-ulose by selenoxide elimination.

C.E. Heath et al./Carbohydrate Research 307 (1998) 371±373
373
was collected with vacuum ®ltration and dried in
vacuo. It was recrystallized from benzene (35 mL)
and hexanes (350 mL) giving the selenide adduct
4.37 (dd, 1 H, J6e,6a 10.3 Hz, H-6e), 4.07 (ddd, 1
H, J5,6e 4.9 Hz, J5,6a 10.3 Hz, H-5), 3.96 (ddd, 1 H,
J3e,4 5.1 Hz, J3a,4 12.1 Hz, H-4), 3.84 (dd, 1 H, H-
6a), 3.50 (s, 3 H, OMe), 2.86 (dd, 1 H, J3e,3a
13.9 Hz, H-3a), 2.79 (dd, 1 H, H-3e); 13C NMR
(CDCl3): ꢃ 217.2 (CO), 137.1, 129.5, 128.6, 126.3,
101.7 (C-1), 100.7 (PhCH), 77.4 (C-4), 69.3 (C-6),
64.3 (C-5), 55.9 (OMe), 42.9 (C-3).
ꢀ
25
(2.32 g. 5.50 mmol, 73%): mp 151±152 C; [ꢀ]d
49.7ꢀ (c 0.15, CHCl3); Rf 0.20; 1H NMR
[(CD3)2CO±D2O]: ꢃ 7.65 (m, 2 H, PhSe), 7.34
(m, 5 H, PhSe, PhCH), 7.22 (m, 3H, PhCH),
5.76 (s, 1 H, PhCH), 4.66 (br d, 1 H, J1,2 1.3 Hz,
H-1), 4.39 (dd, 1 H, J4,5 9.5 Hz, H-4), 4.37 (br
dd, 1 H, J2,3 2.6 Hz, H-2), 4.27 (dd, 1 H, J6e,6a
10.3 Hz, H-6e), 4.18 (ddd, 1 H, J5,6e 5.2 Hz,
J5,6a 10.3 Hz, H-5), 3.89 (dd, 1 H, H-6a), 3.84
(dd, 1 H, J3,4 4.2 Hz, H-3), 3.42 (s, 3 H, OMe);
13C NMR (CDCl3): ꢃ 137.5, 134.0, 132.6, 128.8,
128.2, 127.2, 126.4, 126.3, 101.7 (C-1), 100.8
(PhCH), 75.5 (C-4), 72.9 (C-2), 69.1 (C-6), 61.1
(C-5), 55.1 (OMe), 47.3 (C-3); Anal. Calcd for
C20H22O5Se: C, 57.01; H, 5.26; O, 18.99. Found:
C, 56.78; H, 5.22; O, 18.92.
Acknowledgement
This work was supported by the National Sci-
ence Foundation (CHE-9412515).
References
[1] D. Liotta, W. Markiewicz, and H. Santiesteban,
Tetrahedron Lett., (1977) 4365±4368; D. Liotta, U.
Sunay, H. Santiesteban, and W. Markiewicz, J.
Org. Chem., 46 (1981) 2605±2610; D. Liotta, Acc.
Chem. Res., 17 (1984) 28±34.
[2] D.N. Jones, D. Mundv, and R.D. Whitehouse, J.
Chem. Soc., Chem. Commun., (1970) 86±87; H.J.
Reich, S. Wollowitz, J.E. Trend, F. Chow, and D.F.
Wendelborn, J. Org. Chem., 43 (1978) 1697±1705;
H.J. Reich, Acc. Chem. Res., 12 (1979) 22±30.
[3] K.B. Sharpless and R.F. Lauer, J. Am. Chem. Soc.,
95 (1973) 2697±2699.
[4] K.B. Sharpless and R.F. Lauer, J. Org. Chem., 39
(1974) 429±430; H.J. Reich, S.K. Shah, and F.
Chow, J. Am. Chem. Soc., 101 (1979) 6648±6656;
O.R. Martin, R.J. Rafka, and W.A. Szarek, Car-
bohydr. Res., 185 (1989) 77±89.
[5] N. Kondo, H. Fueno, H. Fujimoto, M. Makino,
H. Nakaoka, I. Aoki, and S. Uemura, J. Org.
Chem., 59 (1994) 5254±5263.
Methyl (R)-4,6-O-benzylidene-3-deoxy-a-d-ery-
thro-hexopyranosid-2-ulose (3).ÐMethyl (R)-4,6-
O-benzylidene-3-Se-phenyl-3-seleno-ꢀ-d-altropyr-
anoside (2, 1.00 g, 2.78 mmol) was dissolved in
absolute ethanol (24 mL). The solution was cooled
in an ice bath, and H2O2 was added dropwise
(30%, 0.19 g, 5.56 mmol). The solution was
allowed to warm to room temperature and was
stirred overnight. Pyridine (3.6 mL) was added, and
the solution was heated to re¯ux for 3 h, after
which time TLC indicated that the selenoxide (Rf
0.0) had been consumed. The reaction was cooled
and diluted with H2O (300 mL). The solution was
extracted with CH2Cl2 (3Â50 mL), and the com-
bined organic layers were washed with H2O
(3Â50 mL). The organic layers were dried over
CaCl2, concentrated in vacuo, and dried in vacuo
overnight. The residue was chromatographed on
silica gel eluting with hexanes (500 mL) and
CH2Cl2 (500 mL). The fractions containing the 2-
ulose were combined and concentrated in vacuo.
The crude product was sublimed at 0.1 torr/150 ꢀC
giving 260 mg (1.12 mmol, 47%): Rf 0.32; 1H NMR
[(CD3)2CO/D2O]: ꢃ 7.50 (m, 2 H, PhCH), 7.39 (m,
3 H, PhCH), 5.68 (s, 1 H, PhCH), 4.60 (s, 1 H, H-1),
[6] D. Hicks and B.O. Fraser-Reid, Synthesis, (1974)
203.
[7] R.W. Binkley, Modern Carbohydrate Chemistry,
Marcel Dekker, New York, 1988, pp 184±187; E.L.
Eliel, N.L. Allinger, S.J. Angyal, and G.A. Morri-
son, Conformational Analysis, American Chemical
Society, Washington, DC, 1981 p 358.
[8] D.R. Hicks and B.O. Fraser-Reid, J. Chem. Soc.,
Chem. Commun., (1976) 869±870.