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DOI:10.15227/orgsyn.069.0066

Organic Syntheses, Coll. Vol. 8, p.583 (1993); Vol. 69, p.66 (1990).

1,3,4,6-TETRA-O-ACETYL-2-DEOXY-α-D-GLUCOPYRANOSE[α-D-arabino-Hexopyranose, 2-deoxy-, tetracetate]

Submitted by Bernd Giese and Kay S. Gröninger1.
Checked by Matthew R. Sivik and Leo A. Paquette.

1. ProcedureA 1-L, round-bottomed flask equipped with a magnetic stirring bar and a reflux condenser with aClaisen head on top fitted with a septum and a dry nitrogen inlet is charged with 20.6 g (50 mmol) of
2,3,4,6,-tetra-O-acetyl-α-D-glucopyranosyl bromide (Note 1) and 400 mL of anhydrous toluene. The
mixture is flushed with nitrogen and brought to reflux with a hot oil bath. A nitrogen atmosphere ismaintained over the well-stirred reaction mixture during this and the ensuing steps. Meanwhile, asolution of 1.64 g (10 mmol) of azobisisobutyronitrile (AIBN) and 16.0 g (55 mmol) of tributylstannane
in 90 mL of anhydrous toluene is prepared and filtered if necessary (Note 2). This solution is added tothe refluxing, well-stirred reaction mixture during 6 hr by a syringe pump through a long needle thatpierces the septum and ends at least 3 cm above the lower end of the cooling zone of the reflux
condenser (Note 3). Ten minutes after all of the solution is added, the reaction mixture is cooled and thesolvent is removed with a rotary evaporator (bath 40°C); 100 mL of hexane and 100 mL of acetonitrile
are added, and the resulting two-phase solution is stirred vigorously for 5 min and then transferred to aseparatory funnel. The lower, acetonitrile layer is separated and the hexane phase washed with 10 mL ofacetonitrile (Note 4). This extraction of the combined acetonitrile solutions is repeated twice using 100mL of hexane each time. The combined acetonitrile phases are then filtered and distilled (rotaryevaporator, bath temp. 40°C). Coevaporation with 40 mL of hexane yields crude solid material that isdissolved in 120 mL of boiling tert-butyl methyl ether. Then 30 mL of hexane is added and the mixture
is left for 4 hr at room temperature. To complete crystallization of the product, another 20 mL of hexane
is added and the mixture is kept for 12 hr at 5°C. The long, colorless needles are filtered and washedonce with 30 mL of hexane/tert-butyl methyl ether (2:1) and two times with 30 mL of pentane to yield
13.2–13.4 g (79–81%) of 1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-glucopyranose, mp 109–110°C; [α]D20 +113°C (C2H5OH, c 1.2).

2. Notes
1. This material was obtained form the Sigma Chemical Company and was recrystallized from diethyl
ether/pentane before use. It can also be prepared by the procedure of Redemann, C. E.; Niemann, C.
Org. Synth., Coll. Vol. III, 1955, 11.
2. Azobisisobutyronitrile (AIBN) and tributylstannane were obtained from the Aldrich Chemical
Company, Inc. The amount of AIBN can be reduced to 0.82 g (5 mmol) without affecting yields. A
small excess (1.1–1.2 equiv) of tributylstannane must be used to ensure total consumption of startingmaterial.
3. This method ensures that AIBN is not thermolyzed in the needle and that tributylstannane is dilutedby the refluxing solvent before reaching the reaction mixture. It is also possible to add thetributylstannane solution by a dropping funnel (l drop every 2 sec) that replaces septum and syringe
pump. This method gives only slightly lower yields (75%) if the stannane solution runs down slowly on
the glass surface of the condenser and does not enter the reaction mixture undiluted.
4. By this procedure most of the tributylbromostannane and other stannyl compounds are removed. It is
important to wait for complete separation of the phases.

5. The product is analytically pure. Anal. calcd. for C14H20O9: C, 50.60; H. 6.07. Found: C, 50.71; H,6.25. 1H NMR (300 MHz, CDCl3) δ: 1.97 (ddd, 1 H, H-2a; J1,2a = 3.7, J2a,2c = 13.6, J2a,3 = 11.6); 2.04,2.05, 2.09, 2.14 (4 s, 12 H, acetyl); 2.28 (ddd, 1 H, H-2e, J1,2e = 1.4, J2e,3 = 5.3); 4.00–4.11 (m, 2 H, H-5,H-6); 4.36 (m, 1 H, H-6''); 5.08 (t, 1 H, H-4, J3,4 = J4,5 = 9.7); 5.32 (ddd, 1 H, H-3); 6.26 (br d, 1 H, H-1).
6. Concentration of the mother liquors gives another 0.4–0.6 g of impure product that can berecrystallized from tert-butyl methyl ether/hexane to give another 0.3–0.5 g (2–3%) of analytically pureproduct.

3. Discussion
The main reaction step of this synthesis of 2-deoxy sugars is a radical rearrangement (23).2Bromine abstraction from the glucosyl bromide 1 by tributyltin radicals yields glucosyl radical 2 that
undergoes acetoxy migration and gives the rearranged radical 3. This rearrangement is a stereoselective
one-step reaction that occurs with rate coefficients of about 103 at 75°C in benzene.3 The driving forceof the rearrangement 2 3 is the formation of the acetal structure at C-1 of 3.4 Hydrogen abstraction
from tributyltin hydride yields 2-deoxy sugar 4 and the tributyltin radical that starts another chain.

This rearrangement offers a general synthesis of α- and β-2-deoxy sugars with pyranoid andfuranoid ring systems (Table I).5TABLE I
SYNTHESIS OF 2-DEOXY SUGARS VIAREDUCTIVE REARRANGEMENT OFGLYCOSYL DERIVATIVES5
Glycosyl Bromide

2-Deoxy Sugar Yield(%)

71

7081

6575

References and Notes
1. Institut für Organische Chemie, TH Darmstadt, Petersenstrasse 22, D-6100 Darmstadt, Germany.
2. Giese, B. in "Stereochemistry of Organic and Bioorganic Transformations," Bartmann, W.;
Sharpless, K. B.; Ed.; VCH; Weinheim and New York: 1987, p. 261; Giese, B.; Gröninger, K. S.
; Witzel, T.; Korth, H.-G.; Sustmann, R. Angew. Chem. 1987, 99, 246; Angew. Chem., Intn. Ed.
Engl. 1987, 26, 233.
3. Korth, H.-G.; Sustmann, R.; Gröninger, K. S.; Leisung, M.; Giese, B. J. Org. Chem. 1988, 53,4364.
4. Schleyer, P. v. R.; Jemmis, E. D.; Spitznagel, G. W. J. Am. Chem. Soc. 1985, 107, 6393.
5. Giese, B.; Gilges, S.; Gröninger, K. S.; Lamberth, C.; Witzel. T. Liebigs Ann. Chem. 1988, 615.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);(Registry Number)
Benzene (71-43-2)
diethyl ether (60-29-7)hydrogen (1333-74-0)
acetonitrile (75-05-8)
bromine (7726-95-6)
nitrogen (7727-37-9)
toluene (108-88-3)
Pentane (109-66-0)
hexane (110-54-3)
tributyltin hydride,
tributylstannane,
tributyltin (688-73-3)

azobisisobutyronitrile (78-67-1)
tributylbromostannane (1461-23-0)
tert-butyl methyl ether (1634-04-4)
2,3,4,6,-tetra-O-acetyl-α-D-glucopyranosyl bromide
1,3,4,6-Tetra-O-acetyl-2-deoxy-α-D-glucopyranose
α-D-arabino-Hexopyranose, 2-deoxy-, tetracetate (16750-06-4)
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