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1,ZAlkylidene and 1,2-ortholaetone derivatives of 3,4,6-tri-0-acetyl-or-D-glucose

R. U. LEMIEUX AND D. H. DETERT Departlnelzt of Chemistry, University of Alberta, Edt?lonton, Alberta

Received February 5, 1968

Reaction of 3,4,6-tri-0-acetyl-1,2-0-(1'-exo-ethoxyethylidene)-a-~-glucopyranose with ketones in the presence of toluenesulfonic acid provides 3,4,6-tri-0-acetyl-1,2-O-alkylidene-a-~-glucoses. With butyrolactone the interchange yielded the 1,2-ortholactone. Canadian Journal of Chemistry, 46, 1039 (1968)

In view of the recent publication by Rees, Tatchell, and Wells (1) on the preparation of 1 ,2-0-all<ylidene-a-D-glucopyranoses from tetra- 0-acetyl-a-D-glucopyranosyl bromide and cad- mium dialkyls, we wish to report the results of our own investigations concerning a general method for the preparation of these 1,2-ketals.

p-Toluenesulfonic acid hydrate was dissolved in N,N-dimethylformamide and an excess of methyl orthoformate was added. The volatile components were then removed by distillation in vactio and the solution was concentrated to an about 2.5 M solution of the acid. In a typical experiment, 0.3 ml of this solution was added to 3.5 ml of a 10 % solution of dimethoxypropane in dry acetone. Tri-0-acetyl- 1,2-0-(1 '-exo- ethoxyethy1idene)-a-D-glucopyranose (1) (2) (750 mg) was added and the solution was left for 20 h at room temperature. The nuclear magnetic resonance (n.m.r.) spectrum of the crude reaction product showed a near quantitative yield of tri-0-acetyl-l,2-0-isopropylidene-a-D- glucopyranose. After two recrystallizations from ethanol the compound melted at 86.5-88", [a], +26" (c, 1 in chloroform). Literature (l), m.p. 87-88", [u], '~ +30.5" (chloroform). Under similar conditions, tri-0-acetyl-1,2-0- cyclopentylidene-a-D-glucopyranose (m.p. 11 3.5 -1 15", [aID2 t34 .5" (c, 1 in chloroform)), tri-0- acetyl-1 ,2-0-cyclohexylidene-a-D-glucopyranose (m.p. 68-69", [a],' +33" (c, 1 in chloroform)), and a mixture of the diastereoisomeric tri-0- acetyl- 1,2-0-benzylidene- a-D-glucopyranoses were prepared. Strictly anhydrous conditions were necessary (3) and were insured by the addition of about 10% trimethyl orthoformate to dried aldehyde or ketone containing the p-toluenesulfonic acid prior to the addition of the 1,2-orthoacetate (1).

The n.m.r. spectra for the 1,2-ketals showed

J,,, = 5, J,,, = 3, J,,, = 3, and J,,, = 9 Hz, values very similar to those reported for acetylated alkyl 1,2-orthoacetate (2) and 1,2-0- alkylidene (1, 4) derivatives of D-glucopyranose. These data indicate a distorted, flattened chair conformation (2) as recently found for com- pounds of this type by X-ray crystallographic analysis (5) rather than the skew-boat suggested by Coxon and Hall (4).

The major isomer formed (about 75%) on reaction of 1 with benzaldehyde had n.m.r. parameters very similar to those presented above. The methine proton of the benzylidene group gave its signal at T 4.13 in close agreement with the chemical shift, T 4.10, for the similar proton of 2-phenyldioxolane. The minor com- ponent, which has this signal at T 3.55, has the n.m.r. parameters for the isomer previously reported (1, 6). This isomer is considered to have the phenyl group in the endo position since J,,, and J,,, = 4.5 Hz and these larger values seem best interpreted as arising from the interaction of the phenyl group with the pyranose ring, as previously discussed by Lemieux and Morgan (2) in connection with the n.m.r. parameters of tri-0-acetyl-a-D-glucopyranose 1,2-(methyl orthopivalate).

When 6butyrolactone was employed as the carbonyl compound, an about equimolar mixture of the exo (2) ([aIDz5 +42" (chloroform)) and erzdo (3) (m.p. 116-117", [aIDz5 +85" (chloroform)) isomers of tri-0-acetyl-1,2-0- (2'-oxacyclopenty1idene)-a-D-glucopyranoe was obtained which could be separated by chromato- graphy (silicic acid; 0.3 % 2,6-lutidine + 3 % methanol in benzene). The n.m.r. parameters of the pyranose-ring protons of the exo-isomer were virtually identical with those of the acety- lated exo-alkyl 1,2-orthoacetates of glucose (2). A significant downfield shift of 0.4 p.p.m. was

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1040 CANADIAN JOURNAL OF CHEMISTRY. VOL. 46, 1968

AcO AcO

1 2 3

observed for H-3 of the en~o-isomer and is 1. R. G. REES, A. R. TATCHELL, and R. D. WELLS. J. Chern. Soc. C, 1768 (1967). believed to arise from its close proximity to the 2. R. U. LEMIEux and A. R. MORGAN. Can. J. Chem.

oxygen atom of the oxacyclopentylidene ring (7). 43, 2199 (1965). ~h~ values of J,,, = 4.7 and J,,, = 7.0 Hz were 3. R. U. LEMIEUX and J. D. T. CIPERA. Can. J. Chem.

34 906 (1956) considerably greater than the 4. B.'COXON and L. D. HALL. Tetrahedron, 20, 1685 values (both 3 Hz) for the exo-isomer. (1964).

Compounds 2 and 3 were also synthesized :bzEzF and FAwcErr. Cryst. 21, from 3,4,6-tri-0-acetyl-a-D-glucopyranosyl chlo- 6. H. B. WOOD, H. W. DIEHL, and H. G. FLETCHER, ride by way of tri-0-acetyl-2-0-(4'-hydroxy- JR. J. Am. Chern. SOC. 79, 1986 (1957).

7. R. U. LEMIEUX and J. D. STEVENS. Can. J. Chem. butyry1)-a-D-glucopyranosyl chloride which was 43, 2059 (1965). converted to the orthoesters by treatment with 8. R. U. LEMIEUX and A. R. MORGAN. IUPAC tetraethylammonium chloride in 2,6-lutidine (2). Symposium, The Chelnistr~ of Natural Products,

Kyoto, Japan, April 12-18, 1964. Abstract of Papers, These compounds are of interest as reagents for ,. 151. the preparation of D-glucopyranosides (8).

A stereoselective synthesis of a-D-glucopyranosides

R. U. LEMIEUX, R. SUEMITSU,' AND S. W. GUNNER^ Departt~lerzt of Chemistry, Utriversity of Alberta, Edmonton, Alberta

Received February 5, 1968

Deoximation of 3,4,6-tri-0-acetyl-2-oxirnino-a-~-arabit~o-l~exopyranosides to the corresponding 2-ulosides followed by borohydride reduction afl'ords the a-D-glucopyranosides in excellent yields. Canadian Journal of Chemistry, 46, 1040 (1968)

A main objective of our research in recent years has been the development of a stereo- selective synthesis of a-D-glucopyranosides which proceeds in good overall yield based either on the glycosylating agent or the alcohol. This has now been accomplished by deoximation of the readily available 3,4,6-tri-0-acetyl-2-oximino-a- D-arabino-hexopyranosides (1) (1) and boro- hydride reduction of the resulting ketoglycoside (2) followed by deacetylation.

The deoximation has been accomplished under a variety of conditions including oxidation with nitrous acid or lead tetraacetate and transoxima- tions with aldehydes and ketones under acid conditions. To date, the latter conditions appear

'University of Alberta Postdoctorate Fellow, 1966-67. ZSee ref. 1.

most reliable and that employing levulinic acid in aqueous hydrochloric acid (2) was used in all the following transformations. Soine deacetyla- tion occurs both during the deoximation and in the borohydride reduction and, consequently, no attempt was made to isolate pure compounds after either of these reactions. Instead, the product was acetylated after removal of the boric acid and isolated as the tetraacetate.

In a typical experiment, isopropyl tri-0-acetyl- 2-oximino-a-D-arabino-hexopyranoside (500 mg) which had been obtained in 89 % yield using di- meric tri-O-acetyl-2-deoxy-2-nitroso-a-~-glu- copyranosyl chloride and 1.2 mole equivalent of isopropyl alcohol (I), was treated with 10 ml of levulinic acid containing 1.5 ml of Nhydrochloric acid at room temperature for 3 h. Extraction with chloroform followed by appropriate washes

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COMMUNICATIONS 1041

CH20.4c

H+

Levulinic AcO AcO

and solvent removal provided a 90 % yield of an oil, [a],' +80° (chloroform), which exhibited a singlet at T 5.06 which was assigned to the anomeric proton of 2. The substance was dis- solved in 10 ml of tetrahydropyran and a solution of 120 mg of sodium borohydride in 2 ml of water was added at 0". The solution was left at room temperature for 1 h and then made acid with excess acetic acid prior to removal of the boric acid with methanol in the usual manner. The residue was acetylated with acetic anhydride at 100". Gas chromatographic examination of the crude product revealed only a trace (< 5 %) of component with the retention time of isopropyl tetra-0-acetyl-a-D-manno- pyranoside. The product crystallized readily and on recrystallization gave an 80% yield of pure isopropyl tetra-0-acetyl-a-D-glucopyranoside. The n.m.r. spectrum of this compound shows a doublet for H1 at T 4.84 (spacing, 4.0 Hz), a quartet for H, at T 5.24 (spacings, 4.0 and 10 Hz), and a triplet for H, at T 4.54 (spacings, 10 Hz). When borodeuteride was used in the reduction, the spectrum of the product showed a singlet instead of the doublet, the quartet was

not present, and the triplet was now a doublet with a spacing of 10 Hz. The signal for H, was now clearly apparent as a rough triplet (virtual long-range coupling of H, with the &'s) centered at T 4.97 with large spacings of about 10 Hz. It was, therefore, clear that indeed the reduction was restricted to the 2-position.

In similar conversions, the phenyl and a- nap h thy1 tetra-0-acetyl-a-D-glucopy ranosides were obtained in 70% and 40% yields, respec- tively. Thus, the procedure shows promise as a general approach for the synthesis of a-D- glucopyranosides and is under further examina- tion.

Acknowledgments

The authors are indebted to the National Research Council of Canada and the Corn Industries Research Foundation for financial assistance.

1. R. U. LEMIEUX, T. L. NAGABHUSHAN, and S. W. GUNNER. Can. J. Cl~em. 46, 405 (1968).

2. C. H. DEPUY and B. W. PONDER. J. Am. Chem. Soc. 81, 4629 (1959).

The photocycloaddition of nitrobenzene to alkenesl

J. L. CHARLTON AND P. DE MAYO Departme~~t of C/~emistry, U~~iuersity of Western Ontario, Lo/zrlo~~, Ontario

Received February 22, 1968

The photochemical cycloaddition of nitrobenzene to cyclohexene at -70 OC gives an unstable crystalline adduct, an analogue of a molozonide, which has been characterized. Similar results have been obtained with norbornene, hex-1-ene, and 1-methylcyclohexene.

Canadian Journal of Chemistry, 46, 1041 (1968)

In 1956 Biichi and Ayer (1) reported that the identified it could be understood that, in part at irradiation of nitrobenzene in 2-methyl-2-butene least, the ethylenic bond had been oxidatively gave a complex mixture of products in poor cleaved. These authors suggested that a deriva- yield. From the structures of those substances tive of the unknown 1,3,2-dioxazolidine' might

'Photochemical Synthesis. 21. Preceding paper: P. de Z1,3,2-Dioxazolidines have been suggested, from time Mayo, J.-P. Pete, and M. Tchir, J. Am. Chem. Soc. 89, to time, as intermediates in various reactions (refs. 4, 5, 5712 (1967). 6; see also refs. 7, 8) with varying degrees of credibility.

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