Formyl glycals

N. G. Ramesh and K. K. Balasubramanian, VUsmeier-Haack reaction of glycals. A short route to C-2 formyl glycals, Tetrahedron Lett. 32 3875 (1991). 

The most common method for the preparation of pyrazoles from other heterocycles is from pyranone-type compounds. Condensation of 2,3-dihydro /7-pyran -ones 787 with various aryl hydrazines in the presence of montmorillonite KSF clay under mild conditions proceeded rapidly to afford enantiomerically pure 5-substituted pyrazoles 788 (Equation 172) <2004TL6033>. Comparable results were obtained when arylhydrazines were reacted with 2-formyl glycals under microwave irradiation <2004TL8587>. Phenylhydrazine and hydrazine were reacted with 3-acetyl-4-hydroxy-6-methyl-2/7-pyran-2-one to afford 4-acetoacetyl-3-methylpyrazolin-5-ones, which were employed in the synthesis of bipyrazoles and pyrazoloisoxazoles <1999JHC1291>. Reaction of 3,3-dialkyl-6-(trifluoromethyl)-2,3-dihy-dro -pyrones with hydrazine hydrate afforded 3-(trifluoromethyl)-5-substituted-pyrazoles <1998RCB1365>. 

Silylated glycals react with benzoquinone in the presence of r-butyllithium to produce C-1-benzo-quinol glycals which can be reduced with sodium dithionite to C-l-p-hydroxyaryl glycals. An unexpected preparation of C-3-aryl-3-deoxy-glycals has been discovered during an attempt to add phenols by acid-catalyzed Michael reaction applied to C-2-formyl glycals. ... 

An unusua] reaction appears to take place when the 2-C-formyl glycal 59 reacts in the presence of boron trifluoride withp-cresol to give the C-3-substituted 60 apparently by direct displacement [96]. More probably, however, the reaction proceeds in the normal way to give the 2,3-unsaturated a-O-glycoside which undergoes Claisen rearrangement (cf. Scheme 14). 

Glycosyl cyanides have been thoroughly used as starting materials in the preparation of 1-formyl, and 1-cyano-glycals, mainly through base-induced elimination procedures (Scheme 10). 

Scheme 10 Synthetic routes to 1-formyl and 1-cyano glycals from glycosyl cyanides.

Two new methods of formation of C-C bond at C-2 of glycals, with retention of the glycal double bond, have been published recently. Vilsmeier-Hack reaction is involved in the formylation of glycals [180], A Friedel-Crafts reaction of acyl chlorides with glycals, in the presence of aluminium chloride, is required for the C-2 acylation of glycals (Scheme 49) [181]. 

Another glycal, on treatment with HTI, afforded stereoselectively a 2-formyl tetrahydrofurfural as the major product [20]. 

The 0X0 reaction, which involves heating an olefin with hydrogen and carbon monoxide under pressure in the presence of dicobalt octacarbonyl, with the introduction of a formyl or (hydroxymethyl) group at one carbon atom, is believed to proceed by the addition of the hydride HCo(CO)4 across the double bond, followed by insertion of CO into the newly formed carbon-cobalt bond. It would be anticipated that the cobalt ion would be nucleophilic and would therefore mainly attack glycals at C-1. In accordance with this view, the products of the reaction with the model glycal 2,3-dihydro-4Ff-pyran have been found to contain 78% of 2-(hy-... 

Several acetylated glycals have been subjected to this reaction, and the main products obtained after deacetylation are (despite an initial report to the contrary ) the 2,6-anhydro-3-deoxyalditols. Thus, for example, 1,5-anhydro-4-deoxy-D-lj/xo-hexitol (42) (a 2,6-anhydro-3-deoxyhexitol), and the it-ribo isomer, were isolated in high combined yield, in the ratio 1 0.7, from di-O-acetyl-D-arabinal, after hydroformylation followed by deacetylation and reduction of the formyl compounds (which are produced together with the anhydrodeoxyalditols). Structural analyses of the products were carried out with the aid of periodic acid degradations, nuclear magnetic resonance spectroscopy, and x-ray crystallographic analysis. ... 

Condensation of syn- or anti-27 with hydrazine afforded new pyrazole derivatives 28 with a stereodefined and protected amino diol side chain [64]. The preparation of push-pull substituted unsaturated monosaccharide derivatives and their use in the synthesis of nucleoside analogs have been reviewed [65]. Thus, the 2-formyl pentose glycals were transformed to the corresponding acyclo-C-nucleosides 29 [66]. Similarly, the benzy-lated 2-formylglycals reacted with hydrazine derivatives to afford the substituted l,2,4-tri-0-benzyl-lC-(lH-pyrazol-4-yl)-D-tetritols the deprotection of which was achieved with Pd/H2 to yield the lC-( 1-methyl-lH-pyrazol-4-yl)-D-tetritols [67]. 3-0-Benzyl-6-deoxy-l,2-0-isopropylidene-o -D-xylo-hept-5-ulofuranurono-nitrile was reacted with f, N-dimethylformamide dimethyl-acetal in THF to furnish the (E)-3-0-benzyl-6-deoxy-6-dimethyl-aminometh-ylene-l,2-0-isopropylidene-Q -D-xylo-hept-5-ulofuranurono-nitrile as a major product, and on treatment with carbon disulfide and methyl iodide under basic conditions afforded 3-0-benzyl-6-deoxy-l,2-0-isopropylidene-6-[bis(methylsulfanyl)methylene]-a-D-xylo-hept-5-ulofuranurono-nitrile. Further reaction with hydrazines yielded the reversed pyrazole-C-nucleoside analogs [68]. 

Reactions of 2-formyl-galactal, presented as an unsaturated sugar derivative with push-pull functionalization, with guanidinium and amidinium salts, respectively were carried out imder basic conditions to furnish the substituted 5-( 1,2,4-tri-O-benzyl-D-lyxo- l,2,3,4-tetrahydroxy-butyl)pyrimidines 92 (Fig. 16). Treatment of the 2-formyl pentose glycals with 2-aminobenzimid-azole and 3-amino-1,2,4-triazole, respectively afforded 3-(l,2,4-tri-0-benz-yl-D-lyxo-l,2,3,4-tetrahydroxy-butyl)benzo[4,5]imidazo[l,2-a]pyrimidine 94... 

The cycloaddition of various 13-dipoles to levoglucosenone has been described (Scheme 7) The rhodium catalyzed hydroformylation of glycals in the presence of xn ortho-tert-butylphenyl) phosphite to afford 2-formyl derivatives such as 33 has appeared. ... 

The reaction of l-(tributylstannyl)-3,4,6-tris-0-(triisopropylsilyl)-D-glucal with n-butyllithium then triflate 29 afforded the protected undecose backbone 30 found in the herbicidins. The preparation of a carbon-bridged analogue of N-acetyllactosamine by reaction of a 1-C-lithiated glycal with a 4-C-formyl protected glucosamine derivative is covered in Chapter 3. 

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