Organic Chemistry: Current Research
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Synthesis and Characterization of Deoxyglycosides from Glycols

Aron Straus^{* *}Correspondence: Aron Straus, Department of Inorganic and Organic Chemistry and Biochemistry, University of Castilla-La Mancha, Albacete, Spain, Email:

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Introduction

Palladium (II) together with a monodentate pesticide matter permits the new direct and α-stereo selective chemical action synthesis of deoxyglycosides from glycols. Initial mechanistic studies counsel that within the presence of N-phenyl-2-(di-tert-butylphosphino) pyrrole because the matter, the reaction return via associate alkoxy metal intermediate that will increase the nucleon acidity and gas nucleophilicity of the alcohol. The strategy is incontestable with a good vary of glycol donors and acceptors, together with substrates bearing olefine functionalities. The ability to perform O-glycosylation reactions during a chemical action and stereo selective manner is one among the most remaining challenges in macromolecule chemistry. Biologically relevant chiral acetyls like deoxyhexoses square measure distinguished elements of natural merchandise, 1 and gift a major artificial challenge owing to the shortage of substituents at C-2 to direct the nucleophile approach. Thus, efforts by our group 2 and others 3 are dedicated to achieving the stereo selective synthesis of those compounds. Recent years have seen a gradual increase within the application of transition-metal chemical action to saccharide synthesis, 4 since the careful alternative of ligand/transition-metal combination offers vital enhancements over ancient strategies in terms of atom economy, high yields, and management of numeric property. The palladium-catalyzed direct activation of one, 2-unsaturated glycols to yield the corresponding a pair of, 3-unsaturated Ferrier merchandise with smart to wonderful property is well established and it's believed to proceed via π-ally intermediates. Herein, we have a tendency to describe the new Pd-catalyzed stereo selective synthesis of deoxy glycosides directly from glycols. merchandise ensuing from addition of the nucleon and alkoxide nucleophile across the carbon–carbon covalent bond square measure fashioned once monodentate N-phenyl-2-(di-tert-butylphosphino)pyrrole is used because the matter. This outcome is probably going derived from a rise in affinity of metal towards the American state nucleophile that permits the reaction to proceed through associate alkoxypalladation-type mechanism to yield the organic compound with high α-stereo control. The matter during a transition-metal-catalyzed reaction plays a key role in stabilizing and activating the central metal atom and fine-tuning the property of the transformation. Initial experiments began with the screening of a series of business mono- and rough pesticide ligands (L1–L8, thirty ten) for his or her ability to push the stereo selective glycosylation of perbenzylated galactal 1 as with glycoside acceptor 2 a6 within the presence of ten mol% of Pd(MeCN)2Cl2 in CH2Cl2 at 50°C. As summarized in Table one, solely monodentate ligands L1, L2, and L3 with PdII were ready to activate the glycal, and 3 a was obtained in low to moderate yield (37%–75%), with L2 giving the most effective α-selectivity (>30:1; Table one, entries 2–4). apparently, no 2,3-unsaturated Ferrier product was discovered in any of the reactions once the pesticide matter was gift, whereas reactions within the absence of matter yielded associate indivisible mixture of Ferrier and organic compound merchandise. Next, we have a tendency to determine to explore solvent effects, reaction temperature, and catalyst loading. The utilization of acetonitrile or methylbenzene was prejudicial to the yield (entries ten and 11), and also the reaction rate considerably diminished at temperature in CH2Cl2 (entry 13). Finally, increasing the PdII loading to twenty five twenty five gave optimum yields and α-stereo control (90% and >30:1 α/β) at intervals seventeen hours (entry fourteen vs. entry three (10 mol%) and entry twelve (20 mol%)). Having established the optimum reaction conditions, our attention then turned to exploring the substrate scope of the coupling reaction between 1 a and a spread of American state nucleophiles.

Description

Altogether cases, the reactions proceeded swimmingly and in smart to wonderful yields and α-selectivity, therefore demonstrating that the chemical action system tolerates the presence of common alcohol and amino alkane protective teams like acetyls, ethers, esters, and carbamates. Glycosylation’s with primary alcohols 2 b–2 d, thioglycoside 2 e, and Boc-protected amino acid amino acid afforded the corresponding organic compound merchandise in 69–96% yield at intervals seventeen h and with α/β ratios starting from quite 30:1 to α solely. Similarly, reactions with secondary alcohols like N-hydroxysuccinimide 2 I additionally afforded the specified merchandise in smart yields (73–85%) and with high α-selectivity (α/β quantitative relation starting from >30:1 to α only; entries five, 6, and 8). the mechanism of our reaction, a 4:1 α/β-anomeric mixture of 3 a was subjected to the reaction conditions within the presence of acceptor 2 a and gave no modification within the anomeric quantitative relation, therefore indicating that the high α-selectivity isn't the results of isomerization. Reaction with deuterated galactal nine yielded oligosaccharide ten (90% yield) with the new fashioned bonds is to every different. Moreover, glycosylation between galactal 1 a and CD3OD yielded α-linked D3-methyl 2-D-glycoside eleven, during which hydrogen atom from the nucleophile is incorporated equatorially at C-2.

Conclusion

These results make sure the American state nucleophile because the H supply which each the C−H/D and also the and also the formation steps square measure preferentially syn-dia stereo selective. The reactions return with wonderful yields and high property for the α-anomer and are tolerant of commonest protective teams. We’ve got incontestable the generality and flexibility of the approach through the stereo selective synthesis of a series of disaccharides, glycol amino acids, and different glycoconjugates. Given the abundance of chiral acetyls in natural merchandise during which olefin functionalities are featured, this technique would possibly realize applications in and on the far side the sphere of carbohydrates.