Addition reactions glycals

Reactions of some furanoid glycals having free 3-hydroxyl (518 and 522) and 3-0-benzyl groups (520 and 524) with AcOF gave different products in the former and the latter groups of compounds, respectively, addition reaction occurred mainly from the same (to give 519 and 523, respectively) and from the opposite sides [to give 521 and 525 (with 526), respectively] of the substituents at C-3 (see Table V). 

This Section deals with the methods of preparation of glycosyl fluorides generally (for the synthesis of glycosyl fluorides by addition reactions to glycals, see Section 11,6), and gives a number of examples from the types of glycosyl fluorides that have been prepared. 

Relevant pyranoid and furanoid compounds (with the exception of the furanoid 3-enes that, as enol ethers, are noted in Section IV. 1) have isolated double bonds in the sense that they are not components of vinyl ethers. In consequence their chemistry is distinct from that of the glycals and their derivatives in particular, their addition reactions are seldom regioselective as are those of the glycals. 

Unlike the carbohydrates with double bonds at positions other than between C-1 and C-2 ( isolated alkenes ), which exhibit normal alkene chemistry, glycals are vinyl ethers and therefore undergo a number of highly selective addition reactions due to the strongly polarized double bonds and the presence of bulky substituents at the C-3 allylic centers. Straightforward addition reaction includes initial electrophilic addition at the double bond, followed by the addition of a nucleophile at C-1 to give the 1,2-trans adduct (O Scheme 19). 

Under the conditions of the addition reaction glycals such as 2-fluoro-glycals can be converted into corresponding 2-deoxy-2-fluoro-2-iodo derivatives [77]. 

As for the introduction of a selenium atom into carbohydrates, addition reactions to glycals are also effective. Thus, the glucal 81 can be treated with phenylselenyl chloride and gives mainly the fraws-diaxial product 153 (O Scheme 69) [112]. Similarly, azidophenylselenylation of perbenzylated glucal 104 proceeds smoothly to give 2-5 e-phenyl-2-selenoglycosylazides 154 and 155 (O Scheme 69) [113]. 

Beginning with a discussion of the utility of tin substituted glycals, Dubois, et al.,12 utilized 2,3,6-tri-O-benzyl-l-tri-n-butylstannyl glucal in coupling reactions with various aromatic substrates. As shown in Scheme 4.2.1, tetrakis triphenylphosphinepalladium catalyzed the reaction with bromobenzene providing an 88% yield of the desired product. Additionally, when p-nitrobenzoyl chloride was used, dichloro dicyanopalladium effected the formation of the illustrated ketone in 71% yield. Unlike the reactions discussed in section 4.1, the products observed were Ci substituted glycals. Further elaborations of this chemistry demonstrated its compatibility with both unprotected hydroxyl groups as well as very bulky aromatic bromides.13 Additional reactions with dibromobenzene are addressed in Chapter 8. 

Under carefully controlled conditions in which the uptake of gas was limited to 2 moles per mole, the products of direct hydroformyla-tion of glycal esters were found to be obtainable. Thus, from di-O-acetyl-D-xylal, 4,5-di-0-acetyl-2,6-anhydro-3-deoxy-D-lyxo- and -xylo-hexose (19 and 20) were isolated in a combined yield of 20% (by way of hydrazone derivatives). Alternatively, these compounds were much more readily prepared by application of the Pfitzner-Moffatt oxidation reaction to the corresponding hydroxymethyl analogs. With tri-O-acetyl-D-glucal, the addition reaction was more suitable for the preparation of the 2,6-anhydroaldose compounds, the yield33 being 70%. 

Addition reactions. CAN serves as a catalyst for the conjugate addition of thiols and selenols to enones under solvent-free conditions. Glycals are transformed into glycosides containing a nitromethyl group at C-2. ... 

Iodo-glycosides can be a valuable alternative to the above-mentioned 2-bromo derivatives. Easily prepared via addition reactions to glycals of NIS or I(coIl)2C104 and alcohols [30,157], these donors were successfully used in the synthesis of aureolic acid oligosaccharides [155,156,158]. 

The addition reaction also worked with other glycals. For example, reaction with tri-O-benzyl-D-galactal 10 and benzamide afforded a 2 1 ratio of diaxiahdiequatorial addition products in 80% yield (Scheme 2). Based on the observed J values for the ring protons, it appeared as if there was no distortion from the normal conformation of the chair in this addition reaction. 

Addition of diphenyldiselenide and sodium azide in the presence of phenyl iodosodiacetate to tri-O-acetyl-D-glucal resulted in 2-azido-2-deoxy-a-phenylselenylglycosides. In the case of tri-O-acetyl-D-galactal the a- and the a-ga/oc/o-analogue was the only product formed (92%). The same addition reaction has been applied to glycals derived from disaccharides. 

Several addition reactions on the exo-glycal trisubstituted double bond have been investigated over the years. These results are arranged below according to the atom introduced in the process, hydrogen, ojygen, nitrogen and carbon. 

The electrophilic fluorination-nucleophiUc addition reaction with Selectfluor-type 1 reagents (13) upon glycals (14) has been studied and optimized (Scheme 3). This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric centre (15). In the fiicose series, Selectfluor adds specifically in a syn manner, yielding a 2-fluoro-saccharide that anomerizes slowly to a more stable intermediate. It turned out that a judicious choice of the protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single-electron transfer occurs in these reactions. The importance of solvent effects and Selectfluor counterion has also been elucidated. ... 

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