Anomeric carbenes

The incorporation of anomeric carbenes in C-glycoside technology has not received much attention. However, as shown in Figure 7.18, anomeric carbenes provide the only known method for the direct cyclopropanation of anomeric centers to date. Advantages to this method include general synthetic accessibility of the carbenes when benzylated sugars are utilized. 

Two examples of the applicability of anomeric carbenes were reported by VaseUa et al. [167,168]. The first demonstrated the utility of olefinic substrates such as Al-phenylmaleimide, acrylonitrile and dimethylmaleate for the formation of glycosidic cyclopropanes. The carbene precursor in this example was the glucose-derived diazirine. As shown in Scheme 7.55, the use of dimethylmaleate produced a mixture of diastereomers with a combined yield of 72%. Although not presented as a schematic, the second and more dramatic example was used to functionalize fullerenes. 

Nucleophilic fluoroalkylation in the anomeric position has been performed with trifluorochloroethylene, or with perfluorovinyl ethers." The compound obtained with trifluorochloroethylene is an irreversible inhibitor of a-glycosidases (Figure 6.44). " Trifluoromethylzinc bromide can be used to perform the difluor-omethylation of hydroxyls in various positions, probably through a carbenic mechanism. 

Fluoroalkyl Glycosides (RFn-(CH2)2-n-0-sugar) and Perfluor-oalkylidene Acetals Derived from Sugars The very low nucleophilicity of fluoroalcohols makes it difficult to substitute of a hydroxyl (anomeric or not). ° This is the reason why this type of ether is not very common. Such ethers have only been isolated in very small quantities in solvolysis reactions, or in carben insertions, performed in fluorous alcohols.Preparation of these ethers has been solved by means of the Mitsunobu reaction. This reaction is known to be dependent on the pA a of the acceptor of the glycosyl the acidity of fluorous alcohols allows a much easier deprotonation than with non fluorinated alcohols." ... 

Dotz and coworkers prepared several interesting and novel glycosylidene carbenes (259-261) by reaction of lithiated glycal 258 with the appropriate metal carbonyl derivative. The synthetic utility of the formed carbenes was demonstrated by reaction with 3-hexyne to give a mixture of complexed and uncomplexed adducts 262 and 263, respectively. The anomeric chromium carhene 264 was converted to 265 hy exposure to ethoxy ethyne (Scheme 48) [70]. The same workers have carried out a similar chromium-mediated henzannulation (266 —> 268), this time with the chromium on the aromatic fragment [71]. Other sugar-hased carhenes have also been prepared [72]. 

When the carbene warhead is connected to the cyclohexane ring via a carbon atom, the tethered carbene precursor occupies the equatorial position, forcing the axial C-H bond to the activated anomeric position (Figure 11.40, left). Of the two axial C-H bonds, the one closest to the pendant carbene is attacked. On the other hand, when the tether starts with an oxygen atom, the anomeric n - interaction comes into play,... 

The intramolecular hydrogen-bond between HOC(3) and the anomeric methoxy group in methyl 4,6-O-benzylidene-a-D-allopyranoside is expected to lead to protonation of the carbene mostly by the kinetic y more highly acidic HOC(2) (Figure 2a) [22]. This is presumably taking place. In contradistinction to the altro-diol, however, the two OH groups are cis-oriented. Stereoelectronic control requires that protonation occurs in the a-plane of the carbene and attack of the nucleophile on the ensuing oxycarbenium cation proceeds in the Jt-plane. HOC(3) is much closer to the 7c-plane than OC(2). 

Free radical chemistry continues to be of importance in the field and a survey has been published on polar and enthalpic effects in free radical reactions. A further short review dealt with free radicals, carbenes and nitrenes at the anomeric centre of carbohydrates. A useful survey has appeared of the application of carbohydrate based chiral auxilliaries in stereoselective syntheses which covers a range of reactions, for example cycloaddition processes, reductions and Strecker reactions. ... 

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