Vasella reaction

Under these conditions, several 5-halofuranosides and 6-halopyranosides ring-opened to the corresponding pent-4-enals and hex-5-enals, respectively [16,17]. Mechanistically, the Bernet-Vasella reaction proceeds via oxidative insertion of zinc into the carbon-bromide bond, followed by reductive elimination with the loss of methoxide to give the aldehyde product (Scheme 3.2) [18]. 

The Bernet-Vasella reductive ring opening has found many applications in carbohydrate chemistry and is a key step in several natural product synthesis [25,26]. However, the instability of the liberated aldehyde can be a problem, leading to side reactions and decomposition [27,28]. To overcome this limitation, the aldehyde has been trapped in situ by nitrogen or carbon nucleophiles. As a result, a series of domino reactions based on the Bernet-Vasella reaction has been described and applied to the total synthesis of chemically and biologically relevant products. 

More recently, primary amines were prepared from methyl glycosides in a single synthetic step by means of a domino Bernet-Vasella reaction/reductive amination using ammonia as the nitrogen source [30]. The protocol involved the overnight... 

On the contrary, treatment of a 1 1 mixture of methyl 5-iodoribofuranoside 3 and nitromethane in THF with 2.6 equivalents of n-BuLi promoted the domino Vasella reaction/Henry addition to give l-nitro-6-hexene 76 in an 85% overall yield as a 1 3 a/p mixture of isomers (Scheme 3.28). The generality of this procedure was demonstrated when the methodology was successfully extended to iodopyranosides with different configurations and protections in the hydroxyl groups. 

One of the most synthetically useful procedures of the preparation of highly advanced synthons is undoubtedly the Vasella reaction [34], It is based on the reductive fragmentation of 6-deoxy-6-halogenopyranosides with zinc in ethanol and provides the open-chain unsaturated sugars in a 60-80% yield (Figure 10.14) n-butyllithium may induce the same process. 

The Vasella reaction is commonly applied to prepare the key intermediates used in the synthesis of biologically important molecules such as (+)-cyclophellitol prepared by Madsen [36] from the Vasella product 44 (Figure 10.15). The same strategy was employed in the preparation of seven-membered azasugars [37],... 

Radical reduction of 1-nitro-C-glycosyl compounds. In 1983, Vasella and co-workers125 reported a stereoselective method for the synthesis of a-C-mannopyranosyl compounds by reduction of 1-nitro-C-mannopyranosyl derivatives with Bu3SnH in the presence of a,a -azoisobutyronitrile (AIBN) radical initiator. These reactions involve the formation of anomeric centered radicals. Thus, in the case of d-manno configuration as in 140, the 1,2-cts-C-pyranosyl compound 145 was obtained in 84% yield. The intermediate pyranosyl radicals 143 prefer a-attack by the tin hydride. Thus for D-glucopyranosyl derivatives, the corresponding l,2-tra x-C-pyranosyl compound 144 is obtained preferentially (Scheme 47). 

Anomeric triphenylphosphonium salts have been used as well as phenylsul-fides,but in the latter case extra stabilization is necessary (see below). Anomeric nitrosugars, which have been extensively studied in C-glycosylation reactions by Vasella, will be covered in Sect. 2.2.1 and ester enolates derived from 3-deoxy-2-ketoulosonic acids (sialic acid and KDO derivatives), which bear a structural similarity to 2-deoxy pyranosides, will be covered in Sect. 4.4. Deprotonation of anomeric phenylsulfones has been discussed in Sect. 2.1.1 and additional transformations on closely related compounds are presented in Scheme 14 [20]. Alkylation of phenylsulfone 54 with epoxide 55 provides adduct 56 which eliminates benzenesulfinic acid at room temperature to give the C(l)-alkylated glycal 57 a similar elimination is also observed with adducts derived from... 

Vasella has applied the concept of anomeric anion stabilization by a nitro group to the /3-D-JV-acetyl-D-glucosamine derivative 177, available in four steps from N-acetyl-n-glucosamine [52] (Scheme 39). Reaction of the tetraethylammonium nitronate derived from 177 with aldehyde 178 provides anti-179 which then undergoes stereoselectively reduction (see Sect. 2.2.1) to provide -C-glycoside 180, intermediate in a synthesis of N-acetyl-neuraminic acid. 

It is interesting to note that the oxa-analogous Michael addition was reported for the first time in 1878 by Loydl et al. [19] in their work on the synthesis of artificial malic acid, which was five years ahead of the discovery of the actual Michael reaction described first by Komnenos [20], Claisen [21], and later Michael in 1887 [22] as one of the most important methods for C—C bond formation. In continuation of the early work on the oxa-Michael addition [23], the inter- and intramolecular additions of alkoxides to enantiopure Michael acceptors has been investigated, leading to the diastereo- and enantioselective synthesis of the corresponding Michael adducts [24]. The intramolecular reaction has often been used as a key step in natural product synthesis, for example as by Nicolaou et al. in the synthesis of Brevetoxin B in 1989 [25]. The addition of oxygen nucleophiles to nitro-alkenes was described by Barrett et al. [26], Kamimura et al. [27], and Brade and Vasella [28]. 

A. Vasella, New reactions and intermediates involving the anomeric center, Pure Appl. Chem. 

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