Annulation Reactions on the Sugar Template

Cycloadditions are widely used methods for carbocycle construction [352], In this context, the Diels-Alder reaction has been studied in carbohydrate chemistry. Using this approach, the sugar can be used as the dienophile or as the diene with a large preference for the former. 

Easily prepared from glycols, enones have been investigated as dienophiles. They react with butadiene under Lewis acid catalysis to form chiral cyclohexenes used in the synthesis of compactin analogs [353]. Levoglucosenone has been used in a Diels-Alder reaction with acetoxy-butadiene to construct a part of the indole alkaloid reserpine [354], and in synthetic studies toward tetrodotoxin [355]. Analogs of the anthracycline rhodomycinone have been similarly prepared [356]. [4 + 2]-Cycloaddition of the same enone with silyloxydiene allowed the creation of the fused ring system present in actinobolin [357]. 

The nitrile oxide-olefin cycloaddition has been used to construct the oxahydrindene part of avermectins. The olefin was introduced at C3 of a glucofuranose unit, whereas the nitrile oxide was created by chain elongation at C5 [361]. 

RCM has also been investigated as a tool to form annulated sugars. Two successive C-branchings at C3 and C4 of aUyl chains are needed. RCM then allows the formation of a cyclohexene ring [362]. This technique has not yet been applied to namral product synthesis. 

Another approach to the tricothecene skeleton proposed by Fraser-Reid takes advantage of carbohydrate enolate chemistry to constmct the A ring [366]. The C ring was formed by intramolecular sulfonate displacement by an appropriate amide enolate. A route to the same skeleton involving [2 + 2] cycloaddition on the double bond of an enone obtained from a glycal has been proposed by Fetizon [367]. Ring expansion of the cyclobutene obtained this way can be effected to constmct the C ring of these compounds. 

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Other methods that rely on the use of the carbohydrate template to construct fused carbocycles have been successfully investigated as strategies for the formation of carbocycles from sugars. Chirality transfer from the sugar to the new carbocycle is observed for these reactions. These annulation reactions are the subject of the second part of this section. 

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