Sugar-derived nitrones cycloaddition

Fisera L (2007) 1,3-Dipolar Cycloadditions of Sugar-Derived Nitrones and their Utilization in Synthesis. 7 287-323... 

The 1,3-dipolar cycloaddition of nitrone 12 (derived from D-glucose) was also used for the preparation of bicyclic aza sugars of type 14 (route a Fig. 5).12 Another classical approach (route b) allowed to prepare the analogs (e.g. 17).13,14... 

An impressive enantiopure synthesis of Amaryllidaceae alkaloids has been achieved through the formation of sugar-derived homochiral alkenyl nitrone 265 (Fig. 1.7).[280] While this reagent required lengthy preparation, it underwent an intramolecular dipolar cycloaddition to establish the required stereochemistry of the polycyclic pyrrolidine skeleton of (—)-haemanthidine (266), which was converted to (+)-pretazettine and (+)-tazettine by established procedures (281). 

Intramolecular cycloaddition of fV-benzyl-substituted 3-O-allylhexose nitrones furnishes chiral oxepane derivatives. The regioselectivity of the cycloaddition depends on several factors such as (1) the structural nature of the nitrone, (2) substitution and stereochemistry at 3-C of the carbohydrate backbone, and (3) substitution at the terminus of the O-allyl moiety. A mixture of an oxepane and a pyran is formed in the intramolecular oxime olefin cycloaddition of a 3-O-allyl carbohydrate-derived oxime <2003T4623>. The highly stereoselective synthesis of oxepanes proceeds by intramolecular nitrone cycloaddition reactions on sugar-derived methallyl ethers <2003TA3899>. 

Isoxazolidines are often used as synthetic precursors of different classes of compounds. Intramolecular cycloaddition of sugar-derived aUcene-nitrones was applied to the synthesis of some chiral cyclopentenone building blocks and natural compounds as exemplified by the synthesis of (-)-neplanocin A 94 starting from D-ribose <05JOC6884>. 

Dipolar Cycloadditions of Sugar-Derived Nitrones and their Utilization in Synthesis... 

Abstract This review is devoted to the stereoselectivity of intermolecular (intramolecular cycloadditions are not included) 1,3-dipolar cycloadditions of sugar-derived nitrones. Stereoselective cycloaddition (transformation of isoxazolidine followed by reduction of the N O bond to produce both an amino and a hydroxy function) allows the synthesis of tailor-made products of possible biological interest such as pol>4iydroxylated pyrrolidines, pyrrolizidines, indolizidines, fi-aminocarbonyl compounds, and disaccharides. Attention is focused on the preparation of isoxazolidinyl nucleosides and to the catalysis of the cycloaddition by Lewis acids. This review has concentrated on the new developments achieved from 1999 to February 2007. 

It should be mentioned that the stereoselectivity of cycloaddition of chiral sugar-derived nitrone to an alkene is difficult to predict, and would appear to be dependent on minor structural changes in either component. Three structural features can influence the stereochemical outcome of nitrone/alkene cycloadditions /Z nitrone isomerization about the C = Nbond, alkene or/and nitrone facial selectivity, and endolexo preferences [6j. 

Cycloaddition of above-mentioned sugar nitrones 42, 43, and 61 with ni-troalkenes 77, including sugar nitroolefins, led with complete regioselectivity to 4,5-trfl 5-4-nitroisoxazoHdines 78-80 in 51-78% global yields (Fig. 17). The endolexo stereoselectivity depends on the type of sugar derivative... 

Stereoselective cycloaddition between functionalized six-membered cyclic nitrone 166 derived from o-lyxose and sugar alkenes was employed for the synthesis of aza-C-disaccharides [72]. Reaction of nitrone 166 and alkene 167 prepared from methyl a-o-mannopyranoside in toluene at reflux led to the isolation of a crystalline cycloadduct 168 in 84% yield. The isoxazohdine 168 was acetylated and cleaved using Mo(CO)6. This was followed by deoxygenation and routine deprotection to give the aza-C-disaccharide 169, isolated as its hydrochloride (44% overall from 168). 

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