Branched-chain sugars radical reactions

Chain extension Aldol reactions Branched-chain sugars Radical reactions Abbreviations... 

The synthesis of type II branched-chain sugars should seem a more difficult task because it needs activation of a carbon atom on the sugar template and a control of the stereochemical course of the carbon-carbon bond formation. Probably because of this apparent difficulty several methods have been devised in the last decade, in particular, in the field of organo-metallic and free radical reactions. 

The recognition of the usefulness of radical reactions as a synthetic tool has prompted the exploration of this method for branched-chain sugars synthesis. Radical addition to an olefin is one of the most popular reactions yet investigated [10], Two approaches have been devised an intramolecular version, which is mostly a 5-exo cyclization and an inter-molecular version in which the radical is trapped by an activated olefin. 

Scheme 17. Preparation of branched-chain sugars via serial radical reactions initiated by tethered radical addition to unsaturated sugars...

Radical reactions have been further utilised in the construction of branched-chain sugars. Unsaturated iodide (24) with allyltributyltin or Bu3SnH and methyl acrylate has afforded the doubly-branched derivatives (25) and (26) by way of intra- and then inter-molecular radical processes. Similarly, bromide (27) gave the 3-C-allyl derivative (28) which, after transformation into enal (29), underwent a further radical cyclisation (Scheme... 

The stereoselectivity of intermolecular free radical reactions has been reviewed including the use of carbohydrate-based radicals for forming branched-chain sugars. A number of intramolecular radical cyclisations affording C-branched compounds have been reported. A 2-deojgr-2-iodo-glycoside on treatment with Bu3SnH affords a C-2 radical which may cyclise onto an appropriate functional... 

A general review has been published on silicon-tethered reactions with parts devoted to the preparation of branched-chain sugars (including nucleosides), through the addition of radicals generated from (bromomethyl)silyl ether tethers to double bonds or by the addition of radicals generated from phenyl selenides onto allylsilyl ether tethers. ... 

As with epoxides, carbanions can add in a 1,4 fashion to enones or nitrosugars. Nitromethane anion has been used [64], Dithiane anion has been successfully used in the addition to nitroolefins [65] and to enones [66], Accordingly, C-5 branched-chain glucose derivatives 47 and 48 have been prepared from nitroolefin 46 (Scheme 20) [67,68], Sugar-derived enones have been also used as acceptors in free radical reactions to trap alkyl radicals as well as anomeric radicals (see Schemes 29 and 30). 

The fused oxazole derivative 100 was synthesized from 3-azido-3-deoxy-l,2 5,6-di-O-isopropylidene-a-D-allofuranose, the key final step being the reaction of methyl 3-amino-3-deoxy-5,6-0-isopropylidene-p-D-alloside with DMF dimethyl acetal. The annelated pyranoside 101 was obtained by cyclization of a branched chain hexosulose derivative, and the fused triazole-piperidinoses such as 102 were made by a radical cyclization of a 3-pyrazolo-6-iodo-sugar derivative. The spiro-isoxazohne 103 and related isomers have been synthesized by dipolar cycloadditions of mesitonitrile oxide to 2-deoxy-2-C-methyl-ene-pentonic acids, themselves available in five steps from D-mannitol. Intra-... 

The good yields obtained in the cyclization of appropriate radical precursors show that this is a convenient method for the synthesis of branched-chain cyclitols from carbohydrates. In addition, an interesting stereoelectronic effect in the cyclization of these acychc sugar derivatives is demonstrated the stabilizing effect of electron-attracting groups vicinal to carbon-centered radicals determines the preferred conformation in the transition state and the stereochemical outcome of the reaction. 

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