ADDITIONAL STEREOCHEMICAL EFFECTS IN CARBOHYDRATES

Carbohydrates are biologically an important group of compounds. As it turns out, collectively they illustrate a number of different stereoelectronic effects, and hence this makes a convenient place to further study these effects. 

The effects that we are going to discuss here apply in a general way to molecules and are represented by continuous mathematical functions. But here we will limit our discussion to the stable conformations of a relatively limited group of compounds, the hexopyranoses (six-carbon sugars consisting of a ring of five carbons and one oxygen, plus an exocyclic carbon). 

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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. 

The stereochemical outcome for addition of r-l,3-dioxolan-4-yl and oxiranyl radicals to phenyl vinyl sulfone has been probed. The results indicated that the symanti selectivity could be altered by changing the group next to the radical in the diox-olanyl case but not in the oxiranyl case (bulky groups had a large xyn-directing effect) (Scheme 39). Several alkenyl-lactones and -lactams have been subjected to hydrosilylation conditions using carbohydrate-derived thiols as homochiral polarity reversal catalysts (yields 25-96% ee 5-95%) " ... 

The stereochemical outcome of the addition of carbanions to ketones yielding tertiary alcohols (or secondary alcohols in the case of aldehydes) is variable and depends on the substrate, the counterion and the solvent. Numerous applications of this strategy to natural product synthesis from carbohydrates can be found in the literature and this approach was fruitful in pioneering syntheses of polyketide-type products. Here again, the template effect of the sugar plays a tremendous role in the stereochemical outcome of the reaction. Chelation controlled nucleophilic addition can also be used to form chiral centers in a highly predictable way. 

Similarly, highly complex structures like anulated (109) and spirocyclic (110) carbohydrate mimics can be obtained from appropriately customized precursors (Figure 5.48). In suitable circumstances use of two aldolases that afford distinct selectivity can effect kinetic regioselective discrimination of the independent addition steps, and thus even enable a stereochemical terminus differentiation [204]. 

Carbohydrate derivatives possess a copious number of functionalized stereogenic centers [1]. Because of its rich and varied functionality as well as its stereochemical signature, they are suitable chiral starting materials for enantiomerically pure compound synthesis [2] as demonstrated in many literature examples [3-7], In addition, when the carbohydrate is in a cyclic structure, especially in the pyranose ring (A Figure 14.1), it has a conformational bias, due to combined steric and stereoelectronic effects [8], that allows to predict and control the stereochemical outcome of many reactions on the carbohydrate template (Figure 14.1). 

A major strategy for the preparation of branched-chain sugars is the intermolecular addition of nonanomeric carbohydrate-based radicals to a 7t-system. Since no special electronic factors, such as radical anomeric effects, are present, the stereoselectivity is controlled sterically, and the stereochemistry of the substituents adjacent to the radical center mainly governs the stereochemical control. Representative results are summarized in Scheme 23. 

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