Chapter 11: Stereoselectivity

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Chapter 11 is in a portable document file (pdf) and can be viewed by clicking the blue Chapter 11 button. The drawing below the button illustrates the dependence of the stereoselecitivity of iodine-atom replacement on the size of the R group. Beside and below this drawing is a summary of Chapter 11.

This equation provides an example of a stereoselective reaction.
Summary of Chapter 11

Stereoselectivity is the preferential formation or reaction of one stereoisomer rather than another in a chemical reaction. In radical reactions stereoselectivity is controlled by a combination of conformational, steric, stereo-electronic, and torsional effects. The stereo-selectivity caused by these effects is generally increased by conducting reactions at lower temperature. For radicals not centered on C-1, steric effects direct reaction to occur along the least-hindered pathway. A primary factor in determining this pathway is the way in which various groups shield a radical center.

As the steric size of influential groups in a molecule reacting with a carbohydrate radical increases, the extent to which the least-hindered pathway is followed also increases. As this size in reacting molecules becomes smaller, stereoselectivity decreases but does not completely disappear; rather, a low level of selectivity remains due to torsional interactions.

Stereoelectronic effects operate in conjunction with conformational effects to determine stereoselectivity in reactions of pyranos-1-yl radicals. The critical factor in forming a particular stereoisomer in such a reaction is the ability of the pyranos-1-yl radical to maintain in the transition state a stabilizing interaction between orbitals on C-1 and the ring oxygen atom. Maintaining this interaction causes different conformations of a radical to yield stereo-isomerically different products. This stereoelectronic, conformation-dependent, transition-state stabilization gives rise to a phenomenon known as the kinetic anomeric effect. This effect provides a basis for predicting and rationalizing stereoselectivity of pyranos-1-yl radical reactions.

Radical cyclization places additional requirements on reaction stereoselectivity. Prominent among these is that in most situations a reaction proceeds through a chair-like transition state that has substituents located in pseudo­equatorial positions. In some instances a boat-like transition state is lower in energy than a chair-like one. This is often the case when structural features such as allylic strain or pseudo-1,3-diaxial interactions destabilize a chair-like transition state. The stereoselectivity of radical reactions provides the basis for several synthetic processes. These include the synthesis of β-glycosides, the use of carbohydrates as chiral auxiliaries, and the incorporation of carbohydrates into enantioselective syntheses.