Page 190 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

170 We discuss several examples to illustrate how reactant structure and mechanism can
lead to stereoselectivity, including stereospecificity. We also consider enantioselective
CHAPTER 2 and enantiospecific reactions, which are reactions that favor one enantiomer of a
Stereochemistry, reaction product.
Conformation,
and Stereoselectivity
2.4.1. Examples of Stereoselective Reactions

Scheme 2.6 gives some examples of the types of stereoselective reactions that are
discussed. The first three examples in the scheme are catalytic hydrogenations. Usually
such reactions favor syn addition of hydrogen from the less hindered face of the double
bond; that is, both hydrogens are added to the same face of the bond. The second
entry illustrates another aspect of catalytic hydrogenation: the tendency of hydroxy
groups to be syn-directive, that is, to favor addition from the same side that is occupied
by the hydroxy group. These features are believed to be related to the interaction of
the alkene with the catalytic surface during hydrogenation and are discussed further in
Section 2.4.2.1. As can be seen from the variable degree of stereoselectivity in Entries
1 and 2, as well as the exception in Entry 3, catalytic hydrogenation is not always
highly stereoselective.
Entries 4 through 6 are examples of stereoselective reduction of cyclic ketones.
Comparing entries 4 and 5 shows that stereoselectivity can be controlled by the choice
of reagents. As we discuss further in Section 2.4.1.2, some hydride donors, e.g., NaBH ,
4
approach from the axial direction to give equatorial alcohol. More bulky reducing
agents favor the equatorial approach and give axial alcohol. Entry 6 illustrates the
tendency of reagents to attack the norbornane ring from the exo direction. Entry 7 is
an example of diastereoselective addition of a Grignard reagent adjacent to a stereo-
center. This is an example of 1,2-asymmetric induction, in which the configuration at
the adjacent stereocenter establishes a preference for the direction of addition to the
carbonyl group. This kind of reaction has been studied extensively and is discussed
in Section 2.4.1.3. One of the issues that must be considered in this case is the
conformation of the reactant. Although the preferred conformation of ring compounds
is often evident, the flexibility of acyclic compounds introduces additional variables.
Entry 8 is another example in which the configuration of the -oxy substituent controls
the direction of addition of hydride to the carbonyl group.

2.4.1.1. Substituent Directing Effects in Heterogeneous and Homogeneous
Hydrogenation The hydrogenation of carbon-carbon double bonds is a very general
reaction. Except for very sterically hindered cases, the reaction usually proceeds
rapidly and cleanly. Hydrogenation can be carried out using either finely dispersed
metal (heterogeneous) or soluble (homogeneous) metal complexes. The hetereogeneous
catalysts are transition metals, particularly platinum, palladium, rhodium, ruthenium,
and nickel. The metals are used as finely dispersed solids or adsorbed on inert supports
such as charcoal or alumina. Homogeneous catalysts are usually complexes of rhodium,
ruthenium, or iridium. Phosphine ligands are common in these catalytic complexes.
Depending upon the conditions and the catalyst, other functional groups may also be
subject to catalytic hydrogenation, but for now we focus on double bonds.

catalyst
RCH CHR + H 2 RCH CH R
2
2