Stereochemistry

Stereochemistry involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation.

Quotes

• The synthesis of chiral compounds in enantiomerically pure form is one of the most important and one of the most challenging goals of modern organic synthesis. Any key step of synthetic importance, which leads to the creation of a stereogenic centre, requires to be studied with regard to its stereoselectivity.
  • S. Breitenlechner, P. Selig, T. Bach, "Chiral Organocatalysts for Enantioselective Photochemical Reactions" in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann

• Now it’s time to add a third dimension to our study. Stereochemistry is the branch of chemistry concerned with the three-dimensional aspects of molecules. We’ll see on many occasions in future chapters that the exact three-dimensional structure of a molecule is often crucial to determining its properties and biological behavior.
  • John McMurry, Organic Chemistry 8th ed. (2012), Ch. 3. Organic Compounds: Alkanes and Their Stereochemistry

• Many chiral objects, such as spiral staircases, do not have stereocenters. The same is true for many chiral molecules. Remember that the only criterion for chirality is the nonsuperimposable nature of object and mirror image.
  • K. Peter C. Vollhardt, Neil E. Schore (2011) Organic chemistry : structure and function 6th ed. Chapter 5. Stereoisomers

• How do we use this idea to distinguish a chiral molecule from an achiral one? Chiral molecules cannot have a plane of symmetry.
  • K. Peter C. Vollhardt, Neil E. Schore (2011) Organic chemistry : structure and function 6th ed. Chapter 5. Stereoisomers

• A compound that contains two (or, as we shall see, even more than two) stereocenters but is superimposable with its mirror image is a meso compound (mesos, Greek, middle). A characteristic feature of a meso compound is the presence of an internal mirror plane, which divides the molecule such that one half is the mirror image of the other half. For example, in 2,3-dibromobutane, the 2R center is the reflection of the 3S center.
  • K. Peter C. Vollhardt, Neil E. Schore (2011) Organic chemistry : structure and function 6th ed. Chapter 5. Stereoisomers

• Chemical reactions, as exemplified by radical halogenation, can be stereoselective or not. Starting from achiral materials, such as butane, a racemic (nonstereoselective) product is formed by halogenation at C2. The two hydrogens at the methylene carbons of butane are equally susceptible to substitution, the halogenation step in the mechanism of radical bromination proceeding through an achiral intermediate and two enantiomeric transition states of equal energy. Similarly, starting from chiral and enantiomerically pure 2-bromobutane, chlorination of the stereocenter also gives a racemic product. However, stereoselectivity is possible in the formation of a new stereocenter, because the chiral environment retained by the molecule results in two unequal modes of attack on the intermediate radical. The two transition states have a diastereomeric relation, a condition that leads to the formation of products at unequal rates.
  • K. Peter C. Vollhardt, Neil E. Schore (2011) Organic chemistry : structure and function 6th ed. Chapter 5. Stereoisomers

• One possible approach is to start with the racemate and separate one enantiomer from the other. This process is called the resolution of enantiomers. Some enantiomers, such as those of tartaric acid, crystallize into mirror-image shapes, which can be manually separated … However, this process is time consuming, not economical for anything but minute-scale separations, and applicable only in rare cases.
  • K. Peter C. Vollhardt, Neil E. Schore (2011) Organic chemistry : structure and function 6th ed. Chapter 5. Stereoisomers

• Stereoanalysis of monosubstituted cyclohexanes involves two distinct stages:

  1. Determination of the topology of the molecule
  2. Assessment of the topology and its effects on the course of a reaction

  • George S. Zweifel and Michael H. Nantz Modern Organic Synthesis (2006), Ch. 2. Stereochemical Considerations in Planning Syntheses

• Depending on the substitution pattern, three principal interactions dictate the conformational equilibrium:
  1. The presence of a single axial substituents (butane-type gauche interaction)
  2. The interaction of a pair of 1,2-diequatorial substituents (butane-type gauche interaction)
  3. The interaction of a pair of cis-1,3-diaxial substituents (1,3-diaxial interaction)
  • George S. Zweifel and Michael H. Nantz Modern Organic Synthesis (2006), Ch. 2. Stereochemical Considerations in Planning Syntheses

• The stereochemical course of reactions at three-, four-, and five-member rings can be reliably predicted by assuming the relative congestion of the two faces. As the ring size increases above six so does the conformational mobility and hence the uncertainty of the stereochemical outcome. Even with seven-member rings, predictions are generally difficult.
  • George S. Zweifel and Michael H. Nantz Modern Organic Synthesis (2006), Ch. 2. Stereochemical Considerations in Planning Syntheses