Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules
Stereochemistry is also known as 3D chemistry because the prefix "stereo-" means "three-dimensionality".
The study of stereochemical problems spans the entire range of organic, inorganic, biological, physical and supramolecular chemistries. Stereochemistry includes methods for determining and describing these relationships; the effect on the physical or biological properties these relationships impart upon the molecules in question, and the manner in which these relationships influence the reactivity of the molecules in question (dynamic stereochemistry).

Stereochemistry

• chemistry in three dimensions
• includes both structure and reactivity effects

Enantiomers

• mirror-image stereoisomers
• like left and right hands
  (see page 172 in your text)
• observed when a carbon atom has four different groups attached to it
  CHXYZ or CX1X2X3X4

Enantiomer Examples






Chirality

• property of having "handedness"
  (different from its mirror image)
• a molecule with any element of symmetry (e.g., a mirror plane) must be achiral

Stereogenic Centers

• chiral centers or stereocenters
• a molecule with a stereogenic center (e.g., CX1X2X3X4) will be chiral
• a stereogenic center cannot be:
  sp- or sp2-hybridized (must be sp3)
  an atom with 2 identical substituents (e.g., any -CH2- group)

Identifying Chiral Molecules

• achiral
  
  
  
• chiral
  

Properties of Enantiomers

• enantiomers have identical physical and chemical properties,
  EXCEPT they
• interact with another chiral molecule differently
  (like trying on left- or right-handed gloves - left and right hands react differently)
• rotate the plane of plane-polarized light by equal amounts but in opposite directions

Optical Activity

• chiral compounds rotate the plane of plane-polarized light
• rotation measured in degrees
  clockwise (dextrorotatory or +) or
  counterclockwise (levorotatory or -)
• polarimeter - instrument for measuring optical activity

Specific Rotation

• standard amount of optical rotation by 1 g/mL of compound
  in a standard 1 decimeter (10 cm) cell
• [a] = a / l C
• where [a] is specific rotation
  a = observed rotation in degrees
  l = path length in dm
  C = concentration in g/mL

Absolute Configuration

• nomenclature method for designating the specific arrangement of groups about a stereogenic center
• differentiates between enantiomers
• uses the same sequence rules for establishing priority of groups as was used for E and Z

R and S Designations

• assign priorities 1-4 (or a-d) to the four different groups on the stereogenic center
• align the lowest priority group (4 or d) behind the stereogenic carbon
• if the direction of a-b-c is clockwise, it is R
• if a-b-c is counterclockwise, it is S

Right- and Left-Hand Views

• textbook analogy - steering wheel
• alternative analogy - your hands
  assign priorities to your fingers in order of height
  a = middle finger, b = pointer finger, c = thumb, d = wrist
  R - this works for your right hand
  S - this works for your left hand
  

Drawing 3-D Structures

• practice with models
• dotted-line & wedge
• Fischer projections
  

Fischer Projections

• a method for depicting stereochemistry at a series of chiral centers
• arrange the chiral center so that:
  • horizontal groups are forward
  • vertical groups are oriented backward

• Note that there are numerous ways to show a given chiral center
  • 12 different Fischer projections represent (R)
  • 12 different Fischer projections represent (S)

Multiple Stereogenic Centers

• compounds with more than 2 stereocenters have more than 2 stereoisomers
  e.g., 2-bromo-3-chlorobutane
  (2R,3R) and (2S,3S) are enantiomers
  (2R,3S) and (2S,3R) are enantiomers
• in general, n stereocenters give 2^n stereoisomers

Diastereomers

• stereoisomers that are not enantiomers
  e.g., (2R,3R) and (2R,3S)
  (not mirror images, but not the same either)
• diastereomers may have different chemical and physical properties

Meso Compounds

• compounds with stereogenic centers but which are not chiral
  e.g., (2R,3S)-2,3-dibromobutane
  (same as its mirror image)
  

Identifying Meso Compounds

• mirror plane of symmetry
• one stereocenter is the mirror image of the other
• cis-1,2-disubstituted cycloalkanes are meso if the two substituents are identical
  

Cyclohexane Derivatives

• chair interconversions affect conformation, but not configuration
• trans-1,2-dichlorocyclohexane is (R,R) or (S,S)
• cis-1,2-dichlorocyclohexane is (R,S)
  • one chair has the R stereocenter with axial Cl and S with equatorial
  • the other chair has R equatorial and S axial
  • the two chair forms are enantiomers but not isolatable

Configurations and Conformations of Disubstituted Cyclohexanes

substitution	cis	trans
1,2-X2	eq,ax <==> ax,eq (R,S) interconverting enantiomers	eq,eq <==> ax,ax (R,R) & (S,S) isolable enantiomers two conformations each
1,2-XY	eq,ax <==> ax,eq isolable enantiomers two conformations each	eq,eq <==> ax,ax isolable enantiomers two conformations each
1,3-X2	eq,eq <==> ax,ax (R,S) - meso compound two conformations	eq,ax <==> ax,eq isolable enantiomers two conformations each
1,3-XY	eq,eq <==> ax,ax isolable enantiomers two conformations each	eq,ax <==> ax,eq isolable enantiomers two conformations each
1,4-X2 no stereocenters	eq,ax <==> ax,eq equivalent conformations	eq,eq <==> ax,ax two conformations
1,4-XY no stereocenters	eq,ax <==> ax,eq two conformations	eq,eq <==> ax,ax two conformations

Racemic Mixtures

• an equal mix of both enantiomers (also called a racemate)
• a common form in the laboratory (but not in nature)
• optical resolution - separating enantiomers from a mix (typically difficult)

Optical Purity / Enantiomeric Excess

• unequal mixtures of enantiomers may occur
• optical purity - compare actual rotation with what a pure enantiomer would give (in %)
• enantiomeric excess - % excess of one pure enantiomer over the other
• % optical purity = % enantiomeric excess
• example - consider a mix of 75% (R) + 25% (S)
  • optical rotation would be 50% (50% inactive racemic + 50% R)
  • enantiomeric excess is also 50% (75% - 25%)

Optical Resolution

• for acids or bases - formation of diastereomeric salts from a naturally ocurring acid or base
• enzymatic resolution - preferential binding or reaction of just one enantiomer

Isomerism - Summary

• isomers - same molecular formula (same collection of atoms used)
• constitutional isomers -differ in the connections between atoms
  different carbon skeletons
  different functional groups
  different locations of a functional group

Stereoisomers - Summary

• stereoisomers - same connections but in different 3D arrangement
• enantiomers - mirror-image stereoisomers
• diastereomers - non-mirror-image stereoisomers:
  cis-trans diastereomers
  other diastereomers