Chem 334 - Fall 2001
Organic Chemistry I
Dr. Carl C. Wamser

Chapter 7 Notes: Stereochemistry

Stereochemistry

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

Enantiomers

• mirror-image stereoisomers
• like left and right hands
• 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., CWXYZ) 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

• steering wheel analogy
  • right turn = R
  • left turn = S

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

Reactions involving stereoisomers

• must know the mechanism to follow what happens at the stereocenter
• starting with an achiral compound, product will be achiral or racemic
  • butane + Br2 ---> racemic 2-bromobutane (achiral 2-butyl radical)
  • 1-butene + RCO3H ---> racemic 1,2-epoxybutane (equal reaction top and bottom)
  • cyclohexene + Br2 ---> racemic trans-1,2-dibromocyclohexane
  • cis- or trans-2-butene + HBr ---> racemic 2-bromobutane
  • cis-2-butene + Br2 ---> racemic 2,3-dibromobutane
  • trans-2-butene + Br2 ---> meso-2,3-dibromobutane
• starting with a chiral compound, you must follow the mechanism
  • (R)-3-methyloctane + Br2 ---> racemic 3-bromo-3-methyloctane
  • stereochemical changes during substitution reactions are explored in the next chapter