Chemistry 331 - Fall 1996
Elements of Organic Chemistry I

Professor Carl C. Wamser

Chapter 6 - Stereochemistry

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

• 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

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

• 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)

• achiral
  
  
  
• chiral
  

• 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

• 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

• 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

• 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

• 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

• 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
  

• practice with models
• dotted-line & wedge
  

• 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

• 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

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

• 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
  

• 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)

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

• achiral reactants always give optically inactive products
• if chiral products are formed, they will be racemic
  e.g., 1-butene + HBr --> 2-bromobutane (racemic)
  intermediate 2-butyl cation can add Br- to either side equally likely
• but chiral reactants can give chiral products (the usual case in nature)

• anti addition (Br2)
  cyclic compounds --> trans-1,2-dibromo product (racemic)
• syn addition (KMnO4)
  cyclic compounds --> cis-1,2-diol product (meso)

• products from acyclic alkenes are more difficult to trace:
  cis-2-butene + KMnO4 (syn) --> 2,3-butanediol (meso - R,S)
  trans-2-butene + KMnO4 (syn) --> 2,3-butanediol (racemic - R,R & S,S)
  
  trans-2-butene + Br2 (anti) --> 2,3-dibromobutane (meso - R,S)
  cis-2-butene + Br2 (anti) --> 2,3-dibromobutane (racemic - R,R & S,S)