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
e.g., CHXYZ or CX1X2X3X4
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)
Properties of Enantiomers
enantiomers have identical physical and chemical properties, EXCEPT they
1) interact with another chiral molecule differently (like trying on left- or right-handed gloves - left and right hands react differently)
2) 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
[alpha] = alpha / l C
where [alpha] is specific rotation
alpha= 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 using sequence rules and designations
of priorities
Sequence Rules
assign priority based on the atoms directly attached to the carbons of the double bond
higher priority goes to:
higher atomic number
break ties by considering the next bonded atoms
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
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
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)
(they are not mirror images, but they are 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
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)
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, including cis-trans isomers
Stereochemistry in Reactions
achiral reactants always give optically inactive products
if chiral products are formed, they will be racemic
butane + Br2 --> 2-bromobutane (racemic)
intermediate 2-butyl radical can add Br to either side
but chiral reactants can give chiral products (the usual case in nature)