Chapter 2.
Stereochemistry
Conformation & configuration
whether
or not interconvertible between two different 3D
arrangements of atoms by single-bond rotation
Configuration
double bonds: Z & E; 120
nonbonding electron pair: the lowest priority; 121 top
cycles: cis & trans; 121 bottom
Carey-Chap2-5ed 1
Configuration (I)
Configuration
tetrahedral atoms: R & S (CIP rules); 122-123
stereogenic centers (stereocenters): chirality
enantiomers: optical activity; [α]D20 = 100α / (c(g/100mL) x l(cm))
– different activity with another chiral compounds
racemate (racemic mixture): different properties; 124 Fig. 2.1
ee (enantiomeric excess; e.e.) = optical purity
ORD (optical rotatory dispersion): 125 Fig. 2.2
– α vs λ; determination of absolute configuration
CD (circular dichroism): circularly polarized light; 126 Fig. 2.3
Carey-Chap2-5ed 2
Configuration (II)
Multiple stereogenic centers: 126-129
diastereomers: 2n; different physical properties
epimers: different at only one stereocenter
Fisher, extended & Newman projections: 128 Fig. 2.5
– erythro/threo & syn/anti: relative configuration
Other stereogenic elements
centers: sulfur, nitrogent, phosphorus; 129 top & middle
axis: allenes, spiro cyles, atropisomers; 129-30
planes & helices: E-cyclooctene & helicenes; 130-31
t1/2 = 1 h at 183.9 oC vs 4 min 0 oC (E-cyclononene)
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Configuration (III)
Chirality & symmetry: 132
achiral
compounds with either a center of symmetry or a
plane of symmetry: meso
Prochiral centers: sp3 atoms with the same two groups
enantiotopic (homotopic): pro-R & pro-S; 133 bottom
diastereotopic (heterotopic): nonequivalent; 135 Fig. 2.6
Prochiral faces: cabonyls and alkenes
two different groups on the sp2 atoms: re & si face; 134
selectivity with chiral environment: enzymes; 135-136
Carey-Chap2-5ed 4
Resolution
Separation of enantiomers: under chiral environment
types: conglomerate, racemic compound, pseudoracemate
formation of diastereomeric relationship: 137 Scheme 2.2
diastereomeric salts: resolving agent; 138 Scheme 2.3
chiralstationary phase (CSP): differential adsorption; 137 Fig.
2.7 [Home Study] Topic 2.1
kinetic resolution: differential reaction rate; 138 Scheme 2.4
– enzymatic kinetic resolution: 141 bottom
– ee depends on relative rate & conversion: 138 Fig. 2.8
– [Home Study] Topic 2.2
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Preparative Column Separation
C&EN
May 14,
2001
p. 45
Carey-Chap2-5ed 6
Conformational Analysis (I)
Conformation of acyclic compounds
ethane: torsional barrier, 2.88 kcal/mol; 142 Fig. 2.10
butane: van der Waals repulsion; 144 Fig. 2.11
rotational barriers in alkanes: 145 top
heteroatoms: 145 middle & 146 Table 2.1
rotational barriers in alkenes: 146 middle
more stable eclipsed conformation: 2.7 kcal/mol
more substituted alkenes: 1,3-allylic strain (A1,3) vs 1,2-allylic
strain (A1,2): 147
Carey-Chap2-5ed 7
Conformational Analysis (II)
Conformation of acyclic compounds
rotational barriers in carbonyls: aldehydes; 148 middle
ketones: alkyl eclipsed; 148-150
1,3-dienes: coplanar = π-π overlap; 150 middle
s-trans (3.9 kcal/mol) < skew ≤ s-cis
conjugated enones: s-trans & s-cis; 151 top
aldehydes: propenal, only s-trans conformation
ketones: steric repulsion between C1 & C4; 151-152
Carey-Chap2-5ed 8
Conformational Analysis (III)
Conformation of cyclic compounds
cyclohexane: chair << twist < boat; 152 mid -153 top
conformational inversion & energy barrier: 153 Fig. 2.13
monosubstituted cyclohexane: chair; 154
equatorial < axial (1.8 kcal/mol): 1,3-diaxial interactions
conformational free energies: A values; 158 Table 2.2
measurement by 1H NMR: the inversion rate; 155 Fig. 2.14
– iodocyclohexane: 157 Fig. 2.16
equilibration between diastereomers: 157 top
– large A value for tBu: conformationally biased equilibrium
Carey-Chap2-5ed 9
Conformational Analysis (IV)
Conformation of cyclic compounds (continued)
dimethylcyclohexanes: 3 regioisomers; 158 bottom
both Me groups at equatorial: ca. 1.8(1.9) for each axial Me
1,3-diaxial Me-Me repulsion: 1.9(1.8) kcal/mol; 159 top
decalins: configurational isomers: trans < cis; 159 bottom
trans: conformationally locked vs cis: flexible (ΔG* = 12.3-12.4)
cycles with sp2 atoms: smaller barriers; 160
cyclohexene (7.7, half chair), cyclohexanone (4.9)
axial Me at C-2 of alkylidenecyclohexane: A1,3 strain; 161
cyclohexanone: axial Me at C-2 (ca 1.8), axial Me at C-3 (1.3-4)
Carey-Chap2-5ed 10
Conformational Analysis (V)
Conformation of other cyclic compounds
strain energies for cycloalkane: 162 Table 2.3
small rings: 3- & 4-ring; torsional & angle strains
medium rings: 8- to 11-ring; cross-ring repulsions
cyclopropane: planar; bent C-C 1.50 Å, ∠H-C-H 115o
cyclobutane: puckered; 162 bottom
smaller inversion barrier and energy preference for cis
cyclopentane: half-chair vs envelope; 163 top
less angle strain but large torsional strain
cycloheptane: 4 conformations; 163 bottom
Carey-Chap2-5ed 11
Conformational Analysis (VI)
Conformation of other cyclic compounds
cyclooctane: 5 conformations; 165 Fig. 2.18
inversion barriers: 5-8 kcal/mol
cyclodecane: 18 conformers; transannular strain
the lowest energy conformers: boat-chair-boat; 166
larger rings: many conformers; 166 Fig. 2.19
diamond lattice: the most stable; cf: adamantane
anomeric effect: [Home Study] Topic 2.3
molecular mechanics: Estrain = E(r) + E(θ) + E(φ) + E(d)
Carey-Chap2-5ed 12
Dynamic Stereochemistry
Stereospecific reactions: mechanism; 169
stereoisomeric
reactants afford stereoisomerically different
products under the same reaction conditions
Stereoselective reactions: 171 Scheme 2.6
a single reactant could give two or more stereoisomeric
products in principle, one of which is formed preferentially
catalytic hydrogenation: entries 1-3, Scheme 2.6
usually syn addition but some exceptions: mechanism; 172
directed hydrogenation: hydroxy(l) groups; 173
homogeneous catalysts: Ir+ & Rh+
Carey-Chap2-5ed 13
Stereoselective Reactions
Reduction of cyclic ketones: entries 4-6, Scheme 2.6
carbonyl: prochiral face; 176 bottom
axial attack: kinetically favored but sterically congested
relief of torsional strain between carbonyl and C-H(eq): 177
small Nu: axial vs bulky Nu: equatorial: 178 Table 2.4
Addition to acyclic carbonyls: entries 7-8, Sch. 2.6
1,2-asymmetric induction: Cram’s rule; 179 top
Felkin-Ahn model: 179 middle; [Home Study] Topic 2.4
1,3-asymmetric induction: RL/C-O ⊥ C=O; 181 top
chelation control:
Carey-Chap2-5ed 14
