Undergraduate Organic Chemistry
More substituted chains react faster (e.g.
epoxidation)
H: More substituted carbon chains de-
crease the heteroatoms bond angle
which makes it closer to the 102 degree
"banana" angle in an epoxide
H: R/R bond angle increases upon epox-
Thorpe-Ingold effect - 5 points
idation which decreases torsional/steric
strain
S: bulky R groups greatly increased the
population of reactive (antiperiplanar)
conformations
Transition state stabilisation due to in-
ductive electron donating effects
Modes of Cyclisation:
Exo: bond breaking outside the forming
ring
Endo: bond breaking inside the forming
ring
Classification of Attack Site:
TET: sp3
TRIG: sp2
DIG: sp
Baldwin's Rules
Generally: All exo-tet and exo-trig
favoured
Exo generally favoured over endo
5-exo usually fastest and product deter-
mining
Enolates:
Enolendo-exo: enolate forming inside the
ring
, Undergraduate Organic Chemistry
Enolexo-exo: enolate forming outside the
ring
Woodward-Hoffman rules
- Definition
- [4,2] - Diels-alder Cycloaddition
- Electrocyclic ring opening of cy-
clobutene
- Claisen Rearrangement (stereochem)
- Group transfer (S-O ylid with adjascent
A ground state pericyclic reaction is sym-
alkene)
metry allowed when the total number of
- [2,2] Ketene cycloaddition
(4q+2)s and (4r)a components is odd
- oxyallyl cation cycloaddition (cyclo-
propanone)
A pericyclic change in the first electron-
- Allyl cation-diene cycloaddition
ically excited state is symmetry allowed
- Allyl anion-alkene cycloaddition and cy-
when the total number of (4q+2)s and
cloreversion
(4r)a components is even
- 1,3-dipolar cycloaddition (ozonolysis,
azomethine ylid)
s=suprafacial - bond formation on same
- Chelotropic cycloaddition (CCl2 car-
sides
bene, SO2-diene with rev.)
a=antrafacial - bond formation on oppo-
- Electrocyclic reaction of cycloproyl
site sides
halide ionization
- Electrocyclic ring opening of cyclohexa-
diene
- 1,n Hydride Shifts: [1,5], [1,7]
- 1,n Alkyl Shifts: [1,2], [1,3] (stere-
ochem), [1,5] (stereochem)
- [2,3]-Wittig rearrangement
cyclic chair-like t.state
Aldol reaction selectivty (zimmer-man Boron enolate more selective due to
traxler) - using LDA or Bu2OTf + i-Pr2NEt shorter B-O bond vs Li-O => tighter,
more sterically controlled transition state
gauche preference of difluoroethane due
to strong stereoelectronic effect of C-H
Gauche Effect
donation into very low energy C-F anti-
bonding orbital
stabilisation due to high energy lone pair
donation into very low energy C-X anti-
, Undergraduate Organic Chemistry
bonding orbital, therefore partial Pi char-
Anomeric Effect
acter and shorter C-X bond length
1st: D-C has a lower ZPE than H-C
(quantum energy levels) therefore H-C
has a lower activation energy therefore
reacts faster
2nd: isotopically varying atom is not part
Primary and Secondary Kinetic Isotope of a bond being broken, usually observed
Effect when it's on a reaction site that changes
hybridization
sp3 to sp2 is faster for lighter isotopes
changing hybridization affects the nor-
mal modes thereby changing the zero
point energy
draw: cis/trans decalin, anomeric effect
for a spiroketal
Steric Arguement: Felkin-Anh
Largest substituent at 90 degrees to car-
bonyl this leads to 2 conformers
Nucleophile attacks at Burgi-dunitz angle
This leads to 2 possible attacks across
either small or medium subsituent
Favoured attack is across R(s)
EWG:
Anh-Eisenstein: Stereoelectronic
Nucleophilic Addition to Carbonyl Stere-
EWG at 90 degrees to carbonyl due to
ocontrol (steric, EWG, metal ion)
orbital energy stabilisation of the LUMO
T. state stabilisation due to C-Nu bond
donation into C-X sigma*
Conforth Evans: Electrostatic
EWG adopts position to minimise overall
dipole
Largest other substituent adopts 90 de-
gree position
More substituted chains react faster (e.g.
epoxidation)
H: More substituted carbon chains de-
crease the heteroatoms bond angle
which makes it closer to the 102 degree
"banana" angle in an epoxide
H: R/R bond angle increases upon epox-
Thorpe-Ingold effect - 5 points
idation which decreases torsional/steric
strain
S: bulky R groups greatly increased the
population of reactive (antiperiplanar)
conformations
Transition state stabilisation due to in-
ductive electron donating effects
Modes of Cyclisation:
Exo: bond breaking outside the forming
ring
Endo: bond breaking inside the forming
ring
Classification of Attack Site:
TET: sp3
TRIG: sp2
DIG: sp
Baldwin's Rules
Generally: All exo-tet and exo-trig
favoured
Exo generally favoured over endo
5-exo usually fastest and product deter-
mining
Enolates:
Enolendo-exo: enolate forming inside the
ring
, Undergraduate Organic Chemistry
Enolexo-exo: enolate forming outside the
ring
Woodward-Hoffman rules
- Definition
- [4,2] - Diels-alder Cycloaddition
- Electrocyclic ring opening of cy-
clobutene
- Claisen Rearrangement (stereochem)
- Group transfer (S-O ylid with adjascent
A ground state pericyclic reaction is sym-
alkene)
metry allowed when the total number of
- [2,2] Ketene cycloaddition
(4q+2)s and (4r)a components is odd
- oxyallyl cation cycloaddition (cyclo-
propanone)
A pericyclic change in the first electron-
- Allyl cation-diene cycloaddition
ically excited state is symmetry allowed
- Allyl anion-alkene cycloaddition and cy-
when the total number of (4q+2)s and
cloreversion
(4r)a components is even
- 1,3-dipolar cycloaddition (ozonolysis,
azomethine ylid)
s=suprafacial - bond formation on same
- Chelotropic cycloaddition (CCl2 car-
sides
bene, SO2-diene with rev.)
a=antrafacial - bond formation on oppo-
- Electrocyclic reaction of cycloproyl
site sides
halide ionization
- Electrocyclic ring opening of cyclohexa-
diene
- 1,n Hydride Shifts: [1,5], [1,7]
- 1,n Alkyl Shifts: [1,2], [1,3] (stere-
ochem), [1,5] (stereochem)
- [2,3]-Wittig rearrangement
cyclic chair-like t.state
Aldol reaction selectivty (zimmer-man Boron enolate more selective due to
traxler) - using LDA or Bu2OTf + i-Pr2NEt shorter B-O bond vs Li-O => tighter,
more sterically controlled transition state
gauche preference of difluoroethane due
to strong stereoelectronic effect of C-H
Gauche Effect
donation into very low energy C-F anti-
bonding orbital
stabilisation due to high energy lone pair
donation into very low energy C-X anti-
, Undergraduate Organic Chemistry
bonding orbital, therefore partial Pi char-
Anomeric Effect
acter and shorter C-X bond length
1st: D-C has a lower ZPE than H-C
(quantum energy levels) therefore H-C
has a lower activation energy therefore
reacts faster
2nd: isotopically varying atom is not part
Primary and Secondary Kinetic Isotope of a bond being broken, usually observed
Effect when it's on a reaction site that changes
hybridization
sp3 to sp2 is faster for lighter isotopes
changing hybridization affects the nor-
mal modes thereby changing the zero
point energy
draw: cis/trans decalin, anomeric effect
for a spiroketal
Steric Arguement: Felkin-Anh
Largest substituent at 90 degrees to car-
bonyl this leads to 2 conformers
Nucleophile attacks at Burgi-dunitz angle
This leads to 2 possible attacks across
either small or medium subsituent
Favoured attack is across R(s)
EWG:
Anh-Eisenstein: Stereoelectronic
Nucleophilic Addition to Carbonyl Stere-
EWG at 90 degrees to carbonyl due to
ocontrol (steric, EWG, metal ion)
orbital energy stabilisation of the LUMO
T. state stabilisation due to C-Nu bond
donation into C-X sigma*
Conforth Evans: Electrostatic
EWG adopts position to minimise overall
dipole
Largest other substituent adopts 90 de-
gree position
