Table Of ContentD. A. Evans An Introduction to Frontier Molecular Orbital Theory-1 Chem 206
■ Problems of the Day
http://www.courses.fas.harvard.edu/~chem206/
The molecule illustrated below can react through either Path A or Path B to
form salt 1 or salt 2. In both instances the carbonyl oxygen functions as the
http://evans.harvard.edu/problems/ nucleophile in an intramolecular alkylation. What is the preferred reaction path
for the transformation in question?
Chemistry 206 O
Path A Br +
O 1
N O
Advanced Organic Chemistry Br Br H Br –
N O
H O
Path B
2
+ Br
Lecture Number 1 N O
H Br –
This is a "thought" question posed to me by Prof. Duilo Arigoni at the ETH in
Introduction to FMO Theory
Zuerich some years ago
■ General Bonding Considerations
■ The H Molecule Revisited (Again!)
2
■ Donor & Acceptor Properties of Bonding & Antibonding States
■ Hyperconjugation and "Negative" Hyperconjugation (First hr exam, 1999)
The three phosphites illustrated below exhibit a 750–fold span in reactivity with a
■ Anomeric and Related Effects test electrophile (eq 1) (Gorenstein, JACS 1984, 106, 7831).
■ Reading Assignment for week: +
(RO) P + El(+) (RO) P–El (1)
3 3
Kirby, Stereoelectronic Effects
OMe
Carey & Sundberg: Part A; Chapter 1 O
P
Fleming, Chapter 1 & 2 O P P OO OMe
O O O
Fukui,Acc. Chem. Res. 1971, 4, 57. (pdf)
A B C
Curnow, J. Chem. Ed. 1998, 75, 910 (pdf)
Rankthephosphitesfromtheleasttothemostnucleophilicand
Alabugin & Zeidan, JACS 2002, 124, 3175 (pdf) provide a concise explanation for your predicted reactivity order.
Monday,
D. A. Evans
September 15, 2003
1-01-Cover Page 9/15/03 8:56 AM
D. A. Evans An Introduction to Frontier Molecular Orbital Theory-1 Chem 206
Universal Effects Governing Chemical Reactions ■ Stereoelectronic Effects
There are three:
■ Steric Effects Geometrical constraints placed upon ground and transition states
by orbital overlap considerations.
Nonbonding interactions (Van der Waals repulsion) between
substituents within a molecule or between reacting molecules Fukui Postulate for reactions:
Me Me "During the course of chemical reactions, the interaction of
S 2
N –
Nu: C Br Nu C R Br: the highest filled (HOMO) and lowest unfilled (antibonding)
R
R R molecular orbital (LUMO) in reacting species is very important
to the stabilization of the transition structure."
RO RO H
O O major
H H ■ General Reaction Types
Me
Me2CuLi RO Me O Radical Reactions (~10%): A• + B• A B
ppp... minor
H
H Polar Reactions (~90%): A(:) +B(+) A B
■ Electronic Effects (Inductive Effects):
The effect of bond and through-space polarization by
Lewis Acid
heteroatom substituents on reaction rates and selectivities Lewis Base
Inductive Effects: Through-bond polarization
FMO concepts extend the donor-acceptor paradigm to
Field Effects: Through-space polarization
non-obvious families of reactions
■ Examples to consider
Me +
S 1
C Br N R C Me + Br:– H2 + 2 Li(0) 2 LiH
R R
R CH –I+ Mg(0)
3 CH –MgBr
3
rate decreases as R becomes more electronegative
"Organic chemists are generally unaware of the impact of
electronic effects on the stereochemical outcome of reactions."
"The distinction between electronic and stereoelectronic effects is
not clear-cut."
1-02-Introduction-1 9/12/03 4:44 PM
D. A. Evans Steric Versus Electronic Effects; A time to be careful!! Chem 206
■ Steric Versus electronic Effects: Some Case Studies
O OSiR3
When steric and electronic (stereoelectronic) effects R SiO
3 TiCl
lead to differing stereochemical consequences 4 diastereoselection
>94:6
EtO
Woerpel etal. JACS 1999, 121, 12208. Nu
OSiR OSiR
R Si 3 3
3
O OAc SnBr O O
4
O
O
H
Me Me Me AlCl3 diastereoselection
93:7
stereoselection 99:1
SiMe
3
H
OSiR
stereoselection >95:5 OSiR3 3
O O O
OAc
SnBr
4 Danishefsky et al JOC 1991, 56, 387
BnO BnO BnO
ppp...
O
EtO C
2
(R) CuLi diastereoselection O AcO
2 H
O 8:1 AcO
EtO2C Bu Ph N N H
OTBS N N
O
O O N only diastereomer
EtO C
OTBS Bu Al 2 N
3 only diastereomer Ph
O
OAc O
R3 Bu OTBS H OAc
Ph N H OAc
O Al O OAc H
Yakura's
EtO rationalization: O H O 60-94%
N
Ph
R O TBS O
Al
Yakura et al
R R Tetrahedron 2000, 56, 7715
Mehta et al, Acc Chem. Res. 2000, 33, 278-286
1-03-Introduction-1a 9/15/03 8:14 AM
D. A. Evans The H Molecular Orbitals & Antibonds Chem 206
2
The H Molecule (again!!)
2 Linear Combination of Atomic Orbitals (LCAO): Orbital Coefficients
Let's combine two hydrogen atoms to form the hydrogen molecule. ■ Rule Two:
Mathematically, linear combinations of the 2 atomic 1s states create
Each MO is constructed by taking a linear combination of the
two new orbitals, one is bonding, and one antibonding: individual atomic orbitals (AO):
■ Rule one: A linear combination of n atomic states will create n MOs. Bonding MO σ = C1ψ1 + C2ψ2
σ∗ (antibonding) Antibonding MO σ∗ = C*1ψ1– C*2ψ2
The coefficients, C and C , represent the contribution of each AO.
1 2
∆E
y
g
ner H 1s 1s H ■ Rule Three: (C1)2 + (C2)2 = 1
E
ψ1 ψ2 The squares of the C-values are a measure of the electron population
in neighborhood of atoms in question
ppp... ∆E
■ Rule Four: bonding(C )2+ antibonding(C* )2= 1
σ (bonding) 1 1
In LCAO method, both wave functions must each contribute
one net orbital
Let's now add the two electrons to the new MO, one from each H atom:
Consider the pi–bond of a C=O function: In the ground state pi-C–O
is polarized toward Oxygen. Note (Rule 4) that the antibonding MO
σ∗ (antibonding)
is polarized in the opposite direction.
∆E1
y
rg C O π∗ (antibonding)
e
n H 1s 1s H
E
ψ1 ψ2
∆E2 y
g
r
e
σ (bonding) n C
E
O
Note that ∆E is greater than ∆E . Why?
1 2
π (bonding)
C O
1-04-Introduction-2 9/15/03 8:38 AM
D. A. Evans Bonding Generalizations Chem 206
■ Bond strengths (Bond dissociation energies) are composed of a ■ Orbital orientation strongly affects the strength of the resulting bond.
covalent contribution (δ E ) and an ionic contribution (δ E ).
cov ionic
For σ Bonds:
Bond Energy (BDE) = δ Ecovalent + δ Eionic (Fleming, page 27) A B Better A B
than
When one compares bond strengths between C–C and C–X, where X
is some other element such as O, N, F, Si, or S, keep in mind that
covalent and ionic contributions vary independently. Hence, the
mapping of trends is not a trivial exercise. For π Bonds: A B Better A B
than
Useful generalizations on covalent bonding
This is a simple notion with very important consequences. It surfaces in
■ Overlap between orbitals of comparable energy is more effective the delocalized bonding which occurs in the competing anti (favored)
than overlap between orbitals of differing energy. syn (disfavored) E2 elimination reactions. Review this situation.
For example, consider elements in Group IV, Carbon and Silicon. We ■ An anti orientation of filled and unfilled orbitals leads to better overlap.
ppp... know that C-C bonds are considerably stronger by Ca. 20 kcal mol-1 This is a corrollary to the preceding generalization.
than C-Si bonds. There are two common situations.
C C C C better than C Si C Si
Case-1: Anti Nonbonding electron pair & C–X bond
σ∗ C–C
σ∗ C–Si
X X
X
σ* C–X lone pair σ* C–X
Si-SP3 LUMO HOMO LUMO
A C A C Better A C
C-SP3 C-SP3 C-SP3 than
σ C–Si •• lone pair
HOMO
σ C–C
H3C–CH3 BDE = 88 kcal/mol H3C–SiH3 BDE ~ 70 kcal/mol Case-2: Two anti sigma bonds
Bond length = 1.534 Å Bond length = 1.87 Å
This trend is even more dramatic with pi-bonds: X Y X
X σ* C–X Better σ C–Y σ* C–X
π C–C = 65 kcal/mol π C–Si = 36 kcal/mol π Si–Si = 23 kcal/mol LUMO than HOMO LUMO
A C C C C C
■ Weak bonds will have corresponding low-lying antibonds.
σ C–Y
Y HOMO
Formation of a weak bond will lead to a corresponding low-lying antibonding Y
orbital. Such structures are reactive as both nucleophiles & electrophiles
1-05-Introduction-3 9/12/03 4:36 PM
D. A. Evans Donor-Acceptor Properties of Bonding and Antibonding States Chem 206
Donor Acceptor Properties of C-C & C-O Bonds Hierarchy of Donor & Acceptor States
Consider the energy level diagrams for both bonding & antibonding Following trends are made on the basis of comparing the bonding and
orbitals for C–C and C–O bonds. antibonding states for the molecule CH –X where X = C, N, O, F, & H.
3
σ* C-C
σ-bonding States: (C–X)
σ* C-O
CH3–CH3
CH3–H
C-SP3 C-SP3
very close!! CH3–NH2
O-SP3 CH3–OH
decreasing σ-donor capacity CH3–F
σ C-C poorest donor
σ C-O
■ The greater electronegativity of oxygen lowers both the bonding
σ-anti-bonding States: (C–X)
ppp... & antibonding C-O states. Hence:
For the latest views, please read
■ σ C–C is a better donor orbital than σ C–O CH3–H Alabugin & Zeidan, JACS 2002, 124, 3175 (pdf)
■ σ∗C–O is a better acceptor orbital than σ∗C–C CH3–CH3
CH3–NH2
Donor Acceptor Properties of CSP3-CSP3 & CSP3-CSP2 Bonds CH3–OH
σ* C–C CH3–F
σ* C–C better acceptor Increasing σ∗-acceptor capacity best acceptor
The following are trends for the energy levels of nonbonding states
C-SP3 C-SP3 of several common molecules. Trend was established by
photoelectron spectroscopy.
C-SP2
Nonbonding States
σ C–C
better donor H P:
σ C–C 3
H S:
■ The greater electronegativity of CSP2 lowers both the bonding & 2 H3N:
antibonding C–C states. Hence: H O:
2
■ σ C -C is a better donor orbital than σ C -C HCl:
SP3 SP3 SP3 SP2
■ σ∗C -C is a better acceptor orbital than σ∗C -C decreasing donor capacity poorest donor
SP3 SP2 SP3 SP3
1-06-donor/acceptor states 9/12/03 5:16 PM
D. A. Evans Hybridization vs Electronegativity Chem 206
Electrons in 2S states "see" a greater effective nuclear charge
There is a linear relationship between %S character &
than electrons in 2P states.
Pauling electronegativity
This becomes apparent when the radial probability functions for S
5
and P-states are examined: The radial probability functions for the
hydrogen atom S & P states are shown below. N
SP
4.5
100 % 100 %
Radial Probability 1 S Orbit2a lS Orbital Radial Probability 2 S Orbital Pauling Electronegativity3.345 NSP3 NSP2 CSP
C
ppp... 2 P Orbital 2.5 CSP3 SP2
2
Å Å 20 25 30 35 40 45 50 55
% S-Character
3 S Orbital 3 P Orbital There is a direct relationship between %S character &
hydrocarbon acidity
60
CH (56)
55 4
S-states have greater radial penetration due to the nodal properties of the wave
function. Electrons in S-states "see" a higher nuclear charge.
50
d
ci
Above observation correctly implies that the stability of nonbonding electron n A 45
pairs is directly proportional to the % of S-character in the doubly occupied orbital bo CH (44)
ar 6 6
C
of 40
Least stable Most stable a
k
P
C C C 35
SP3 SP2 SP
PhCC-H (29)
30
The above trend indicates that the greater the % of S-character at
a given atom, the greater the electronegativity of that atom.
25
20 25 30 35 40 45 50 55
% S-Character
1-07-electroneg/hybrization 9/12/03 4:49 PM
D. A. Evans Hyperconjugation: Carbocation Stabilization Chem 206
■ The interaction of a vicinal bonding orbital with a p-orbital is referred
Physical Evidence for Hyperconjugation
to as hyperconjugation.
This is a traditional vehicle for using valence bond to denote charge
■ Bonds participating in the hyperconjugative interaction, e.g. C–R,
delocalization.
will be lengthened while the C(+)–C bond will be shortened.
R + R+
H H
H C C H C C First X-ray Structure of an Aliphatic Carbocation
H H
H H
The graphic illustrates the fact that the C-R bonding electrons can
"delocalize" to stabilize the electron deficient carbocationic center.
+
1.431 Å [F5Sb–F–SbF5]–
Note that the general rules of drawing resonance structures still hold:
the positions of all atoms must not be changed. +
C
ppp... Stereoelectronic Requirement for Hyperconjugation: 100.6 ° 1.608 Å Me Me
Syn-planar orientation between interacting orbitals
Me
The Molecular Orbital Description
σ∗ C–R σ∗ C–R T. Laube, Angew. Chem. Int. Ed. 1986, 25, 349
+ +
The Adamantane Reference
C H C H (MM-2) 1.528 Å
H H
H
110 °
σ C–R σ C–R Me 1.530 Å
Me
■ Take a linear combination of σ C–R and CSP p-orbital: Me
2
"The new occupied bonding orbital is lower in energy. When you
stabilize the electrons is a system you stabilize the system itself."
1-08-Hyperconj (+)-1 9/12/03 4:53 PM
D. A. Evans "Negative" Hyperconjugation Chem 206
antibonding σ∗ C–R
■ Delocalization of nonbonding electron pairs into vicinal antibonding Syn Orientation
orbitals is also possible
– R
R ●● R: ●●
filled
R ●● R ●● H C X H C X+ H C X hybrid orbital
H C X H H C X H H H H
H H
H H
This decloalization is referred to as "Negative" hyperconjugation antibonding σ∗ C–R
Anti Orientation
R R:– R
Since nonbonding electrons prefer hybrid orbitals rather that P filled
orbitals, this orbital can adopt either a syn or anti relationship H C X H C X+ H C X hybrid orbital
to the vicinal C–R bond. H ●● H
H ●●
The Molecular Orbital Description
■ Overlap between two orbitals is better in the anti orientation as
σ∗ C–R stated in "Bonding Generalizations" handout.
The Expected Structural Perturbations
X Nonbonding e– pair
Change in Structure Spectroscopic Probe
●●
■ Shorter C–X bond X-ray crystallography
■ Longer C–R bond X-ray crystallography
As the antibonding C–R orbital
σ C–R decreases in energy, the magnitude ■ Stronger C–X bond Infrared Spectroscopy
of this interaction will increase
■ Weaker C–R bond Infrared Spectroscopy
Note that σ C–R is slightly destabilized
■ Greater e-density at R NMR Spectroscopy
■ Less e-density at X NMR Spectroscopy
1-09-Neg-Hyperconj 9/12/03 4:53 PM
