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?
O
Chemistry 206
O Path A 1 Br +
N O
–
Br Br H Br
Advanced Organic Chemistry 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
(First hr exam, 1999)
■ Hyperconjugation and "Negative" Hyperconjugation
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)3P + El(+) (RO)3P–El (1)
Kirby, Stereoelectronic Effects
OMe
Carey & Sundberg: Part A; Chapter 1 O
P
O P O OMe
Fleming, Chapter 1 & 2 P O
O O O
Fukui,Acc. Chem. Res. 1971, 4, 57. (pdf) A B C
Curnow, J. Chem. Ed. 1998, 75, 910 (pdf)
Rank the phosphites from the least to the most nucleophilic and
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:
Geometrical constraints placed upon ground and transition states
■ Steric Effects
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
SN2
–
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
p. 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 +
C Br SN1 R C Me + Br:– H2 + 2 Li(0) 2 LiH
R R
R
CH3–I + Mg(0)
CH3–MgBr
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 R3SiO
lead to differing stereochemical consequences TiCl4 diastereoselection
>94:6
EtO
Woerpel etal. JACS 1999, 121, 12208. Nu
R3Si OSiR3 OSiR3
O
OAc SnBr
4 O O
O
O
H
Me Me Me AlCl3 diastereoselection
93:7
stereoselection 99:1
SiMe3
H
stereoselection >95:5 OSiR3 OSiR3
O O O
OAc
SnBr4
Danishefsky et al JOC 1991, 56, 387
BnO BnO BnO
pp..
O
EtO2C
(R)2CuLi diastereoselection O AcO
H
O 8:1 AcO
EtO2C Bu N H
Ph N
OTBS N N
O
O
O N only diastereomer
OTBS Bu
3Al EtO2C only diastereomer N Ph
O
OAc O
Bu H
OAc
R3 OTBS
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
Energy Energy
Energy
D. A. Evans The H2 Molecular Orbitals & Antibonds Chem 206
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):
Bonding MO σ = C1ψ1 + C2ψ2
■ Rule one: A linear combination of n atomic states will create n MOs.
σ∗ (antibonding) Antibonding MO σ∗ = C*1ψ1– C*2ψ2
The coefficients, C1 and C2, represent the contribution of each AO.
∆E
2 2
H 1s 1s H ■ Rule Three: (C1) + (C2) = 1
ψ1 ψ2 The squares of the C-values are a measure of the electron population
in neighborhood of atoms in question
p. ∆E
2 2
σ (bonding) ■ Rule Four: bonding(C1) + antibonding(C*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
σ∗ (antibonding) is polarized toward Oxygen. Note (Rule 4) that the antibonding MO
is polarized in the opposite direction.
∆E1
C O
π∗ (antibonding)
H 1s 1s H
ψ1 ψ2
∆E2
σ (bonding) C
O
Note that ∆E1 is greater than ∆E2. Why?
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 Ecov) and an ionic contribution (δ Eionic).
For σ Bonds:
Bond Energy (BDE) = δ Ecovalent + δ Eionic (Fleming, page 27) Better
A B 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.
p. -1
know that C-C bonds are considerably stronger by Ca. 20 kcal mol 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 Better
A C A C
C-SP3 C-SP3 C-SP
3 than
lone pair
σ C–Si ••
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
X Y X
This trend is even more dramatic with pi-bonds:
X σ* C–X Better σ C–Y σ* C–X
LUMO than HOMO LUMO
π C–C = 65 kcal/mol π C–Si = 36 kcal/mol π Si–Si = 23 kcal/mol
A C C C C C
■ Weak bonds will have corresponding low-lying antibonds. σ C–Y
HOMO
Y
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 CH3–X where X = C, N, O, F, & H.
σ* C-C
σ-bonding States: (C–X)
σ* C-O
CH3–CH3
CH3–H
3 3
C-SP C-SP
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)
p. & 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
∗
Increasing σ -acceptor capacity
σ* C–C better acceptor 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.
2
C-SP
Nonbonding States
σ C–C
better donor
σ C–C H3P:
H2S:
■ The greater electronegativity of CSP2 lowers both the bonding & H
3N:
antibonding C–C states. Hence: H
2O:
HCl:
■ σ CSP3-CSP3 is a better donor orbital than σ CSP3-CSP2
∗ ∗ decreasing donor capacity poorest donor
■ σ CSP3-CSP2 is a better acceptor orbital than σ CSP3-CSP3
1-06-donor/acceptor states 9/12/03 5:16 PM
Radial Probability
Radial Probability
Pauling Electronegativity
Pka of Carbon Acid
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
N
hydrogen atom S & P states are shown below. SP
4.5
100 % 100 %
4
1 S Orbital
N
SP2
N
SP3
3.5
C
SP
3
2 S Orbital 2 S Orbital
C
SP2
2.5
pp.. 2 P Orbital CSP3
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
6 0
CH (56)
4
5 5
S-states have greater radial penetration due to the nodal properties of the wave
function. Electrons in S-states "see" a higher nuclear charge.
5 0
Above observation correctly implies that the stability of nonbonding electron 4 5
pairs is directly proportional to the % of S-character in the doubly occupied orbital C H (44)
6 6
4 0
Least stable Most stable
3 5
CSP3 CSP2 CSP
PhCC-H (29)
3 0
The above trend indicates that the greater the % of S-character at
a given atom, the greater the electronegativity of that atom. 2 5
2 0 2 5 3 0 3 5 4 0 4 5 5 0 5 5
% 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
pp..
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
H H
C C (MM-2) 1.528 Å
H H
H
110 °
σ C–R σ C–R
Me 1.530 Å
Me
Me
■ Take a linear combination of σ C–R and CSP2 p-orbital:
"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
antibonding σ∗ C–R
This decloalization is referred to as "Negative" hyperconjugation
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
