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Welcome to Chem 206Fall Term, 2005, David A. Evans
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Chem 206 Teaching Fellows
Regan Thomson
Pavel Nagornyy
Keith Fandrick
Yimon Aye
Meredeth McGowan
These individuals are your mentors. They are here to help you through this
course. Please take advantage of this opportunity.
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Dr. Regan Thomson
PhD: Australian Nat. Univ
Postdoctoral Fellow
Evans Research Group
Raised: New Zealand
Lab No. Converse 308B
Lab Phone: [email protected]
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Pavel Nagornyy
Undergrad: Oregon State
5th-yr Graduate Student
Evans Research Group
Lab No. Converse 316
Lab Phone: 617-496-8569
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Keith Fandrick
Undergrad: UC San Diego
5rd-yr Graduate Student
Evans Research Group
Lab No. Converse 306B
Lab Phone: 617-495-3245
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Meredeth McGowen
Undergrad: Dartmouth
2nd-yr Graduate Student
Jacobsen Research Group
Lab No. Mallinckrodt 202
Lab Phone: [email protected]
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Yimon Aye
Undergrad: Oxford Univ. UK
2nd-yr Graduate Student
Evans Research Group
Lab No. Converse 316
Lab Phone: [email protected]
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Mon, Sept 24th: Study card day
Mon, Oct 10th: Columbus Day Class will be held
Fri, Oct 14th: Exam 1
Mon, Nov 21th: Exam 2Wed, Nov 24th: Class will not be held
Thurs, Nov 24th: Thanksgiving recess begins
Mon, Dec 19th: Exam 3
Wed, Dec 21st Winter recess begins
Friday, January 23rd Scheduled Final Exam
Significant Dates this Fall
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Textbooks
Carey & Sundberg, Advanced Organic Chemistry, Parts A,B
Kirby, A. J. Stereoelectronic Effects (See DAE)
Fleming, I. Frontier Orbitals and Organic Chemical Reactions.
Web Problems (>500)
http://daecr1.chem.harvard.edu/problems/
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Course Grading
3 one-Hour Exams
10 Problem Sets
Final Examination
We will grade your best effort. We will take your final exam score
and manufacture an imaginary hr exam score (IHE). If this
score is better than any two of your normalized hourly exam scores,the IHE score will replace those low scores. The IHE score will
also be used in the event that an hourly exam was missed.
300 pts
200 pts
300 pts
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Sections
Sections will begin this week.Sign up prior to 5 PM this Wednesday
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First Reading Assignment
! Reading Assignment for week:
Kirby, Stereoelectronic EffectsCarey & Sundberg: Part A; Chapter 1
Fleming, Chapter 1 & 2Fukui,Acc. Chem. Res.1971, 4, 57. (pdf)
Alabugin & Zeidan, JACS2002, 124, 3175 (pdf)
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Chem 206D. A. Evans
D. A. EvansMonday,September 19, 2005
http://www.courses.fas.harvard.edu/~chem206/
! Reading Assignment for week:
Kirby, Stereoelectronic Effects
Carey & Sundberg: Part A; Chapter 1
Fleming, Chapter 1 & 2Fukui,Acc. Chem. Res.1971, 4, 57. (pdf)
Alabugin & Zeidan, JACS2002, 124, 3175 (pdf)
Chemistry 206
Advanced Organic Chemistry
Lecture Number 1
Introduction to FMO Theory
! General Bonding Considerations! The H2 Molecule Revisited (Again!)! Donor & Acceptor Properties of Bonding & Antibonding States! Hyperconjugation and "Negative" Hyperconjugation! Anomeric and Related Effects
An Introduction to Frontier Molecular Orbital Theory-1
! Problems of the Day
The molecule illustrated below can react through either Path A or Path B toform salt 1 or salt 2. In both instances the carbonyl oxygen functions as thenucleophile in an intramolecular alkylation. What is the preferred reaction
path for the transformation in question?
+
+
Br
Br 1
2
Path A
Path B
BrNH
OBr
O
O
BrON
H
O
ONH
Br
This is a "thought" question posed to me by Prof. Duilo Arigoni at the ETH inZuerich some years ago
http://evans.harvard.edu/problems/
O
PO
OMe
O
PO OMe
OP
O
O
A B C
(RO)3P +
(First hr exam, 1999)
The three phosphites illustrated below exhibit a 750fold span in reactivity witha test electrophile (eq 1) (Gorenstein, JACS1984, 106, 7831).
Rank the phosphites from the least to the most nucleophilic andprovide a concise explanation for your predicted reactivity order.
El(+) (RO)3PEl (1)+
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Chem 206D. A. Evans An Introduction to Frontier Molecular Orbital Theory-1
minor
major
Br: Nu:
Nonbonding interactions (Van der Waals repulsion) betweensubstituents within a molecule or between reacting molecules
! Steric EffectsUniversal Effects Governing Chemical Reactions
There are three:
C Br
Me
RR
C R
R
Me
Nu
RO
H
SN2
O
Me2CuLi
RO
H
OH
Me
RO
H
OMe
H
! Electronic Effects (Inductive Effects):
Inductive Effects: Through-bond polarizationField Effects: Through-space polarization
The effect of bond and through-space polarization byheteroatom substituents on reaction rates and selectivities
+ Br:
+SN1
rate decreases as R becomes more electronegative
CR
R
Me
Br C MeR
R
"During the course of chemical reactions, the interaction of
the highest filled (HOMO) and lowest unfilled (antibonding)
molecular orbital (LUMO) in reacting species is very important
to the stabilization of the transition structure."
Geometrical constraints placed upon ground and transition statesby orbital overlap considerations.
!Stereoelectronic Effects
Fukui Postulate for reactions:
!General Reaction TypesRadical Reactions (~10%): A B+ A B
Polar Reactions (~90%): A(:) B(+)+ A B
Lewis BaseLewis Acid
FMO concepts extend the donor-acceptor paradigm tonon-obvious families of reactions
"Organic chemists are generally unaware of the impact ofelectronic effects on the stereochemical outcome of reactions."
"The distinction between electronic and stereoelectronic effects isnot clear-cut."
!Examples to considerH2 2 Li(0)+
CH3I Mg(0)+ CH3MgBr
2 LiH
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Chem 206D. A. Evans The H2 Molecular Orbitals & Antibonds
The H2 Molecule (again!!)
Let's combine two hydrogen atoms to form the hydrogen molecule.
Mathematically, linear combinations of the 2 atomic 1s states create
two new orbitals, one is bonding, and one antibonding:
Energy
1s 1s
!" (antibonding)
! Rule one: A linear combination of n atomic states will create n MOs.
#E
#E
Let's now add the two electrons to the new MO, one from each H atom:
Note that #E1 is greater than #E2. Why?
! (bonding)
! (bonding)
#E2
#E1
!" (antibonding)
1s1s
$2
$2
$1
$1
Energy
H H
HH
+C1!1" = C2!2
Linear Combination of Atomic Orbitals (LCAO): Orbital Coefficients
Each MO is constructed by taking a linear combination of theindividual atomic orbitals (AO):
Bonding MO
Antibonding MO C*2!2"# = C*1!1
The coefficients, C1 and C2, represent the contribution of each AO.
! Rule Three: (C1)2 + (C2)
2 = 1
= 1antibonding(C*1)2+bonding(C1)
2! Rule Four:
Energy
$# (antibonding)
$ (bonding)
Consider the pibond of a C=O function: In the ground state pi-COis polarized toward Oxygen. Note (Rule 4) that the antibonding MOis polarized in the opposite direction.
C
C
O
C O
The squares of the C-values are a measure of the electron populationin neighborhood of atoms in question
In LCAO method, both wave functions must each contributeone net orbital
! Rule Two:
O
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Chem 206D. A. Evans Bonding Generalizations
When one compares bond strengths between CC and CX, where Xis some other element such as O, N, F, Si, or S, keep in mind thatcovalent and ionic contributions vary independently. Hence, the
mapping of trends is not a trivial exercise.
Bond Energy (BDE) = !Ecovalent + !Eionic (Fleming, page 27)!Bond strengths (Bond dissociation energies) are composed of acovalent contribution (!Ecov) and an ionic contribution (!Eionic).
!" CSi!" CC
! CSi
! CC
Bond length = 1.87 Bond length = 1.534 H3CSiH3 BDE ~ 70 kcal/molH3CCH3 BDE = 88 kcal/mol
Useful generalizations on covalent bonding
For example, consider elements in Group IV, Carbon and Silicon. We
know that C-C bonds are considerably stronger by Ca. 20 kcal mol-1than C-Si bonds.
! Overlap between orbitals of comparable energy is more effectivethan overlap between orbitals of differing energy.
C-SP3
Si-SP3
C-SP3C-SP3
better thanC C C C C Si SiC
!Weak bonds will have corresponding low-lying antibonds.!SiSi = 23 kcal/mol!CSi = 36 kcal/mol!CC = 65 kcal/mol
This trend is even more dramatic with pi-bonds:
Formation of a weak bond will lead to a corresponding low-lying antibondingorbital. Such structures are reactive as both nucleophiles & electrophiles
Betterthan
For ! Bonds:
For " Bonds:
! Orbital orientation strongly affects the strength of the resulting bond.Better
than
This is a simple notion with very important consequences. It surfacesin the delocalized bonding which occurs in the competing anti(favored) syn (disfavored) E2 elimination reactions. Review thissituation.
A B A B
BABA
Betterthan
Betterthan
Case-2: Two anti sigma bonds
! CYHOMO
!* CXLUMO
!* CXLUMO
lone pairHOMO
!* CXLUMO
!* CXLUMO
lone pairHOMO
Case-1: Anti Nonbonding electron pair & CX bond
! Anti orientation of filled and unfilled orbitals leads to better overlap.This is a corrollary to the preceding generalization.
There are two common situations.
! CYHOMO
A C A C
C CC C
A C
X
A
Y
C
XY
Y
X X
XX
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Chem 206D. A. Evans Donor-Acceptor Properties of Bonding and Antibonding States
C-SP3
!!"CO is a better acceptor orbital than !"CC
!! CC is a better donor orbital than ! CO
! The greater electronegativity of oxygen lowers both the bonding& antibonding C-O states. Hence:
Consider the energy level diagrams for both bonding & antibondingorbitals for CC and CO bonds.
Donor Acceptor Properties of C-C & C-O Bonds
O-SP3
!* C-O
! C-O
C-SP3
! C-C
!* C-C
!!"
CSP3-CSP2 is a better acceptor orbital than!"
CSP3-CSP3
C-SP3
!* CC
! CC
C-SP
3
! CC
!* CC
C-SP2
Donor Acceptor Properties of CSP3-CSP3 & CSP3-CSP2 Bonds
! The greater electronegativity of CSP2 lowers both the bonding &antibonding CC states. Hence:
!! CSP3-CSP3 is a better donor orbital than ! CSP3-CSP2
better donor
better acceptor
decreasing donor capacity
Nonbonding States
poorest donor
The following are trends for the energy levels of nonbonding states
of several common molecules. Trend was established byphotoelectron spectroscopy.
best acceptor
poorest donor
Increasing!"-acceptor capacity
!-anti-bonding States: (CX)
!-bonding States: (CX)
decreasing!-donor capacity
Following trends are made on the basis of comparing the bonding andantibonding states for the molecule CH3X where X = C, N, O, F, & H.
Hierarchy of Donor & Acceptor States
CH3CH3CH3H
CH3NH2
CH3OH
CH3F
CH3H
CH3CH3
CH3NH2
CH3OH
CH3F
For the latest views, please readAlabugin & Zeidan, JACS2002, 124, 3175 (pdf)
very close!!
HCl:
H2O:
H3N:H2S:
H3P:
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Chem 206D. A. Evans Hybridization vs Electronegativity
3 P Orbital
This becomes apparent when the radial probability functions for Sand P-states are examined: The radial probability functions for the
hydrogen atom S & P states are shown below.
3 S Orbital
Electrons in 2S states "see" a greater effective nuclear chargethan electrons in 2P states.
Above observation correctly implies that the stability of nonbonding electronpairs is directly proportional to the % of S-character in the doubly occupied orbital
Least stable Most stable
The above trend indicates that the greater the % of S-characterat a given atom, the greater the electronegativity of that atom.
RadialProbability
100 %
2 P Orbital
2 S Orbital2 S Orbital
1 S Orbital
100 %
RadialProbability
S-states have greater radial penetration due to the nodal properties of the wave
function. Electrons in S-states "see" a higher nuclear charge.
CSP3 CSP2 CSP
2
2.5
3
3.5
4
4.5
5
PaulingElectronegativity
20 25 30 35 40 45 50 55
% S-Character
CSP3
CSP2
CSP
NSP3
NSP2
NSP
25
30
35
40
45
50
55
60
PkaofCarbonAcid
20 25 30 35 40 45 50 55
% S-Character
CH4
(56)
C6H
6(44)
PhCC-H (29)
There is a direct relationship between %S character &hydrocarbon acidity
There is a linear relationship between %S character &Pauling electronegativity
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Chem 206D. A. Evans Hyperconjugation: Carbocation Stabilization
The graphic illustrates the fact that the C-R bonding electrons can"delocalize" to stabilize the electron deficient carbocationic center.
Note that the general rules of drawing resonance structures still hold:the positions of all atoms must not be changed.
! The interaction of a vicinal bonding orbital with a p-orbital is referredto as hyperconjugation.
C C
R
H
HH
HC
H
HCH
H
R
This is a traditional vehicle for using valence bond to denote chargedelocalization.
+
Syn-planar orientation between interacting orbitals
Stereoelectronic Requirement for Hyperconjugation:
"The new occupied bonding orbital is lower in energy. When youstabilize the electrons is a system you stabilize the system itself."
! Take a linear combination of ! CR and CSP2 p-orbital:
! CR
!" CR
! CR
!" CR
The Molecular Orbital Description
CH
HC
H
H
+ +
[F5SbFSbF5]
The Adamantane Reference(MM-2)
T. Laube, Angew. Chem. Int. Ed.1986, 25, 349
First X-ray Structure of an Aliphatic Carbocation
110
100.6
1.530
1.608
1.528
1.431
Bonds participating in the hyperconjugative interaction, e.g. CR,will be lengthened while the C(+)C bond will be shortened.
Physical Evidence for Hyperconjugation
Me
Me
Me
H
Me
Me
Me
C+
+
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"Negative" HyperconjugationD. A. Evans Chem 206
! Delocalization of nonbonding electron pairs into vicinal antibondingorbitals is also possible
C X
R
H
HHH X H
H
CH
H
R ""
This decloalization is referred to as "Negative" hyperconjugation
""
As the antibonding CR orbital
decreases in energy, the magnitude
of this interaction will increase! CR
!!
!" CR
The Molecular Orbital Description
X
Since nonbonding electrons prefer hybrid orbitals rather that Porbitals, this orbital can adopt either a syn or anti relationship
to the vicinal CR bond.
Nonbonding e pair
Note that ! CR is slightly destabilized
antibonding !" CR
! Overlap between two orbitals is better in the anti orientation asstated in "Bonding Generalizations" handout.
+
Anti Orientation
filledhybrid orbital
filledhybrid orbital
antibonding !" CRSyn Orientation
+C X
H
H
C X
H
HCH
CH
H
R
X
H
R
XC X
H
H
C X
H
H
R:
R:
""
""""
""
R
R
NMR Spectroscopy! Greater e-density at R
! Less e-density at X NMR Spectroscopy
! Longer CR bond X-ray crystallography
Infrared Spectroscopy! Weaker CR bond
! Stronger CX bond Infrared Spectroscopy
X-ray crystallography! Shorter CX bond
Spectroscopic ProbeChange in Structure
The Expected Structural Perturbations
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Chem 206D. A. Evans Lone Pair Delocalization: N2F2
This molecule can exist as either cis ortrans isomers
The interaction of filled orbitals with adjacent antibonding orbitals canhave an ordering effect on the structure which will stabilize a particular
geometry. Here are several examples:
Case 1: N2F2
There are two logical reasons why the trans isomer should be morestable than the cis isomer.
! The nonbonding lone pair orbitals in the cis isomer will be destabilizingdue to electron-electron repulsion.
! The individual CF dipoles are mutually repulsive (pointing in samedirection) in the cis isomer.
N N
F F
N
F
N
F
The cis Isomer
! Note that two such interactions occur in the molecule even thoughonly one has been illustrated.
! Note that by taking a linear combination of the nonbonding andantibonding orbitals you generate a more stable bonding situation.
!" NF
filledN-SP2
antibonding!" NF
filledN-SP2
In fact the cis isomer is favored by 3 kcal/ mol at 25 C.
Let's look at the interaction with the lone pairs with the adjacent CFantibonding orbitals.
(LUMO)
N
F
N
F
(HOMO)
The trans IsomerNow carry out the same analysis with the same 2
orbitals present in the trans isomer.
filledN-SP2antibonding!" NF
! In this geometry the "small lobe" of the filled N-SP2 is required tooverlap with the large lobe of the antibonding CF orbital. Hence, whenthe new MO's are generated the new bonding orbital is not as stabilizingas for the cis isomer.
filledN-SP2
(HOMO)
!" NF
(LUMO)N N
F
F
Conclusions
! Lone pair delocalization appears to override electron-electron anddipole-dipole repulsion in the stabilization of the cis isomer.
! This HOMO-LUMO delocalization is stronger in the cis isomer dueto better orbital overlap.
Important Take-home Lesson
Orbital orientation is important for optimal orbital overlap.
forms stronger pi-bond than
forms strongersigma-bond than
This is a simple notion with very important consequences. It surfaces inthe delocalized bonding which occurs in the competing anti (favored)syn (disfavored) E2 elimination reactions. Review this situation.
A B A B
A B BA
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