《前沿分子轨道理论》

Nu:
R
C R
Br
Br:
RO H
O
O
major
■ General Reaction Types
O
p. p.
minor
Radical Reactions (~10%): Polar Reactions (~90%):
A• + B• A(:) + B(+)
Lewis Acid
A A
B B
■ Electronic Effects (Inductive Effects):
1-02-Introduction-1
9/12/03 4:44 PM
D. A. Evans
Steric Versus Electronic Effects; A time to be careful!!
O R3SiO EtO O R3Si OSiR3 O TiCl4 Nu OSiR3
Chem 206
O
OAc
SnBr4 BnO
O
O Danishefsky et al JOC 1991, 56, 387 BnO
p. p.
BnO
O EtO2C O EtO2C (R)2CuLi Bu OTBS O OTBS diastereoselection 8:1 O Ph N O only diastereomer Bu OTBS OAc OAc O H Ph N O H N N N N O OAc OAc H H N R R O TBS Al R O Yakura et al Tetrahedron 2000, 56, 7715 O Ph 60-94% AcO AcO H H N O only diastereomer Ph
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:
(RO)3P OMe O P O A O
■ Reading Assignment for week:
Kirby, Stereoelectronic Effects Carey & Sundberg: Part A; Chapter 1 Fleming, Chapter 1 & 2 Fukui,Acc. Chem. Res. 1971, 4, 57. (pdf) Curnow, J. Chem. Ed. 1998, 75, 910 (pdf) Alabugin & Zeidan, JACS 2002, 124, 3175 (pdf) D. A. Evans
Bu3Al
R3 O Al O
EtO2C
EtO
Yakura's rationalization:
Mehta et al, Acc Chem. Res. 2000, 33, 278-286
1-03-Introduction-1a
9/15/03 8:14 AM
D. A. Evans
The H2 Molecular Orbitals & Antibonds The H2 Molecule (again!!)
The effect of bond and through-space polarization by heteroatom substituents on reaction rates and selectivities Inductive Effects: Through-bond polarization Field Effects: Through-space polarization
Nonbonding interactions (Van der Waals repulsion) between substituents within a molecule or between reacting molecules
Me S N2 Me Nu C R RO H H Me Me2CuLi RO Me H H R
This is a "thought" question posed to me by Prof. Duilo Arigoni at the ETH in Zuerich some years ago
(First hr exam, 1999)
The three phosphites illustrated below exhibit a 750–fold span in reactivity with a test electrophile (eq 1) (Gorenstein, JACS 1984, 106, 7831).
–
Geometrical constraints placed upon ground and transition states by orbital overlap considerations. Fukui Postulate for reactions:
"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."
Monday, September 15, 2003
D. A. Evans
An Introduction to Frontier Molecular Orbital Theory-1
■ Stereoelectronic Effects
Chem 206
Universal Effects Governing Chemical Reactions There are three: ■ Steric Effects
Chemistry 206 Advanced Organic Chemistry
Lecture Number 1
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 nucleophile in an intramolecular alkylation. What is the preferred reaction path for the transformation in question? O O Br N H O Br
Path B Path A 1
Br
+
N O – H Br O
2
+
N O H Br –
Br
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
1-01-Cover Page 9/15/03 8:56 AM
+
El(+)
O P O B
+ (RO)3P–El
(1)
O P OMe O C
Rank the phosphites from the least to the most nucleophilic and provide a concise explanation for your predicted reactivity order.
Woerpel etal. JACS 1999, 121, 12208.
diastereoselection >94:6 OSiR3 H O diastereoselection 93:7 H OSiR3
O
OAc
SnBr4 Me SiMe3
O Me
Me
AlCl3
stereoselection 99:1 stereoselection >95:5 OSiR3
LewisBaidu NhomakorabeaBase
FMO concepts extend the donor-acceptor paradigm to non-obvious families of reactions ■ Examples to consider
Me R C R Br
S N1
+
R R C Me + Br:–
H2
Chem 206
Linear Combination of Atomic Orbitals (LCAO): Orbital Coefficients ■ Rule Two: Each MO is constructed by taking a linear combination of the individual atomic orbitals (AO): Bonding MO Antibonding MO σ = C1ψ1 + C2ψ2 σ∗ = C*1ψ1 – C*2ψ2
The squares of the C-values are a measure of the electron population in neighborhood of atoms in question ■ Rule Four: bonding(C1)2 + antibonding(C*1)2= 1 In LCAO method, both wave functions must each contribute one net orbital 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 is polarized in the opposite direction.
■ Rule one: A linear combination of n atomic states will create n MOs. σ∗ (antibonding) ∆E Energy H ψ1 p. p. ∆E σ (bonding) 1s 1s H ψ2
The coefficients, C1 and C2, represent the contribution of each AO. ■ Rule Three: (C1)2 + (C2)2 = 1
■ Steric Versus electronic Effects: Some Case Studies
When steric and electronic (stereoelectronic) effects lead to differing stereochemical consequences
D. A. Evans
An Introduction to Frontier Molecular Orbital Theory-1
■ Problems of the Day
Chem 206
http://www.courses.fas.harvard.edu/~chem206/ http://evans.harvard.edu/problems/
+
2 Li(0) Mg(0)
2 LiH CH3–MgBr
CH3–I +
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."