10/11/2010 Lecture 19 Huckel Molecular Orbital Theory Conjugated Dienes, Hckel Molecular Orbitals and Electrophilic addition to conjugated

dienes Polyene systems that have alternating single and double bonds are called conjugated. CH2=CH-CH=CH-CH3 is conjugated: the double and single bonds alternate allowing for -orbital overlap. CH2=CH-CH2-CH=CH2 is not conjugated: the CH2 group interposed between the double bonds prevents -orbital overlap. The -orbital overlap results in a slight increase in stability referred to as Resonance Stabilization To better understand the effects of resonance and also the reactions of conjugated systems we will introduce a simplified molecular orbital description based on the work of the German mathematician and physicist, Erich Hckel. Hckel Molecular Orbitals In the Hckel molecular orbital treatment only the -bonding is considered. The underlying -framework is ignored. For each atom involved in the -bonding a p-orbital is assigned. There are as many -orbitals as there are p-orbital components: a system with two porbitals (such as a simple enes) has two -orbitals; a system with three p-orbitals (such as a allylic cations, enolate or carboxylate anions) has three orbitals; a system with four porbitals (conjugated dienes or conjugated enones) has four -orbitals, and so on. The energy levels of the orbitals increases with the introduction of nodes changes in the sign (+/-) or phase of the orbitals. Depending upon the position of the nodes and the signs (or phases) of the orbitals, the orbitals are designated as: bonding; non-bonding; or anti-bonding. Hckel MOs for a simple ene For a simple ene there are two sp2 carbon atoms and each one has a p-orbital. These are combined to make two -orbitals: -bonding (p1 + p2), and *-antibonding (p1 - p2). For Hckel MOs it is more convenient to just draw pictures:

Hckel MOs for a three p-orbital system the allyl system The allyl system is one of the more important systems: as it describes allyls, enols and enolates, enamines, amides, and carboxylates.

Reactions involving allylic cations

Reactions involving allylic radicals

Reactions involving allylic type anions

Hckel MOs for conjugated dienes and enones

Hckel MOs for pentadienyl systems

For Electrophilic Aromatic Substitution the Wieland intermediate is a pentadienyl cation.

For -dicarbonyl enolates the intermediate is a pentadienyl anion.

The pentadienyl anion is also the Meisenheimer intermediate in Nucleophilic Aromatic Substitution

10/13/2010 Lecture 20 Diels Alder - [4]+[2] cycloaddition 1) The Diels-Alder cycloaddition reaction is classified as a pericyclic reaction. a) Pericyclic reactions take place by the concerted cyclic redistribution of bonding electrons. b) In pericyclic reactions neither ions nor radicals are involved as intermediates, however, many pericyclic reactions are affected by resonance and inductive effects present in the reacting partners. c) The basic Diels-Alder Reaction

d) The formation of the Diels-Alder adduct is an exothermic reaction: three pi bonds lost, two sigma bonds and one pi bond gained. At high temperatures, entropic contributions become more significant and retro Diels-Alder reactions are favored. G= H-T S e) However, many cycloaddition reactions require moderate heating to overcome the activation energy. So a cycloaddition may require heating to make the reaction "go," but if it is heated too much the equilibrium will favor retrocycloaddition. 2) The compound cyclopentadiene slowly undergoes cycloaddition with itself: one molecule of cyclopentadiene acts as a 4 pi-electron diene and the other as a 2 pi-electron dieneophile. The product is a Diels-Alder "adduct" called dicyclopentadiene. This dimeric material can be cracked back to cyclopentadiene by heating at 150C for an hour and then distilling off the diene monomer

3) In the Diels-Alder reaction there are two reaction components: a DIENE (must be a conjugated diene); and a DIENOPHILE (an ene usually with electron withdrawing substituents). a) The DIENE Component is usually the electron rich component in the reaction. b) The diene component must be able to achieve a cisoid conformation in order to react. This is called the s-cis conformer the s is for the single bond c) The DIENOPHILE Component is usually the electron poor component in the reaction. i) Typical dienophiles are enes that have electron withdrawing groups:

4) Dienophile without EWG are slower to react. a) Consider the following reactions. In each reaction, the dieneophile differs in substituent:
Acrylaldehyde contains an aldehyde electron withdrawing substituent; ethylene has no substituents; and methoxyethylene contains and Electron donating group. In terms of reactivity, notice the reaction conditions and reaction yields below:

i) These differences may be attributed to the energy gap between the diene HOMO and the dienophile LUMO electron withdrawing groups on the dienophile reduces the energy of the LUMO and thereby reduces the energy difference between the reacting partners. Experimentally, the energy of the HOMO is the negative of the ionization potential of the molecule; the energy of the LUMO is the electron affinity of the molecule

b) Stereochemistry is maintained in the Diels Alder reaction. i) Consider the dienophile

ii) at the diene, trans/trans configurations will undergo Diels Alder as well as some trans/cis
arrangements; however, cis/cis dienes are usually too sterically hindered to achieve the s-cis conformation necessary for Diels-Alder reactions

c) Diels Alder reactions are good ways for forming bicyclic systems (1) concept of endo and exo

5) Orbital Correlations for the Diels-Alder Reaction. Use the Huckel MOs to map to ethylene (dieneophile) and butadiene (diene)

a) More advanced correlations for acrolein and butadiene

10/15/2010 Lecture 21 Diels Alder - [4]+[2] cycloaddition Part II

1) The Diels-Alder reaction proceeds stereospecifically with respect to both component reactants. A stereospecific reaction is one in which one stereoisomer of a reactant gives exclusively one stereoisomer in the product, and in which another stereoisomer of the reactant gives a different stereoisomer of the product. A good example of a stereospecific reaction is the SN2 substitution reaction: because it proceeds with inversion of configuration, one enantiomer of the reactant gives only one enantiomer of the product. A stereoselective reaction is one in which one stereoisomer of the reactant gives predominantly, but not exclusively, one stereoisomer of the product. a) When the Diels-Alder reaction between (E,E)-2,4-heptadiene and maleic anhydride is actually carried out, only two diastereomeric racemates are isolated, and one (designated as the endo isomer) is formed in great preponderance over the other (designated as the exo isomer). The observed stereochemistry of these two products can be rationalized only in terms of a suprafacial addition with respect to both participating reactants. Consequently, the stereochemistry of the reactants is mirrored in the products: groups which are trans to each other in the dienophile are trans to each other in the product, and groups that are trans to the center C-C bond of the diene are cis to each other in the product. The difference between the endo and exo products arises from the different relative orientations of the diene and the dienophile as they approach each other to establish the initial HOMO-LUMO overlap
CH 3 O H H H O H O H CH 2CH 3 H H CH 2CH 3 O CH 3 H O

endo

exo

b) The terms endo and exo were first used by Bredt in his work with the bicyclo[2.2.1]heptane (norbornane) ring system. This ring system has both a convex and a concave surface. The convex surface, from which all substituents project out from the surface, is called the exo surface. The concave surface, from which all substituents project into the cavity, is called the endo surface

convex surface concave surface ex o

end o

c) The endo product is favored in Diels Alder reaction due to secondary orbital interactions between the carbonyl group of the dienophile (colored blue, below) and the newly forming bond (colored red below). Only an endo approach allows the orbitals on the carbonyl to interact with this new system, thereby reducing the energy of the endo transition state.

i.

For bridged structures, endo and exo is somewhat easy to visualize. For example

ii.

For non-bridged partners, it is more difficult to see the endo products. Here the hydrogen atoms on the diene replace the bridge from the previous picture, so they will point up like the bridge. With the hydrogen atoms pointing up, the substituents must point down in the endo transition state.

2) Secondary orbital interactions favor the endo transition state in which the electron withdrawing group of the dienophile comes in on the side of the diene rather than away from it, however, in some cases you may have multiple endo products

i) Consider the following reaction

ii) How to predict which endo product is favored? The relative orientations of substituents on the diene and the dienophile can be predicted based upon stereoelectronic contributions in the transition state. iii) Consider the individual electronic contributions from the diene and the dieneophile. Consider either bond polarization or resonance it doesnt matter. Any electron withdrawing group on the dieneophile (such as an aldehyde) will polarize the attached carbon - whereas any electron donating group (such as the methoxy) will polarize the attached carbon +

iv) Next, consider the two possible endo transition states:

(1) Note that the favored transition state aligns opposite partial charges. By orienting

the + and - charges in the major resonance contributors the major products can be predicted

3) Summary a. stereochemistry at the diene and the dienophile:

b. bicyclic endo / exo (Facial selectivity)

c. regioselectivity - acyclic endo / exo

d. enatoselectivity. Cycloaddition products are chiral if they do not contain any

elements of symmetry including axes of symmetry. Without asymmetric induction, both enantiomers are formed in equal parts
4) Scope

5) Practice Problems
O a) O O type CN b) Cl type Diels-Alder Reaction type Diels-Alder Reaction H 3C O H CN Cl d) H H O O type Diels-Alder Reaction
(singlet state)

CO2 Me c)

H CH 3 CO 2Me CH 3 H CH 3 O O

O O CH2 Cl2 Diels-Alder Reaction