Third Year Organic Chemistry Course CHM 3 A

Third Year Organic Chemistry Course CHM 3 A 2 Frontier Molecular Orbitals and Pericyclic Reactions - Prof Jon A Preece School of Chemistry University of Birmingham

Prof Preece’s Powerpoint Lecture Presentations and answers to questions can be found at… www. nanochem. bham. ac. uk Teaching Resources Username: Undergradchem Password: Preece 57 nano Queries on course after reading around the subject to j. a. preece@bham. ac. uk. Be Specific with the problem(s) in your email. Give me three times when you are free to see me. I will email you back with a time to see me.

Course Synopsis Part Contents

Part 1. Frontier Molecular Orbitals Constructing molecular orbitals and identifying the frontier molecular orbitals Part 2. Thermal Pericyclic Reactions (i) Electrocyclic Reactions using FMO Theory (ii) Cycloaddition Reactions using FMO Theory Part 3. Photochemical Pericyclic Reactions (i) Electrocyclic Reactions using FMO Theory (ii) Cycloaddition Reactions using FMO Theory

Second Year Organic Chemistry Course CHM 3 A 2 Recommended Reading I Fleming Frontier Orbitals and Organic Chemical Reactions, John Wiley and Sons, 1996. Part 1: Ch 1 and Ch 2 Part 2 and 3: Ch 4

Second Year Organic Chemistry Course CHM 3 A 2 Frontier Molecular Orbitals and Pericyclic Reactions Part 1(i): The Questions FMO Analysis Can Answer 100% 0%

Ionic And Radical Reactions To date you have seen two broad categories of reaction: (i) Ionic reactions Here pairs of electrons move in one direction e. g. SN 2, SN 1, E 2 and E 1 mechnisms (ii) Radical reactions Here single electrons move in a correlated manner e. g. chlorination of alkanes

Pericyclic Reactions Pericyclic reactions are third distinct class. They involve cyclic transition states In which all bond breaking and bond making steps take place in commensurate manner And there is no sense of the flow of electrons.

Pericyclic Reactions: Electrocyclic Reactions Stereospecific Reaction Clockwise Anti-Clockwise 100% 0% There is no real senses of flow for the electrons in pericyclic reactions

Pericyclic Reactions: Cycloaddition Reactions Stereospecific Reaction Kinetic Product 100% Thermodynamic Product 0% Regiospecific Reaction 0% 100%

Revision: 1, 3–Syndiaxial Interactions 1, 3 -syndiaxial interactions 1 axial equitorial 2 3

Thermodynamic and Kinetic Control Kinetic Product Thermodynamic Product Formed in Cycloaddition Reaction Not Formed in Cycloaddition Reaction

Pericyclic Reactions: Sigmatropic Reactions Stereospecific Reaction 100% Regiospecific Reaction 0%

Pericyclic Reactions: Why are they so specific? Pericyclic reactions show high degrees of (i) Stereoselectivity (ii) Regioselectivity, and (iii) Diastereoselectivity Thus, an obvious question to ask ourselves at this point is why are pericyclic reactions so selective? To help begin to answer this question we shall briefly need to revise the SN 2 reaction mechanism where YOU WILL remember that this reaction type was highly stereoselective leading to inversion of chiral centres.

Revision: SN 2 Reaction Mechanism Nucleophile attacks from behind the C-Cl s-bond. This is where the s*-antibonding orbital of the C-Cl bond is situated.

The concerted flow of both pairs of electrons in the SN 2 reaction mechanism leads to the transition state which allows the stereochemical information to be retained, i. e. a stereoselective reaction. This SN 2 reaction mechanism should be contrasted to the SN 1 reaction mechanism where the arrow-pushing is the same but the two pairs electrons do not flow in a concerted fashion. Instead, the haloalkane C-Cl bond heterolytically cleaves to give the planar sp 2 hybridised carbocation reactive intermediate. Now the nucleophile can attack from either side of the carbocation leading to racemisation, i. e. a non-stereoselective reaction.

Revision: Transition States Discussion of reaction mechanisms frequently include discussions of the nature of the transition state for each step in a reaction sequence – or at least for the slowest or rate limiting step. A transition state is the point of highest energy in a reaction or in each step of a reaction involving more than one step. The nature of the transition state will determine whether the reaction is a difficult one, requiring a high activation enthalpy (DG‡), or an easy one. Transition states are always energy maxima, I. e. at the top of the energy hill, and therefore, can never be isolated: there are no barriers to prevent them from immediately “rolling” downhill to form the reaction products or intermediates (or even reform the starting materials). A transition states structure is difficult to identify accurately. It involves partial bond cleavage and partial bond formation. However, it is nigh on impossible to estimate whether the transition state is an early one (looks more like the starting materials) or a late one (looks more like the products)

Revision: Transition States Starting Material Product

Pericyclic Reactions: Transition States Thus, now we can start to understand why pericyclic reactions are so highly stereo-, regio-, and diasteroselective. Pericyclic reactions involve concerted flow of pairs of electrons going through transition states which retains stereochemical information that was present in the starting material.

Pericyclic Reactions Involve Cyclic Transition States Cyclic Transition State

Pericyclic reactions involve ene and polyene units. Thus, the transition states involve the overlap of pmolecular orbitals in the case of electrocyclic and cycloaddition reactions, and a p-molecular orbital and s-molecular orbital in the case of sigmatropic reactions. How do the orbitals overlap?

Frontier Molecular Orbitals In order to understand the selectivity of pericyclic reactions, we need to understand these molecular orbitals and how they overlap. In particular, we need to know how the Frontier Molecular Orbitals (FMOs) interact in the starting material(s) which lead to the cyclic transition states. We will first revise some simple molecular orbitals of a C-H s-bond a C=C p-bond and then extend this analysis to highly conjugated linear polyenes and related structures/

Second Year Organic Chemistry Course CHM 2 C 3 B Frontier Molecular Orbitals and Pericyclic Reactions Part 1(ii): Frontier Molecular Orbitals

CHM 2 C 3 B – Introduction to FMOs – – Learning Objectives Part 1 – Frontier Molecular Orbitals After completing PART 1 of this course you should have an understanding of, and be able to demonstrate, the following terms, ideas and methods. (i) Given a set of n p-orbitals you should be able to construct a molecular orbital energy level diagram which results from their combination. (ii) In this diagram you should be able to identify for each MO nodes the symmetric (S) or antisymmetric (A) nature of the MO towards a C 2 axis or mirror plane the bonding, nonbonding or antibonding nature of it (iii) For a set of n molecular orbitals you should be able to identify the frontier molecular orbitals. the highest occupied molecular orbital (HOMO ) the lowest unoccupied molecular orbital (LUMO) (iv) The HOMO (thermal reaction) interactions are important when evaluating the probability of an unimolecular reaction occurring and the stereochemical outcome – see electrocyclic reactions. The HOMO/LUMO (thermal reaction) interactions of the reacting species are important when evaluating the probability of (i) a bimolecular reaction occurring and the stereochemical outcome– see cycloaddition reactions, and (ii) a unimolecular reaction occurring and the stereochemical outcome – see sigmatropic reactions. The geometry, phase relationship and energy of interacting HOMOs and LUMOS is important for evaluating the probability of a reaction occurring and the stereochemical outcome.

s-Bond Two s Atomic Orbitals Molecular Orbitals

s-Bond One s Atomic Orbital and One sp 3 Atomic Orbital Molecular Orbitals

p-Bond: Two p Atomic Orbitals Molecular Orbitals

The linear combination of n atomic orbitals leads to the formation of n molecular orbitals

A SIMPLE Mathematical Description of a MO The combination of two (or more) p-atomic orbitals (or any orbitals) to afford 2 p-molecular orbitals can be described by the following simple mathematical relationship p* = ccf 1 + cdf 2 p = caf 1 + cbf 2 fm = Electronic distribution in the atomic orbitals Cn = Coeffecient: a measure of the contribution which the atomic orbital is making to the molecular orbital

The probability of finding an electron in an occupied molecular orbital is 1. The probability of finding an electron in an occupied molecular orbital is the Sc 2 Thus, for the ethene p-molecular orbitals… p* = ccf 1 + cdf 2 Sc 2 = cc 2 + cd 2 = 1 1 2 Cc = 1/√ 2 Cd = -1/√ 2 Negative Sc 2 = ca 2 + cb 2 = 1 p = caf 1 + cbf 2 1 2 Ca = 1/√ 2 Cb = 1/√ 2

So what about the combination of 3 or 4 or 5 or 6 p-atomic orbitals. That is to systems… consider conjugated

The Allyl Cation, Radical and Anion – 3 p AOs to give 3 p MOs

Allyl Cation Allyl Radical Allyl Anion

Thus, allyl systems result from the combination of 3 conjugated p-orbitals. Therefore, this will result in 3 p-molecular orbitals. When we constructed the p-molecular orbitals of ethene, each contributing AO was the same size, i. e. the coeffecient c were 1/√ 2 or -1/ √ 2. When there are three or more p-atomic orbitals combining the size of each contributing p-atomic orbital will not be equal (but they will be symmetrical about the centre). Finally, we refer to the p-MOs and p*-MOs as 1, 2, 3 (… n)

The Allyl p-Molecular Orbitals We can consider the molecular orbital (the electron density) being described by a SINE WAVE starting and finishing one bond length beyond the molecule… 3 = 2 Nodes Nodal position 4/3 = 1. 33 3 1. 33 Nodes 2 = 1 Nodes 1 = 0 Nodes Nodal position 4/2 = 2 Nodal position 4/1 = 4 2 2 1 2 3 4 4 1

For our analysis of molecular orbitals we do not have to concern ourselves with the coefficients. We can draw the p-AOs that make up the p-MOs all the same size. However, we have to always remember they are not the same size. But it is of the utmost importance that we know how to calculate where the nodes are placed

Bonding, Non-Bonding, and Anti-bonding Levels Anti-bonding Non-bonding Bonding We can consider the molecular orbital (the electron density) being described by a sine wave starting and finishing one bond length beyond the molecule…

LUMOs and HOMOs LUMO = Lowest Unoccupied Molecular Orbital HOMO = Highest Occupied Molecular Orbital Allyl Cation (2 e) LUMO HOMO Allyl Radical (3 e) Allyl Anion (4 e) LUMO HOMO

Question 1: 4 p-Molecular Orbital System – Butadiene Construct the p-molecular orbitals of butadiene. Identify the number of nodes, nodal positions, HOMO and LUMO. n Number of Nodes Nodal Position

Answer 1: 4 p-Molecular Orbital System – Butadiene Construct the p-molecular orbitals of butadiene. Identify the number of nodes, nodal positions, HOMO and LUMO. n 4 Number of Nodes Nodal Position 3 5/4 = 1. 25 3 2 LUMO 5/3 = 1. 66 2 1 HOMO 5/2 = 2. 5 1 0 5/1 = 5 1 2 3 4 5

A Reminder: Sinusodal Wave Function

Coefficients, cn Each molecular orbital is described by an equation… n = c a f 1 + c b f 2 + c c f 3 + c n f n Where c is referred to as the coefficient Such that the… Sc 2 = 1 That is to say the probability of finding an electron in a molecular orbital is 1

3 = c a f 1 + c b f 2 + c c f 3 + c d f 4

We Keep FMO Analysis Simple!! For the purpose of this course and the third year course (Applied Frontier Molecular Orbitals and Stereoelectronic Effects) you are expected (i) to be able to place the nodal planes in the correct place (ii) but not to be able to assign the coefficients to the molecular orbitals. That is to say you can draw the p-orbitals that make up each molecular orbital as the same size, whilst remembering that in reality they are not and for high level FMO analysis this needs to be taken into account.

Question 2: 5 p-Molecular Orbital System – Pentadienyl Construct the p-molecular orbitals of the cyclopentenyl system. Identify the number of nodes and nodal positions. n Number of Nodes Nodal Position Molecular Orbitals

Answer 2: 5 p-Molecular Orbital System – Pentadienyl Construct the p-molecular orbitals of the cyclopentenyl system. Identify the number of nodes and nodal positions. n 5 Number of Nodes Molecular Orbitals Nodal Position 4 6/5 = 1. 2 4 3 6/4 = 1. 5 3 2 6/3 = 2 2 1 6/2 = 3 1 0 6/1 = 6 1 2 3 4 5 6

Question 3: Pentadienyl Cation, Radical & Anion Introduce the electrons and identify the HOMOs and LUMOs

Answer 3: Pentadienyl Cation, Radical & Anion Introduce the electrons and identify the HOMOs and LUMOs

Question 4: Pentadienyl Cation & Anion Generate the cation and anion and draw the resonance structures of the above species

Answer 4: Pentadienyl Cation, Radical & Anion Generate the cation and anion and draw the resonance structures of the above species

6 p-Molecular Orbital System – 1, 3, 5 -Hexatriene

7 p-Molecular Orbital System

Question 5: 6 p MO System By shading the p atomic orbitals, generate the molecular orbitals for hexa-1, 3, 5 -triene. Identify the number of nodes characterising each molecular orbital. With reference to both a mirror plane (m) and a two-fold axis, designate the orbitals as symmetric (S) or antisymmetric (A). Using arrows to represent electrons, associate the six p-electrons with the appropriate molecular orbitals of hexa-1, 3, 5 -triene in its ground state. Finally, identify the HOMO and LUMO.

Answer 5: 6 p MO System By shading the p atomic orbitals, generate the molecular orbitals for hexa-1, 3, 5 -triene. Identify the number of nodes characterising each molecular orbital. With reference to both a mirror plane (m) and a two-fold axis, designate the orbitals as symmetric (S) or antisymmetric (A). Using arrows to represent electrons, associate the six p-electrons with the appropriate molecular orbitals of hexa-1, 3, 5 -triene in its ground state. Finally, identify the HOMO and LUMO.

Question 6: MO System Protonation of A affords B. Draw the three resonance structures of B in which the positive charge has formally been shifted from the oxygen atom onto three of the five carbon atoms. Considering only these three resonance structures, how many (i) carbon atoms are involved in the hybrid structure, (ii) carbon p-orbitals are there, (iii) p-electrons are associated with the carbon atoms, and (iv) molecular orbitals are associated with the combination of these carbon p-orbitals In an analogous fashion to how question 1 was set out, draw out the molecular orbitals resulting from the p-orbital combination on this carbon framework, making sure you identify all of the items listed in question 1.

Answer 6: 5 p MO System Protonation of A affords B. Draw the three resonance structures of B in which the positive charge has formally been shifted from the oxygen atom onto three of the five carbon atoms. Considering only these three resonance structures, how many (i) carbon atoms are involved in the hybrid structure, (ii) carbon p-orbitals are there, (iii) p-electrons are associated with the carbon atoms, and (iv) molecular orbitals are associated with the combination of these carbon p-orbitals In an anologous fashion to how question 5 was set out, draw out the molecular orbitals resulting from the p-orbital combination on this carbon framework, making sure you identify all of the items listed in question 5.

Second Year Organic Chemistry Course CHM 2 C 3 B Frontier Molecular Orbitals and Pericyclic Reactions Part 1(iii): HOMO and LUMO Combination

What is the Driving Force for Controlling Pericyclic Reactions? The driving force which controls the product outcome in pericyclic reactions is the in phase combination of the FMOs (the HOMO and LUMO) of the reacting species in the transition state. FMO Theory is Extremely Powerful.

Pericyclic Reactions Involve Conjugated Polyene Systems Pericyclic reactions involve conjugated polyene systems. Enes and Polyenes are made by the linear combination of p-AOs. Thus, we first need to construct the molecular orbitals of polyenes. Then we need to identify the Frontier Molecular Orbitals. Finally, we will need to construct the correct geometry for orbital overlap of the FMOs in the transition states of the reactions.

HOMOs and LUMOs Highest Occupied Molecular Orbitals Lowest Unoccupied Molecular Orbitals In bimolecular reactions (like the SN 2 and the Diels-Alder reaction), interaction between the two molecular components is represented by interaction between suitable molecular orbitals of each. The extent of the interaction depends upon the geometry of approach of the components since the relative geometry affects the amount of possible overlap. It also depends on the phase relationship of the orbitals – and also upon their energy of separation, a small energy favouring a greater interaction. Generally, the two reactants will interact, via the highest occupied molecular orbital (HOMO) of one component and the lowest unoccupied molecular orbital (LUMO) of the other component, the so-called frontier molecular orbitals (FMOs). Consider the next five frames to appreciate this paragraph of text. Consider an SN 2 Reaction…

Revision: Transition State Geometries of Nucleophiles Attacking sp 3 Tetrahedral Centres Inversion of Configuration Supports this Attack Angle LUMO Nucleophile. HOMO LUMO

The orbital containing the lone pair of electrons on the Nu is the… HOMO (Highest Occupied Molecular Orbital) The s* orbital of the C-X bond is the… LUMO (Lowest Unoccupied Molecular Orbital) Any bimolecular reaction can be analysed in this fashion

Frontier Molecular Orbital Theory (FMOs) This analysis of FMOs (HOMOs and LUMOs) for such a simple reactions may seem pointless for a simple SN 2 reaction. It is not! Understand it. Appreciate that for a bimolecular reaction the HOMO of one component interacts with the LUMO of the second component. (Additionally, for unimolecular reaction the HOMO of the molecular component dictates the reaction course). In this course we will examine the use of FMOs to explain and predict the outcomes of a class of reactions referred to as pericyclic. The use of FMOs is an extremely powerful tool to the synthetic organic chemist when analysing and predicting the outcome of pericyclic reactions.

CHM 3 A 2 – Introduction to FMOs – – Summary Sheet Part 1 – Frontier Molecular Orbitals Molecular orbital theory is a powerful and versatile asset to the practice of organic chemistry. As a theory of bonding it has almost superseded the valence bond theory. Molecular orbital theory has proven amenable to pictorial non-mathematical expression, given the right answers to some decisive questions in organic chemistry, proven theory of most theoretical chemists, given insight into not only to theory of bonding, but also to theory of making and breaking chemical bonds, and proven a theory which has been able to explain the pattern of reactivity in a class of reactions, known as pericyclic reactions. In this course we will concentrate solely on the use of MO theory in predicting the outcome of pericyclic reactions. But it should not be forgotten that MO theory is applicable to other types of chemical reraction To understand the importance of MO theory, we shall consider three types of pericyclic reactions and show frontier molecular orbitals of the reactants can be used in a predicative nature to work out whether the reaction will proceed and what the stereo/regiochemical outcome will be. The three types of pericyclic reactions we will consider are electrcyclic reactions cycloaddition reactions sigmatropic reactions We will see how it is possible to predict the stereoselectivity, diastereoselectivity, and regioselectivity of pericyclic reactions by the analysis of the FMOs of the transition states

The precise construction of the p-molecular orbitals by the linear combination of p-atomic orbitals is extremely important if FMO theory is to yield the correct stereochemical product outcomes, Key points to note when constructing p-molecular orbitals from the combination of p-AOs are (i) (iii) (iv) (v) the combination of n Aos always affords n MOs The lowest p-MOs ( 1) has no nodal planes The next highest ( 2) has one nodal plane, and so on The nodal planes need to be placed exactly in the Mos as described in the lecture notes Electrons fill from the lowest MO first with no more than two electrons in each MO.