Frontier Molecular Orbitals and Pericyclic Reactions

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Frontier Molecular Orbitals,and,Pericyclic Reactions,Third Year,Organic Chemistry Course,CHM3A2,-,Prof Jon A Preece,-,School of Chemistry,University of Birmingham,Prof Preeces Powerpoint Lecture Presentations,and answers to questions can be found at,www.nanochem.bham.ac.uk,Username: Undergradchem,Password: Preece57nano,Teaching Resources,Queries on course,after reading around,the subject,to .,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.,PartContents,1,Pericyclic Reactions,These lectures,will begin with a definition of,Pericyclic reactions, and will be exemplified by considering examples of,cycloaddation,sigmatropic, and,electrocyclic,reactions. It will be highlighted how it is possible to use,FMO theory,(and other theories) to predict the,constitution,and,stereochemical,outcome of the products. Attention will be drawn to the,cyclic transition state,and the number of electrons involved (,Huckel,or,Mobius,), highlighting that when,4n+2,electrons are involved the reaction proceeds readily under thermal conditions, and the reversibility of such reactions. The concept of,Linear Combination of Atomic Orbitals,to form a bond(s) (and antibond(s) will be revised, and extended to the linear combination of frontier molecular orbitals. The,p,-molecular orbitals,of ethene, butadiene and 1,3,5-hexatriene will be considered and the identities of the,HOMO,and,LUMO,will be established, as well as the FMOs of a CH bond,.,2i,Electrocyclic Reactions,This lecture will extend the predicative nature of FMO theory regarding the stereochemical outcomes to,electrocyclic,reactions for 4 and 6,-electron transition states (by defining the,disrotatory,or,conrotatory,movement of the termini of the HOMO in the Transition State).,2ii,Cycloaddition Reactions,These lectures will introduce,cycloaddition,reactions and the concepts of (i),phase relationships,of the FMOs, (ii),geometry of approach,of the FMOs,(,suprafacial,and,antarafacial,will be defined), and (iii),minimum energy differences between the HOMO and LUMO,. These concepts will be exemplified by several Diels-Alder and related reactions. Attention will be drawn to the nature (chemical and stereochemistry) of substituents and their stereochemistry in the product.,3,Photochemically Induced Pericyclic reactions,These lecture will extend the predicative nature of FMO theory regarding the outcomes of electrocyclic reactions and cycloaddition reactions by considering how they can be induced photochemically, to give alternative stereochemical outcomes and allow reactions that did not go thermally.,Course Synopsis,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,CHM3A2,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,CHM3A2,Frontier Molecular Orbitals and,Pericyclic Reactions,Part 1(i):,The Questions FMO Analysis Can Answer,100%,0%,Ionic And Radical Reactions,(i)Ionic reactions,Here,pairs of electrons,move in,one direction,e.g. S,N,2, S,N,1, E2 and E1 mechnisms,(ii)Radical reactions,Here,single electrons,move in a,correlated manner,e.g. chlorination of alkanes,To date you have seen two broad categories of reaction:,Pericyclic Reactions,Pericyclic reactions are the 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,100%,0%,Clockwise,Anti-Clockwise,There is no real senses of flow for the electrons in pericyclic reactions,Stereospecific Reaction,Pericyclic Reactions: Cycloaddition Reactions,100%,0%,100%,0%,Stereospecific Reaction,Regiospecific Reaction,Kinetic Product,Thermodynamic Product,1,3-syndiaxial interactions,1,2,3,Revision: 1,3Syndiaxial Interactions,axial,equitorial,Thermodynamic and Kinetic Control,Kinetic,Product,Formed in Cycloaddition Reaction,Thermodynamic,Product,Not Formed in Cycloaddition Reaction,Pericyclic Reactions: Sigmatropic Reactions,100%,0%,Stereospecific,Reaction,Regiospecific,Reaction,Pericyclic Reactions: Why are they so specific?,Thus, an obvious question to ask ourselves at this point is why are pericyclic reactions so selective?,Pericyclic reactions show high degrees of,(i) Stereoselectivity,(ii) Regioselectivity, and,(iii)Diastereoselectivity,To help begin to answer this question we shall briefly need to revise the S,N,2 reaction mechanism where YOU WILL remember that this reaction type was highly stereoselective leading to inversion of chiral centres.,Revision: S,N,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 S,N,2 reaction mechanism leads to the,transition state,which allows the stereochemical information to be retained,i.e. a stereoselective reaction,.,This S,N,2 reaction mechanism should be contrasted to the S,N,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 (,D,G,), 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),Product,Starting,Material,Revision: Transition States,Pericyclic Reactions: Transition States,Pericyclic reactions involve,concerted flow of pairs of electrons going through,transition states,which retains,stereochemical information,that was present in the starting material.,Thus, now we can start to understand why pericyclic reactions are so highly stereo-, regio-, and diasteroselective.,Pericyclic Reactions Involve Cyclic Transition States,Cyclic Transition State,Pericyclic reactions involve ene and polyene units.,Thus, the transition states involve the overlap of,p,-molecular 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?,In order to understand the selectivity of pericyclic reactions, we need to understand these molecular orbitals and how they overlap.,Frontier Molecular Orbitals,We will first revise some simple molecular orbitals of a C-H,s,-bond and a C=C,p,-bond and then extend this analysis to highly conjugated linear polyenes and related structures/,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.,Second Year Organic Chemistry Course,CHM2C3B,Frontier Molecular Orbitals and,Pericyclic Reactions,Part 1(ii):,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.,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.,Learning Objectives Part 1,Frontier Molecular Orbitals,CHM2C3B, Introduction to FMOs ,Molecular Orbitals,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,The linear combination of,n atomic orbitals,leads to the formation of,n molecular orbitals,C,n,= Coeffecient: a measure of the contribution which the atomic orbital is making to the molecular orbital,f,m,= Electronic distribution in the atomic orbitals,A,SIMPLE,Mathematical Description of a MO,p,=,c,a,f,1,+ c,b,f,2,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,*,=,c,c,f,1,+ c,d,f,2,The probability of finding an electron in an occupied molecular orbital is 1.,p,=,c,a,f,1,+ c,b,f,2,p,*,=,c,c,f,1,+ c,d,f,2,S,c,2,=,c,c,2,+ c,d,2,= 1,S,c,2,=,c,a,2,+ c,b,2,= 1,C,c,= 1/2,C,a,= 1/2,C,b,= 1/2,C,d,= -1/2,Negative,The probability of finding an electron in an occupied molecular orbital is the,S,c,2,Thus, for the ethene,p,-molecular orbitals,1,2,1,2,So what about the combination of 3 or 4 or 5 or 6 p-atomic orbitals.,That is to consider conjugated systems,The Allyl Cation, Radical and Anion 3p 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,y,1,y,2,y,3,(,y,n,),The Allyl,p,-Molecular Orbitals,y,1,y,2,y,3,1,2,3,4,Nodal,position,4,/,1,= 4,Nodal,position,4,/,2,= 2,Nodal,position,4,/,3,Nodes,2,4,We can consider the molecular orbital (the electron density) being described by a,SINE WAVE,starting and finishing one bond length beyond the molecule,y,1,= 0 Nodes,y,2,= 1 Nodes,y,3,= 2 Nodes,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,HOMO =,H,ighest,O,ccupied,M,olecular,O,rbital,LUMO =,L,owest,U,noccupied,M,olecular,O,rbital,LUMO,Allyl,Radical,(3e),Allyl,Anion,(4e),HOMO,LUMO,HOMO,LUMO,HOMO,Allyl,Cation,(2e),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.,Nodal,Position,Number of,Nodes,y,n,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.,Nodal,Position,1,2,3,4,5,5/1 = 5,Number of,Nodes,0,1,2,3,y,1,y,2,y,3,y,4,y,n,HOMO,LUMO,A Reminder: Sinusodal Wave Function,Coefficients, c,n,n,=,c,a,f,1,+,c,b,f,2,+,c,c,f,3,+,c,n,f,n,That is to say the probability of finding an electron in a molecular orbital is 1,Each molecular orbital is described by an equation,S,c,2,=,1,Where c is referred to as the coefficient,Such that the,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.,Nodal,Position,Number of,Nodes,y,n,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.,Nodal,Position,6/1 = 6,6/2 = 3,6/3 = 2,Number of,Nodes,0,1,2,3,y,1,y,2,y,3,y,4,y,n,4,y,5,1,2,3,4,6,5,Molecular,Orbitals,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: 6p 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: 6p 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: 5p 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,CHM2C3B,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.,In bimolecular reactions (like the S,N,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 S,N,2 Reaction,HOMOs and LUMOs,Highest Occupied Molecular Orbitals,Lowest Unoccupied Molecular Orbitals,Revision: Transition State Geometries of Nucleophiles Attacking sp,3,Tetrahedral Centres,Inversion of Configuration Supports this