Pericyclic Reactions page 1

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1 Pericyclic Reactions page INTRDUCTIN T PERICCLIC REACTINS. Reaction classes In the broadest sense there are three reaction classes, characterised by the way that the electrons behave in reaction mechanisms. Ionic reactions, the most common, involve charge buildup, with electron pairs moving in one direction under the influence of various structural features. The electron pair movements involved in bond making and bond breaking may be synchronous, as in the S N 2 reaction, or stepwise, as in electrophilic additions to alkenes, but the driving forces are the same electron deficiency (electrophilicity, acidity, oxidation potential, etc.) or electron excess (nucleophilicity, basicity, reduction potential). Radical reactions differ in that they proceed through a stepwise redistribution of single, rather than paired, electrons. Such reactions are also driven by structural factors, particularly hypovalency, but proceed without the (necessary) buildup of charge. The third distinct reaction class is pericyclic reactions. A working definition is a reaction that takes place as a continuous, concerted reorganisation of electrons. Pericyclic reactions are distinct in proceeding through cyclic transition structures in which the participating molecular orbitals (Ms) maintain bonding interactions throughout. Pericyclic reactions are commonly represented using curly arrows, but it will soon be obvious that this is deceptive the bonding changes in a pericyclic reaction might be represented using arrows, but any impression of pairwise movement in one direction is false. In a pericyclic reaction, the Ms of the starting material(s) smoothly evolve into the Ms of the product(s). We will see later how Woodward and Hoffmann reached the conclusion that this 'evolution' must take place with the conservation of orbital symmetry, i.e. each starting M correlates with a product M that possesses the same symmetry properties.

2 Pericyclic Reactions page 2.2 Pericyclic reaction types We will consider three major subclasses of pericyclic reaction, illustrated below in schemes showing both the 'deceptive' mechanistic arrows and a representation of the characterising cyclic transition structure..2. Cycloadditions These are pericyclic reactions in which two picomponents combine to generate a new ring through the formation of two new sigmabonds. Such reactions are usually stereospecific, with the stereochemistry of the starting materials determining that of the products. The Diels Alder reaction is a [4 + 2] cycloaddition heat concerted TS is a closed orbital loop cis product only reaction is stereospecific trans product only.2.2 Electrocyclic reactions These are pericyclic reactions in which a ring is opened (or closed) through the conversion of a sigmabond into a pibond (or the reverse). Ringopening of a cyclobutene is an electrocyclic reaction heat concerted TS is a closed orbital loop (E,Z) product only.2.3 Sigmatropic rearrangements These are pericyclic reactions in which a sigma bond 'appears to move' across a conjugated system to a new site. The Claisen rearrangement is a [3,3] sigmatropic shift 2 heat concerted TS is a closed orbital loop 3 (E) product only

3 Pericyclic Reactions page 3.3 General features of pericyclic reactions Pericyclic reactions have been known for over 00 years, and can be highly, even fully, selective, making them valuable in synthesis. They have the following general features: Concerted Reversible Single transition structure (TS) with no intermediates chanisms explained through analysis of frontier molecular orbitals (FMs) Forward or reverse reactions provide the same analysis [n + m] CCLADDITIN appropriate conjugated π system n m sigma bond ELECTRCCLIC REACTIN Typical reaction profile TS [n,m] SIGMATRPIC REARRANGEMENT n m n m Energy A B Reaction coordinate All of these reactions are subject to strict selection rules whose origin will become clear when FM principles are applied and the following interrelated factors taken into account: The mode of activation, i.e. heat (thermal) or light (photochemical) The number of electrons involved in the transition structure The stereochemistry of the starting materials and the products The last of these points is particularly important pericyclic reactions are stereospecific. This is what makes them so valuable in synthesis and generations of chemists have investigated the reaction mechanisms. The examples below illustrate some of the intriguing possibilities..3. Cycloadditions H 00 heat [4 + 2] cycloaddition 6electron TS H H 002 light [2 + 2] cycloaddition 4electron TS photochemical (not thermal) H

4 Pericyclic Reactions page C 50 C [4 + 2] cycloaddition 6electron TS.3.2 Electrocyclic reactions C electrocyclic ringclosure 6electron TS E,Z,E cis C >99.5% <0.% electrocyclic ringopening 4electron TS 006 light electrocyclic ringclosure 4electron TS photochemical (not thermal).3.3 Sigmatropic rearrangements C [,5] hydrogen transfer 6electron TS 008 H 200 C [3,3] Claisen rearrangement 6electron TS 009 H 220 C then H 2 [3,3] oxycope rearrangement 6electron TS H

5 Pericyclic Reactions page 5.4 chanistic analysis of pericyclic reactions The underlying principles of pericyclic reactions have emerged in various forms, and we will focus on the frontier molecular orbital (FM) approach developed by Fukui in the 950s. This allows the interpretation of a molecular interaction to be restricted to an analysis of the interactions between the highest occupied and lowest unoccupied molecular orbitals (HMs and LUMs) of the reacting partners. ther important theories and interpretations that will be touched upon include the following: Conservation of orbital symmetry (Woodward Hoffmann) This is the first theory that successfully explained and predicted the outcome of pericyclic reactions. It correlates all the relevant orbitals in the starting material(s) and product(s). We will see a few examples of the vehicle for this type of analysis, the orbital correlation diagram, but we won't need to go too deeply into the theory. Aromatic transition structure (DewarZimmerman) This is an easy concept to apply to all reaction types, but it's not so easy to understand why it is valid, especially in comparison with the FM approach that we will generally choose. We will begin with some revision of the principles and terminology of covalent bonding, with an emphasis on pi systems.

6 Pericyclic Reactions page 6.5 Frontier molecular orbitals and interaction diagrams Molecular orbitals are constructed by the linear combination of atomic orbitals (LCA) method. This topic is revised here so that the key features of FMs, namely their energy and symmetry properties, can be called upon during our mechanistic analysis of pericyclic reactions. We need to know how to draw the HMs and LUMs of π systems..5. The C H bond Using the LCA method, we can construct a diagram showing the possible combinations of a hydrogen s orbital and a carbon sp 3 hybrid orbital to provide a picture of a C H bond such as those in methane. This will serve our purposes but should be recognised as deceptive, as methane has eight valence electrons and hence four Ms. We have used hybridisation to 'mix' them and simplify the picture. Molecular orbitals of a C H bond LUM C sp 3 E H s HM.5.2 The C C sigma bond In ethane there are 4 valence electrons, and therefore 7 filled Ms, but we will again simplify the picture. The interaction diagram below will be used to represent the most significant orbital interactions that contribute to a C C (sigma) bond. Molecular orbitals of a C C bond LUM E C 2p C 2p HM

7 Pericyclic Reactions page The C C π bond The molecular orbital for the pi (π) bond in ethene is higher in energy than the (five) other occupied Ms and the system can be represented by the diagram below, showing the possible combinations of two carbon 2p atomic orbitals. It should be borne in mind that pi bonding, with its 'sideways' overlap, is inherently weaker than sigma bonding, so both the drop in energy due to bonding and the HMLUM gap are lower. Molecular orbitals of a C=C π bond π LUM C 2p C 2p π HM ANTIBNDING CMBINATIN: ψ π* = 0.707φ 0.707φ 2 BNDING CMBINATIN: ψ π = 0.707φ φ 2 [see Appendix ] The C 2p orbital is the highest energy orbital on an sp 2 carbon, so this diagram actually shows the highest occupied molecular orbital (HM) and the lowest unoccupied molecular orbital (LUM) of ethene. These are the frontier molecular orbitals (FMs) of the molecule..5.4 The π orbitals of,3butadiene Combining four carbon 2p orbitals provides us with the molecular orbitals of butadiene. In order of increasing energy, these have zero,, 2 and 3 nodes respectively. The total of four electrons fill the two lowest π Ms, so the HM and LUM are ψ 2 and ψ 3 respectively. The c values vary between two values in this system, although for most purposes it is only required that a diagram correctly depicts the relative phases. πmolecular orbitals of,3butadiene ψ 4 Four p orbitals ψ 3 ψ 2 E ψ ψ 2 BNDING ψ 3 ψ 4 ANTIBNDING ψ

8 Pericyclic Reactions page The π orbitals of allyl (propenyl) cation and anion The allyl cation, anion and radical all have the same orbitals, but each system contains a different number of electrons. We can construct the M of the allyl system by the linear combination of a C=C pi bond (made from two C 2p orbitals) with a third C 2p orbital, as below. Notice that, compared with the C=C π bond, the energies of both the HM and the LUM are lower in the allyl cation and higher in the allyl anion. The significance of this will become more obvious in the context of perturbation by substituent effects (see later). πmolecular orbitals of the allyl anion ψ 3 ψ 3 LUM π ψ 2 ψ 2 C 2p HM π ψ ψ πmolecular orbitals of the allyl cation ψ 3 ψ 3 π LUM ψ 2 ψ 2 C 2p π HM ψ ψ

9 Pericyclic Reactions page 9.6 Electron distribution in covalent bonds In ethene the lobes of the pi bond have the same size (the two C 2p As contribute equally to the M). This is not the case in an unsymmetrical covalent bond, since the electron distribution is subject to the different influences of each contributing atom. Unless a covalent bond is completely symmetrical, its electron density will tend to be polarised. This is a manifestation of ionic character, and the limiting case is, of course, a fully ionic bond. A comparison of the C=C and C= pi bonds illustrates this in terms of M energies. We constructed the orbital interaction diagram for a C=C π bond (see.5.3). The diagram for a C= π bond is similar, but this time the two orbitals involved are not the same. Molecular orbitals of a C= π bond π C side view C top view π LUM C c = 0.7 π C C In a symmetrical πbond the lobes have equal size C 2p 2p π HM C The following points should be borne in mind when considering orbital interactions: When the interacting orbitals are close in energy, the interaction is larger. 2 When the overlap of the orbitals is larger, the interaction is larger. 3 When orbitals of different energies interact, the molecular orbital (M) contains more of the atomic orbital (A) which is closer to it in energy. The last of these points is important when comparing C=C with C=. There is uneven electron distribution in the C= orbitals (the c values are unequal); has more electron density in π C= but C has more in π* C=. As well as the bonded atoms themselves, double bond substituents can induce uneven distribution of electron density in π systems. This is particularly significant in the context of the [4 + 2] (DielsAlder) cycloaddition (see 2..3).

10 Pericyclic Reactions page 0.7 Describing reactions as HM LUM interactions So far we have used orbital interaction diagrams to describe the bonding stabilisation that occurs in a transition structure when two different atoms join to form a new bond, and using the same principles it is possible to construct an orbital interaction diagram for a two reacting molecules. The starting point for this has to be the recognition that, as two molecules approach, three major forces operate: The occupied orbitals of one molecule repel the occupied orbitals of the other. This is known as filled shell repulsion. 2 Any positive charge on one molecule attracts any negative charge on the other (and repels any positive). This is Coulombic attraction. 3 The occupied orbitals (especially the HMs) of each molecule interact with the unoccupied orbitals (especially the LUMs) of the other, causing an attraction between the molecules. The interaction is greatest when the interacting HM and LUM are close in energy. In hard/soft acid/base (HSAB) terms, the situation in (2) drives the hardhard interaction (ionic bonding). The situation in (3) describes the softsoft interaction (covalent bonding). The HMLUM interaction is particularly important for pericyclic reactions, and is quantified in the third (frontier orbital) term of the KlopmanSalem equation. Klopman and Salem showed that a chemical reaction can be analysed in orbital terms by summing the interactions 3 above for whole molecules when they approach each other (perturbation theory). They developed the following equation, which contains separate expressions for the electrostatic and covalent interactions. These can be of the bonding type (unlikecharge ionic and filledempty covalent) or the repulsion type (likecharge ionic or filledshell repulsions). AN EQUATIN FR ESTIMATING CHEMICAL REACTIVIT The energy ( E) gained and lost when the orbitals of one reactant overlap with those of another can be expressed in the following equation, developed by Klopman and Salem using Perturbation Theory: ΔE = ( q a + q b ) β ab S ab Q Q k l k <l εr kl occ. r unocc. + + s occ. s unocc. 2(Σ abc rac sbβ ab) 2 r E r E s where q a and q b β and S Q k and Q l ε R kl c ra E r are the electron populations in the atomic orbitals a and b are resonance and overlap integrals are the total charges on atoms k and l is the local dielectric constant is the distance between the atoms k and l is the coefficient of atomic orbital a in molecular orbital r, where r refers to the molecular orbitals on one molecule and s refers to those on the other is the energy of molecular orbital r This complex expression can be simplified by assuming that the only significant covalent interactions are those between the HMs and LUMs (frontier orbitals) of the two reacting molecules, and ignoring all the others.

11 Pericyclic Reactions page A SIMPLIFIED EQUATIN FR CHEMICAL REACTIVIT Since the interactions of all other orbitals have much larger (E r E s ) values, we can simplify the above equation by using only the HM of a nucleophile and the LUM of an electrophile: ΔE = Q nuc Q elec εr 2(c + nuc c elec β) 2 EHM(nuc) E LUM(elec) Coulombic term frontier orbital term Notice that the frontier orbital term will be dependent upon the following properties:. The coefficients (sizes) of the overlapping orbitals 2. The extent of the orbital overlap 3. The energy differences between the interacting HMs and LUMs It is by the analysis of the properties 3, in an essentially qualitative way, of the HMs and LUMs involved in a pericyclic reaction, that various aspects of mechanism, kinetics and selectivity can be interpreted. But more importantly, pericyclic reactions are also subject to a series of selection rules based on the symmetry properties of the interacting orbitals.

12 Pericyclic Reactions page 2 Appendix. rbital Coefficients The electron distribution function ψ for a molecular orbital is the sum of the atomic orbitals which contribute, i.e. ψ M = Σ c i φ i where the coefficient c is a measure of the contribution that each atomic orbital makes to the molecular orbital. For a C=C π bond the bonding (π) and antibonding (π*) combinations are thus: π π* = = c φ + c 2 φ 2 c φ c 2 φ 2 The squares of the c values are a measure of the electron population in the neighbourhood of the atom in question. nly one electron in each spin state can be in each orbital, so the following must be true: Σ c 2 = For a symmetrical C=C π bond the c values must be the same, so the π and π* combinations become: π π* = = 0.707φ φ φ 0.707φ 2