Lecture Notes on Cycloaddition Reactions - Mechanisms | CHEM 6311, Study notes of Mechanics

Download Lecture Notes on Cycloaddition Reactions - Mechanisms | CHEM 6311 and more Study notes Mechanics in PDF only on Docsity! 257 Xl. Cycloaddition reactions A. These are reactions of two acyclic molecules to form a cyclic molecule. 1. There are a very large number of these reactions in the organic world. 2. They are extremely useful in a synthetic sense, since two C-C bonds are formed. 3. We will not have time to give a comprehensive treat- ment. a. Chapters 10 and 11 in Lowry & Richardson do this. b. You do not have to read all of this material. B. We will concentrate on only one reaction: the dimerization of ethylene to cyclobutane. 1. Energy considerations a. The two C-C σ bonds formed are stronger than the two C-C π bonds broken. i) This is the result despite the ring strain. ii) Using Benson’s tables: H H H H H H H H H H H H H H H H + ∆H = -19 kcal/mol 11.1 b. ∆S, however, is negative. i) Two molecules become one. ii) Using Benson’s tables: ∆S298 = - 44 cal / mol - ° K c. Thus, ∆G298 = - 5.9 kcal/mol. i) The reaction is still exothermic and should be ob- servable, however ii) Although ∆H = -19 kcal/mol, ∆H‡ for this reaction as shown is incredibly high - about 43 kcal/mol. (a) There is no way that it will be observed experimen- tally under normal conditions. (b) One must use very forcing conditions (high tem- peratures, high pressure). 2. Mechanistic questions a.The activation barrier is a function of the reaction mechanism. 258 b. For the thermally driven reaction (considered above): i) One clue about the reaction mechanism is that, under some conditions, polymers are formed, i.e. -CH2CH2-(CH2CH2)n-. ii) Another clue, as we shall see later, is that the reac- tion is completely (or almost completely) stereo non-selective. c. The photochemical reaction is intriguingly different. i) It is quite general, olefins bearing substituents of almost any kind will still produce a cyclobutane. ii) There is virtually no activation energy associated with the reaction if one disregards the amount of energy required to excite the olefin dimer to the excited state. iii) Furthermore, the photochemical reaction not only is stereoselective but it is also stereospecific. C. Before we look at the mechanism for the thermal and photochemical dimerization reaction of olefins, it is useful to first consider another much more simple reaction: H2 + D2 → 2HD 1. This could be considered to be a special sort of cy- cloaddition reaction: H H D D + H H D D H H D D + 11.2 2. Many experiments have been carried out on this reac- tion. a. Part of the reason for this is that although experimentaly Ea = 41 kcal/mol , an essentially exact M.O. calculation has given Ea = 152 kcal/mol ! b. Yet for the dissociation reaction H-H → 2H•, ∆G = only 109 kcal/mol. 3. One possibility that people considered was that this might be a radical chain mechanism, i.e. H-H → H• + H• initiation H• + D2 → H-D + D• chain propagation D• + H2 → H-D + H• 261 two electrons in AS need to go up is greater than the energy need to break the H-H bond (i.e. the energy difference between AS at the ground state and the P.E. of H.). Thus, the potential energy surface for the H2 + D2 reaction is very replusive. Shown below are two views of the H2 + H2 reaction. Each sheet is worth 0.05 atomic units (~30 kcal/mol). These are all potential energies, so a surface with the most negative value is the most stable one. When r1 = r2, that plane defines all possible rectangular shapes. The line given by r1 = r2 = R defines all possible squares and, finally the geometries for R = 0 are those for all linear ar- rangements of the H2 molecules. These calculations are taken from, J. Am. Chem. Soc., 98, 6427 (1976). 262 As can be seen there are two tubes of low energy which correspond to the two ways H2 units can be combined in this coordinate system. Each tube is well- insulated; the potential steeply rises beyond the tube. b. An alternative bimolecular reaction path (the only other one) forms a tetrahedral molecule at the T.S.: D D H H + D D H H D H H D + 11.5 i) By applying group theory one can easily get the MO’s for the H4 tetrahedron. ii) Again this is a symmetry forbidden reaction with an extremely large activation barrier. 263 D D H H + D D H H D H H D + 11.6 A triply degenerate set of MOs c. An alternative to the dimerization reaction is given by: H D D H HH H D D H HH H D D H HH + + 11.7 ii)This pathway involves no HOMO-LUMO crossing (∴ symmetry allowed). iii) There are, however, two problems with this approach. (a) This is a termolecular collision. (i) No known reactions proceed via a real three-body collision. (ii) Furthermore, the ∆S‡ must be extremely negative and since ∆G‡ = ∆H‡ - T∆S‡, ∆H‡ would have to be extremely small. (b) Calculations have given an Ea (∆H‡) for this reac- tion to be 67 kcal/mol. While this is certainly smaller than 151 kcal/mol, it is nonetheless is somewhat too large compared to an experimental barrier of (∆G‡) 43 kcal/mol. iii)The working assumptions by the experimental physical chemists suggesting this (in 1973) were: 266 m1m2 AA AS SA SS C C H H H H C C H H H H m1 m2 H H H H H H H H H H H H H H H H H H HH H H H H H H HH H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H 11.13 c. An orbital correlation diagram for this concerted process then would be (note: σ lower than π, σ* higher than π*) AA AS SA SS m1m2 AA AS SA SS m1m2 C C H H H H C C H H H H C C H H H H C C H H H H +m1 m2 m1 m2 11.14 267 i) The HOMO and LUMO cross (look carefully at the orbital shapes). ii) Just as with H2 + D2 this is symmetry forbidden. iii) There must be a lower activation energy process. 2. The non-concerted thermal reaction pathway a. The most simple would be to allow one C-C bond to form at a faster rate than the other: C C H H H H C C H H H H C C H H H H C C H H H H + m2 m2 C C H H H H C C H H H H m2 11.15 b. For the same reason as the H2 + D2 reaction, the crossing point for the concerted reaction occurs at a higher energy than the energy of a p orbital, therefore, C H H H H C H H H H 11.16 should lie at a much lower energy than the T.S. for a concerted rxn. Futhermore, the mirror plane of symmetry, m1, is now not present and so the reaction becomes symmetry allowed. (Work this out for yourself.) c. An idealized potential energy surface for the reac- tion looks like this (the energy units are arbitary): C H H H H C H H H H C HH HH C H H H H C C HH HH C C H H H H C C HH HH C C HH HH 11.17 1 2 3 4 4 4 3 3 2 5 6 7 r1 r2 r1 r1 r2 r2 268 i) Although formation of the diradical will certainly be a very endothermic reaction, once it is formed it can “wander around”. ii) Large regions of space spanning θ1. θ2, θ3 are extremely flat. This is called a twixtyI surface. C C H H H H C C H H H H φ1 φ2 φ3 11.18 iii) It seems reasonable that the diradical would be formed via: C C H H H H CC H H H H C C H H H H C CH H H H + 11.19 iv) Therefore, there are three mechanistic possibilities for this reaction: + + + concerted synchronous concerted asynchronous nonconcerted 11.20 Reaction Path P o te n ti al E n eg ry Reaction Path P o te n ti al E n eg ry Reaction Path P o te n ti al E n eg ry 271 The buildup time is τ1 = 150 ± 30 fs and the decay time is τ2 = 700 ± 40 fs for this compound. This clearly is an intermediate and not a transition state species. The precursor cyclopentanone decays with a τ = 120 ± 20 fs. When cyclobutanone is used then the interme- diate species, trimethylene, has a much shorter lifetime, τ1 = τ2 = 120 ± 20 fs (see part b), whereas, stabilizing the teramethylene diradical by putting methyl substitu ents which can undergo hyperconjugation greatly increases the lifetime τ2 = 1400 ± 200 fs (see part c). Furthermore, τ2 = 190 fs for 1,3 cyclopentadiyl (why?). This is all consistent with the formation of diradical intermediates of varying lifetimes. The situation for tetramethylene is shown below. The barrier height for the diradical is estimated to be ~4 kcal/mol. e. Other evidence in favor of the diradical path: i) Substituents that stabilize radicals accelerate the reaction: (a) Thus for X = OR, halogen or alkyl (which stabilize radicals) dimerizations are faster. H H H X 11.24 (b) In fact for F2C=CF2 the radical is so stable that polymerization is a major side reaction. ii) The regioselectivity is consistent with radicals: 272 H H Cl Cl X CH2 Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl 11.25 iii) The reaction is stereo-nonselective: F F F F D H H D F F F F D H D H + + DH F F D H F F D H D H F F F F D H H D F F F F + 11.26 a) The diradical has a long enough lifetime to rotate freely. τrot has been estimated to be ~200 fs - Chem Phys. Letts. 303, 249 (1999). b) The products are formed in 1:1 ratio from either set of reactants. f. Sometimes a zwitterionic intermediate is formed. D + A δ- δ+ D A + D A + - - D A 11.27 D D = -OR, -NR2, -SR, etc. A A = -CN, -C(O)R, -CO2R, -NO2, etc. g. Evidence for a zwitterionic pathway comes from a variety of sources: i) Hammett type substituent effects 273 Ar + NC CN NC CN Ar CN CN CN CN ρ = -7.1 11.28 The very negative value of ρ is consistent with a zwitterion being formed so that electron density is lost from the arene (and builds up on one of the tetracyano-ethylene carbon atoms). ii) Solvent effects: in the above reaction, the rate in CH3CN = 6.3 x 104 times greater than the rate in cyclohexane. iii) The formation of intensely colored solutions - charge transfer complexes D + A δ- δ+ D A + - D A + - hν 11.29 low wavelength absorptions iv) Secondary D isotope effects: H2 OEt + N N CO2Me CO2Me N NEtO CO2Me CO2Me 11.30 H1 H1 H2 H1 H1 slow N NEtO CO2Me CO2Me H2 H1 H1 fast kH1/kD = 0.83 kH2/kD = 1.12 vi) The interception of intermediates. H OEt + N N CO2Me CO2Me N NEtO CO2Me CO2Me 11.31 H H H H H slow H2O N NEtO CO2Me CO2Me H H H OH2 N HNEtO CO2Me CO2Me H H H HO 276 AA AS SA SS SS SA AS AA * * + exciplex m1 m1 m2 m1m2 m1m2 11.35 m2 a. Excitation of an electron from the SA orbital which is strongly antibonding between the ethylenes to the AS orbital which is strongly bonding between the ethylenes, consequently will allow the olefins to ap- proach each other. This is called the exciplex. There is a neat experimental example of this phenomena on the next page which is derived from a series of very fanciful molecules, called pagodanes - see Pure and Applied Chem. 67, 673 (1995). Oxidation of the bis- olefin causes the C=C bonds to stretch by approxi- mately 0.10Å and a collapse of the non-bonded C--C distances between the two olefins by 0.55Å. Notice that oxidation of the totally saturated pagodane by two electrons also leads to the same intermediate. Here the metrical changes are opposite in sign but nearly the same in magnitude. 277 b. The reaction between the first excited state of the olefin dimer and the first excited state of the cyclobutane is symmetry allowed! c. There is one problem, however, with this scheme. i) Notice that the one electron in SA must rise up very high in energy to the σ* level. This should energetically be very unfavorable. ii) Another way to put this is that the 1st excited state of an olefin lies in the UV range ( > 165 nm absorp- tion); the 1st excited state of an alkane (σ ⇒ σ* ~ 135nm ) is much higher. iii) There then should be no driving force for this reaction since the exciplex can return back (by flores- cence) to ground state olefin dimer. d. There is a way around this, but we have to look at the properties of the electronic state in a molecule: Ψ ⇒ ψlψ2 a product function of orbitals i) There is a symmetry associated with each state, this can be determined by multiplying each orbital function times another according to the following rules: S x S = S S x A = A A x A = S 278 ii) Thus the first few excited states of the olefin dimer and cyclobutane are the following: (a) For the olefin dimer: AA AS SA SS m1m2 AA AS SA SS m1m2 (SS)2 (SA)2 (SS)2 (AS)2 (SS)2 (SA)1 (AS)1 (SS)2 (SA)1 (AA)1 (SS)1 (SA)2 (AS)1 (SS)1 (SA)2 (AA)1 SS Ψ1states AA Ψ 2 AS Ψ 3 AS Ψ 4 AA Ψ 5 SS Ψ 6 11.36 (b) for cyclobutane: this is the ground state of cyclobutane AA SA AS SS m1m2 AA SA AS SS m1m2 (SS)2 (AS)2 (SS)2 (SA)2 (SS)2 (AS)1 (SA)1 (SS)2 (AS)1 (AA)1 (SS)1 (AS)2 (SA)1 (SS)1 (AS)2 (AA)1 SS Ψ1states AA Ψ 2 SA Ψ 3 SA Ψ 4 AA Ψ 5 SS Ψ 6 11.37 this is the ground state of the olefin dimer iii) One can then energetically order the relative energies for the ground and excited electronic states of the olefin dimer and cyclobutane. It is now im- perative to correlate states of the same symmetry. The hypothetical scheme then is: 281 (i) Note: vertical excitation from P to Q produces a vibrationally excited state Q which can decay via R in any number of places without any ∆H‡ contribution. (ii) The equilibrium distance for the doubly excited SS state is actually point S - halfway between reactants and products. This decays to T from the conical inter- section of the two surfaces. f. In general the potential energy surface of a photo- chemical process can be represented by: This is a representation of two competing thermal and photochemical processes. In the photochemical world life is much more difficult due to surface crossings, internal conversion, conical intersections and the like! i) One might think that the photochemistry of H2 + D2 should follow the olefin dimerization since there is a relationship between the two thermal processes. Unfortunately this is not the case. ii) The potential energy surface for the lowest doubly excited state of the H2 + H2 reaction is shown on the next page. It is strongly repulsive in all directions. In fact the H2 distances are quite long compared to the ground state (see previous PE surfaces). The surface for the lowest singly excited state is shown by two views on the next page. 282 This is the lowest doubly excited state Here are two views of the lowest singly excited state 283 iii)Notice that there is a low energy cell formed. This is the exciplex. The exciplex is a square of ~1.5Å dimensions. This can be compared to H2 in the ground state where the H-H distance is 0.74Å. F. The Diels-Alder reaction. This reaction dates back to O. Diels and K Alder, J. Liebig’s Ann. Chem., 460, 98 (1928)! The parent reaction is: + 11.44 This was reported by L. Joshel and L. W. Butz, J. Am. Chem. Soc., 63, 3350 (1941). This has been a reaction which has been around for a long time. It is very useful because it is a very stereospecific reaction which tolerates many functional groups and so it is extensively used to build larger cyclic molecules from to acyclic pieces. 1. There are again three basic paths that one can consider for the reaction: + 11.45 concerted synchronous concerted asynchronous nonconcerted 2. Since the reaction is stereospecific, the nonconcerted path seems rather unlikely. However, an argument devel- oped for the two possible variants of the concerted reaction between two physical organic chemists, M.J.S. Dewar and Ken Houk. 286 8. The results are shown below. Let us only consider the results for norbornene; those for norbornadiene are very similar. A species with the molecular weight of the precursor (94 amu) rises and decays with a time constant of 160 ± 20 fs. There is another species at 66 amu which rises with a time constant of 30 ± 5 fs and decays at 220 ± 20 fs. This is a real intermediate since its intensity drops off with time and it has the same molecular weight as cyclopentadiene. A careful analysis was made of the decay of the 94 amu peak and the rise of the 66 amu peak. They do not match and in fact differ by a factor of 5. Therefore, the 94 and 66 amu peaks must represent separate trajectories (reaction paths). 9. The interpretation of these results was initially thought to be that there were two reaction paths, a concerted path leads to the species decaying with the 220 fs rate since the time constant for stretching a C-C bond is ~40 fs and, therefore, this is exactly in the range of the 287 + + * * (π,π*) (π2) biradical collapsed products 160 fs 220 fs 30 fs ~0 fs and 11.49 184 kcal/mol conical intersection 30 fs buildup. So this is then a concerted asynchronous route. The species with the 160 fs lifetime is a diradical intermediate. This is certainly a novel mecha- nism. Later MO calculations were reported by Houk et. al. - Pure App. Chem. 70, 1947 (1998) - which offered an alternative explanation. The initial photon pulse produces a highly vibrationally excited state where one electron has been promoted from the π to the π* orbital. This then decays into a conical intersection. Either one bond breaks to produce a diradical inter- mediate which then undergoes closure to form a variety of products. Alternatively two bonds are broken to form excited state cyclopentadiene which then decays. The full scheme is shown below. 10. The moral of this story, at this point in time, is then that the femtosecond spectroscopy study of this reaction does not correlate with what occurs in the ground state thermal reaction. For most Diels-Alder reactions the synchronous concerted path is the most reasonable. 288 G. This is only a very small part of the story about cycloaddi- tion reactions. 1. Basically one must always deal with a spectrum of mechanistic behvior: A A A A B B B B + r1 r2 X X X X r1 r2 concerted, synchronous concerted, asynchronous nonconcerted 11.50 2. What makes cycloaddition reactions so useful and a study of their mechanisms so important is that the stere- ochemistry - including regiochemistry (see below) - can be predicted and used to form much larger organic molecules. A B A B C D C D + A B D C r1 r2 X 11.51 In other words cycloadditions form an important tool to synthesize natural products, etc. But you will have to take a couple more organic classes - physical organic and synthesis - to learn about this!