Two different bond-containing molecules react to forma cyclic compound
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Two conventions for naming cycloadditions are used in the literature.
Number of atoms or number of electrons1
The older convention is that m and n denote the number of atoms in each component.
Woodward and Hoffmann altered the convention to make m and n denote the number of electrons in each component.
The number of electrons and the number of atoms are the same for reactions involving neutral species such as the Diels–Alder reaction, but theyare not the same for reactions involving charged or dipolar species.
For example, the 1,3-dipolar cycloaddition is a [3 + 2] cycloaddition according to the older convention and a [4 + 2] cycloaddition according to the newer one.
Always be careful to note which convention is being used.
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Cycloadditions are classified according to the number of electrons that interact in the reaction
Cycloaddition reactions
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Electrocyclic reactions of cations and anions
Three-atom electrocyclizations (4 electrons)
Azomethine ylids can be trapped by [3 + 2] cycloadditionreactions with dipolarophiles.4
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Why?????
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Define the type of pericyclic reactions for the following reactions and determine if they are 4n + 2 or 4n systems.
Questions
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There are 3 types: (1) occupied-occupied (2) unoccupied-unoccupied (3) occupied-unoccupied.
Energy consequences of the interaction between orbitals
Energy consequences of the interaction between orbitals
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Energy consequences of the interaction between orbitals
Energy consequences of the interaction between orbitals
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For occupied-unoccupied interactions, interactionsbetween orbitals are greater if the individual energies are similar, and less if they are significantly different (Fig d and e). Thus, the largest (favorable) energy interactions occur when there is the least energy difference between the interacting orbitals.
Energy consequences of the interaction between orbitals
Energy consequences of the interaction between orbitals
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Energy consequences of the interaction between orbitals
Energy consequences of the interaction between orbitals
Figure 7.4
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These occupied-unoccupied interactions, correspond to interactions between the HOMO of one molecule and the LUMO of the other (Fig 7.4). If the two reacting molecules have similar energy levels, the HOMO-LUMO interactions in each direction will both contribute significantly (Fig 7.4a). Whereas if the levels are differentin energy, the dominant interaction will be the one where there is the lesser difference in energies (Fig 7.4b).
Energy consequences of the interaction between orbitals
Energy consequences of the interaction between orbitals
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In the TS of cycloaddition, stabilization comes chiefly from overlap between the HOMO of one reactant and the LUMO of the other.
Energy consequences of the interaction between orbitals
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There are two possible ways to form bonds to the atoms of a pi bond.1
Woodward and Hofmann designated addition to lobes on the same side of a pi system as suprafacial addition on that pi system and called addition to lobes on opposite sides of a pisystem antrafacial addition.1 These modes of addition are
identified by the symbols s and a, respectively.
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Cycloaddition of a four-electron unit reacting antrafacially witha two-electron unit reacting suprafacially would be classified as a [4a + 2s] reaction.1
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Frontier Orbital Analysis of a [4 + 2] Cycloaddition Reaction
Supra, supra Supra, supra
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Frontier Orbital Analysis of a [4 + 2] Cycloaddition Reaction
In the course of a pericyclic cycloaddition, the p-orbitals at the ends of the conjugated system of each component form sigma bonds to the p-orbitals at the ends of the conjugated system of the other component.1,2
The p-orbitals must therefore approach each other head on, (see Fig. 2.84,the diene actually comes down on the top of the dienophile) with the new sigma-bonds forming between C-1 and C-1' and between C-4 and C-2'. At the same time, a new pi-bond forms between C-2 and C-3 of the diene.1,2
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A [2 + 2] Cycloaddition Reaction
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Frontier MO Analysis of the [2 + 2] Cycloaddition Reaction
Thermal
Fig 33.23 [2 + 2] thermal cycloaddition. Supra, supra: geometrically possible, but symmetry-forbidden. Supra, antara: symmetry-allowed, but geometrically difficult.
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Frontier MO Analysis of the [2 + 2] Cycloaddition Reaction
Photochemical
Fig 33.22 symmetry-allowed photochemical [2 + 2] cycloaddition: two molecules of ethylene, one excited and one in the ground state. Interaction is bonding.
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Antrafacial overlap
Almost all pericyclic cycloadditions are suprafacial on both components.
Straightforward antarafacial attack in cycloadditions is therefore very rare.
Antrafacial overlap on one component in a cycloaddition would need a most unusually long and flexible conjugated system.
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Woodward-Hoffmann rules for [i + j] cycloadditions1
PhotochemicalThermalNo. of electrons
(i + j)
supra, supraantara, antara
supra, antaraantara, supra
4n
supra, antaraantara, supra
supra, supraantara, antara
4n + 2
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Antrafacial overlap
The [14 + 2] reaction shown proceeds antrafacially.1,2
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Antrafacial overlap
The [14 + 2] reaction shown proceeds antrafacially.1,2
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The Diels-Alder reaction is a [4 + 2] cycloaddition.
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Otto Diels and his research student Kurt Alder worked at the University of Kiel and discovered this reaction in 1928. They won the Nobel Prize in 1950.
The Diels-Alder reaction is a [4 + 2] cycloaddition.
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Fixed transoid dienes are unreactive.2a,2
The dienes must have the s-cis conformation.2
Dienes in which one or both substituents at C1 and C4 are cis to the other double bond react very slowly.1
The most reactive dienes are those in which the diene unit is forced to maintain an s-cis conformation e.g. cyclopentadieneundergoes Diels-Alder dimerization at RT.1,2
Factors affecting the rate of the Diels-Alder reaction
(1) The diene
(a) Conformation of the diene
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(b) Aromaticity1
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(2) Electron-demand in Diels-Alder reactions
Very slow1
Fast1
Most Diels–Alder reactions occur with what is called normal electron-demand, in which an electron-rich (bears electron-donating group) diene reacts with an electron-poor (bearing electron-withdrawing group e.g. carbonyl, CN, sulfonyl, NO2) dienophile.2
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Electron-demand in Diels-Alder reactions1
Frontier MO theory can be used to understand the dependence of the rate of the Diels–Alder reaction on the electronic nature of the substrates. As in any reaction, the rate of the Diels–Alder reaction is determined by the energy of its TS. In the TS of most (normal electron-demand) Diels–Alder reactions, the HOMO of the diene interacts with the LUMO of the dienophile.
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Electron-demand in Diels-Alder reactions
Very electron-poor dienes can undergo Diels–Alder reactions with electron-rich dienophiles in the inverse electron-demand Diels–Alder reaction. The dominant interaction in the TS of inverse electron-demand Diels–Alder reactions is between the LUMOdiene and the HOMOdienophile.1
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Electron-demand in Diels-Alder reactions1
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Electron-demand in Diels-Alder reactions
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Lewis-acid catalysis of the Diels-Alder reactions.
Recognizing a Diels–Alder product.
Regioselectivity.
Influence of Lewis-acid catalysis on regioselectivity of the Diels-Alder reactions.
Stereospecificity.
Stereoselectivity: endo vs exo.
LEARNING OUTCOMES
LECTURE 5
LEARNING OUTCOMES
LECTURE 5
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(3) Lewis-acid catalysis of the Diels-Alder reactions
Lewis acids (e.g. BF3, AlCl3, TiCl4, SnCl4,..) are known to catalyseDiels–Alder reactions. They coordinate to a Lewis base site, normally a heteroatom such as a carbonyl oxygen of the dieneophile. The coordination of a Lewis acid makes the dienophile more electron-deficient.1
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(3) Lewis-acid catalysis of the Diels-Alder reactions
The energy of the HOMO and LUMO of the dieneophile is decreasedcompared to the uncomplexed dienophile and hence the HOMOdiene- LUMOdienophile gap is further reduced. Consequently, the rate of the Diels–Alder reactions is further enhanced.1
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Lewis-acid catalysis of the Diels-Alder reactions
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We can easily recognize a Diels–Alder product as follows:
Recognizing a Diels–Alder product1
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Recognizing a Diels–Alder product1
The simplest way to find the starting materials is to draw the reverse Diels–Alder reaction.
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The Diels-Alder reaction between an unsymmetrical diene and an unsymmetrical dienophile can lead to the formation of a mixture of regioisomersdepending upon the relative orientation of the diene and the dienophile in the TS.1
Generally, the more powerful the electron-donating and electron-withdrawing substituents, the more regioselective is the reaction.2
Regioselectivity
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Regioselectivity
(1) Draw an “ionic” stepwise mechanism.
(2) Orbital coefficient arguments.
How can we determine the regioselectivity of the reaction?
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Regioselectivity
The simplest way to predict which product will be formed is to draw an “ionic” stepwise mechanism for the reaction to establish which end of the diene will react with which end of the dienophile.
Of course this stepwise mechanism is not completely correct but it does lead to the correct orientation of the reagents.
(1) Draw an “ionic” stepwise mechanism.
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Regioselectivity
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Regioselectivity
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Regioselectivity
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Regioselectivity
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Regioselectivity
The Diels-Alder reaction is generally highly regioselective and the formation of ortho and para adducts predominate over the meta adduct.2
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Regioselectivity1
• Sometimes, looking at the resonance structures can not explain many cases.
• In such cases, orbital coefficient arguments should be used.1
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Regioselectivity1
The regioselectivity of inverse electron-demand Diels–Alder reactions, 1,3-dipolar cycloadditions, and other cycloadditions can similarly be explained by resonance and orbital coefficient arguments.
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ProblemsWhat are the products of the following reactions? Examine your answer by “ionic” stepwise mechanism and orbital coefficient arguments (using Fig 1A) and compare between the results of the two methods.
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Stereospecificity
The stereochemical relationships among substituents in a suprafacialcomponent of a cycloaddition are preserved in the cycloadduct.1
Groups that are cis (or trans) to one another in the dienophile become cis(or trans) to one another in the product. The two out groups in the dienebecome cis to one another in the product, as do the two in groups.1
Because one diastereomeric starting material gives one diastereomericproduct, cycloadditions are said to be stereospecific.1
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StereospecificityDienophile Groups that are cis (or trans) to one another in the dienophile
become cis (or trans) to one another in the product.
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StereospecificityDiene The two out groups in the diene become cis to one another
in the product, as do the two in groups.1
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Stereospecificity
The stereochemical relationships among substituents in a suprafacialcomponent of a cycloaddition are preserved in the cycloadduct.1
Groups that are cis (or trans) to one another in the dienophile become cis(or trans) to one another in the product. The two out groups in the dienebecome cis to one another in the product, as do the two in groups.1
Because one diastereomeric starting material gives one diastereomericproduct, cycloadditions are said to be stereospecific.1
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Stereospecificity1,3-dipolar cycloadditions
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Electrocyclic reactions of cations and anions
Three-atom electrocyclizations (4 electrons)
Since cycloaddition is stereospecific (suprafacial on both components), the stereochemistry of the products can tell us thestereochemistry of the intermediate ylid (4 pi electron system), and confirms that the ring opening is conrotatory.4
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Electrocyclic reactions of cations and anions
Three-atom electrocyclizations (4 electrons)
Heating of oxiranes (epoxides) give the corresponding carbonyl ylids, which can be trapped by cycloaddition reactions.1,2
These ring openings proceed stereospecifically by conrotatorypaths.1,2
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Write the structure of the product of the following reaction and predict its stereochemistry.
Questions
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Predict the stereochemistry of the product of the following reaction.
