Electrocyclizations
Now let us answer the question, “How is the new bond formed?” In the case of an electro- cyclic reaction, this involves the rotation of the two ends of the conjugated system to permit σ-type overlap of the 2p orbitals at the ends of the chain, as shown in Figure 6.4.
This rotation can be in the same direction (clockwise for both or counterclockwise for both), when it is known as a conrotatory ring closure, or in opposite directions, when it is known as a disrotatory ring closure. If the FMO is symmetric with respect to a twofold axis of symmetry, the C2 axis of symmetry is preserved throughout the reaction by a con- rotatory process and is lost during a disrotatory process, and if the FMO is symmetric with respect to a mirror plane, the reverse is true.
When the reaction symmetry matches the symmetry of the FMO involved, the reaction is favorable because it leads to bonding overlap of the terminal lobes—it is symmetry- allowed in the ground state. When the reaction symmetry does not match the symmetry of the FMO, however, the reaction becomes very unfavorable because it leads to antibonding overlap of the terminal lobes—it is symmetry-forbidden in the ground state. This is illus- trated in Figure 6.4, which shows that, if the lobes at the end of the conjugated system are out of phase, a conrotatory ring closure is required to give bonding overlap, and that if the lobes are in phase, a disrotatory ring closure is required to give bonding overlap. Because ψ2 for the 1,3-diene system is symmetric with respect to a C2 axis, we expect that (2E,4E)-2,4-hexadiene should give trans-3,4-dimethylcyclobutene as the product of the reaction and that heating trans-3,4-dimethylcyclobutene should give (2E,4E)- and/or (2Z,4Z)-2,4-hexadiene.
Cycloaddition reactions are the prototypical bimolecular pericyclic reactions. By far the most widely used cycloaddition reaction is the Diels-Alder reaction between a diene and a dienophile to give a cyclohexene-based product. To discuss the Diels-Alder reaction, we first need to define some stereochemical terms. When an addition occurs to a π-bonded com- pound, if the two new σ bonds are formed on the same face of the molecule, the addition is said to be suprafacial with respect to that reactant. This term is gradually replacing the older one, syn addition, in discussions of the stereochemistry of additions to unsaturated systems.
Me Me
Me Me Me Me
Me Me
mirror plane of reactant is preserved in product
Me Me
Me Me
Me Me Me Me
C2 axis of symmetry in reactant is preserved
in product
Me Me ψ3
Me Me
ψ2
Figure 6.3 Possible electrocyclic ring closures of (2E,4E)-2,4-hexadiene
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CONROTATORY bonding overlap throughout
FAVORED
DISROTATORY antibonding overlap throughout
NOT FAVORED terminal lobes out of phase
CONROTATORY antibonding overlap throughout
NOT FAVORED
DISROTATORY bonding overlap throughout
FAVORED terminal lobes in phase Figure 6.4 Orbital symmetry
and electrocyclization
When the addition occurs such that the two new σ bonds are formed on opposite faces of the reactant, the addition is antarafacial; this term is gradually replacing the older one, anti addition. Other addition reactions that we have studied already fall into these two classes:
hydroboration is a suprafacial addition to an alkene, whereas the addition of bromine to an alkene is antarafacial.
In a cycloaddition reaction, two new σ bonds are formed at the expense of two π bonds. This means that the reaction may be suprafacial with respect to both reactants, suprafacial with respect to one and antarafacial with respect to the other, or antarafacial with respect to both (this combination is quite rare and can be ignored in most cases). The stereochemical consequences of each of these reaction pathways are shown in Figure 6.5.
Note how suprafacial addition leads to retention of relative configuration at the reacting centers, whereas antarafacial addition leads to inversion of relative configuration.
Cycloadditions
Cycloaddition reactions are occasionally described using a system that shows the number of π electrons in each reacting species as well as the stereochemistry of the addition with respect to that reacting species. For example, the Diels-Alder reaction is the reaction between a diene (with four π electrons) and a dienophile (with two π electrons). Using this system, it is desig- nated as a 4π + 2π cycloaddition. In addition, the reaction is suprafacial with respect to the diene (4πs) and the dienophile (2πs), so the complete representation of the reaction in this system is [4πs + 2πs]. A simpler system denotes the cycloaddition by the number of atoms in the two reacting species. The Diels-Alder reaction is a [4 + 2] cycloaddition in this system, also.
Cycloaddition reactions are very amenable to the same simplified FMO analysis that we used for electrocyclizations. In other words, only the terminal lobes of the reacting species
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x w
z y a bd c
w x
z y a
dc
b suprafacial- suprafacial
x w
z y a bd c
w x
y z a
dc
b suprafacial (polyene)- antarafacial
x w
z y a bd c
w x
y z b
dc
a antarafacial- antarafacial ret.
ref.
ret.
ref.
ret.
ref. ref.
inv.
inv.
ref. ret\f.
inv.
Figure 6.5 Stereochemical outcomes of cycloadditions:
“ret.” indicates retention of configuration and “inv.”
indicates relative inversion of configuration relative to the reference centers, labeled “ref.”
need be considered explicitly. The two possible HOMO-LUMO combinations for the [4 + 2] and [6 + 2] cycloadditions are shown in Figure 6.6, which illustrates this simplified approach. Based on this simple analysis, we anticipate that the [4 + 2]
cycloaddition will be symmetry- allowed when suprafacial with respect to both participating reactants, whereas the related [6 + 2] cycloaddition, which forms a cyclooctadiene, will be symmetry-forbidden unless the reaction is suprafacial with respect to one participant and antarafacial with respect to the other. In both reac- tions, the two species react through complementary FMOs; one uses the HOMO, and the other uses the LUMO. This observation may be extended to state that in all multiorbital pericyclic reactions, one unoccupied orbital is used in the overlap that initiates the reaction. Note how the suprafacial overlap at both ends of each reacting species in the [6 + 2] cycloaddition involves one antibonding interaction; this indi- cates that the reaction with this stereochemistry has a symmetry-imposed barrier—
it is symmetry- forbidden. Extending this analysis to cycloadditions in general reveals that [m + n] cycloadditions are symmetry- allowed in the ground state with suprafacial- suprafacial (or antarafacial- antarafacial) stereochemistry when m + n
= 4n + 2 (i.e., 2, 6, 10, 14) and symmetry-forbidden when m + n = 4n (i.e., 4, 8, 12).
Problems
6-2 The cycloaddition reaction below is symmetry-allowed either
suprafacial- suprafacial or antarafacial-antarafacial. What would be the difference observed in the products of the two reactions?
D
D
+ O
O
O
O O
O D
D
HOMO (π) LUMO (ψ3)
HOMO (ψ2)
LUMO (π*)
HOMO (π) LUMO (ψ4)
HOMO (ψ3)
LUMO (π*)
[4+2] [6+2]
Figure 6.6 Simplified frontier orbital analysis for cycloaddition reactions
(continues)
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6-3 The antarafacial-antarafacial overlap in Figure 6.5 is shown as given below. What are the other possible stereochemical outcomes of an antarafacial-antarafacial cycloaddition in this system?
x
w z
y
a b c
d
wx zy
b c a d
Thermal and Photochemical Reactions
In the discussion that follows, the ideas will be developed in terms of thermal reactions:
reactions that occur in the ground state of the molecule. In addition, most of the discus- sion will be primarily concerned with the lobes at the end of the conjugated π systems (the terminal lobes).
However, the activation energy of organic reactions may be supplied by visible or ultraviolet light as well as by heat. When carried out photochemically, these reactions may be treated as occurring through the excited state of one of the reacting species.7 The absorption of light by a conjugated system is accompanied by promotion of an electron from a lower energy ground-state orbital to the ground-state LUMO, making the ground-state LUMO the HOMO of the excited state. This results in a reversal of the symmetry types of the HOMO and LUMO in the excited state compared to the ground state. As we shall see, this has important effects on the stereochemistry of a pericyclic reaction.