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positions 1 and 5.
Both these [1,5] hydrogen shifts occur by a symmetry-allowed suprafacial pathway, as illustrated in FIGURE
30.13. In contrast with these thermal [1,5] sigmatropic hydrogen shifts, however, thermal [1,3] hydrogen shifts
are unknown. If they were to occur, they would have to proceed by a strained antarafacial reaction pathway.
FIGURE 30.13 An orbital view of a suprafacial [1,5] hydrogen shift.
Two other important sigmatropic reactions are the Claisen rearrangement of either an allyl aryl ether
( ) or an allyl vinyl ( ) ether, and the Cope rearrangement of
a 1,5 hexadiene to an isomeric 1,5-diene. These two rearrangements, along with the Diels–Alder reaction, are
among the most generally useful pericyclic reactions for organic synthesis. Thousands of examples of all three
are known.
Like the Diels–Alder reaction discussed in Section 14.4 and Section 14.5, the Claisen rearrangement takes
place in a single step through a pericyclic mechanism in which a reorganization of bonding electrons occurs
in a six-membered, cyclic transition state. The 6-allyl-2,4-cyclohexadienone intermediate then isomerizes to
o-allylphenol (FIGURE 30.14).
1118 30 • Orbitals and Organic Chemistry: Pericyclic Reactions
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FIGURE 30.14 Mechanism of Claisen rearrangement. C─O bond-breaking and C─C bond-making occur simultaneously.
Evidence for this mechanism comes from the observation that the rearrangement takes place with
transposition of the allyl group. That is, allyl phenyl ether containing a 14C label on the allyl ether carbon atom
yields o-allylphenol in which the label is on the terminal vinylic carbon (green in FIGURE 30.14).
PROBLEM
30-8
Draw a curved-arrow mechanism for the Cope arrangement just shown.
The Cope rearrangement that converts a 1,5-diene to an isomeric 1,5-diene is somewhat limited but a
modification called the Oxy Cope Rearrangement is wider in scope. As shown in the following example, a 1-5
diene with an –OH next to the double bond can be converted into an oxy-anion by reaction with a strong base
such as potassium hydride (KH). A Cope rearrangement then occurs, and reaction with aqueous acid gives an
enol that tautomerizes to an aldehyde.
Although biological examples of pericyclic reactions are relatively rare, a much-studied example occurs in
bacteria during biosynthesis of the essential amino acid phenylalanine. Phenylalanine arises from the
precursor chorismate through a Claisen rearrangement to prephenate, followed by decarboxylation to
phenylpyruvate and reductive amination (FIGURE 30.16). You might note that the reductive amination of
phenylpyruvate is the exact reverse of the transamination process shown in FIGURE 29.17, by which amino
acids are deaminated. In addition, the reductive amination of ketones is a standard method for preparing
amines in the laboratory, as we saw in Section 24.6.
30.8 • Some Examples of Sigmatropic Rearrangements 1119
FIGURE 30.15 Suprafacial [3,3] (a) Cope and (b) Claisen rearrangements.
FIGURE 30.16 Pathway for the bacterial biosynthesis of phenylalanine from chorismate, involving a Claisen rearrangement.
PROBLEM
30-9
Propose a mechanism to account for the fact that heating 1-deuterioindene scrambles the isotope
label to all three positions on the five-membered ring.
PROBLEM
30-10
What product would you expect from Claisen rearrangement of 2-butenyl phenyl ether?
1120 30 • Orbitals and Organic Chemistry: Pericyclic Reactions
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PROBLEM
30-11
When a 2,6-disubstituted allyl phenyl ether is heated in an attempted Claisen rearrangement,
migration occurs to give the p-allyl product as the result of two sequential pericyclic reactions.
Explain.
30.9 A Summary of Rules for Pericyclic Reactions
How can you keep straight all the rules about pericyclic reactions? The summary in TABLE 30.1, TABLE
30.2, and TABLE 30.3 can be distilled into a mnemonic phrase that provides an easy way to predict the
stereochemical outcome of any pericyclic reaction:
The Electrons Circle Around (TECA)
Thermal reactions with an Even number of electron
pairs are Conrotatory or Antarafacial.
A change either from thermal to photochemical or from an even to an odd number of electron pairs changes
the outcome from conrotatory/antarafacial to disrotatory/suprafacial. A change from both thermal and even to
photochemical and odd causes no change because two negatives make a positive.
These selection rules are summarized in TABLE 30.4; knowing them gives you the ability to predict the
stereochemistry of literally thousands of pericyclic reactions.
TABLE 30.4 Stereochemical Rules for Pericyclic Reactions
Electronic state Electron pairs Stereochemistry
Ground state (thermal) Even number
Odd number
Antara–con
Supra–dis
Excited state (photochemical) Even number
Odd number
Supra–dis
Antara–con
PROBLEM
30-12
Predict the stereochemistry of the following pericyclic reactions:
(a) The thermal cyclization of a conjugated tetraene
(b) The photochemical cyclization of a conjugated tetraene
(c) A photochemical [4 + 4] cycloaddition
(d) A thermal [2 + 6] cycloaddition
(e) A photochemical [3,5] sigmatropic rearrangement
30.9 • A Summary of Rules for Pericyclic Reactions 1121
CHEMISTRY MATTERS
Vitamin D, the Sunshine Vitamin
Vitamin D, discovered in 1918, is a general name for two related compounds, cholecalciferol (vitamin D3)
and ergocalciferol (vitamin D2). Both are derived from steroids (Section 27.6) and differ only in the nature of
the hydrocarbon side chain attached to the five-membered ring. Cholecalciferol comes primarily from dairy
products and fish; ergocalciferol comes from some vegetables.
FIGURE 30.17 Here are the sunbathers, again, with their chemical work complete. (credit: “Tanning” by Meraj Chhaya/Flickr, CC BY 2.0)
The function of vitamin D in the body is to control the calcification of bones by increasing intestinal absorption
of calcium. When sufficient vitamin D is present, approximately 30% of ingested calcium is absorbed, but in the
absence of vitamin D, calcium absorption falls to about 10%. A deficiency of vitamin D thus leads to poor bone
growth and to the diseases rickets in children and osteoporosis in adults.
Actually, neither vitamin D2 nor D3 is present in foods. Rather, foods contain the precursor molecules
7-dehydrocholesterol and ergosterol. In the presence of sunlight, both precursors are converted in the outer,
epidermal layer of skin to the active vitamins, hence the nickname for vitamin D, the “sunshine vitamin.”
Pericyclic reactions are unusual in living organisms, and the photochemical synthesis of vitamin D is one of
only a few well-studied examples. The reaction takes place in two steps, an electrocyclic ring-opening of a
cyclohexadiene to yield an open-chain hexatriene, followed by a sigmatropic [1,7] H shift to yield an isomeric
hexatriene. Only the initial electrocyclic ring-opening requires irradiation by so-called UVB light of 295 to 300
nm wavelength. The subsequent sigmatropic [1,7] H shift occurs spontaneously by a thermal isomerization.
Following synthesis under the skin, further metabolic processing of cholecalciferol and ergocalciferol in the
liver and kidney introduces two additional –OH groups to give the active forms of the vitamin, calcitriol and
ergocalcitriol.
1122 30 • Chemistry Matters
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	Chapter 30 Orbitals and Organic Chemistry: Pericyclic Reactions
	30.9 A Summary of Rules for Pericyclic Reactions
	Chemistry Matters — Vitamin D, the Sunshine Vitamin