Pericyclic Reactions and Organic Photochemistry
1. Pericyclic reactions, the FMO method and the Woodward–Hoffmann rules
A pericyclic reaction reorganises bonds in one concerted step through a cyclic array of overlapping orbitals, with no intermediates. The three main classes are electrocyclic reactions (a conjugated polyene closes to a ring with one new σ bond, or the reverse), cycloadditions (two π systems join with two new σ bonds; [4 + 2], [2 + 2]) and sigmatropic rearrangements (a σ bond migrates across a π system; [1,5], [3,3]). Whether a pathway is allowed depends only on orbital symmetry, and the rules differ for heat and light because light promotes an electron and changes the HOMO.
In the frontier-molecular-orbital (FMO) method one examines the HOMO of one component against the LUMO of the other (for a cycloaddition) or the terminal lobes of the polyene HOMO (for an electrocyclic reaction): the reaction is allowed if the new bonds form between lobes of the same phase. The generalised Woodward–Hoffmann rule states that a thermal pericyclic reaction is allowed when the total number of (4q + 2)ₛ and (4r)ₐ components is odd; a photochemical reaction is allowed when it is even. A component is suprafacial (s) if both new bonds form on the same face and antarafacial (a) if on opposite faces. The Diels–Alder reaction is π4ₛ + π2ₛ: one (4q + 2)ₛ component (the π2ₛ), odd, so thermally allowed; a thermal π2ₛ + π2ₛ has two, even, so forbidden, but photochemically allowed.
| Reaction | Electrons | Thermal | Photochemical |
|---|---|---|---|
| Electrocyclic | 4n | conrotatory | disrotatory |
| Electrocyclic | 4n + 2 | disrotatory | conrotatory |
| Cycloaddition (supra–supra) | 4n + 2 ([4 + 2]) | allowed | forbidden |
| Cycloaddition (supra–supra) | 4n ([2 + 2]) | forbidden | allowed |
| [1,j]-H sigmatropic, suprafacial | [1,5] (6 e) | allowed | forbidden |
| [1,j]-H sigmatropic, suprafacial | [1,3], [1,7] (4n e) | forbidden (antarafacial needed) | allowed |
| [3,3] (Cope, Claisen) | 6 e | allowed, supra–supra, chair | — |
2. Electrocyclic reactions
The HOMO of a 4π diene has terminal lobes of opposite phase, so both termini must rotate the same way — conrotatory — to bring like phases together; the HOMO of a 6π triene has terminal lobes of the same phase, so the termini turn in opposite directions — disrotatory. Light promotes an electron into the next orbital and reverses each rule. The consequences are stereospecific and examined constantly. cis-3,4-Dimethylcyclobutene opens thermally (conrotatory) to (2E,4Z)-hexa-2,4-diene only, and the trans isomer to (2E,4E). (2E,4Z,6E)-Octa-2,4,6-triene closes thermally (disrotatory) to cis-5,6-dimethylcyclohexa-1,3-diene, and photochemically (conrotatory) to the trans isomer. In nature, UV light opens the B ring of 7-dehydrocholesterol by a conrotatory 6π electrocyclic reaction to previtamin D₃, which then undergoes a thermal antarafacial [1,7]-H shift to vitamin D₃.
3. Cycloadditions: the Diels–Alder reaction
The Diels–Alder reaction of a conjugated diene with a dienophile forms a cyclohexene with two new σ bonds, through a six-electron, suprafacial–suprafacial transition state. Its features are all examined. The diene must adopt the s-cis conformation (cyclopentadiene, locked s-cis, is very reactive; dienes forced s-trans do not react). Normal electron demand: an electron-rich diene (HOMO) reacts fastest with an electron-poor dienophile (LUMO) — maleic anhydride, acrylates, quinones — and Lewis acids accelerate it by lowering the dienophile LUMO. It is stereospecific: substituents cis on the dienophile end up cis in the product, and the "outside" groups of an (E,E)-diene end up cis to each other. It is endo-selective under kinetic control, the electron-withdrawing group of the dienophile lying under the diene in the transition state because of secondary orbital overlap; the exo adduct is often more stable and forms on heating. Regioselectivity follows the "ortho, para" rule — a 1-substituted diene gives the 1,2 ("ortho") product and a 2-substituted diene the 1,4 ("para") product — explained by the largest HOMO and LUMO coefficients. Retro-Diels–Alder and hetero-Diels–Alder (C=O or C=N as dienophile) extend it, and in synthesis it builds six-membered rings with up to four stereocentres in one step.
4. Sigmatropic rearrangements: [1,5]-H shifts, Cope and Claisen
A sigmatropic shift is named [i, j] by counting the atoms of each fragment that the migrating σ bond moves across. Suprafacial [1,5]-H shifts are thermally allowed and fast — they scramble the substituents of cyclopentadienes at room temperature — while suprafacial [1,3]-H and [1,7]-H shifts are thermally forbidden (the [1,7] goes antarafacially in the flexible previtamin D). The Cope rearrangement is the [3,3] shift of a 1,5-diene through a chair-like transition state, so the stereochemistry of the product follows from placing substituents equatorially in the chair; the oxy-Cope of a 3-hydroxy-1,5-diene gives an enol that tautomerises to a δ,ε-unsaturated carbonyl and becomes irreversible, and its potassium alkoxide (the anionic oxy-Cope) is accelerated by 10¹⁰–10¹⁷. The Claisen rearrangement is the [3,3] shift of an allyl vinyl ether to a γ,δ-unsaturated carbonyl compound, driven by forming C=O. The aromatic Claisen of an allyl aryl ether gives an ortho-allylphenol after tautomerisation; if both ortho positions are blocked, a second [3,3] (Cope) carries the allyl group to para. Variants — the Johnson–Claisen (orthoester), Eschenmoser–Claisen (amide acetal) and Ireland–Claisen (silyl ketene acetal of an allyl ester) — make the method general for γ,δ-unsaturated esters, amides and acids with predictable alkene geometry and stereocentres.
5. Photochemistry of alkenes, arenes and carbonyls; photo-oxidation and photo-reduction
A photon at 300 nm carries about 400 kJ/mol, enough to break bonds or to open reaction paths closed to the ground state. Alkenes undergo E/Z isomerisation through a twisted excited state, reaching a photostationary state that can be rich in the less stable isomer (sensitised isomerisation of stilbenes, the retinal isomerisation of vision); they undergo [2 + 2] photocycloaddition to cyclobutanes, especially enones with alkenes from the triplet state. The di-π-methane rearrangement (Zimmerman) turns a 1,4-diene — two π systems on one sp³ carbon — into a vinylcyclopropane through diradical intermediates. Arenes photoisomerise to valence isomers (benzvalene, Dewar benzene, prismane) and add alkenes in ortho, meta and para modes. Carbonyls absorb through the weak n → π* transition, and the excited oxygen behaves like an alkoxy radical, which explains the reactions below.
| Reaction | What happens | Typical outcome |
|---|---|---|
| Norrish type I | α-cleavage of the C(O)–C bond from the excited state | acyl + alkyl radicals; decarbonylation, recombination or ketene/aldehyde formation |
| Norrish type II | intramolecular abstraction of a γ-hydrogen through a six-membered transition state → 1,4-diradical | cleavage to an enol (→ smaller ketone) and an alkene, or Yang cyclisation to a cyclobutanol |
| Paternò–Büchi | [2 + 2] photocycloaddition of an excited C=O to an alkene | oxetane |
| Photoreduction | the triplet ketone abstracts H from a donor (propan-2-ol) | benzophenone → benzopinacol, with quantum yield near 2 |
Photo-oxidation mostly goes through singlet oxygen, ¹O₂, formed when a triplet sensitiser (rose bengal, methylene blue, porphyrins) transfers energy to ground-state triplet O₂. Singlet oxygen is an electrophilic dienophile and enophile: with alkenes bearing allylic hydrogens it gives allylic hydroperoxides by an ene reaction with a shifted double bond; with dienes it gives endoperoxides by [4 + 2] cycloaddition (cyclopentadiene, the ascaridole synthesis from α-terpinene); with electron-rich alkenes it gives 1,2-dioxetanes by [2 + 2], which cleave with chemiluminescence.
6. Photo-Curtius and Wolff rearrangements; Barton and Hofmann–Löffler–Freytag reactions
Photo-Curtius: irradiation of an acyl azide RCON₃ expels N₂ and gives the isocyanate R–N=C=O, as the thermal Curtius does, although part of the photochemical reaction goes through a free acyl nitrene that can insert into C–H bonds. Wolff rearrangement: an α-diazoketone RCOCHN₂, on irradiation (or with Ag⁺ or heat), loses N₂ and the R group migrates to give a ketene, R–CH=C=O, which water, alcohols or amines trap as acids, esters or amides. Combined with making the diazoketone from an acid chloride, it is the Arndt–Eistert homologation (RCOOH → RCH₂COOH), and with cyclic diazoketones the photo-Wolff contracts the ring by one carbon.
Two reactions functionalise an unactivated C–H bond by intramolecular 1,5-hydrogen abstraction through a six-membered transition state. In the Barton reaction an alkyl nitrite R–O–N=O is photolysed; the alkoxy radical abstracts a hydrogen from the δ-carbon, the resulting carbon radical captures NO, and the δ-nitroso alcohol tautomerises to an oxime. Barton used it to functionalise the C18 methyl group of a steroid in a short synthesis of aldosterone. In the Hofmann–Löffler–Freytag reaction an N-haloamine in strong acid, on heating or irradiation, forms an aminium radical that abstracts a δ-hydrogen; the carbon radical takes the halogen, and base then closes the δ-haloamine to a pyrrolidine.
Key takeaways
- Woodward–Hoffmann: thermal reactions are allowed when the count of (4q + 2)ₛ and (4r)ₐ components is odd; FMO: new bonds join lobes of the same phase.
- Electrocyclic: thermal 4n conrotatory, thermal 4n + 2 disrotatory, light reverses both; cis-3,4-dimethylcyclobutene → (2E,4Z)-diene; (2E,4Z,6E)-octatriene → cis-dimethylcyclohexadiene thermally.
- Diels–Alder: s-cis diene, electron-poor dienophile, suprafacial and stereospecific, endo under kinetic control, "ortho/para" regiochemistry; thermal [2 + 2] is forbidden, photochemical allowed.
- Cope and Claisen are [3,3] shifts through chair transition states; Claisen gives γ,δ-unsaturated carbonyls and ortho-allylphenols; anionic oxy-Cope is hugely accelerated; [1,5]-H shifts are thermally suprafacial.
- Norrish I α-cleaves, Norrish II abstracts a γ-H (six-membered TS), Paternò–Büchi gives oxetanes, di-π-methane gives vinylcyclopropanes, ¹O₂ does ene, [4 + 2] and [2 + 2]; Wolff gives ketenes; Barton and HLF abstract δ-H through six-membered TSs.
Practice questions (17)
Attempt each one before opening the answer. Every explanation names the tempting wrong option as well as the right one, because that is where marks are lost.
cis-3,4-Dimethylcyclobutene is heated. The product is
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Answer: A — (2E,4Z)-hexa-2,4-diene
Ring opening of a cyclobutene is a 4π electrocyclic reaction, thermally conrotatory. Rotating both termini the same way turns the two cis methyls one outward and one inward, giving (2E,4Z). The disrotatory path, which would give E,E or Z,Z, is thermally forbidden; trans-3,4-dimethylcyclobutene gives the E,E diene.(2E,4Z,6E)-Octa-2,4,6-triene is (i) heated and (ii) irradiated. The 5,6-dimethylcyclohexa-1,3-dienes formed are
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Answer: A — (i) cis, (ii) trans
A 6π electrocyclisation is thermally disrotatory: with both terminal methyls "outside" (E,E termini), disrotation brings them to the same face — cis. Light reverses the rule to conrotatory, giving trans. Confusing 4π with 6π rules swaps the answers.Which of the following processes are thermally allowed?
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Answer: A — [π4ₛ + π2ₛ] cycloaddition; B — Suprafacial [1,5]-hydrogen shift
The Diels–Alder has one (4q + 2)ₛ component and a suprafacial [1,5]-H shift is a six-electron process, both odd counts and thermally allowed. [2ₛ + 2ₛ] has two (4q + 2)ₛ components (even) and a suprafacial [1,3]-H shift is a four-electron suprafacial process — both thermally forbidden, though photochemically allowed.How many π electrons take part in the cyclic transition state of a Diels–Alder reaction?
Numerical answer — type the value.
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Answer: 6
Four from the diene and two from the dienophile make a six-electron, aromatic-like (Hückel) transition state, which is why the [4 + 2] cycloaddition is thermally allowed. Two new σ bonds and one new π bond result.Cyclopentadiene reacts with maleic anhydride at room temperature. The major product is
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Answer: A — the endo adduct, formed faster because of secondary orbital overlap
Under kinetic control the anhydride carbonyls lie under the diene in the transition state, where the C=O π* orbitals overlap with C2 and C3 of the diene; the endo adduct forms faster even though the exo is thermodynamically favoured and appears on prolonged heating. A thermal [2 + 2] is forbidden.Butadiene adds to dimethyl maleate (cis) and, separately, to dimethyl fumarate (trans). What are the relative configurations of the two ester groups in the products?
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Answer: A — cis from maleate and trans from fumarate
The dienophile adds suprafacially, so its geometry is transferred intact: cis-diester → cis-4,5-disubstituted cyclohexene, trans → trans. This stereospecificity is a hallmark of the concerted mechanism; a stepwise diradical path would scramble it.Allyl phenyl ether is heated to about 200 °C. The main product is
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Answer: A — 2-allylphenol
The aromatic Claisen rearrangement is a [3,3] shift that bonds the terminal allyl carbon to the ortho position, giving a cyclohexadienone that tautomerises to 2-allylphenol, with the allyl group inverted. Para substitution happens only when both ortho positions are blocked, by a further Cope step.Why is the potassium alkoxide of a 3-hydroxy-1,5-diene (anionic oxy-Cope) so much faster than the neutral oxy-Cope rearrangement?
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Answer: A — The alkoxide weakens the adjacent C3–C4 σ bond that breaks and the product is a stabilised enolate
Charge donation from O⁻ into the σ* of the bond being broken lowers the barrier enormously (rate increases of 10¹⁰ or more, with 18-crown-6 to free the anion), and the product is an enolate rather than a neutral enol. It remains a thermal [3,3] shift.What is the energy of one mole of photons of wavelength 300 nm, in kJ/mol, to one decimal place? (h = 6.626 × 10⁻³⁴ J s, c = 2.998 × 10⁸ m/s, N_A = 6.022 × 10²³ mol⁻¹)
Numerical answer — type the value.
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Answer: 398.8
E = N_Ahc/λ = 6.022 × 10²³ × 6.626 × 10⁻³⁴ × 2.998 × 10⁸/(3.00 × 10⁻⁷) = 3.988 × 10⁵ J/mol = 398.8 kJ/mol — more than a C–C bond (about 350 kJ/mol), which is why UV light can cleave bonds directly.2-Hexanone undergoes a Norrish type II cleavage. How many carbon atoms does the alkene fragment contain?
Numerical answer — type the value.
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Answer: 3
The excited C=O abstracts a γ-hydrogen (on C5) through a six-membered transition state; the 1,4-diradical cleaves the C3–C4 bond, giving the enol of acetone (C1–C3) and propene (C4–C6). Norrish type I α-cleavage would instead give acetyl and butyl radicals.Irradiation of benzophenone with 2-methylpropene gives a four-membered ring containing oxygen. This is the
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Answer: A — Paternò–Büchi reaction, giving an oxetane
The n,π* triplet of the ketone adds to the alkene through a 1,4-diradical that closes to an oxetane — a photochemical [2 + 2] of C=O and C=C. The regiochemistry follows the more stable diradical (O bonded to the less substituted alkene carbon first).The di-π-methane rearrangement converts a 1,4-diene into
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Answer: A — a vinylcyclopropane
On excitation the two π systems attached to one sp³ carbon bond to each other (a cyclopropyldicarbinyl diradical), a σ bond shifts, and the new diradical closes to a three-membered ring, leaving one alkene outside it: a vinylcyclopropane. It is the textbook photochemical reaction with no ground-state counterpart.Which reactions are typical of singlet oxygen generated by photosensitisation?
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Answer: A — Ene reaction with an alkene bearing allylic H, giving an allylic hydroperoxide; B — [4 + 2] cycloaddition with a diene, giving an endoperoxide; C — [2 + 2] cycloaddition with an electron-rich alkene, giving a 1,2-dioxetane
¹O₂, made by energy transfer from a triplet sensitiser, is an electrophilic enophile and dienophile: ene reaction, [4 + 2] and [2 + 2] are its three modes. Pinacol formation is photoreduction of a ketone triplet by a hydrogen donor, not an oxygen reaction.Benzophenone irradiated in propan-2-ol gives mainly
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Answer: A — benzopinacol
The n,π* triplet abstracts H from the alcohol’s C–H to give the diphenylketyl radical and the (CH₃)₂C•OH radical, which passes a second H to another benzophenone; two ketyls couple to benzopinacol, so the quantum yield approaches 2. This is photo-reduction.An α-diazoketone RCOCHN₂ is irradiated in methanol. The product is
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Answer: A — the homologated ester RCH₂COOCH₃, via a ketene (Wolff rearrangement)
Loss of N₂ and 1,2-migration of R gives the ketene R–CH=C=O, which methanol adds to give the methyl ester with one more CH₂ than RCOOH had — the Arndt–Eistert homologation. An isocyanate would come from an acyl azide (photo-Curtius), not a diazoketone.In the Barton nitrite photolysis and the Hofmann–Löffler–Freytag reaction, the hydrogen is transferred intramolecularly through a cyclic transition state. How many atoms does that ring contain, including the hydrogen?
Numerical answer — type the value.
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Answer: 6
The O• (Barton) or N•⁺ (HLF) radical, the carbon chain to the δ-carbon (three intervening carbons plus Cδ) and the transferring H make a six-membered chair-like ring: a 1,5-hydrogen shift. That geometry is why the δ-position is selectively functionalised, and why HLF ends in a pyrrolidine.The Hofmann–Löffler–Freytag reaction of an N-chloroamine in strong acid, followed by base, gives
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Answer: A — a pyrrolidine
The protonated N-chloroamine gives an aminium radical that abstracts the δ-hydrogen; the carbon radical takes Cl from another molecule, and on basification the amine displaces the δ-chloride intramolecularly, closing a five-membered ring. Losing a carbon describes the Hofmann rearrangement of amides.