Q3(c). Indenone, Wittig and octalone mechanisms

Introduction. Three carbonyl mechanisms: (i) Grignard addition to a lactone, then an intramolecular aldol and dehydration; (ii) a Wittig olefination with an allylic ylide; (iii) an acid-catalysed isomerisation of an α-acetoxy enone (the starting alcohol and the dione have the same formula, C₁₁H₁₆O₂), which moves the oxidation level from C-2 to C-6 through dienol intermediates.

(i) 3-Benzylidenephthalide → 2,3-diphenylinden-1-one

1. PhMgBr adds to the lactone C=O: a tetrahedral alkoxide.
2. The ring reopens: the C–O bond to the enol-ether carbon breaks, releasing an enolate of a benzyl ketone; on work-up the enol tautomerises: 1-(2-benzoylphenyl)-2-phenylethan-1-one (a 1,4-diketone).
3. H₂SO₄: the benzylic CH₂ enolises; the enol attacks the protonated benzophenone C=O (intramolecular aldol, 5-membered ring): 3-hydroxy-2,3-diphenylindan-1-one.
4. E1 dehydration: the tertiary, doubly benzylic OH leaves easily; loss of the C-2 H gives the conjugated indenone.

Scheme: Atom balance: C₁₅H₁₀O₂ + Ph → C₂₁H₁₆O₂ (diketone) → C₂₁H₁₄O + H₂O.

(ii) Pyrrole-2-carbaldehyde with CH₂=CH-CH=PPh₃

Reading of the question: no product is printed; the neutral allylic ylide is taken as a Wittig partner.

1. The ylide carbon (nucleophilic) adds to the aldehyde C=O: a betaine / directly a four-membered oxaphosphetane ([2+2]).
2. The oxaphosphetane collapses (syn cycloreversion), driven by the strong P=O bond: Ph₃P=O is expelled and the new C=C forms.
3. Product: 2-(buta-1,3-dien-1-yl)-1H-pyrrole, C₈H₉N. The allylic ylide is semi-stabilised, so E and Z isomers form; E is favoured on heating.
4. Heat is needed because the pyrrole aldehyde is a vinylogous amide (N lone pair conjugated to C=O), so its C=O is a weak electrophile.

Scheme: Wittig olefination.

If instead the butadienylphosphonium salt and a base were used, the pyrrolide nitrogen would first add to the vinylphosphonium (conjugate addition) and an intramolecular Wittig would close a new N-containing ring (Schweizer annulation).

(iii) 2-Acetoxy-10-methyl-Δ⁴-octal-3-one → 10-methyldecalin-3,6-dione

1. H₂SO₄–MeOH removes the acetyl group (acid-catalysed transesterification): 2-hydroxy-Δ⁴-3-ketone (C₁₁H₁₆O₂).
2. The enone forms its heteroannular dienol (3-hydroxy-3,5-diene; in MeOH partly the 3-methoxy dienol ether): H is removed from C-6.
3. The 2-OH is now allylic to the C3=C4 bond; protonated, it leaves as water to give a pentadienyl cation spread over C-2, C-4 and C-6.
4. Methanol (or water) adds at the C-6 terminus; the C-3 enol then reverts to the ketone with C-2 as a CH₂: 6-methoxy (6-hydroxy)-Δ⁴-3-ketone.
5. Step 2, H₃O⁺: dienolisation again (loss of H-6) gives the enol ether / enol of a C-6 ketone; hydrolysis and protonation at C-4 and C-5 give the saturated 3,6-dione, with the C-5 H trans to the angular methyl (trans ring fusion).

Scheme: The oxygen function is moved from C-2 to C-6 through dienols; one resonance form of the cation is drawn.

Conclusion. (i) Grignard addition and ring opening, intramolecular aldol, E1 dehydration: 2,3-diphenylinden-1-one. (ii) Wittig olefination: 2-(buta-1,3-dienyl)-1H-pyrrole + Ph₃P=O. (iii) Deacetylation, dienolisation, loss of the 2-OH as a pentadienyl cation, capture at C-6 and tautomerisation: the 3,6-dione.

Application. Indenones and 2,3-diarylindenones are oestrogen-receptor ligands; dienol and dienol-ether chemistry of Δ⁴-3-keto steroids is used industrially to introduce oxygen at C-6 of corticosteroids.