Q2(a). Diels–Alder and lactam closure; Cope; Stevens

Introduction. All three are pericyclic or sigmatropic steps: (i) a [4+2] cycloaddition followed by an intramolecular acylation of the amine, (ii) a [3,3]-sigmatropic (Cope) shift, (iii) a [1,2]-shift of an ammonium ylide.

(i) Diels–Alder reaction, then lactam formation

Scheme: The tethered amine opens the neighbouring anhydride carbonyl to a six-membered lactam.

1. The (E,E)-diene (s-cis as drawn) adds suprafacially to maleic anhydride, a strong dienophile. The endo transition state (secondary orbital overlap of the C=O groups with C-2/C-3 of the diene) is preferred.
2. An (E,E)-1,4-disubstituted diene puts both its outer groups (Ph and the aminoethyl chain) on the same face, and endo addition puts the anhydride on that face too: the four new substituents are all cis.
3. The -CH₂CH₂NH₂ arm now sits next to, and cis to, one anhydride carbonyl. The amine attacks it (nucleophilic acyl substitution), the anhydride opens, and a six-membered lactam (δ-lactam) closes. The other carbonyl becomes an uncombined CO₂H.

Product: an all-cis octahydroisoquinolin-1-one carrying CO₂H (C-8) and Ph (C-7), C₁₆H₁₇NO₃ (= diene + anhydride, no atoms lost).

(ii) Cope rearrangement

Scheme: The new σ bond links the two terminal CH₂ carbons; the CHO ends up conjugated.

1. The substrate contains a 1,5-diene: CH₂=C(CH₃)-CH(CHO)-C(CH₃)₂-CH=CH₂. On heating, the C3–C4 σ bond (between the CH bearing CHO and the CMe₂) breaks while a new bond forms between C-1 and C-6, through a six-membered chair transition state (suprafacial on both allyl units).
2. The two new π bonds are C2=C3 (now conjugated with CHO) and C4=C5 (=CMe₂). Gaining an α,β-unsaturated aldehyde and two trisubstituted C=C bonds (from a monosubstituted and a 1,1-disubstituted one) drives the equilibrium to the product.
3. In the chair the CHO group sits equatorial, which gives the E double bond.

Product: 3,7-dimethylocta-2,6-dienal (citral), mainly the E isomer, geranial (C₁₀H₁₆O, an isomer of the reactant).

(iii) Stevens rearrangement

Scheme: The allyl group moves from N⁺ to the ylide carbon.

1. A strong base (NaNH₂ or PhLi, implied by “Stevens rearrangement”) removes a proton from the benzylic CH₂, the most acidic C–H next to N⁺ (stabilised by both Ph and N⁺): a nitrogen ylide.
2. The N–allyl bond breaks homolytically to a radical pair held in a solvent cage; the allyl radical recombines at the carbanion carbon ([1,2]-shift). Allyl and benzyl migrate best because their radicals are stabilised.
3. For an allyl group the concerted [2,3]-sigmatropic route through the C=C gives the same constitution here, because the allyl group is unsubstituted.

Product: N-methyl-N-(1-phenylbut-3-en-1-yl)aniline, PhCH(CH₂CH=CH₂)N(CH₃)Ph (racemic).

Conclusion. (i) Endo Diels–Alder adduct that closes to an all-cis δ-lactam carboxylic acid; (ii) citral (mainly geranial) by Cope rearrangement; (iii) PhCH(CH₂CH=CH₂)N(Me)Ph by Stevens [1,2]-shift of the benzylic ylide.

Application. Tandem Diels–Alder/lactamisation builds the hydroisoquinoline cores of alkaloids in one pot; the Cope route to citral is the basis of industrial citral and vitamin A precursors.