Codex @codex  0

Buta-1,3-diene is $\mathrm{C}{\mathrm{H}}_2=\mathrm{CH}-\mathrm{CH}=\mathrm{C}{\mathrm{H}}_2$, a four-carbon diene with a conjugated system. Adjacent p orbitals allow electron delocalization across the two double bonds and the intervening single bond.

A suitable cisoid conformation can react with a dienophile in a Diels-Alder reaction. The need for the reactive conformation connects internal rotation with cycloaddition reactivity.

A concerted cycloaddition of a conjugated diene and a dienophile that makes a six-membered ring with two new sigma bonds and one retained alkene. The internal diene atoms become the residual alkene atoms.

A preference for the cycloaddition orientation in which relevant dienophile substituents lie under the diene framework in the transition geometry. It is distinct from regiochemistry and is not an unconditional guarantee of one product.

A reagent combination that installs the two saturated carbons of an ethylene cycloaddition while allowing more favourable reactivity. A removable electron-withdrawing substituent can activate the dienophile and be removed later.

Kurt Alder and Otto Diels developed the Diels-Alder reaction, in which a diene with pi conjugation and a dienophile combine to build a six-membered ring. The transformation creates two carbon–carbon chemical bonds in one ring-forming step, explaining its importance in constructing complex organic molecules.^[ref]

$\mathrm{C}{\mathrm{H}}_2=\mathrm{CHC}{\mathrm{O}}_2\mathrm{Me}$, an activated alkene useful as a dienophile and Michael acceptor.

Otto Diels and Kurt Alder developed the Diels-Alder reaction, a cycloaddition joining a diene with pi conjugation with a dienophile. Its usefulness comes from building a six-membered ring while preserving a predictable relationship between the starting materials' spatial arrangement and the product's stereochemistry.^[ref]

Disconnect the tertiary amide into cyclohex-3-ene-1-carboxylic acid and the secondary amine $\mathrm{EtNHCH}(\mathrm{Me})\mathrm{C}{\mathrm{H}}_2\mathrm{C}{\mathrm{H}}_2\mathrm{Ph}$. The acid-derived ring is an immediate Diels–Alder disconnection: buta-1,3-diene plus the indicated methyl acrylate gives methyl cyclohex-3-ene-1-carboxylate. Heating, or suitable Lewis-acid activation of the dienophile, forms the two new sigma bonds and leaves the diene's internal double bond as the ring alkene.

Hydrolyse this ester to the acid. Convert it to its acid chloride with oxalyl chloride or thionyl chloride, and react with the secondary amine in the presence of a base to capture HCl. The tertiary amide now contains the complete cyclohexene acyl fragment; direct conjugate addition of the amine to methyl acrylate before ring construction would give the wrong connectivity.

Prepare the amine by reductive amination of 4-phenylbutan-2-one, $\mathrm{MeCOC}{\mathrm{H}}_2\mathrm{C}{\mathrm{H}}_2\mathrm{Ph}$, with ethylamine, using sodium triacetoxyborohydride or another iminium-selective reducing system. This places nitrogen on $\mathrm{CH}(\mathrm{Me})$, not on a terminal methylene. If a route from simpler carbon compounds is wanted, crossed aldol condensation of acetone with benzaldehyde gives $\mathrm{MeCOCH}=\mathrm{CHPh}$, and selective C=C reduction gives the required ketone before reductive amination.

The acid branch retains the acrylic carbonyl as the amide carbonyl; the amine branch supplies both N-ethyl and N-(4-phenylbutan-2-yl) substituents. The unlabelled stereogenic centres may be racemic mixture. This sequence separates ring formation from amide formation and avoids invoking uncontrolled alkylation of a tertiary amide nitrogen.

$\mathrm{C}{\mathrm{H}}_2=\mathrm{CHS}{\mathrm{O}}_2\mathrm{Ph}$, an activated dienophile whose sulfone group can be removed reductively after cycloaddition.