Conjugate addition, annulation, cascades

Robinson annulation: 4-(cyclohexen-1-yl)morpholine (an enamine) with dioxane, Δ gives 4,4a,5,6,7,8-hexahydro-2(3H)-naphthalenone (the annulated cyclohexenone).

Michael addition: dimethyl malonate (a malonate ester) and acrolein (an α,β-unsaturated aldehyde) with NaOMe, MeOH gives dimethyl 2-(2-oxoethyl)malonate (the 1,5-dicarbonyl (Michael adduct)). 58% yield.

Decarboxylation: 2-benzyl-2-bromopropanedioic acid (an α-halo acid) with Δ gives 2-bromo-3-phenylpropanoic acid (the decarboxylated product).

Enolate cascade: 2'-hydroxyacetophenone (an aryl ketone) and cyclobutanone (a four-membered cyclic ketone) with pyrrolidine (pKa = 11.3 protonated) gives 3,4-dihydrospiro[1-benzopyran-2,1'-cyclobutane]-4-one (the cyclized product).

Robinson annulation: 2-methyl-1,3-cyclohexanedione (a 1,3-diketone) and methyl vinyl ketone (an α,β-unsaturated ketone) with 1) KOH, CH3OH, Δ; Δ gives (+-)-Wieland-Miescher ketone (the annulated cyclohexenone).

Michael addition: chalcone (an α,β-unsaturated ketone) with KCN, AcOH; CH3CH2OH, H2O gives gamma-oxo-alpha-phenylbenzenebutanenitrile (the 1,5-dicarbonyl (Michael adduct)).

Decarboxylation: methyl 2-oxocyclodecane-1-carboxylate (a β-keto ester) with aq. NaOH; Δ gives cyclodecanone (the decarboxylated product).

Robinson annulation: 2-methylcyclohexanone (a six-membered cyclic ketone) with 1) NaH, 48 h / RT; 2) then add but-3-yn-2-one gives 4a-methyl-5,6,7,8-tetrahydronaphthalen-2(4aH)-one (the annulated cyclohexenone).

Michael addition: phenylacetonitrile and methyl acrylate (an α,β-unsaturated ester) with 2 eq; tBuOK gives methyl 5-cyano-2-oxo-5-phenylcyclohexanecarboxylate (the 1,5-dicarbonyl (Michael adduct)).

Decarboxylation: 2-acetylbutyrolactone (a β-keto ester) with HCl; H2O, Δ gives 5-chloropentan-2-one (the decarboxylated product).

Robinson annulation: 5-methoxy-1-methyl-2-tetralone (a six-membered cyclic ketone) and 1-chloro-3-pentanone (a primary alkyl chloride) with TsOH; PhMe gives the annulated cyclohexenone. 58% yield.

Michael addition: an α,β-unsaturated ketone with 1); Me2CuLi; Et2O; 2) H+ gives (5R)-2,3-dimethyl-5-prop-1-en-2-ylcyclohexan-1-one (the 1,5-dicarbonyl (Michael adduct)).

Robinson annulation: 2-methylcyclohexanone (a six-membered cyclic ketone) and 3-(triethylsilyl)but-3-en-2-one (an α,β-unsaturated ketone) with KOtBu / tBuOH gives the annulated cyclohexenone.

Michael addition: an α,β-unsaturated ester with CH3NO2, DBU, RT 1 h gives the 1,5-dicarbonyl (Michael adduct).

Michael addition: an α,β-unsaturated ester with 1,3-cyclopentanedione, DCE, 80 C, 3 d gives the 1,5-dicarbonyl (Michael adduct).

Robinson annulation: methyl 3-oxo-4-pentenoate (an α,β-unsaturated ketone) and 5-methoxy-1-methyl-2-tetralone (an aryl alkyl ether) with NaOMe; MeOH gives the annulated cyclohexenone. 32% yield.

Robinson annulation: 5-methoxy-2-tetralone (a six-membered cyclic ketone) with 1) nBuLi; 2) add; 3) acidic workup gives the annulated cyclohexenone. 42% yield.

Robinson annulation: a six-membered cyclic ketone and 4-chloro-2-butanone (a primary alkyl chloride) with TsOH; PhMe gives the annulated cyclohexenone. 30% yield.

Robinson annulation: a six-membered cyclic ketone and 1-penten-3-one (an α,β-unsaturated ketone) with NaOMe, MeOH / PhH gives the annulated cyclohexenone.

Michael addition: 2-isopropyl-5-methylcyclopentanone (a five-membered cyclic ketone) and 1-methoxy-3-buten-2-one (an α,β-unsaturated ketone) with KOEt, EtOH gives the 1,5-dicarbonyl (Michael adduct).

Decarboxylation: 2-furancarboxylic acid with 200 - 205 °C; (– CO2) gives furan (the decarboxylated product).

Decarboxylation: diethyl 2,5-dioxocyclohexane-1,4-dicarboxylate (a β-keto ester) with 185-195 °C; H2O gives 1,4-cyclohexanedione (the decarboxylated product).