Organocatalytic Allylic Amination of Morita–Baylis–Hillman Carbonates­

Abstract

An organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates with aromatic amines in the presence of β-isocupreidine is described. Chiral allylic amines were obtained in almost quantitative yields (90–96%) with moderate enantioselectivity. Recrystallization afforded products in good yields (45–73%) and high optical purity (82–99% ee). This method provides a facile and efficient route to obtain optically active β-lactams, including the building block of the cholesterol-lowering drug Ezetimibe.

Synthesis of β‐Amino Acid Derivatives via Enantioselective Lewis Base Catalyzed N‐Allylation of Halogenated Amides with Morita‐Baylis‐Hillman Carbonates

“…Multiple reported studies employing these chiral amines for asymmetric alkylation of diverse MBH derivatives strongly supported the choice of the type of chiral catalyst. [10][11][12][13] During the optimization studies we evaluated influence of the catalyst and solvent, concentration, catalyst loading, stoichiometry of the reactants and the reaction temperature (please see the Supporting information for details of optimization studies). In the presence of (DHQD) 2 PHAL, the allylation of trifluoroacetamide 3 a with MBH carbonate 4 a yielded the desired product S-5 a with good level of stereoselectivity.…”

“…For development of the enantioselective Lewis base catalyzed allylation, the N-centered nucleophiles should meet several requirements. [11] We envisioned that using the halogenated acetamides as pronucleophiles and surrogates of ammonia would be effective. The nucleophilicity of these compounds would be lower than that of the parent nucleophile, ammonia, which would render them less reactive than the Lewis base catalyst (Scheme 1c).…”

“…For development of the enantioselective Lewis base catalyzed allylation, the N ‐centered nucleophiles should meet several requirements [11] . We envisioned that using the halogenated acetamides as pronucleophiles and surrogates of ammonia would be effective.…”

“…The acidity of these compounds should be sufficient to allow for their activation by deprotonation using a suitable leaving group from the allylic electrophile making allylic carbonates perfect reaction partners. We hypothesized that, in this scenario, the addition of Lewis base catalyst would produce the activated electrophile and basic leaving group which would activate the pronucleophile via deprotonation, a common strategy in substitution of Morita‐Baylis‐Hillman (MBH) derivatives [11–12,13a,c] . The subsequent addition of the activated pronucleophile to the activated electrophile would form the desired C−N bond and release the Lewis base catalysts thus closing the catalytic cycle.…”

Lewis-Base-Catalyzed N-Allylation of Silyl Carbamate Latent Pronucleophiles with Allylic Fluorides

“…Further investigations were geared toward the use of chiral Lewis base catalysts to achieve enantioselective allylations. We focused on dimeric cinchona alkaloid derived catalysts that have shown good levels of stereocontrol in related reactions. − , Optimization effort focused on the identity of the catalyst, catalyst loading, solvent, stoichiometry, and temperature (see Supporting Information). With the interplay of high yield and high enantioselectivity, the optimal reaction conditions involved the use of 10 mol % of (DHQD) 2 PHAL in the presence of excess of the pronucleophile in chlorobenzene at room temperature (Scheme ).…”