Asymmetric synthesis of 3-aminodihydrocoumarins via the chiral guanidine catalyzed cascade reaction of azlactones

Abstract

A new asymmetric preparative method of 3-aminodihydrocoumarins via reactions of azlactones and 2-nitrovinylphenols using chiral bifunctional guanidine catalysts.

Applications of N′-monofunctionalised TsDPEN derivatives in asymmetric catalysis

“…[43] Of a series of organocatalysts tested, 29a proved to be the most effective one for the formation of highly enantiomerically-pure 3-aminodihydrocoumarin products containing tertiary amine derivative groups which would otherwise be very difficult to prepare (Figure 22). [44] Using 5 mol% catalyst, the cascade reaction could be scaled up to a gram scale for one example. A cyclisation was also reported with an analogous ligand type to that described above, resulting in the formation of cyclohexanes through a Michael-Henry reaction sequence which created six stereogeneic centres in one step.…”

Recent Advances in Azlactone Transformations

“…Last year, Wang's group reported the first chiral phosphoric acid catalyzed enantioselective [2+2] cycloaddition reactions between azlactones (58) and N-substituted -carbolines (59) (Scheme 16). [38] From the initial generation of an α-amino-lactam intermediate (C), a sequential phosphoric acid-catalyzed asymmetric penicillin-penillonic acid (PPA) rearrangement occurs, leading to the desired imidazoline-5-ones (60) in low to excellent yields (ranging from 36 to 99 %) and excellent enantiomeric excesses (88-99 % ee).…”

“…Recently, Liu's group also developed a protocol to access substituted dihydrocoumarins ( 159 , 160 and 161 ) with high diastereo‐ and enantioselectivities through a conjugate addition/lactonization cascade between 2‐(2‐nitrovinyl)phenols ( 156 ) and azlactones ( 157 ) (Scheme ) . The amino acid backbone and sulfonamide substituent of the bifunctional guanidine organocatalyst ( 158 ) had a strong influence on the enantioselectivity.…”

Recent Advances in Chiral Guanidine‐Catalyzed Enantioselective Reactions

“…Recently, the same group also developed a cascade conjugation addition‐lactonization between 2‐nitrovinyl‐phenols and azlactones for the generation of 4‐nitromethyl 3‐aminochromanones (Scheme ) . After screening various amino amide‐based catalysts, 11 f was proven to be the best catalyst for this system.…”