A catalytic asymmetric hetero-Diels–Alder reaction of olefinic azlactones and isatins: facile access to chiral spirooxindole dihydropyranones

Abstract

A catalytic asymmetric hetero-Diels-Alder (HDA) reaction has been achieved through hydrogen-bond directed γ-addition of olefinic azlactones to isatins. This methodology provides an efficient access to spirooxindole dihydropyranones in moderate to good yields and with excellent enantioselectivities.

Alkylidene Meldrum's Acids as Platforms for the Vinylogous Synthesis of Dihydropyranones

“…Additionally, although more sterically hindered ethyl‐derivative 3 o proved to be unreactive, the cyclic‐analogue, namely the indenyl‐derived Meldrum's acid 3 p , was transformed into the corresponding tetracyclic product 5 pa in 75 % ee (64 % yield). Subsequently, we wondered whether this Meldrum's acid‐based platform 3 a could react with other ketones, known as good starting materials for the efficient enantioselective vinylogous synthesis of 5,6‐dihydropyran‐2‐ones 1 [7, 8a–e,g–i] . However, in our case, we expected to extend the chemical diversity with the formation of isomeric and non‐racemic 3,6‐dihydropyran‐2‐one architectures 5 .…”

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

“…A large number of computational studies were conducted to explain the enantioselection of the process, resulting in the transition state shown which depicts a critical methanol bridge, explaining the need for this as an additive within the reaction to give optimal stereoselectivities. Similarly, Xu and co-workers have used β-ICPD in the cycloaddition between isatin framework 87 and olefinic azlactones 88 to give adduct 89 ( Scheme 21 ) [ 64 ].…”

Base Induced Condensation of Malononitrile with Erlenmeyer Azlactones: An Unexpected Synthesis of Multi‐Substituted Δ2‐Pyrrolines and Their Cytotoxicity

“…Some other important reactions are aza‐ene reaction with enamines, lactone ring oxygen replacement from other hetero atoms like N ‐ or S ‐containing substrates, incorporation of allyl functionality in a selective manner to the Erlenmeyer azlactones core structure . Alkylidene azlactones have been used in asymmetric hetero‐Diels‐Alder reactions, undergo reaction with isatins and vinyl cyclopropanes, which process through [4+2] annulations and [3+2]‐cycloaddition, respectively. Although most reactions of Erlenmeyer azlactones rely on cycloaddition, few of them are concerned with their ring opening reactions.…”