Enantioselective Cascade Reaction of α‐Cyano Ketones and Isatylidene Malononitriles: Asymmetric Construction of Spiro[4H‐pyran‐oxindoles]

Abstract

α‐Cyano ketones have been employed for the first time as Michael donors in the construction of chiral spiro compounds. By using only 2 mol‐% of a chiral multifunctional organocatalyst, chiral spiro[4H‐pyran‐oxindole] derivatives were prepared in yields of 97–99 % with enantioselectivities of 76–97 % ee. This method provides a new approach to the synthesis of chiral spirocyclic oxindoles.

Applications of N′-monofunctionalised TsDPEN derivatives in asymmetric catalysis

“…(Figure 35). [66] In this case the cascade cyclisation took place to form the heterocyclic product in remarkably high ees. The initial screening with the N-benzylated malononitrile gave a product of 72% but then switching to the N-methylated derivative with the addition of 1 mol% of morpholine at lower temperature raised the ee to 90%.…”

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…Wu and co‐workers devised an enantioselective domino Michael/cyclization reaction between isatylidenemalononitriles 615 and α‐cyano ketones 139 for the synthesis of spiro[4 H ‐pyran‐oxindole] derivatives 635 . Quinidine‐derived thiourea catalyst 636 provided good to excellent ee values for the desired products (Scheme ) . It was found that both the hydrogen bonding moiety and the tertiary amine moiety of the catalyst were required for achieving such good results.…”

“…It was found that both the hydrogen bonding moiety and the tertiary amine moiety of the catalyst were required for achieving such good results. For example, with catalyst 637 , which is lacking the tertiary amine moiety in its structure, only a racemic product was obtained …”

Non-Covalent Organocatalyzed Domino Reactions Involving Oxindoles: Recent Advances

“…The synthesis of several spiro[4 H -pyran-oxindole] derivatives 26 was proposed by Wu and co-workers by using α-cyano ketones 25 as nucleophiles ( Scheme 6 ) [ 31 ]. In the presence of very low loadings of quinidine-derived thiourea organocatalyst XVII (2 mol %) and morpholine (1 mol %) in dichloromethane at 0 or −10 °C, the cascade process takes place within less than two hours and accommodates a broad range of substrates affording the expected products in excellent yields and high enantioselectivities.…”