Stereoselective Synthesis of Hydropyrano[3,2‐b]indoles via Organocatalytic Asymmetric Inverse‐Electron‐Demand Oxa‐Diels–Alder Reaction

Abstract

Enantio‐ and diastereoselective inverse‐electron‐demand oxa‐Diels–Alder reactions are described between (Z)‐2‐ylideneoxindoles and aldehydes in the presence of a chiral secondary amine catalyst. The corresponding hydropyrano[3,2‐b]indoles are produced in up to 77% yield with up to 99% ee. Convenient synthetic transformations of the products readily lead to pharmacologically interesting scaffolds bearing multiple functional groups. This method may also provide an alternative approach for the asymmetric synthesis of 2‐spirocyclo‐3‐oxindoles.

Organocatalytic Strategies for the Development of the Enantioselective Inverse‐electron‐demand Hetero‐Diels‐Alder Reaction

“…Nevertheless, a reduction step is again required in order to obtain the final compounds with high diastereoselectivities as the intermediate hemiacetal species cannot be obtained in a diastereoselective manner. [27] On another hand, the use of α,β-unsaturated aliphatic aldehydes has permitted the development of the vinylogous version of the amine-catalyzed HOMO-raising controlled reaction, allowing the synthesis of differently substituted heterocyclic compounds via IEDHDAR through dienamine intermediates. Thus, Chen described the asymmetric inverse-electrondemand aza-Diels-Alder reaction between cyclic 1-aza-1,3butadienes and α,β-unsaturated aldehydes in the presence of a secondary amine catalyst.…”

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

“…In the same year, Han's group used the (Z)-2-ylideneoxindole 27 and aldehyde 71 to obtain hydropyrano [3,2-b] indole 73 (Scheme 12b). [52] The substrate scope is very broad. The hemiacetal intermediates can be transformed into various pharmacologically interesting scaffolds.…”

Aminocatalytic Privileged Diversity‐Oriented Synthesis (ApDOS): An Efficient Strategy to Populate Relevant Chemical Spaces

“…Conceptually similarly, when N ‐protected ( Z )‐2‐ylideneoxindoles 30 were deployed as electron‐poor heterodienes, a library of densely functionalized hydropyrano[3,2‐ b ]indoles 31 was prepared. In most cases the reactions proceeded with good yields and remarkable stereoselectivities (Scheme b) …”