The asymmetric organocatalysis is definitely one of the most powerful and versatile tools for the rapid construction of various spirocyclic oxindoles. In the past few years, a number of successful strategies based on organocatalysis have been developed for the construction of 3,3′-spirocyclic oxindoles in high yields and excellent enantioselectivities under mild conditions. In this review, recent advances in this area are summarized and classified according to the spiro ring fused at the 3-position of the oxindole core.

Recent Advances in Asymmetric Organocatalytic Construction of 3,3′-Spirocyclic Oxindoles

A novel organocatalytic asymmetric [3 + 2] cycloaddition reaction between methyleneindolinones and allylic compounds yielding complex spirocyclopentaneoxindoles has been developed. It provides extraordinary levels of enantioselective control involving a chiral phosphine as a nucleophilic organocatalyst. Simple precursors were used under mild conditions to construct oxindole derivatives with high enantiopurity and structural diversity. This method should be useful in medicinal chemistry and diversity-oriented syntheses of these intriguing compounds.

Core-Structure-Motivated Design of a Phosphine-Catalyzed [3 + 2] Cycloaddition Reaction: Enantioselective Syntheses of Spirocyclopenteneoxindoles

The Morita—Baylis—Hillman (MBH) carbonates (II), (IV), and (VII) serve as C3 synthons in asymmetric [3 + 2] annulation reactions to give a series of 3-spirocyclopentene-2-oxindoles with two contiguous quaternary centers such as (III), (V), or (VIII) as present in various alkaloids.

Highly Enantioselective [3+2] Annulation of Morita–Baylis–Hillman Adducts Mediated by L‐Threonine‐Derived Phosphines: Synthesis of 3‐Spirocyclopentene‐2‐oxindoles having Two Contiguous Quaternary Centers

Advances in nucleophilic phosphine catalysis of alkenes, allenes, alkynes, and MBHADs

Chiral Lewis basic tertiary amines or phosphines can enable properly modified Morita–Baylis–Hillman (MBH) adducts to undergo asymmetric allylic substitutions with a wide range of nucleophiles. In addition, assisted by a Bronsted base, chiral Lewis bases can also catalytically convert modified MBH adducts into allylic ylides, which can be engaged in a variety of asymmetric annulation reactions. This tutorial review will focus on such chiral Lewis base-catalysed asymmetric transformations of MBH adducts, especially those developed over the past five years, allowing for the rapid construction of densely functionalised chiral molecules with high levels of regio- and stereoselectivities.

Organocatalytic asymmetric transformations of modified Morita–Baylis–Hillman adducts

A Phosphine-Catalyzed [3 + 2] Annulation Reaction of Modified Allylic Compounds and N-Tosylimines

Phosphine-catalyzed [4 + 3] annulation for the synthesis of highly functionalized bicyclo[3.2.2]nonadienes.

A phosphine-catalyzed [4 + 3] annulation of modified allylic carbonates with methyl coumalate was developed. This strategy offered a powerful method for the construction of bicyclo[3.2.2]nonadiene skeleton with high stereoselectivity.

Phosphine-Catalyzed [4 + 3] Annulation for the Synthesis of Highly Functionalized Bicyclo[3.2.2]nonadienes.

A phosphine-catalyzed annulation of modified allylic ylides with various aromatic imines to form 3-pyrrolines was developed. The presence of a substituent in the allylic compound is crucial for this reaction. Without the substituent, (E)-dienylimines will be produced via the dimerization of the allylic compounds.

Suqing Zheng

Papers

A Phosphine-Catalyzed [3 + 2] Annulation Reaction of Modified Allylic Compounds and N-Tosylimines

Phosphine-catalyzed [4 + 3] annulation for the synthesis of highly functionalized bicyclo[3.2.2]nonadienes.

Phosphine-Catalyzed [4 + 3] Annulation for the Synthesis of Highly Functionalized Bicyclo[3.2.2]nonadienes.

A Phosphine-Catalyzed [3 + 2] Annulation Reaction of Modified Allylic Compounds and N-Tosylimines.