Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo‐ and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well‐developed. However, the efficient synthesis of chiral 3‐substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N‐aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5‐tricyclic lactone core structure of Speradine A.

A reaction intermediate is a key molecular entity that has been used in explaining how starting materials converts into the final products in the reaction, and it is usually unstable, highly reactive, and short-lived. Extensive efforts have been devoted in identifying and characterizing such species via advanced physico-chemical analytical techniques. As an appealing alternative, trapping experiments are powerful tools in this field. This trapping strategy opens an opportunity to discover multicomponent reactions. In this work, we report various highly diastereoselective and enantioselective four-component reactions (containing alcohols, diazoesters, enamines/indoles and aldehydes) which involve the coupling of in situ generated intermediates (iminium and enol). The reaction conditions presented herein to produce over 100 examples of four-component reaction products proceed under mild reaction conditions and show high functional group tolerance to a broad range of substrates. Based on experimental and computational analyses, a plausible mechanism of this multicomponent reaction is proposed.

We design and develop a general strategy for the assembly of multisubstituted 1,3-diene derivatives. This methodology proceeds through the cleavage of cyclopropenes via the rearrangement of the cyclopropyl radical to the allyl radical after the addition of a carbon-centered radical with a leaving group onto the strained double bond, leading to 1,3-diene products with the release of the leaving group. This approach represents a reaction mode for carbon-centered radical-mediated functionalization of cyclopropenes with ring cleavage. The transformation occurs under mild reaction conditions and shows high functional group tolerance. These highly valuable and modifiable 1,3-diene products show good antitumor activity against HCT116 cells.

Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo-and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well-developed. However, the efficient synthesis of chiral 3-substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N-aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (> 90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5-tricyclic lactone core structure of Speradine A.

Reaction intermediate is a key molecular entity that has been used in explaining how the starting materials converts into the final products in the reaction, and it is always unstable, high-reactive, and short-lived. Extensive efforts have been devoted in identifying and characterizing such species via advanced physico-chemical analytical techniques. As an appealing alternative, trapping experiment with additional chemicals represents an efficient and powerful tool in this field. More importantly, this trapping strategy opens an opportunity to discovering new multicomponent reactions, and theoretically, novel multicomponent reactions with a ‘higher order’ variant could be developed via assembling two reaction intermediates. Herein, we report a highly diastereoselective and enantioselective four-component reactions (containing alcohols, diazoesters, enamines/indoles and aldehydes) that involve the coupling of in situ generated two intermediates (iminium and enol). These four-component reactions proceed under mild reaction conditions and show high functional group tolerance as well as broad substrate scope, affording the desired four-component coupling products (> 100 examples) with high efficiency. Notably, present four-component reaction is well compatible with a number of classic MCRs. A plausible mechanism with cross interception of the two active intermediates is also proposed based on a set of experimental and computational analyses. We hope that this strategy provides a new avenue for the development of novel higher-order MCRs in future research.