Copper-catalyzed multicomponent assembly of γ-butenolides via the interception of carbonyl ylides with iminium ions.

A Cu(I)-catalyzed three-component reaction of cyclopropenes, enamines and aldehydes has been realized. This reaction proceeds via the interception of carbonyl oxonium ylide intermediates with α, ß-unsaturated iminium ions that are in situ generated from enamines and aldehydes under the catalysis of Cu(MeCN)4PF6, leading to the desired γ-butenolide derivatives in good yields and with moderate diastereoselectivities. Access to these derivatives with tethered ketone and alkynal groups will expand the structural diversity of multi-substituted butenolides.

An enantioselective four-component reaction via assembling two reaction intermediates.

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.

Multicomponent Assembly of Complex Oxindoles by Enantioselective Cooperative Catalysis.

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.

Functionalization of DNA-Tagged Alkenes with Diazo Compounds via Photocatalysis.

To explore potential chemical space using DNA-encoded library (DEL) technology, the development of various types of robust DNA-compatible reactions is urgently needed. Diazo compounds, which serve as valuable building blocks and important synthons in synthetic chemistry, have been rarely applied in DEL synthesis, probably because of their potential modifications of the bases and phosphate backbone of DNA. Herein we report two cases of DNA-compatible reactions with alkenes and diazo compounds, providing corresponding hydroalkylation and cyclopropanation products in moderate to excellent yields. Notably, these transformations not only provide new access to C(sp3)-C(sp3) bond formation in DELs with excellent functional group tolerance but also represent practical ligation methods to introduce functionalized molecules into DNA.

Asymmetric Multicomponent Reactions for Efficient Construction of Homopropargyl Amine Carboxylic Esters.

Developing an efficient and highly enantioselective protocol to access homopropargyl amines is of high interest to the synthetic community and also remains a formidable challenge for organic chemists. Here, we present integrated Rh2(OAc)4- and BINOL-derived chiral phosphoric acid cooperatively catalyzed three-component reactions of alkynyldiazoacetates, imines with various nucleophiles including alcohols, indoles, and N,N-disubstituted anilines, affording the corresponding homopropargyl amines containing two vicinal chiral centers in satisfactory yields with high to excellent diastereo- and enantioselectivities.