Synthesis of 1-pyrroline derivatives via cyclization of terminal alkynes with 2-azaallyls.

An efficient transition-metal-free cyclization reaction to prepare 1-pyrroline derivatives bearing various functional groups is described. In this method, a simple combination of a base and a solvent allows the cyclization reaction of terminal alkynes and 2-azaallyls to be carried out efficiently under mild and metal-free conditions. This cyclization reaction will provide an efficient method for the synthesis of medicinally relevant polysubstituted and multifunctionalized pyrrolines.

Radical C(sp3)-S Coupling for the Synthesis of α-Amino Sulfides.

A unique transition-metal-free radical thiolation of 2-azaallyl anions has been developed. Easily accessible thiosulfonates and 2-azaallyls undergo the tandem process of single-electron transfer and radical-radical coupling to construct C(sp3)-S bonds. This robust protocol enables a mild and chemoselective coupling between 2-azaallyl anions and thiosulfonates to access α-amino sulfides in 50-92% yields (25 examples). The scalability of this protocol was demonstrated by telescopic gram-scale experiments. Mechanistic studies provide significant evidence for this radical thiolation reaction.

α-Branched amines through radical coupling with 2-azaallyl anions, redox active esters and alkenes.

α-Branched amines are fundamental building blocks in a variety of natural products and pharmaceuticals. Herein is reported a unique cascade reaction that enables the preparation of α-branched amines bearing aryl or alkyl groups at the ß- or γ-positions. The cascade is initiated by reduction of redox active esters to alkyl radicals. The resulting alkyl radicals are trapped by styrene derivatives, leading to benzylic radicals. The persistent 2-azaallyl radicals and benzylic radicals are proposed to undergo a radical-radical coupling leading to functionalized amine products. Evidence is provided that the role of the nickel catalyst is to promote formation of the alkyl radical from the redox active ester and not promote the C-C bond formation. The synthetic method introduced herein tolerates a variety of imines and redox active esters, allowing for efficient construction of amine building blocks.

Super-Electron-Donor 2-Azaallyl Anions Enable Construction of Isoquinolines.

Herein is introduced the application of "super-electron-donor"(SED) 2-azaallyl anions in a tandem reduction/radical cyclization/radical coupling/aromatization protocol that enables the rapid construction of isoquinolines. The value of this transition-metal-free method is highlighted by the wide range of isoquinoline ethyl amines prepared with good functional group tolerance and yields. An operationally simple gram scale synthesis is also conducted, confirming the scalability.