Access to Functionalized Cyclohex-2-enones from a Multicomponent Cascade Reaction of Readily Available Alkynes, Ketones, and Ethyl Acetoacetate.

The synthesis of cyclohex-2-enone derivatives is a topic of current interest in organic chemistry. A novel three-component cascade reaction of alkynes with ketones and ethyl acetoacetate has been uncovered. This process provides di- and trisubstituted cyclohex-2-enones in good yields with excellent functional group tolerance. A variety of terminal alkynes and a wide range of aryl, alkyl, and cyclic ketones are viable in this transformation. Successful scale-up preparation and synthetic transformations have demonstrated the potential of this simple operating protocol.

Reduction of Delta2-isoxazolines to beta-hydroxy ketones with iron and ammonium chloride as reducing agent.

A detailed study of a procedure for the selective reduction of Delta(2)-isoxazolines to the corresponding beta-hydroxy ketones is reported. The use of iron and ammonium chloride as the reducing agent in the presence of water results in a facile and chemoselective protocol for the preparation of beta-hydroxy ketones, including the conjugated beta-hydroxy ketones.

Pd-catalyzed carboetherification of beta,gamma-unsaturated oximes: a novel approach to Delta2-isoxazolines.

A novel route to the synthesis of Delta2-isoxazoline derivatives is described. Reaction of beta,gamma-unsaturated oximes with aryl bromides via palladium-catalyzed carboetherification affords 3,5-disubstituted Delta2-isoxazolines in good yields. The use of Xantphos as ligand is crucial for the transformation. The carboetherification products can be further converted to beta-hydroxy ketones in the presence of Fe powder and NH4Cl.

Palladium-catalyzed sequential one-pot reaction of aryl bromides with O-homoallylhydroxylamines: synthesis of N-aryl-beta-amino alcohols.

The palladium-catalyzed sequential one-pot N-arylation-carbo-amination-C-arylation of O-homoallylhydroxylamines with two different aryl bromides provides rapid entry to differentially arylated N-aryl-3-arylmethylisoxazolidines in good yields with excellent diastereoselectivity. The obtained isoxazolidines can be reductively cleaved to cis-N-aryl-beta-amino alcohols in short times and in high yields at room temperature.

Preparation of a 7-arylthieno[3,2-d]pyrimidin-4-amine library.

A focused kinase library of 7-arylthieno[3,2-d]pyrimidin-4-amine analogues is readily prepared via solution-phase parallel synthesis. This strategy relies on a key cyclization of a 3-aminothiophene-2-carboxamide with a formamide to construct the thienopyrimidine core. Further elaborations of this core via substitution and Suzuki coupling reactions allow the introduction of other diversity points. This methodology is demonstrated through the preparation of a 72-membered library of 7-arylthieno[3,2-d]pyrimidin-4-amines in good yields and high purities.