Synthesis of the Aminocyclitol Core of Jogyamycin via an Enantioselective Pd-Catalyzed Trimethylenemethane (TMM) Cycloaddition.

The use of ß-nitroenamines as a new class of acceptors in the enantioselective Pd-catalyzed trimethylenemethane cycloaddition afforded differentiated 1,2-dinitrogen bearing cyclopentanes with three contiguous stereocenters. The utility of these acceptors was demonstrated with the efficient construction of the core of jogyamycin and aminocyclopentitols. Further elaboration of the cycloadducts provided a concise synthetic approach toward joygamycin.

Regio- and enantioselective synthesis of pyrrolidines bearing a quaternary center by palladium-catalyzed asymmetric [3 + 2] cycloaddition of trimethylenemethanes.

Herein we describe the first use of disubstituted donors in the palladium-catalyzed trimethylenemethane (TMM) cycloaddition resulting in an enantioselective synthesis of highly substituted pyrrolidines. These cyanoalkyl donors 1 form all-carbon quaternary centers in a catalytic, asymmetric, and intermolecular manner uniquely using diamidophosphite ligands L2 and L3, generating synthetically important chiral building blocks in good yields and selectivities.

Development of diamidophosphite ligands and their application to the palladium-catalyzed vinyl-substituted trimethylenemethane asymmetric [3 + 2] cycloaddition.

A palladium-catalyzed asymmetric [3 + 2] cycloaddition of a vinyl-substituted trimethylenemethane (TMM) donor with α,ß-unsaturated acyl imidazoles is described. A newly designed bisdiamidophosphite ligand derived from (S,S)-trans-1,2-cyclohexanediamine and (2R,4R)-pentanediol has been instrumental for the development of this process. This transformation generates tetrasubstituted cyclopentanes bearing three contiguous stereocenters in high yields, with good diastereo- and enantioselectivity.

Novel epoxide formation in the reaction of 2-bromo-3-methyl-1,4-naphthoquinone with 1,3-propanedithiol.

A novel epoxide 2 was formed as the major product in the reaction of 2-bromo-3-methyl-1,4-naphthoquinone with 1,3-propanedithiol in the presence of triethylamine in 92% yield. Molecular oxygen is suggested to be the source of the added oxygen in 2, an oxidation product of its precursor 3. A strong base such as triethylamine is required to abstract the methyl hydrogen of 1,4-naphthoquinones, leading to the formation of 3 as well as 2.