Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters.

Oxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin-derived N-Cbz ketimines. The method requires only a low catalyst loading (2 mol %) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either Takemoto's catalyst or a cinchona alkaloid derivative.

Synthesis of α-substituted vinylsulfonium salts and their application as annulation reagents in the formation of epoxide- and cyclopropane-fused heterocycles.

The discovery of new methods for the synthesis of classes of potentially bioactive molecules remains an important goal for synthetic chemists. Vinylsulfonium salts have been used for the synthesis of a wide variety of small heterocyclic motifs; however, further developments to this important class of reagents has been focused on reaction with new substrates rather than development of new vinylsulfonium salts. We herein report the synthesis of a range of α-substituted vinylsulfonium tetraphenylborates (10 examples) in a 3 step procedure from commercially available styrenes.

Organocatalytic route to dihydrocoumarins and dihydroquinolinones in all stereochemical configurations.

A straightforward stereodivergent route to dihydrocoumarins and dihydroquinolinones based on cinchona alkaloid catalyzed addition reactions of monothiomalonates (MTMs) to functionalized nitroolefins followed by deprotection and chemoselective cyclization has been developed. The synthesis proceeds under mild conditions and yields heterocycles with adjacent quaternary and tertiary stereogenic centers in very high yields and stereoselectivities. Moreover, full control over the relative and absolute configuration is achieved by the use of (pseudo)enantiomeric catalysts and the difference in reactivity of thioester versus oxoester moieties.

Organocatalytic stereoselective synthesis of acyclic γ-nitrothioesters with all-carbon quaternary stereogenic centers.

A method for the stereoselective synthesis of acyclic thioesters bearing adjacent quaternary and tertiary stereogenic centers under mild organocatalytic conditions was developed. α-Substituted monothiomalonates (MTMs) were used as thioester enolate equivalents. They reacted cleanly with nitroolefins in the presence of 1-6 mol % of cinchona alkaloid urea derivatives, and provided access to γ-nitrothioesters with quaternary stereocenters in high yields and diastereo- and enantioselectivities.

Stereoselective metal-free synthesis of β-amino thioesters with tertiary and quaternary stereogenic centers.

β-Amino thioesters are important natural building blocks for the synthesis of numerous bioactive molecules. An organocatalyzed Mannich reaction was developed which provides direct and highly stereoselective access to acyclic β(2)- and β(2,3,3)-amino thioesters with adjacent tertiary and quaternary stereocenters. Mechanistic studies showed that the stereochemical course of the reaction can be controlled by the choice of the substrates.

Diastereoselective synthesis of CF3-substituted, epoxide-fused heterocycles with β-(trifluoromethyl)vinylsulfonium salts.

CF(3)-substituted vinyl diphenylsulfonium triflate is an effective annulation reagent for the formation of α-CF(3) substituted, epoxide-fused heterocycles (pyrrolidines, piperidines, and tetrahydrofurans). This simple method affords a variety of valuable heterocyclic building blocks in a highly diastereoselective manner (dr >20:1).

An efficient synthesis of imidazolinium salts using vinyl sulfonium salts.

The synthesis of imidazolinium salts from the reaction of formamidines and (2-bromoethyl)diphenylsulfonium triflate is described. A variety of symmetrical and unsymmetrical imidazolinium triflate salts were synthesized in high yield in short reaction times under mild conditions. Aromatic and aliphatic N-substituents work well.