Yoshizumi Yasui

Enantioselective Synthesis of 3,3-Disubstituted Oxindoles through Pd-Catalyzed Cyanoamidation

The first enantioselective cyanoamidation of olefins provides quick access to a variety of 3,3-disubstituted oxindoles. The combination of Pd(dba)2, an optically active phosphoramidite, and N, N-dimethylpropylene urea (DMPU) in decalin were found to be the best conditions.

Gold(I)-Catalyzed Tandem Reactions Initiated by Hydroamination of Alkynyl Carbamates: Application to the Synthesis of Nitidine

As a convenient and direct synthesis of 1,2-dihydroisoquinolines, the gold(I)-catalyzed intramolecular hydroamination of (2-alkynyl)benzyl carbamates has been developed. The reaction with cationic gold(I) complex [AuCl(PPh(3))/AgNTf(2)] proceeded at room temperature, giving the desired 6-endo adducts. The addition of alcohol efficiently promoted the reaction, and the amount of the catalyst could be reduced to 1 mol %. However, the alkynes bearing either an electron-deficient aryl group or an alkyl group resulted in predominant production of 5-exo adducts. In such cases, use of a bulky gold catalyst, AuCl[(o-biPh)((t)Bu)(2)P]Cl/AgNTf(2), improved the regioselectivity, giving the 6-endo adducts in better yields. Furthermore, the hydroamination of alkynyl carbamates bearing an acetal or enone was successfully applied to the concise synthesis of tetracyclic heterocycles such as nitidine via the single catalyst-mediated tandem cyclization which consists of a condensation or a Michael addition of the resulting enecarbamates.

Intra- and intermolecular amidation of CC unsaturated bonds through palladium-catalyzed reactions of carbamoyl derivatives

Toward concise access to functionalized amides and lactams, palladium-catalyzed amidations of alkynes and alkenes with formamide derivatives were developed. Cyanoformamides having an alkynyl group were found to undergo intermolecular cyanoamidation in the presence of palladium catalyst to afford alpha-alkylidene lactams. Whereas, when cyanoformamides that possess a 1,1-disubstituted alkenyl group were used as starting materials, alpha,alpha-disubstituted lactams were obtained. The latter reaction was extended to enantioselective transformation by utilizing optically active phosphoramidites as ligand. Furthermore, chloroformamides having a 1,1,2-trisubsituted alkenyl group were found to give alpha-vinyl-lactams in the presence of palladium catalyst, base and silver salt. Additionally, formal intermolecular hydroamidation of alkenes was performed through one-pot hydroboration-carbamoylation sequence.

Synthetic study toward ecteinascidin 743: concise construction of the diazabicyclo[3.3.1]nonane skeleton and assembly of the pentacyclic core.

Synthesis of the pentacyclic core of ecteinascidin 743 is described. This synthesis features concise construction of the diazabicyclo[3.3.1]nonane skeleton using gold(I)-catalyzed one-pot keto amide formation, acid-promoted enamide formation, and oxidative Friedel-Crafts cyclization as the key steps.

Conformations of large macrocycles and ring-in-ring complexes

A kinetically directed, stepwise approach towards molecular Borromean links enabled the isolation and structural characterization of synthetic intermediates along the way. Here we report the synthesis and crystal structures of three flexible macrocyclic intermediates and a new ring-in-ring complex, anchored together through ruthenium(II) centers, which contains open terpyridine caps in the inner Ring II. Terpyridines circumvent the conformational cis/trans limitations of bipyridines and the new ring-in-ring complex forms tetrametallic complexes with Zn(II), Pt(II) and Ru(III) metal ions. Analysis of the four macrocyclic structures provides a good foundation for the conformational flexibility in these complexes and demonstrates the robust applicability of the terpyridine design elements towards the engineered synthesis of ring-in-ring topologies.