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.

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.

Synthetic studies on vincorine: access to the 3a,8a-dialkyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole skeleton.

Synthetic studies on vincorine are described; the conversion of 3-aminoethyl-3-alkyloxindoles to 3a,8a-dialkyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indoles has been achieved through an addition-cyclization sequence, and a fully functionalized key intermediate was constructed with this method.

Synthesis, X-ray crystal structures, and computational studies of 1,1'-bridged 4,4'-diaryl-2,2'-bibenzimidazoles: building blocks for supramolecular structures.

A series of C-shaped, 1,1'-alkyl-bridged 4,4'-diaryl-2,2'-bibenzimidazoles has been synthesized. The crystal structures of these compounds have been determined and packing diagrams demonstrate that these molecules either form linear intercalated molecular chains or include solvent molecules in the solid state. Crystal structures are compared to computational structures determined using density functional theory, with the BMK/DZV(2d,p) method. The C-shaped or tweezer-like geometry enables them to act as building blocks for supramolecular architectures.

Intra- and intermolecular amidation of C-C 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.

Toward general access to the aspidosperma-type terpenoid indole alkaloids: synthesis of the key 3,3-disubstituted piperidones through enantioselective intramolecular heck-type reaction of chloroformamides.

An enantioselective intramolecular Heck-type reaction of chloroformamides has been developed for the synthesis of 3,3-disubstituted piperidones. The desired piperidone was formed in the presence of a palladium catalyst, an optically active phosphoramidite ligand, K3PO4 and Ag3PO4. The obtained piperidone was converted to epieburnamonine.

Concise synthesis of the CDE ring system of tetrahydroisoquinoline alkaloids using carbophilic Lewis acid-catalyzed hydroamidation and oxidative Friedel-Crafts cyclization.

A concise synthesis of the CDE ring system of the tetrahydroisoquinoline antitumor alkaloids such as saframycins, renieramycins, and ecteinascidins has been developed. Both Au(I)-catalyzed intramolecular hydroamidation of alkynylamide and NBS-mediated oxidative Friedel-Crafts cyclization of the resulting 2-ketopiperazine were utilized as key reactions.

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.

One-pot amidation of olefins through Pd-catalyzed coupling of alkylboranes and carbamoyl chlorides.

A one-pot synthesis of C1-elongated amides starting from olefins and carbamoyl chlorides has been developed. Alkylboranes, generated by hydroboration of terminal olefins with 9-BBN-H, underwent smooth coupling with carbamoyl chlorides in the presence of palladium catalyst and Cs2CO3.

Concise synthesis of 1,2-dihydroisoquinolines and 1H-isochromenes by carbophilic lewis acid-catalyzed tandem nucleophilic addition and cyclization of 2-(1-alkynyl)arylaldimines and 2-(1-alkynyl)arylaldehydes.

By using carbophilic Lewis acids, In(OTf)3, NiCl2, and AuCl(PPh3)/AgNTf2, a concise and efficient synthesis of 1,3-disubstituted 1,2-dihydroisoquinolines has been achieved via tandem nucleophilic addition and cyclization of 2-(1-alkynyl)arylaldimines. Addition of proton sources such as water, CF3CH2OH, and 2,6-di-tert-butyl-4-methoxyphenol was essential for the Lewis acid-catalyzed tandem reactions with organometallic reagents. By switching these catalysts, various types of nucleophiles such as allylstannanes, silyl enol ethers, alkenylboronic acids, and active methylene compounds could be introduced at the C1 position of 1,2-dihydroisoquinolines in this transformation. Furthermore, this method proved to be applicable to the synthesis of 1H-isochromene derivatives via the same tandem reaction of 2-(1-alkynyl)arylaldehydes.

Synthesis of 4,4'-bisaryl-2,2'-bisbenzimidazoles as building blocks for supramolecular structures.

A series of 4,4'-bisaryl-2,2'-bisbenzimidazoles has been synthesized from the corresponding 4,4'-dibromo-2,2'-bisbenzimidazoles by Negishi coupling reactions. This procedure affords highly substituted bisbenzimidazoles. [reaction: see text]