Development of diverse adjustable axially chiral biphenyl ligands and catalysts.

Development of highly efficient and practical chiral ligands and catalysts is an eternal theme in asymmetric synthesis. Here, we report the design, synthesis, and evaluation of a new kind of adjustable axially chiral biphenyl ligands and catalysts, in which six model reactions including asymmetric additions of diethylzinc or alkynes to aldehydes in the presence of axially chiral [1,1'-biphenyl]-2,2'-diol ligands, palladium-catalyzed asymmetric cycloadditions in the presence of phosphoramidite ligands, and chiral phosphoric acid-catalyzed asymmetric synthesis of 1,1'-spirobiindane-7,7'-diol derivative and [4 + 3] cyclization were attempted. The results showed that variation of 2,2'-substituent groups could provide different types of ligands and catalysts, and adjustment of substituent groups at the 3,3', 5,5', 6,6'-positions could make ligands and catalysts more efficient in the asymmetric catalytic synthesis.

Synthesis of Spirotetrahydrofuran Oxindoles via Palladium-Catalyzed [4 + 1] Cycloaddition of Diphenyl 2-Oxoindolin-3-yl Phosphates and 2-Methylidenetrimethylene Carbonate.

A novel palladium-catalyzed [4 + 1] cycloaddition to give spirotetrahydrofuran oxindoles has been developed, in which diphenyl 2-oxoindolin-3-yl phosphates were used as the both electrophilic and nucleophilic C synthons at C-3 of the oxindole unit and 2-methylidenetrimethylene carbonate was used as the 1,4-dipole. The cycloannulation was performed at room temperature and provided the corresponding spirotetrahydrofuran oxindoles in good to excellent yields. The present method affords a new strategy for the construction of spirooxindole derivatives with unique three-dimensional structures.

Synthesis of Chiral Propargylamines, Chiral 1,2-Dihydronaphtho[2,1-b]furans and Naphtho[2,1-b]furans with C-Alkynyl N,N'-di-(tert-butoxycarbonyl)-aminals and β-Naphthols.

Chiral phosphoric acid-catalyzed couplings of C-alkynyl N,N'-di-(tert-butoxycarbonyl)-aminals with β-naphthols led to chiral propargylamines in moderate to high yields with high to excellent enantioselectivity, in which the reactions underwent sequential chiral phosphoric acid-catalyzed in situ formation of N-(tert-butoxycarbonyl)-imines (N-Boc-imines) from the aminals, and 1,2-addition of β-naphthols to the N-Boc-imines. Chiral 1,2-dihydronaphtho[2,1-b]furans and naphtho[2,1-b]furans were prepared with satisfactory results when 10 mol% AgOAc and 20 mol% 2,6-lutidine or 1.2 equiv.

Development of Axially Chiral Cyclo-Biaryldiol Ligands with Adjustable Dihedral Angles.

A new type of axially chiral cyclo-[1,1'-biphenyl]-2,2'-diol (CYCNOL) ligands with adjustable dihedral angles have been developed by varying the bridge chain length. Eight-, nine- and ten-membered cyclo-ligands were prepared and evaluated by using two representative examples: enantioselective additions of diethylzinc to aldehydes and organometallic reagents to enones. The results revealed that the fine regulation of dihedral angles through variation of the bridge chain length was effective in the asymmetric synthesis.