Access to chiral dihydrophenanthridines via a palladium(0)-catalyzed Suzuki coupling and C-H arylation cascade reaction using new chiral-bridged biphenyl bifunctional ligands.

A class of chiral-bridged biphenyl phosphine-carboxylate bifunctional ligands CB-Phos has been developed and successfully applied to Pd(0)-catalyzed single enantioselective C-H arylation and a one pot cascade reaction involving Suzuki cross-coupling and C-H arylation. The catalytic system provides a new and convenient way for the synthesis of versatile chiral dihydrophenanthridines with rich structures and broad functional group tolerance. Good to excellent yields with high enantioselectivities were generally achieved. The reaction mechanism of the cascade reaction was also preliminarily discussed.

Solvent-Free Buchwald-Hartwig Amination of Heteroaryl Chlorides by N-Heterocyclic Carbene-Palladium Complex (SIPr)Ph2Pd(cin)Cl at Room Temperature.

Using the robust N-heterocyclic carbene-palladium complex (SIPr)Ph2Pd(cin)Cl, a highly efficient and easy-to-operate method has been developed at room temperature for the solvent-free Buchwald-Hartwig amination of heteroaryl chlorides with various amines. The amount of catalyst can be as low as 0.05 wt %. The system was demonstrated on 47 substrates and successfully applied to the synthesis of commercial pharmaceuticals and candidate drugs with high yields. Furthermore, the protocol can be used to prepare aniline derivatives on a multigram scale without yield loss.

Iridium-Catalyzed Intramolecular Asymmetric Allylic Etherification of Pyrimidinemethanols: Enantioselective Construction of Multifunctionalized Pyrimidine-Fused Oxazepines.

An iridium-catalyzed intramolecular asymmetric allylic etherification of pyrimidinemethanols is described. In the presence of chiral-bridged biphenyl phosphoramidite ligand L3 and triethylborane, this process provided a class of novel pyrimidine-fused oxazepanes in up to 99% yield with 99.5% enantiomeric excess. The work addresses the challenge of insufficient nucleophilicity of aliphatic alcohols for allyl substitution and indicates the vital value of chiral-bridged biphenyl phosphoramidites. Various multifunctionalized transformations of the products further demonstrate the robust synthetic utility of this methodology.

Copper-catalyzed (4+1) and (3+2) cyclizations of iodonium ylides with alkynes.

The copper(ii)-catalyzed (4+1) cyclizations and copper(i)-catalyzed (3+2) cycloadditions of iodonium ylides and alkynes were successfully developed by employing efficient and safe iodonium ylides instead of traditional diazo compounds. Highly functionalized dimethyl (E)-3-benzylideneindoline-2,2-dicarboxylates and methyl 5-(2-hydroxyphenyl)-2-methoxy-4-phenylfuran-3-carboxylates were conveniently prepared in moderate to excellent yields. The possible reaction mechanisms were also discussed.

Pd-catalyzed asymmetric Suzuki-Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position.

Pd-catalyzed asymmetric Suzuki-Miyaura couplings of 3-methyl-2-bromophenylamides, 3-methyl-2-bromo-1-nitrobenzene and 1-naphthaleneboronic acids have been successfully developed and the corresponding axially chiral biaryl compounds were obtained in very high yields (up to 99%) with good enantioselectivities (up to 88% ee) under mild conditions. The chiral-bridged biphenyl monophosphine ligands developed by our group exhibit significant superiority to the naphthyl counterpart MOP in both reactivity and enantioselectivity control. The large steric hindrance from π-conjugated ortho-substituents of the bromobenzene substrates and the Pd···O interaction between carbonyl and palladium seem essential to achieve high enantioselectivity.