Zhiwu Lu

Chiral nitriles are valuable molecules in modern organic synthesis and drug discovery. Selectively differentiating the two nitrile groups of widely available malononitrile derivatives is a straightforward yet underdeveloped route to construct enantioenriched nitriles. Here we report an enantioselective nickel-catalyzed desymmetrization of malononitriles for the generation of nitrile-containing all-carbon quaternary stereocenters. This protocol involves a nickel-catalyzed addition of aryl boronic acids to alkynes followed by a selective nitrile insertion, providing unprecedented access to enantioenriched 5–7-membered α-cyano cycloenones with a fully substituted olefin from a broad range of substrates. The synthetic utility of these nitrile products is demonstrated by gram-scale synthesis and conversion to several useful functional groups.

A copper-catalyzed efficient enantioselective construction of chiral quaternary carbon-containing chromanes and 3,4-dihydropyrans is reported. The desymmetric C–O coupling is enabled by a chiral dimethylcyclohexane-1,2-diamine ligand and provides the desired products in good yields with high enantioselectivities. This method presents a broad substrate scope and is applicable to diversely substituted aryl bromides and alkenyl bromides. The application is demonstrated by a gram-scale synthesis and derivatization of the products toward valuable building blocks.

Cyclic sulfonamides (sultams) play a unique role in drug discovery and synthetic chemistry. A direct synthesis of sultams by an intramolecular C(sp³)–H amidation reaction using an iron complex in situ derived from Fe(ClO₄)₂ and aminopyridine ligand is reported. This strategy features a readily available catalyst and tolerates a broad variety of substrates as demonstrated by 22 examples (up to 89% yield). A one-pot iron-catalyzed amidation/oxidation procedure for the synthesis of cyclic N-sulfonyl ketimines is also realized with up to 92% yield (eight examples). The synthetic utility of the method is validated by a gram-scale reaction and derivatization of the products to ring-fused sultams.

The chromanone scaffold is a privileged structure in heterocyclic chemistry and drug discovery.

A highly efficient asymmetric ring addition reaction of oxabenzonorbornadienes with thiophenols using an iridium/(S)-xyl-binap catalyst is developed. This catalyst system overcomes catalyst poisoning and background reactions and allows the formation of exclusive thiol addition products in high yields (up to 97% yield) with excellent enantioselectivities (up to 98% ee). Particularly noteworthy is that no competitive ring-opened side products are observed. X-ray crystal structure analysis confirmed the adduct is solely in the exo-configuration.

A palladium/(R)‐Binap catalyst for asymmetric ring opening reaction of azabenzonorbornadienes with amines was developed that afforded the corresponding substituted dihydronaphthalenes in good yields (up to 97%) with excellent enantioselectivities (up to >99% ee). To the best of our knowledge, this represents the first palladium‐catalyzed asymmetric ring opening reaction of azabenzonorbornadienes with heteronucleophiles. magnified image

A new palladium/zinc co‐catalyst system associated with chiral (R)‐Difluorphos for asymmetric ring‐opening reaction of oxabenzonorbornadienes with phenols is reported. This catalyst system allows the formation of cis‐2‐aryloxy‐1,2‐dihydronaphthalen‐1‐ol products in good yields (up to 95 % yield) with excellent enantioselectivities (up to 99 % ee). The cis‐configuration of the product has been confirmed by X‐ray crystal structure analysis. To the best of our knowledge, it represents the first example in ring‐opening reactions of bicycloalkenes with heteronucleophiles in a syn‐stereoselective manner.

A chiral palladium/copper (Pd/Cu) co‐catalytic system which could enable asymmetric ring opening reaction of azabenzonorbornadienes with terminal alkynes is reported. This system comprises palladium(II) acetate [Pd(OAc)₂]/(R)‐xyl‐Binap and copper(I) triflate (CuOTf). A good substrate scope was found, with excellent enantioselective outcomes (up to >99.9 % ee). A reaction mechanism involving two metal complexes is also proposed. magnified image