Nickel-Catalyzed Regio- and Enantioselective Migratory Hydrocyanation of Internal Alkenes: Expanding the Scope to α,ω-Diaryl Internal Alkenes.

Metal-hydride-catalyzed migratory functionalization of alkenes witnessed extensive development in the past few years. However, the asymmetric version of this reaction has remained largely underdeveloped owing to the difficulty in simultaneous control of both regio- and stereoselectivity. In addition, exploring the wider alkene substrate scope to enable more synthetically valuable applications represents another challenge in this field. In this context, a nickel-catalyzed asymmetric hydrocyanation of internal alkenes involving a chain-walking process is demonstrated. The reaction exhibits excellent regio- and enantioselectivity, proceeds under mild reaction conditions, and delivers benzylic nitriles in high yields. Even α,ω-diaryl internal alkenes, which are known to be one of the most challenging substrates of this type, could be successfully converted to the desired products with good regio- and stereoselectivity by modifying the electronic and steric effects. Theoretical calculations suggest that the η3-benzyl coordination mode and the aryl substituent (3,5-(OMe)2C6H3) on the diphosphite ligand are both key factors in regulating regio- and enantioselectivity.

Cobalt-Catalyzed Hydrocyanation of Methylenecyclopropanes to Homoallylic Nitriles.

We describe herein a novel synthesis of various homoallylic nitriles via cobalt-catalyzed hydrocyanation of methylenecyclopropanes. Excellent selectivity, mild reaction conditions, good functional group compatibility, gram-scale reaction, and product transformations demonstrate the power of this protocol. This extraordinary selectivity can probably be attributed to the stronger aptitude of the alkyl-cobalt cyanide intermediate to undergo reductive elimination rather than ß-hydride elimination.

Nickel-Catalyzed Migratory Hydrocyanation of Internal Alkenes: Unexpected Diastereomeric-Ligand-Controlled Regiodivergence.

A regiodivergent nickel-catalyzed hydrocyanation of a broad range of internal alkenes involving a chain-walking process is reported. When appropriate diastereomeric biaryl diphosphite ligands are applied, the same starting materials can be converted to either linear or branched nitriles with good yields and high regioselectivities. DFT calculations suggested that the catalyst architecture determines the regioselectivity by modulating electronic and steric interactions. In addition, moderate enantioselectivities were observed when branched nitriles were produced.

Enantioselective Synthesis of 4-Cyanotetrahydroquinolines via Ni-Catalyzed Hydrocyanation of 1,2-Dihydroquinolines.

A Ni-catalyzed asymmetric hydrocyanation that enables the formation of 4-cyanotetrahydroquinolines in good yields with excellent enantioselectivities is presented herein. A variety of functional groups are well-tolerated, and a gram-scale reaction supports the synthetic potential of the transformation. Additionally, several crucial intermediates for pharmaceutically active agents, including a PGD2 receptor antagonist, are now accessible through asymmetric synthesis using this new protocol.

Synthesis of trifluoromethyl-containing isoindolinones from tertiary enamides via a cascade radical addition and cyclization process.

A radical trifluoromethylation reaction of tertiary enamides was investigated and trifluoromethyl-containing isoindolinones were prepared under mild conditions. Using TMSCF3 as a radical source, PhI(OAc)2 as an oxidant and KHF2 as an additive, tertiary enamides were converted to isoindolinones via a cascade addition and cyclization process in moderate to good yields.