One-Step Process for the Regiodivergent Double Hydrocyanation of 1,3-Butadiene.

In industry, the two important nitrile starting materials, adiponitrile and 2-methylglutaronitrile, are primarily manufactured through the well-known DuPont process, which consists of a tandem sequence including first hydrocyanation, isomerization and second hydrocyanation. However, this mature process has the intrinsic defects of step efficiency and regioselectivity. Herein, we report a nickel-catalyzed divergent, one-step double hydrocyanation of 1,3-butadiene to produce either adiponitrile or 2-methylglutaronitrile in high regioselectivity.

Pd-Catalyzed Hydrocyanation of Methylenecyclopropanes: A Highly Selective Ring-Opening Access to 2-Substituted Allylic Nitriles.

Transition-metal-catalyzed hydrofunctionalization of methylenecyclopropanes presents a useful but challenging transformation due to the complex selectivity and multiple reaction pathways. We describe herein an unprecedented highly efficient and selective palladium-catalyzed hydrocyanation of methylenecyclopropanes to give various 2-substituted allylic nitriles. Mechanistic studies demonstrated that the transformation may undergo Markovnikov-type hydrometalation and β-carbon elimination.

Enantioselective Synthesis of Axially Chiral Allylic Nitriles via Nickel-Catalyzed Desymmetric Cyanation of Biaryl Diallylic Alcohols.

Axially chiral nitriles are common motifs in organic photoelectric materials, biological compounds, and agrochemicals. Unfortunately, the limited synthetic approaches to axially chiral nitriles have impeded their availability. Herein, we report the first nickel-catalyzed desymmetric allylic cyanation of biaryl allylic alcohols for the synthesis of axially chiral nitrile structures in high yields with excellent enantioselectivities (up to 90 % yield and >99 % ee).

Nickel-Catalyzed Cyanation of Allylic Alcohols: High Degree of Chiral Inversion in Aqueous Reaction Media.

Nickel-catalyzed aqueous cyanation of allylic alcohols is herein described. This catalytic protocol provided environmentally friendly and operationally simple access to a variety of allylic nitriles in good yields. For chiral allylic alcohols, the reaction gave chiral allylic nitriles with a high degree of chiral inversion.

3-Methylpyridine: Synthesis and Applications.

3-Methylpyridine holds a pivotal role in organic chemistry as it constitutes a fundamental structure in numerous biologically active compounds. Its significance is underscored by its involvement in synthesizing vitamin B3 and developing pyridine insecticides, garnering considerable attention. Consequently, chemists have dedicated efforts to devising efficient and environmentally friendly methods for its preparation.

Enantioselective Synthesis of Axially and Centrally Chiral Styrenes via Nickel-Catalyzed Desymmetric Hydrocyanation of Biaryl Dienes.

Herein, a highly regio-, enantio-, and diastereoselective nickel-catalyzed desymmetric hydrocyanation of biaryl dienes for the simultaneous construction of axial and central chiralities is presented, which offers a convenient approach to a variety of tirenes containing the union of an axially chiral biaryl and a centrally α-chiral nitrile under mild conditions using a commercially available catalyst. The synthetic utility is highlighted by the development of a novel axially chiral phosphine ligand and biphenyl-based chiral diene ligand and their potential applications in the field of asymmetric catalytic reactions.

Palladium-Catalyzed Hydrocyanation of Ynoates: En Route to the Stereodivergent Synthesis of β-Cyanated α,β-Unsaturated Esters via Ligand Controlled Regio- and Stereoselectivity.

A Pd-catalyzed highly regio- and stereoselective hydrocyanation was developed, providing a novel approach to the stereodivergent synthesis of β-cyano-substituted acrylates in good yields with a wide substrate scope. The judicious selection of ligands was crucial for elegant control over the stereodivergence. Furthermore, the success of the -hydrocyanation hinges on the right matching of Pd and , which not only ensured the catalytic activity but also prevented the formation of α-cyanation products.

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.

Nickel-Catalyzed Enantioselective Hydrothiocarbonylation of Cyclopropenes.

Hydrothiocarbonylation of olefins using carbon monoxide and thiols is a powerful method to synthesize thioesters from simple building blocks. Owing to the intrinsic challenges of catalyst poisoning, transition-metal-catalyzed asymmetric thiocarbonylation, particularly when utilizing earth abundant metals, remains rare in the literature. Herein, we report a nickel-catalyzed enantioselective hydrothiocarbonylation of cyclopropenes for the synthesis of a diverse collection of functionalized thioesters in good to excellent yields with high stereoselectivity.

Highly Diastereoselective Synthesis of Polysubstituted Cyclopropanecarbonitriles via Palladium-Catalyzed Cyanoesterification of Cyclopropenes.

We herein develop a highly diastereoselective synthesis of cyano-substituted cyclopropanes via palladium-catalyzed direct cyanoesterification of cyclopropenes, which features mild reaction conditions, good functional group compatibility, and simple operation. This transformation represents a stepwise, highly atom economic, and scalable protocol for obtaining synthetically useful cyclopropanecarbonitriles.

Palladium-Catalyzed Alkyne Hydrocyanation toward Ligand-Controlled Stereodivergent Synthesis of (E)- and (Z)-Trisubstituted Acrylonitriles.

We herein describe a palladium-catalyzed hydrocyanation of propiolamides for the stereodivergent synthesis of trisubstituted acrylonitriles. This synthetic method tolerated various primary, secondary and tertiary propiolamides. The cautious selection of a suitable ligand is essential to the success of this stereodivergent process.

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 β-hydride elimination.

Nickel-Catalyzed Asymmetric Hydroaryloxy- and Hydroalkoxycarbonylation of Cyclopropenes.

The asymmetric Reppe carbonylation reactions provide a straightforward access to α-chiral carbonyl compounds. The reported paradigms predominantly adopted precious palladium as the catalyst. Here we report a nickel-catalyzed asymmetric carbonylation of cyclopropenes with phenyl formate and CO/ROH, respectively.

Nickel-Catalyzed Isomerization/Allylic Cyanation of Alkenyl Alcohols.

Herein reported is a nickel-catalyzed isomerization/allylic cyanation of alkenyl alcohols, which complements current methods for the allylic substitution reactions. The specific diphosphite ligand and methanol as the solvent are crucial for the success for this transformation. A gram-scale regioconvergent experiment and formal synthesis of quebrachamine demonstrate the high potential of this methodology.

Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydrocyanation of Silyl-Substituted 1,3-Diynes.

A regiodivergent nickel-catalyzed hydrocyanation of 1-aryl-4-silyl-1,3-diynes is reported. When appropriate bisphosphine and phosphine-phosphite ligands are applied, the same starting materials can be converted into two different enynyl nitriles with good yields and high regioselectivities. The DFT calculations unveiled that the structural features of different ligands bring divergent alkyne insertion modes, which in turn lead to different regioselectivities.

Regio-, Chemo-, and Enantioselective Ni-Catalyzed Hydrocyanation of 1,3-Dienes.

A regio-, chemo-, and enantioselective nickel-catalyzed hydrocyanation of 1,3-dienes is reported. The key to the success of this asymmetric transformation is the use of a specific multichiral diphosphite ligand. In addition to aryl-substituted 1,3-dienes, highly challenging aliphatic 1,3-diene substrates can also be preferentially converted to the corresponding 1,2-adducts in decent yields with the highest enantioselectivities to date.

Ni-Catalyzed Isomerization-Hydrocyanation Tandem Reactions: Access to Linear Nitriles from Aliphatic Internal Olefins.

A highly regioselective nickel-based catalyst system for the isomerization/hydrocyanation of aliphatic internal olefins is described. This benign tandem reaction provides facile access to a wide variety of aliphatic nitriles in good yields with excellent regioselectivities. Thanks to Lewis acid-free conditions, the protocol features board functional groups tolerance, including secondary amine and unprotected alcohol groups.

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.

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.

Enantioselective Nickel-Catalyzed Migratory Hydrocyanation of Nonconjugated Dienes.

Metal-catalyzed chain-walking reactions have recently emerged as a powerful strategy to functionalize remote positions in organic molecules. However, a chain-walking protocol for nonconjugated dienes remains scarcely reported, and developments are currently ongoing. In this Communication, a nickel-catalyzed asymmetric hydrocyanation of nonconjugated dienes involving a chain-walking process is demonstrated.

Direct access to pentenedinitriles via Ni-catalyzed dihydrocyanation of 1,3-enynes.

A highly regio- and stereoselective dihydrocyanation of 1,3-enynes was implemented by nickel/diphosphine catalysts. This reaction represents the first example of Ni-catalyzed dihydrocyanation of 1,3-enynes using TMSCN and MeOH as HCN surrogates. In this transformation, the main key feature is a multistep combination by using a single catalyst system.

Highly Regio- and Stereoselective Ni-Catalyzed Hydrocyanation of 1,3-Enynes.

A highly regio- and stereoselective hydrocyanation of 1,3-enynes was implemented by nickel/diphosphine catalysts. A wide range of highly regio- and stereoselective alkenyl nitriles were efficiently prepared. In this transformation, both the tethered alkene and the ligand play key roles in the reactivity and selectivity.

Access to 1,3-Dinitriles by Enantioselective Auto-tandem Catalysis: Merging Allylic Cyanation with Asymmetric Hydrocyanation.

Enantioselective auto-tandem catalysis represents a challenging yet highlight attractive topic in the field of asymmetric catalysis. In this context, we describe a dual catalytic cycle that merges allylic cyanation and asymmetric hydrocyanation. The one-pot conversion of a broad array of allylic alcohols into their corresponding 1,3-dinitriles proceeds in good yield with high enantioselectivity.

Cu(i)-Catalyzed asymmetric intramolecular addition of aryl pinacolboronic esters to unactivated ketones: enantioselective synthesis of 2,3-dihydrobenzofuran-3-ol derivatives.

An (S,S)-QuinoxP*-supported Cu(i) catalyst has been disclosed for highly enantioselective intramolecular addition of aryl pinacolboronic esters to unactivated ketones under mild reaction conditions. This protocol showcases a broad substrate tolerance and allows access to various chiral 2,3-dihydrobenzofuran-3-ol derivatives in generally good yields with excellent enantioselectivities.