20132-77-8

Upstream product

• 39724-77-1 3-(p-tolyl)but-2-enenitrile 
• 1195-32-0 1-methyl-4-isopropenylbenzene 
• 625-28-5 Isovaleronitrile 
• 152714-09-5 3-(4'-methylphenyl)cyclobutan-1-one 
• 622-97-9 1-ethenyl-4-methylbenzene 
• 130240-32-3 (E)-3-(p-tolyl)-2-butenenitrile 
• 122-00-9 para-methylacetophenone 

Downstream Products

• 1358804-68-8 1-(1-p-tolylethyl)cyclobutanecarbonitrile 

Relevant academic research and scientific papers

Development of an Operationally Simple, Scalable, and HCN-Free Transfer Hydrocyanation Protocol Using an Air-Stable Nickel Precatalyst

Hydrocyanation reactions enable access to synthetically valuable nitriles from readily available alkene precursors. However, hydrocyanation reactions using hydrogen cyanide (HCN) or similarly toxic reagents on laboratory scale can be particularly challenging due to their hazardous nature. In addition, such processes typically require air- and temperature-sensitive Ni(0) precatalysts, further reducing the operational simplicity of this transformation. Herein, we report a HCN-free transfer hydrocyanation of alkenes and alkynes that employs commercially available aliphatic nitriles as sacrificial HCN donors in combination with a catalytic amount of air-stable and inexpensive NiCl2as a precatalyst and a cocatalytic Lewis acid. The scalability and robustness of the catalytic process were demonstrated by the hydrocyanation of α-methylstyrene on a 100 mmol scale (11.4 g of product obtained) using 1 mol % of the Ni catalyst. In addition, the feasibility of the dehydrocyanation protocol using the air-stable Ni(II) precatalyst and norbornadiene as a sacrificial acceptor was showcased by the selective conversion of an aliphatic nitrile into the corresponding alkene.

Cooperative Palladium/Lewis Acid-Catalyzed Transfer Hydrocyanation of Alkenes and Alkynes Using 1-Methylcyclohexa-2,5-diene-1-carbonitrile

Catalytic transfer hydrocyanation represents a clean and safe alternative to hydrocyanation processes using toxic HCN gas. Such reactions provide access to pharmaceutically important nitrile derivatives starting with alkenes and alkynes. Herein, an efficient and practical cooperative palladium/Lewis acid-catalyzed transfer hydrocyanation of alkenes and alkynes is presented using 1-methylcyclohexa-2,5-diene-1-carbonitrile as a benign and readily available HCN source. A large set of nitrile derivatives (>50 examples) are prepared from both aliphatic and aromatic alkenes with good to excellent anti-Markovnikov selectivity. A range of aliphatic alkenes engage in selective hydrocyanation to provide the corresponding nitriles. The introduced method is useful for chain walking hydrocyanation of internal alkenes to afford terminal nitriles in good regioselectivities. This protocol is also applicable to late-stage modification of bioactive molecules.

Photocatalytic Neophyl Rearrangement and Reduction of Distal Carbon Radicals by Iminyl Radical-Mediated C?C Bond Cleavage

The control of selectivity in the reactions of the highly reactive open-shell carbon radicals is an attractive but often challenging task. Building on the strategy of photoinduced iminyl radical-mediated C?C bond cleavage, we have developed photocatalytic neophyl rearrangement and reduction of distal carbon radicals under visible light irradiation of O-acyl oximes. This mild protocol tolerates a wide range of readily available O-acyl oximes, enabling facile synthesis of diversely substituted α,β-unsaturated nitriles and β-functionalized saturated nitriles in a highly selective manner. (Figure presented.).

Asymmetric hydrogenation of α,β-unsaturated nitriles with base-activated iridium N,P ligand complexes

Although many chiral catalysts are known that allow highly enantioselective hydrogenation of a wide range of olefins, no suitable catalysts for the asymmetric hydrogenation of α,β-unsaturated nitriles have been reported so far. We have found that Ir N,P ligand complexes, which under normal conditions do not show any reactivity towards α,β-unsaturated nitriles, become highly active catalysts upon addition of N,N- diisopropylethylamine. The base-activated catalysts enable conjugate reduction of α,β-unsaturated nitriles with H2 at low catalyst loadings, affording the corresponding saturated nitriles with high conversion and excellent enantioselectivity. In contrast, alkenes lacking a conjugated cyano group do not react under these conditions, making it possible to selectively reduce the conjugated C=C bond of an α,β-unsaturated nitrile, while leaving other types of C=C bonds in the molecule intact.

NOVEL TRPV3 MODULATORS

Disclosed herein are modulators of TRPV3 of formula (I) wherein G1, X1, X2, X3, X4, X5, G2, Z1, Ra, Rb, u, and p are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also presented.

NOVEL TRPV3 MODULATORS

Disclosed herein are modulators of TRPV3 of formula (I), wherein G1, X1, X2, X3, X4, X5, G2, Z1, Ra, Rb, u, and p are as defined in the specifica