22031-57-8

Upstream product

• 460-19-5 ethanedinitrile 
• 931-48-6 2-cyclohexylacetylene 
• 1070-71-9 propiolonitrile 
• 110-82-7 cyclohexane 
• 18293-53-3 2-trimethylsilylacetonitrile 
• 2043-61-0 cyclohexanecarbaldehyde 
• 2537-48-6 diethyl 1-cyanomethylphosphonate 
• 78978-57-1 2-(tert-butyldimethylsilyl)acetonitrile 
• 83398-36-1 (triphenylsilyl)acetonitrile 
• 50488-52-3 diphenyl (cyanomethyl)phosphonate 
• 75-05-8 acetonitrile 
• 16640-68-9 cyanomethylene triphenylphosphorane 
• 175355-34-7 N-(cyclohexylmethylene)-4-methylbenzenesulfonamide 
• 1428990-72-0 C₂₂H₂₈NO₃P 

Downstream Products

• 1269823-23-5 3-(4-(7H-pyrrolo[2,3-c]pyridazin-4-yl)-1H-pyrazol-1-yl)-3-cyclohexylpropane nitrile 
• 1269823-24-6 (4-(1-(2-cyano-1-cyclohexylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-c]pyridazin-7-yl)methyl pivalate 
• 62658-55-3 N-((E)-3-Cyclohexyl-allyl)-guanidine 
• 4441-52-5 (E)-3-Cyclohexyl-2-propenylamin 

Relevant academic research and scientific papers

PROCESS FOR HYDROCYANATION OF TERMINAL ALKYNES

The present invention refers to a process for a Rh-catalyzed Anti-Markovnikov hydrocyanation of terminal alkynes which process discloses, for the first time, the highly stereo- and regio-selective hydrocyanation of terminal alkynes to furnish E- configured alkenyl nitriles and the catalyst used in the present process.

Rh-Catalyzed Anti-Markovnikov Hydrocyanation of Terminal Alkynes

We report the first highly stereo- and regioselective hydrocyanation of terminal alkynes to furnish E-configured alkenyl nitriles. Acrylonitriles can be accessed on gram scale with broad substrate scope and functional group tolerance. The hydrocyanation reaction employs acetone cyanohydrin as a practical alternative to HCN gas.

Palladium-catalyzed heck-type cross-couplings of unactivated alkyl iodides

A palladium-catalyzed, intermolecular Heck-type coupling of alkyl iodides and alkenes is described. This process is successful with a variety of primary and secondary unactivated alkyl iodides as reaction partners, including those with hydrogen atoms in t

Monodisperse amorphous CuB23 alloy short nanotubes: Novel efficient catalysts for Heck coupling of inactivated alkyl halides and alkenes

Heck-type coupling of inactivated alkyl halides and alkenes, catalyzed by amorphous CuB23 alloy short nanotubes, has been developed. Such couplings occur on the surfaces of nanotubes via a single-electron oxidative reaction. The results indicate that CuB23 nanotubes are efficient catalysts to replace Pd and Ni complexes for such Heck-type coupling. This journal is

Part I: The development of the catalytic wittig reaction

We have developed the first catalytic (in phosphane) Wittig reaction (CWR). The utilization of an organosilane was pivotal for success as it allowed for the chemoselective reduction of a phosphane oxide. Protocol optimization evaluated the phosphane oxide precatalyst structure, loading, organosilane, temperature, solvent, and base. These studies demonstrated that to maintain viable catalytic performance it was necessary to employ cyclic phosphane oxide precatalysts of type 1. Initial substrate studies utilized sodium carbonate as a base, and further experimentation identified N,N-diisopropylethylamine (DIPEA) as a soluble alternative. The use of DIPEA improved the ease of use, broadened the substrate scope, and decreased the precatalyst loading. The optimized protocols were compatible with alkyl, aryl, and heterocyclic (furyl, indolyl, pyridyl, pyrrolyl, and thienyl) aldehydes to produce both di- and trisubstituted olefins in moderate-to-high yields (60-96 %) by using a precatalyst loading of 4-10 mol %. Kinetic E/Z selectivity was generally 66:34; complete E selectivity for disubstituted α,β-unsaturated products was achieved through a phosphane-mediated isomerization event. The CWR was applied to the synthesis of 54, a known precursor to the anti-Alzheimer drug donepezil hydrochloride, on a multigram scale (12.2 g, 74 % yield). In addition, to our knowledge, the described CWR is the only transition-/heavy-metal-free catalytic olefination process, excluding proton-catalyzed elimination reactions. A point of difference: By utilizing an organosilane to chemoselectively reduce a phosphane oxide precatalyst to a phosphane (see scheme), the first catalytic (in phosphane) Wittig reaction has been developed. The methodology has been applied to the synthesis of 22 disubstituted and 24 trisubstituted olefins, including a multigram synthesis of a precursor to the anti-Alzheimer drug donepezil hydrochloride.

Highly Z-selective synthesis of a,b-unsaturated nitriles using the Horner-Wadsworth-Emmons reaction

A new HWE reagent, (o-tBuC6H4O)2P(O)CH2CN (2e), reacts with various types of aldehydes to give Z-a,bunsaturated nitriles with 86% to >99% Z-selectivity. Especially, the reaction of 2e with bulkier aldehydes, both aromatic and aliphatic, gave the Z-olefins with extremely high selectivity. The combination of t-BuOK and 18-crown-6 (1 equiv) is the base of choice for aromatic aldehydes and t-BuOK is generally the base of choice for aliphatic aldehydes.

Stereoselective olefination of N-sulfonyl imines with stabilized phosphonium ylides for the synthesis of electron-deficient alkenes

An unprecedented protocol has been developed for thestereoselective synthesis of structurally diverse electron-deficient alkenes in moderate to excellent yields from readily accessible N-sulfonyl imines and stabilized phosphonium ylides. Significantly, the olefination reaction of N-sulfonylimines with nitrile-stabilized phosphonium ylides affords an array of α,β-unsaturated nitriles with high Z selectivity, and the reactions with ester-, amide-, and ketone-stabilized phosphonium ylides afford α,β-unsaturated esters, amides, and ketones with high E selectivity, respectively. Spectroscopic analysis of the reaction mixtures and trapping of the intermediates allow plausible mechanisms to be proposed. Initialimine/ylide addition leads to the formation of betaines that cyclize to form 1,2-azaphosphetanes that subsequently eliminate iminophosphoranes to yield alkenes. For the synthesis of electron-deficient 1,2-disubstituted alkenes, the presence of an electron-withdrawing group in the betaine allows rapid interconversion between its two diastereomers through proton transfer. The Z/E selectivity for alkene synthesis is determined by the different rates at which the two betaine diastereomers form the corresponding 1,2-azaphosphetane diastereomers. In contrast, the Z/E selectivity for the synthesis of electron-deficient trisubstituted alkenes originates from the diastereoselective addition of stabilized phosphonium ylides to N-sulfonyl imines.

HETEROCYCLIC COMPOUNDS AS JANUS KINASE INHIBITORS

The invention provides compounds of formula (I) or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for suppressing an immune response or treating cancer or a hematologic malignancy using compounds of formula (I).

CATALYTIC WITTIG AND MITSUNOBU REACTIONS

A catalytic Wittig method utilizing a phosphine including the steps of providing a phosphine oxide precatalyst and reducing the phosphine oxide precatalyst to produce the phosphine; forming a phosphonium ylide precursor from the phosphine and a reactant; generating a phosphonium ylide from the phosphonium ylide precursor; reacting the phosphonium yiide precursor with the aldehyde, ketone, or ester to form the olefin and the phosphine oxide which then reenters the cycle. The invention is also directed to a Mitsunobu reaction catalytic in phosphine.

A facile, one-pot synthesis of β-substituted (Z)-acrylonitriles utilizing an α-diaminoboryl carbanion

A simple three-step single-pot procedure for Z-stereoselective synthesis of β-monosubstituted acrylonitriles has been established. The reaction involves olefination of aldehydes with an in situ generated α-diaminoboryl carbanion species. Various aromatic and aliphatic aldehydes were smoothly converted into the corresponding (Z)-olefin products (up to 96:4 ratio) in good yields (80-98%).