56427-44-2

Usage

InChI:InChI=1/C9H10O2/c1-2-7-5-3-4-6-8(7)9(10)11/h3-6H,2H2,1H3,(H,10,11)

Upstream product

• 64-17-5 ethanol 
• 612-19-1 2-ethylbenzoic acid 
• 28272-96-0 2-vinylbenzaldehyde 
• 76118-05-3 2-ethylbenzoyl chloride 
• 1829-28-3 ethyl 2-iodobenzoate 
• 557-20-0 diethylzinc 
• 577-56-0 2-acetyl-benzoic acid 
• 1973-22-4 1-bromo-2-ethylbenzene 
• 2633-75-2 ethylzinc chloride 
• 578-54-1 ortho-ethylaniline 
• 34136-59-9 o-ethylbenzonitrile 
• 118-90-1 ortho-methylbenzoic acid 

Downstream Products

• 104174-11-0 2-(2-ethyl-phenyl)-propan-2-ol 
• 1467-06-7 2-ethylbenzyl chloride 
• 74533-20-3 2-(2-ethylphenyl)acetonitrile 
• 105337-78-8 ethyl 2-(2-ethylphenyl)acetate 
• 94204-38-3 diethyl 2-(2-ethylphenyl)malonate 
• 1213455-73-2 (R)-2-(o-ethylphenyl)pyrrolidine 
• 103859-06-9 1-ethyl-2-(α-chloro-isopropyl)-benzene 

Relevant academic research and scientific papers

Zinc-Catalyzed Asymmetric Hydrosilylation of Cyclic Imines: Synthesis of Chiral 2-Aryl-Substituted Pyrrolidines as Pharmaceutical Building Blocks

The first successful enantioselective hydrosilylation of cyclic imines promoted by a chiral zinc complex is reported. In situ generated zinc-ProPhenol complex with silane afforded pharmaceutically relevant enantioenriched 2-aryl-substituted pyrrolidines in high yields and with excellent enantioselectivities (up to 99% ee). The synthetic utility of presented methodology is demonstrated in an efficient synthesis of the corresponding chiral cyclic amines, being pharmaceutical drug precursors to the Aticaprant and Larotrectinib. (Figure presented.).

Understanding the Use of Phosphine-(EWO) Ligands in Negishi Cross-Coupling: Experimental and Density Functional Theory Mechanistic Study

The easily prepared hemilabile ligand 1-(PPh2),2-(trans-CH═CHCOPh)-C6F4(PhPEWO-F) and other PEWO ligands are well-known promoters of C-C reductive eliminations and very effective in Negishi couplings. As an example, the efficient Negishi coupling of (C6F5)-I and Zn(C6F5)2is reported. The thorough experimental study of the steps involved in the catalytic cycle uncovers the potential weakness of this ligand that could frustrate at some points the desired cycle and provide some simple precautions to keep the catalytic cycle working efficiently. Density functional theory (DFT) calculations complete the experimental study and provide insight into nonobservable transition states and intermediates, comparing the potential conflict between reductive elimination and olefin insertion. Our results showcase the importance the transmetalation step, facilitated by the strong trans effect of the electron-withdrawing ligand, and the choice of organozinc nucleophiles, critical to ensure fast group exchange and a positive outcome of the catalytic reactions.

Experimental study of the mechanism of the palladium-catalyzed aryl-alkyl negishi coupling using hybrid phosphine-electron-withdrawing olefin ligands

A detailed study of the Negishi cross-coupling reaction of ArI (Ar = 2-C6H4CO2Et) and ZnEt2 with palladium catalysts containing conventional phosphines versus one using a chelating hybrid phosphine-electron-withdrawing olefin (P-EWO) ligand reveals that for conventional phosphines (e.g., PPh3) β-H elimination from intermediate [PdArEt(PPh3)2] is competitive with Ar-Et reductive elimination and is responsible for part of the undesired reduction product ArH. In contrast, with the EWO phosphine, the β-H elimination from intermediate [PdArEt(P-EWO)] is slow compared to the fast Ar-Et reductive elimination, and the undesired reduction product ArH observed proceeds in this case of hydrolysis of ZnArEt, formed in transmetalations where Ar is transferred from Pd to Zn. The rate of these transmetalations is comparable to the rate of reductive eliminations. Consequently, undesired transmetalations affording [PdEt2(P-EWO)] and ZnArEt are more effective at early stages of the reactions and less effective when the ethylating agent becomes poorer in ZnEt2 and richer in ZnEtX (X = I), as the reaction proceeds. Careful analysis of the experiments reveals the detailed changing evolution of the reaction, not only providing the main features of the catalytic cycle but also deducing how the reagents in the system change with time and what the effects on the products of these changes are.

Phosphines with tethered electron-withdrawing olefins as ligands for efficient Pd-catalyzed aryl-alkyl coupling

A group of phosphine/alkene ligands L = Ph2P(2-RC 6F4) (R = CH=CHMe, CH=CHPh, CH=CHCOPh) or Ph 2P(CH2)2CF=CF2 and their [PdCl 2L] complexes have been prepared. These phosphines are easy to prepare and fairly stable toward oxidation. Their palladium complexes feature chelated L structures with the double bond coordinated as the Z isomer, except for Ph2P(CH2)2CF=CF2, where the double bond is not coordinated and the complex is a dimer with Cl bridges. The ligands have been tested for their activity in the Negishi palladium-catalyzed aryl-alkyl coupling, where there is a competition of coupling and reduction products. Only the ligands forming chelated PdII complexes rise the coupling/reduction ratio to values 42/58 or higher. Of these, it is the ligand bearing the more electron-withdrawing substituent (R = CH=CHCOPh) that is the one producing remarkably high selectivity toward coupling: 90/10 under the usual Negishi conditions, and noticeably higher (97/3) if the proportion of ZnEt 2 in the reaction is lowered. These results fit well with the hypothesis that chelating phosphines with tethered electron-acceptor olefins improve the selectivity toward coupling products mostly because they reduce the activation barrier for C-C coupling, and not because they protect the complex from β-H elimination.

Superior effect of a π-acceptor ligand (phosphine-electron-deficient olefin ligand) in the Negishi coupling involving alkylzinc reagents

(Chemical Equation Presented) Palladium-catalyzed Negishi cross-coupling involving primary and secondary alkyls, even in the presence of β-H, can be achieved at ambient temperature using chelating ligands containing a phosphine and an electron-deficient olefin. The superior effects of the ligands were shown not only in the desired cross-coupling product yields but also in the fast reaction at mild conditions. This reaction has been also scaled up to 50 g in 0.005 mol % catalyst (20,000 TONs) at room temperature.

Protoberberins from Reissert Compounds VI [1]. Diastereoselective Synthesis and Relative Configuration of 2-Benzoyl-1-cyano-1-(1-phenylalkyl)-1,2-dihydroisoquinolines

The alkylation of Reissert compounds 8 by sec-benzyl bromides 4, 7, and 10 diastereoselectively affords the title compounds 11 and 12. X-Ray structure analysis confirms an opposite configuration of the chiral centers in 11 and 12. The benzyl bromides 4, 7, and 10 are prepared by standard procedures.

Photoreactivity of Conjugated Bichromophoric Molecules; Photoreaction of o-Vinylbenzaldehyde with Secondary Amines

Irradiation of o-vinylbenzaldehyde 8 in the presence of secondary amines 9 results in N-H addition across the two chromophores to give o-ethylbenzamides 6; photolysis of o-(2-dialkylaminoethyl)benzaldehydes 5a and 5b also affords 6 via photoexpulsion followed by recombination of the 8 and 9 which are formed.