405199-23-7

Upstream product

• 108454-55-3 3-(4-methoxyphenyl)-2-butenoic acid ethyl ester 
• 7706-82-3 (Z)-3-(4-methoxyphenyl)-2-butenoic acid ethyl ester 
• 7706-82-3 (E)-ethyl 3-(4-methoxyphenyl)but-2-enoate 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 123-11-5 4-methoxy-benzaldehyde 
• 60512-57-4 1-(2,2-dibromovinyl)-4-methoxybenzene 
• 51718-85-5 ethyl 3-(4-methoxyphenyl)propynoate 
• 61292-83-9 (+/-)-ethyl 3-(4-methoxyphenyl)butanoate 
• 18310-76-4 3-(4'-methoxyphenyl)butanoyl chloride 
• 6555-30-2 3-(4-methoxyphenyl)butyric acid 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 64-17-5 ethanol 
• 103987-50-4 3-(4-methoxyphenyl)-2-buten-1-al 

Relevant academic research and scientific papers

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

A chiral phenol–NHC ligand enabled the copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters. The phenol moiety of the chiral NHC ligand played a critical role in producing the enantiomerically enriched products. The catalyst worked well for various (Z)-isomer substrates. Opposite enantiomers were obtained from (Z)- and (E)-isomers, with a higher enantiomeric excess from the (Z)-isomer.

Pyrrolidine-Based P,O Ligands from Carbohydrates: Easily Accessible and Modular Ligands for the Ir-Catalyzed Asymmetric Hydrogenation of Minimally Functionalized Olefins

The potential of P,O-iminosugar based ligands in the Ir-catalyzed asymmetric hydrogenation of minimally functionalized olefins is presented. These new ligands were prepared from easily available carbohydrates (D-mannose, D-ribose and D-arabinose). The stereochemical and polyfunctional diversity of carbohydrates allowed the modulation of the ligands, both from their electronic properties and the rigidity of their backbone. High enantioselectivities (ee’s up to 99 %) can be reached in the hydrogenation of selected tri- and disubstituted substrates.

Catalytic, Enantioselective β-Protonation through a Cooperative Activation Strategy

The NHC-catalyzed transformation of unsaturated aldehydes into saturated esters through an organocatalytic homoenolate process has been thoroughly studied. Leveraging a unique “Umpolung”-mediated β-protonation, this process has evolved from a test bed for homoenolate reactivity to a broader platform for asymmetric catalysis. Inspired by our success in using the β-protonation process to generate enals from ynals with good E/Z selectivity, our early studies found that an asymmetric variation of this reaction was not only feasible, but also adaptable to a kinetic resolution of secondary alcohols through NHC-catalyzed acylation. In-depth analysis of this process determined that careful catalyst and solvent pairing is critical for optimal yield and selectivity; proper choice of nonpolar solvent provided improved yield through suppression of an oxidative side reaction, while employment of a cooperative catalytic approach through inclusion of a hydrogen bond donor cocatalyst significantly improved enantioselectivity.

Alternatives to Phosphinooxazoline (t-BuPHOX) Ligands in the Metal-Catalyzed Hydrogenation of Minimally Functionalized Olefins and Cyclic β-Enamides

This study presents a new series of readily accessible iridium- and rhodium-phosphite/oxazoline catalytic systems that can efficiently hydrogenate, for the first time, both minimally functionalized olefins and functionalized olefins (62 examples in total) in high enantioselectivities (ees up to >99%) and conversions. The phosphite-oxazoline ligands, which are readily available in only two synthetic steps, are derived from previous privileged 4-alkyl-2-[2-(diphenylphosphino)phenyl]-2-oxazoline (PHOX) ligands by replacing the phosphine moiety by a biaryl phosphite group and/or the introduction of a methylene spacer between the oxazoline and the phenyl ring. The modular design of the ligands has given us the opportunity not only to overcome the limitations of the iridium-PHOX catalytic systems in the hydrogenation of minimally functionalized Z-olefins and 1,1-disubstituted olefins, but also to expand their use to unfunctionalized olefins containing other challenging scaffolds (e.g., exocyclic benzofused and triaryl-substituted olefins) and also to olefins with poorly coordinative groups (e.g., α,β-unsaturated lactams, lactones, alkenylboronic esters, etc.) with enantioselectivities typically >95% ee. Moreover, both enantiomers of the hydrogenation product could be obtained by simply changing the configuration of the biaryl phosphite moiety. Remarkably, the new catalytic systems also provided excellent enantioselectivities (up to 99% ee) in the asymmetric hydrogenation of another challenging class of olefins – the functionalized cyclic β-enamides. Again, both enantiomers of the reduced amides could be obtained by changing the metal from Ir to Rh. We also demonstrated that environmentally friendly propylene carbonate can be used with no loss of enantioselectivity. Another advantage of the new ligands over the PHOX ligands is that the best ligands are derived from the affordable (S)-phenylglycinol rather than from the expensive (S)-tert-leucinol. (Figure presented.).

Chiral ferrocene-based P,S ligands for Ir-catalyzed hydrogenation of minimally functionalized olefins. Scope and limitations

A family of 12 modular ferrocenyl planar chiral phosphine-thioethers (P,S) has been studied in the asymmetric hydrogenation of minimally functionalized alkenes. These ligands differ by the substituent on sulfur or by the linker between the ferrocene moiety and the sulfur atom (no linker, methylene or methyl substituted methylene linker bearing an additional element of chirality). The cationic iridium(cod) complexes of the different P,S ligands have been efficiently synthesized. For the majority of the ligands, coordination yielded only a single diastereoisomer with full control of the absolute configuration on sulfur. The different iridium complexes have been used in the hydrogenation of various di, tri, and tetrasubstituted minimally functionalized olefins. Conversions and enantioselectivities are highly dependent on the ligand and substrate structure. Full conversions and low-to-excellent enantioselectivities could be obtained (maximum ee from 14 to 94% for 1,1-disubsituted alkenes, from 17 to 99% for trisubstituted olefins, and 34% for the tetrasubstituted alkene).

Iridium-Catalyzed Asymmetric Hydrogenation with Simple Cyclohexane-Based P/S Ligands: In Situ HP-NMR and DFT Calculations for the Characterization of Reaction Intermediates

We report a reduced but structurally valuable phosphite/phosphinite-thioether ligand library for the Ir-hydrogenation of 40 minimally functionalized alkenes, including relevant examples with poorly coordinative groups. We found that enantiomeric excesses are mainly dependent on the substrate structure and on some ligand parameters (i.e., the type of thioether/phosphorus moieties and the configuration of the phosphite group), whereas the substituents of the biaryl phosphite moiety had little impact. By tuning the ligand parameters we were able to find highly selective catalysts for a range of substrates (ees up to 99%). These phosphite/phosphinite-thioether ligands have a simple backbone and thus yield simple NMR spectra that reduce signal overlap and facilitate the identification of relevant intermediates. Therefore, by combining HP-NMR spectroscopy and theoretical studies, we were also able to identify the catalytically competent Ir-dihydride alkene species, which made it possible to explain the enantioselectivity obtained.

A theoretically-guided optimization of a new family of modular P,S-ligands for iridium-catalyzed hydrogenation of minimally functionalized olefins

A library of modular iridium complexes derived from thioether-phosphite/phosphinite ligands has been evaluated in the asymmetric iridium-catalyzed hydrogenation of minimally functionalized olefins. The modular ligand design has been shown to be crucial in finding highly selective catalysts for each substrate. A DFT study of the transition state responsible for the enantiocontrol in the Ir-catalyzed hydrogenation is also described and used for further optimization of the crucial stereodefining moieties. Excellent enantioselectivities (enantiomeric excess (ee) values up to 99%) have been obtained for a range of substrates, including E- and Z-trisubstituted and disubstituted olefins, α,β-unsaturated enones, tri- and disubstituted alkenylboronic esters, and olefins with trifluoromethyl substituents.

A modular furanoside thioether-phosphite/phosphinite/ phosphine ligand library for asymmetric iridium-catalyzed hydrogenation of minimally functionalized olefins: Scope and limitations

A highly modular furanoside thioether-phosphite/phosphinite/phosphine ligand library has been synthesized for the iridium-catalyzed asymmetric hydrogenation of minimally functionalized olefins. These ligands can be prepared efficiently from easily accessible D-(+)-xylose. We found that their effectiveness at transferring the chiral information in the product can be tuned by correctly choosing the ligand components. Enantioselectivities were therefore excellent (ees up to 99%) in a wide range of E- and Z-trisubstituted alkenes using 5-deoxyribofuranoside thioether-phosphite ligands. It should be pointed out that these catalysts are also very tolerant to the presence of a neighbouring polar group. For 1,1-disubstituted substrates, both enantiomers of the hydrogenation product can be obtained in high enantioselectivities simply by changing the configuration of the biaryl phosphite moiety. The asymmetric hydrogenation was also performed using propylene carbonate as solvent, which allowed the iridium catalysts to be reused while maintaining the excellent enantioselectivities. Copyright

Expanded scope of the asymmetric hydrogenation of minimally functionalized olefins catalyzed by iridium complexes with phosphite-thiazoline ligands

We have replaced the oxazoline group with a thiazoline moiety in one of the most successful of the phosphite-oxazoline ligand families for the Ir-catalyzed hydrogenation of minimally functionalized olefins. A small but structurally important library of Ir phosphite-thiazoline precatalysts (Ir-L1-L2a-e) has been developed by changing the substituents/configurations at the biaryl phosphite group. We found that the replacement of the oxazoline with a thiazoline moiety in the ligand design is beneficial in terms of substrate scope.

A phosphite-pyridine/iridium complex library as highly selective catalysts for the hydrogenation of minimally functionalized olefins

A modular library of readily available phosphite-pyridine ligands has been successfully applied for the first time in the iridium-catalyzed asymmetric hydrogenation of a broad range of minimally functionalized olefins. The modular ligand design has been shown to be crucial in finding highly selective catalytic systems for each substrate. Excellent enantioselectivities (ees up to 99%) have therefore been obtained in a wide range of E- and Z-trisubstituted alkenes, including more demanding triaryl-substituted olefins and dihydronaphthalenes. This good performance extends to the very challenging class of terminal disubstituted olefins, and to olefins containing neighbouring polar groups (ees up to 99%). Both enantiomers of the reduction product can be obtained in excellent enantioselectivities by simply changing the configuration of the carbon next to the phosphite moiety. The hydrogenations were also performed using propylene carbonate as solvent, which allowed the iridium catalyst to be reused and maintained the excellent Copyright