68975-03-1

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• 73746-77-7 4-((4S,5S)-4-Methoxymethyl-5-phenyl-4,5-dihydro-oxazol-2-yl)-5-phenyl-pentan-1-ol 
• 73746-73-3 C₂₅H₃₅NO₃Si 
• 542-28-9 3,4,5,6-tetrahydro-2H-pyran-2-one 
• 100-39-0 benzyl bromide 
• 51594-38-8 (4S)-4r-methoxymethyl-2-phenethyl-5t-phenyl-4,5-dihydro-oxazole 
• 73746-69-7 (4S,5S)-2-<4-<(Trimethylsilyl)oxy>butyl>-4-(methoxymethyl)-5-phenyl-2-oxazoline 
• 98011-25-7 (E)-3-benzylidenetetrahydro-2H-pyran-2-one 
• 100-52-7 benzaldehyde 
• 40541-35-3 3-((Ξ)-benzylidene)-tetrahydro-pyran-2-one 
• 201230-82-2 carbon monoxide 
• 58927-91-6 cis-5-phenyl-3-penten-1-ol 
• 73746-82-4 4-((4S,5S)-4-Methoxymethyl-5-phenyl-4,5-dihydro-oxazol-2-yl)-butan-1-ol 
• 2427-16-9 5-hydroxy-pentanenitrile 

Relevant academic research and scientific papers

Mechanism of the asymmetric hydrogenation of exocyclic α,β- unsaturated carbonyl compounds with an iridium/BiphPhox catalyst: NMR and DFT studies

The mechanism of the asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds with the (aS)-Ir/iPr-BiphPhox catalyst was studied by NMR experiments and DFT computational analyses. Computed optical yields of the asymmetric hydrogenation proceeding by an iridium(I)/iridium(III) mechanism involving a transition state stabilized through two intramolecular hydrogen bonds are in good accordance with the experimental ee values. H in a fix: The title studies show an equilibrium of dinuclear iridium hydrides at low temperature after hydrogenation of the precatalyst. Computations of the conceivable R and S pathways allowed elucidation of the mechanism for enantioselection, thus affording computed optical yields which are consistent with the experimental values. The structure S1 features hydrogen bonding between the catalyst and the carbonyl group of the substrate. Copyright

Indene Derived Phosphorus-Thioether Ligands for the Ir-Catalyzed Asymmetric Hydrogenation of Olefins with Diverse Substitution Patterns and Different Functional Groups

A family of phosphite/phosphinite-thioether ligands have been tested in the Ir-catalyzed asymmetric hydrogenation of a range of olefins (50 substrates in total). The presented ligands are synthesized in three steps from cheap indene and they are air-stable solids. Their modular architecture has been crucial to maximize the catalytic performance for each type of substrate. Improving most Ir-catalysts reported so far, this ligand family presents a broader substrate scope, covering different substitution patterns with different functional groups, ranging from unfunctionalized olefins, through olefins with poorly coordinative groups, to olefins with coordinative functional groups. α,β-Unsaturated acyclic and cyclic esters, ketones and amides werehydrogenated in enantioselectivities ranging from 83 to 99% ee. Enantioselectivities ranging from 91 to 98% ee were also achieved for challenging substrates such as unfunctionalized 1,1′-disubstituted olefins, functionalized tri- and 1,1′-disubstituted vinyl phosphonates, and β-cyclic enamides. The catalytic performance of the Ir-ligand assemblies was maintained when the environmentally benign 1,2-propylene carbonate was used as solvent. (Figure presented.).

Rhodium-catalyzed asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds

A highly enantioselective hydrogenation of exocyclic α,β-unsaturated carbonyl compounds catalyzed by Rh/bisphosphine-thiourea (ZhaoPhos) has been developed, giving the corresponding α-chiral cyclic lactones, lactams and ketones with high yields and excellent enantioselectivities (up to 99% yield and 99% ee). Remarkably, the hydrogen bond between the substrate and the catalyst plays a critical role in this transformation. The synthetic utility of this protocol has been demonstrated by efficient synthesis of chiral 3-(4-fluorobenzyl)piperidine, a key chiral fragment of bioactive molecules.

Ir/Thioether-Carbene, -Phosphinite, and -Phosphite Complexes for Asymmetric Hydrogenation. A Case for Comparison

We studied for the first time the potential of novel and simple Ir/thioether-NHC complexes in the asymmetric hydrogenation of unfunctionalized olefins and cyclic β-enamides. For comparison, we prepared and applied the analogues thioether-phosphinite/phosphite complexes. We found that the efficiency of the new Ir/thioether-NHC catalyst precursors varies with the type of olefin. Thus, while the Ir/thioether-NHC catalyst precursors provided lower catalytic performance than their related Ir/thioether-P complexes in the hydrogenation of olefins lacking a coordinating group, the catalysts had similar good performance for the reduction of functionalized olefins (e.g., tri- and disubstituted enol phosphonate derivatives). Catalytic results together with the studies of the reactivity toward H2 indicated that the thioether-carbene design favors the formation of inactive trinuclear species, which are responsible for the low activities obtained with these carbene-type catalysts. Nevertheless, this catalyst deactivation can be avoided by using functionalized olefins such as enol phosphonates. We also report the discovery of simple-to-synthesize Ir/thioether-P catalysts containing a simple backbone that gave high enantioselectivities for some trisubstituted olefins, some challenging 1,1′-disubstituted olefins, and cyclic β-enamides.

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.).

Accessing non-natural reactivity by irradiating nicotinamide-dependent enzymes with light

Enzymes are ideal for use in asymmetric catalysis by the chemical industry, because their chemical compositions can be tailored to a specific substrate and selectivity pattern while providing efficiencies and selectivities that surpass those of classical synthetic methods. However, enzymes are limited to reactions that are found in nature and, as such, facilitate fewer types of transformation than do other forms of catalysis. Thus, a longstanding challenge in the field of biologically mediated catalysis has been to develop enzymes with new catalytic functions. Here we describe a method for achieving catalytic promiscuity that uses the photoexcited state of nicotinamide co-factors (molecules that assist enzyme-mediated catalysis). Under irradiation with visible light, the nicotinamide-dependent enzyme known as ketoreductase can be transformed from a carbonyl reductase into an initiator of radical species and a chiral source of hydrogen atoms. We demonstrate this new reactivity through a highly enantioselective radical dehalogenation of lactones - a challenging transformation for small-molecule catalysts. Mechanistic experiments support the theory that a radical species acts as an intermediate in this reaction, with NADH and NADPH (the reduced forms of nicotinamide adenine nucleotide and nicotinamide adenine dinucleotide phosphate, respectively) serving as both a photoreductant and the source of hydrogen atoms. To our knowledge, this method represents the first example of photo-induced enzyme promiscuity, and highlights the potential for accessing new reactivity from existing enzymes simply by using the excited states of common biological co-factors. This represents a departure from existing light-driven biocatalytic techniques, which are typically explored in the context of co-factor regeneration.

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).

Distal-selective hydroformylation using scaffolding catalysis

In hydroformylation, phosphorus-based directing groups have been consistently successful at placing the aldehyde on the carbon proximal to the directing group. The design and synthesis of a novel catalytic directing group are reported that promotes aldehyde formation on the carbon distal relative to the directing functionality. This scaffolding ligand, which operates through a reversible covalent bond to the substrate, has been applied to the diastereoselective hydroformylation of homoallylic alcohols to afford δ-lactones selectively. Altering the distance between the alcohol and the olefin revealed that homoallylic alcohols gives the distal lactone with the highest levels of regioselectivity.

SpinPhox/iridium(I)-catalyzed asymmetric hydrogenation of cyclic α-alkylidene carbonyl compounds

Optically active medium-sized cyclic carbonyl compounds bearing an α-chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/IrI catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the Ci￡C bonds in the exocyclic α,β-unsaturated cyclic carbonyls, including a broad range of α-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging α-alkylidenelactam substrates with six- or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an α-chiral carbon center in generally excellent enantiomeric excesses (up to 98 % ee). Synthetic utility of the protocol has also been demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen and its analogue, as well as biologically important ε-aminocaproic acid derivatives. Take it for a spin: SpinPhox/IrI complexes are highly efficient and versatile in the enantioselective hydrogenation of a broad spectrum of exocyclic α,β-unsaturated carbonyl compounds, especially the challenging α-alkylidene lactam substrates with six- or seven-membered rings. The synthetic utility of the present protocol is demonstrated in the asymmetric synthesis of biologically important loxoprofen and ε-aminocaproic acid derivatives. Copyright

Highly enantioselective iridium-catalyzed hydrogenation of α,β-unsaturated esters

α,β-Unsaturated esters have been employed as substrates in iridium-catalyzed asymmetric hydrogenation. Full conversions and good to excellent enantioselectivities (up to 99 % ee) were obtained for a broad range of substrates with both aromatic- and aliphatic substituents on the prochiral carbon. The hydrogenated products are highly useful as building blocks in the synthesis of a variety of natural products and pharmaceuticals. Asymmetric hydrogenation: A variety of α,β-unsaturated esters were hydrogenated with high enantioselectivities (see scheme). The hydrogenated products have been used in synthetic transformations as well as in formal total syntheses. Copyright