59452-86-7

Upstream product

• 105-39-5 chloroacetic acid ethyl ester 
• 586-37-8 1-(3-Methoxyphenyl)ethanone 
• 626-20-0 3-methoxystyrene 
• 201230-82-2 carbon monoxide 
• 68-12-2 N,N-dimethyl-formamide 
• 766-85-8 3-methoxy-1-iodobenzene 
• 107-18-6 allyl alcohol 
• 135657-28-2 ethyl 2-hydroxy-3-(3-methoxyphenyl)-3-butenoate 
• 121-71-1 3-Hydroxyacetophenone 
• 191725-61-8 1-methoxy-2-(3'-methoxyphenyl)propene 
• 130788-39-5 2-hydroxy-3-(3-methoxyphenyl)-3-butenoic acid 
• 120125-63-5 cis/trans-ethyl 2-(3-methoxyphenyl)-2-methyl-1-oxirane-1-carboxylate 

Downstream Products

• 130788-41-9 3'-methoxy-1-methyl-2,3-dihydro-[1,1'-biphenyl]-4(1H)-one 
• 120125-64-6 3-(m-methoxyphenyl)butan-2-ol 
• 59452-93-6 2-(3-Methoxyphenyl)-propionaldehyd-methylimin 
• 171020-79-4 (3S,4R)-3-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-4-[(S)-1-(3-methoxy-phenyl)-ethyl]-azetidin-2-one 
• 193401-42-2 (2R,3S)-3-acetoxy-2-bromo-N-[2-(3-methoxyphenyl)-1-propen-1-yl]-N-((S)-1-phenylethyl)butanamide 
• 171020-80-7 (3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-[(S)-1-(3-methoxy-phenyl)-ethyl]-azetidin-2-one 
• 130788-30-6 4-(3-methoxyphenyl)-4-methyl-cyclohexanone 
• 130788-33-9 (+)-E-trans-2(R),4(S)-4-(3-methoxyphenyl)-2,4-dimethylcyclohexanone oxime 
• 130788-34-0 (-)-trans-5(S),7(R)-hexahydro-5-(3-methoxyphenyl)-5,7-dimethyl-2H-azepine-2-one 
• 135657-30-6 (-)-trans-5(S),7(R)-hexahydro-5-(3-methoxyphenyl)-1,5,7-trimethyl-2-azepinone 
• 130788-31-7 2(S)-2-methoxymethyl-N-<4'-(3-methoxyphenyl)-4'-methylcyclohexylidene>-1-pyrrolidinamine 
• 130788-35-1 (+)-5(S),7(R)-5-(3-methoxyphenyl)-5-methyl-7-(N-methyltrifluoroacetamido)octan-2-one 
• 130855-86-6 (+)-cis-2(R),4(R)-4-(3-methoxyphenyl)-2,4-dimethylcyclohexanone 
• 130788-32-8 (+)-trans-2(R),4(S)-4-(3-methoxyphenyl)-2,4-dimethylcyclohexanone 

Relevant academic research and scientific papers

An Asymmetric SN2 Dynamic Kinetic Resolution

The SN2 reaction exhibits the classic Walden inversion, indicative of the stereospecific backside attack of the nucleophile on the stereogenic center. Observation of the inversion of the stereocenter provides evidence for an SN2-type displacement. However, this maxim is contingent on substitution proceeding on a discrete stereocenter. Here we report an SN2 reaction that leads to enantioenrichment of product despite starting from a racemic mixture of starting material. The enantioconvergent reaction proceeds through a dynamic Walden cycle, involving an equilibrating mixture of enantiomers, initiated by a chiral aminocatalyst and terminated by a stereoselective SN2 reaction at a tertiary carbon to provide a quaternary carbon stereocenter. A combination of computational, kinetic, and empirical studies elucidates the multifaceted role of the chiral organocatalyst to provide a model example of the Curtin-Hammett principle. These examples challenge the notion of enantioenriched products exclusively arising from predefined stereocenters when operating through an SN2 mechanism. Based on these principles, examples are included to highlight the generality of the mechanism. We anticipate the asymmetric SN2 dynamic kinetic resolution to be used for a variety of future reactions.

Copper-catalyzed vinylogous aerobic oxidation of unsaturated compounds with air

A mild and operationally simple copper-catalyzed vinylogous aerobic oxidation of β,γ- and α,β-unsaturated esters is described. This method features good yields, broad substrate scope, excellent chemo- and regioselectivity, and good functional group tolerance. This method is additionally capable of oxidizing β,γ- and α,β-unsaturated aldehydes, ketones, amides, nitriles, and sulfones. Furthermore, the present catalytic system is suitable for bisvinylogous and trisvinylogous oxidation. Tetramethylguanidine (TMG) was found to be crucial in its role as a base, but we also speculate that it serves as a ligand to copper(II) triflate to produce the active copper(II) catalyst. Mechanistic experiments conducted suggest a plausible reaction pathway via an allylcopper(II) species. Finally, the breadth of scope and power of this methodology are demonstrated through its application to complex natural product substrates.

Asymmetric α-Allylation of Aldehydes with Alkynes by Integrating Chiral Hydridopalladium and Enamine Catalysis

A palladium-catalyzed asymmetric α-allylation of aldehydes with alkynes has been established by integrating the catalysis of enamine and chiral hydridopalladium complex that is reversibly formed from the oxidative addition of Pd(0) to chiral phosphoric acid. The ternary catalyst system, consisting of an achiral palladium complex, a primary amine, and a chiral phosphoric acid allows the reaction to tolerate a wide scope of α,α-disubstituted aldehydes and alkynes, affording the corresponding allylation products in high yields and with excellent levels of enantioselectivity.

Pummerer Cyclization Revisited: Unraveling of Acyl Oxonium Ion and Vinyl Sulfide Pathways

Two viable pathways (vinyl sulfide and acyl oxonium ion) for the Pummerer cyclization have been unraveled that expand the reaction scope and capabilities. Use of Br?nsted-enhanced Lewis acidity was key to realization of the vinyl sulfide pathway, whereas selective complexation of the sulfur lone pair facilitated the unprecedented acyl oxonium ion pathway. Preliminary mechanistic investigations support these hypotheses. A range of substrates have been explored to understand the reaction parameters.

Dynamic kinetic asymmetric amination of alcohols: From a mixture of four isomers to diastereo- and enantiopure α-branched amines

The first dynamic kinetic asymmetric amination of alcohols via borrowing hydrogen methodology is presented. Under the cooperative catalysis by an iridium complex and a chiral phosphoric acid, α-branched alcohols that exist as a mixture of four isomers undergo racemization by two orthogonal mechanisms and are converted to diastereo- and enantiopure amines bearing adjacent stereocenters. The preparation of diastereo- and enantiopure 1,2-amino alcohols is also realized using this catalytic system.

Beyond classical reactivity patterns: Hydroformylation of vinyl and allyl arenes to valuable β- And γ-aldehyde intermediates using supramolecular catalysis

In this study, we report on properties of a series of rhodium complexes of bisphosphine and bisphosphite L1-L7 ligands, which are equipped with an integral anion binding site (the DIM pocket), and their application in the regioselective hydroformylation of vinyl and allyl arenes bearing an anionic group. In principle, the binding site of the ligand is used to preorganize a substrate molecule through noncovalent interactions with its anionic group to promote otherwise unfavorable reaction pathways. We demonstrate that this strategy allows for unprecedented reversal of selectivity to form otherwise disfavored β-aldehyde products in the hydroformylation of vinyl 2- and 3-carboxyarenes, with chemo- and regioselectivity up to 100%. The catalyst has a wide substrate scope, including the most challenging substrates with internal double bonds. Coordination studies of the catalysts under catalytically relevant conditions reveal the formation of the hydridobiscarbonyl rhodium complexes [Rh(Ln)(CO)2H]. The titration studies confirm that the rhodium complexes can bind anionic species in the DIM binding site of the ligand. Furthermore, kinetic studies and in situ spectroscopic investigations for the most active catalyst give insight into the operational mode of the system, and reveal that the catalytically active species are involved in complex equilibria with unusual dormant (reversibly inactivated) species. In principle, this involves the competitive inhibition of the recognition center by product binding, as well as the inhibition of the metal center via reversible coordination of either a substrate or a product molecule. Despite the inhibition effects, the substrate preorganization gives rise to very high activities and efficiencies (TON > 18‰000 and TOF > 6000 mol mol-1 h-1), which are adequate for commercial applications.

Broad scope hydrofunctionalization of styrene derivatives using iron-catalyzed hydromagnesiation

The highly regioselective iron-catalyzed formal hydrofunctionalization of styrene derivatives with a diverse range of electrophiles has been developed using a single, operationally simple hydromagnesiation procedure and only commercially available, bench-stable reagents. Using just 0.5 mol % FeCl2·4H2O and N,N,N',N'-tetramethylethylenediamine, hydromagnesiation and electrophilic trapping have been used to form new carbon-carbon bonds (13 examples) and carbon-heteroatom bonds (5 examples) including the products of formal cross-coupling reactions, hydroboration, hydroamination, hydrosilylation, and hydrofluorination.

Synthesis of chiral butenolides using amino-thiocarbamate-catalyzed asymmetric bromolactonization

The asymmetric cyclization of 4,4-disubstituted 3-butenoic acids is studied. Amino-thiocarbamates are used as the catalysts and N-bromosuccinimide is used as the stoichiometric halogen source. The resulting γ-butanolide products are readily converted into the corresponding γ-butenolides (up to 58% ee) derivatives in one-pot.

Dynamic kinetic resolution of 2-phenylpropanal derivatives to yield β-chiral primary amines via bioamination

The amination of racemic α-chiral aldehydes, 2-phenylpropanal derivatives, was investigated employing ω-transaminases. By medium and substrate engineering the optical purity of the resulting β-chiral chiral amine could be enhanced to reach optical purities up to 99% ee. Using enantiocomplementary ω-transaminases allowed us to access the (R)- as well as the (S)-enantiomer in most cases. It is important to note that the stereopreference of the ω-transaminases found for α-chiral aldehydes did not correlate with the stereopreference previously observed for the amination of methyl ketones. In one case the stereopreference switched even upon exchanging a methyl substituent to a methoxy group.

Flow Chemistry Syntheses of Styrenes, Unsymmetrical Stilbenes and Branched Aldehydes

Two tandem flow chemistry processes have been developed. A single palladium-catalysed Heck reaction with ethylene gas provides an efficient synthesis for functionalised styrenes. Through further elaboration the catalyst becomes multi-functional and performs a second Heck reaction providing a single continuous process for the synthesis of unsymmetrical stilbenes. In addition, the continuous, rhodium-catalysed, hydroformylation of styrene derivatives with syngas affords branched aldehydes with good selectivity. Incorporation of an in-line aqueous wash and liquid-liquid separation allowed for the ethylene Heck reaction to be telescoped into the hydroformylation step such that a single flow synthesis of branched aldehydes directly from aryl iodides was achieved. The tube-in-tube semi-permeable membrane-based gas reactor and liquid-liquid separator both play an essential role in enabling these telescoped flow processes.