55332-36-0

Upstream product

• 33131-46-3 2-(4-methoxyphenyl)-3-methylcrotonic acid 
• 75-30-9 2-iodo-propane 
• 104-01-8 4-Methoxyphenylacetic acid 
• 124931-82-4 4-Methoxyphenylacetic acid (S)-(-)-2'-hydroxy-1,1'-binaphthyl-2-yl ester 
• 83022-73-5 2-(4-Methoxy-phenyl)-3-methyl-butyric acid methyl ester 

Downstream Products

• 309271-62-3 (S)-4-(4-methoxyphenyl)-5-methylhexanoic acid 
• 866454-92-4 ethyl (2RS,4S)-2-cyano-4-(4-methoxyphenyl)-5-methylhexanoate 
• 675831-38-6 (2S)-2-(4-methoxyphenyl)-3-methylbutan-1-ol 

Relevant academic research and scientific papers

Enantioselective Hydrogenation of Tetrasubstituted α,β-Unsaturated Carboxylic Acids Enabled by Cobalt(II) Catalysis: Scope and Mechanistic Insights

Chiral carboxylic acids are important compounds because of their prevalence in pharmaceuticals, natural products and agrochemicals. Asymmetric hydrogenation of α,β-unsaturated carboxylic acids has been widely recognized as one of the most efficient synthetic approaches to afford such compounds. Although related asymmetric hydrogenation of di- and trisubstituted unsaturated acids with noble metals is well established, asymmetric hydrogenation of challenging tetrasubstituted α,β-unsaturated carboxylic acids is rarely reported. We demonstrate enantioselective hydrogenation of cyclic and acyclic tetrasubstituted α,β-unsaturated carboxylic acids via cobalt(II) catalysis. This protocol showed broad substrate scope and gave chiral carboxylic acids in good yields with excellent enantiocontrol (up to 98 % yield and 99 % ee). Combined experimental and computational mechanistic studies support a CoII catalytic cycle involving migratory insertion and σ-bond metathesis processes. DFT calculations reveal that enantioselectivity may originate from the steric effect between the phenyl groups of the ligand and the substrate.

Highly enantioselective direct alkylation of arylacetic acids with chiral lithium amides as traceless auxiliaries

A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. The protocol is operationally simple, and the chiral reagent is readily recoverable.

Process-scale total synthesis of nature-identical (-)-(S,S)-7- hydroxycalamenal in high enantiomeric purity through catalytic enantioselective hydrogenation

A process-scale stereoselective synthesis of nature-identical (-)-(S,S)-7-hydroxycalamenal (=(-)-(5S,85)-5,6,7,8-tetrahydro-3-hydroxy-5- methyl-8-(1-methylethyl)naphthalene-2-carbaldehyde; (-)-1α) in 96% enantiomeric excess (ee) with the aid of chiral Ru

1,1′-binaphthalene-2,2′-diol as a chiral auxiliary. Diastereoselective alkylation of binaphthyl esters, complex-induced proximity effects in enolate formation, and one-step synthesis of an optically active β-substituted ketone

Diastereoselective alkylation of enolates derived from (S)-naphthyl phenylacetate 1 with LDA in THF gave the S,S-isomer as a major product. The diastereoselectivity increased as the bulkiness of the alkylating agent was increased. The low diastereomeric excess (～70%) of methylation was markedly raised to 92% by the use of n-BuLi as a base due to the complex-induced proximity effect (CIPE) in enolate formation. This highly diastereoselective methylation was used to synthesize the clinically important anti-inflammatory drugs (S)-naproxen (60) and (S)-suprofen (68). The stereochemistry of ketene trimethylsilyl acetals generated from several phenylacetates was investigated to understand the origin of the diastereoselectivity in this alkylation. Methyl phenylacetate (46) predominantly gave a (Z)-enolate by kinetic deprotonation, while the (E)-enolate was predominantly obtained from phenyl phenylacetate (47). An optically active ketone (88) was synthesized from binaphthyl ester 84 by a one-pot procedure involving the 1,4-addition, followed by the 1,2-addition, of organometallics. The CIPE again played a crucial role in the high enantiomeric excess in this case.

Synthesis of Optically Active α-Isopropyl-4-substituted Phenylacetic Acids by Asymmetric Hydrogenation

Homogeneous hydrogenation of 2-phenyl-3-methyl-2-butenoic acid derivatives in the presence of a catalytic amount of such chiral phosphine-rhodium complexes as Rh/(R)-BINAP, Rh/(R)-, or (S)-Cy-BINAP, Rh/(R)-p-tolyl-BINAP, and Rh/(R)-p-methoxyphenyl-BINAP afforded the corresponding phenylacetic acid derivatives in high enantiomeric excesses and in quantitative chemical yields.The optically activa phenylacetic acid derivatives are useful intermediates of agrochemicals and pharmaceuticals.

ENZYMATIC RESOLUTION OF METHYL 2-ALKYL-2-ARYLACETATES

Horse liver esterase, used as its inexpensive commercial acetone powder, catalyzes the selective hydrolysis of methy 2-alkyl-2-arylacetates to afford R(-)-2-alkyl-2-arylacetic acids and S(+)-methyl 2-alkyl-2-arylacetates.