685128-72-7

Upstream product

• 104-53-0 3-phenyl-propionaldehyde 
• 127180-75-0 2-(S)-chloro-3-phenyl-propan-1-ol 
• 7474-06-8 (S)-2-chloro-3-phenyl-propionic acid 
• 63-91-2 L-phenylalanine 

Downstream Products

• 127180-75-0 2-(S)-chloro-3-phenyl-propan-1-ol 
• 1311386-65-8 C₁₀H₁₁ClO 
• 1234572-21-4 (R)-tert-butyl 4-((2-benzylaziridin-1-yl)methyl)piperidine-1-carboxylate 
• 1234572-18-9 (R)-2-benzyl-1-((S)-1-(naphthalen-2-yl)ethyl)aziridine 
• 1234572-17-8 (R)-2-benzyl-1-((S)-1-phenylethyl)aziridine 

Relevant academic research and scientific papers

Direct Organocatalytic Asymmetric α-Chlorination of Aldehydes

The direct organocatalytic enantioselective α-chlorination of aldehydes has been developed. The reaction proceeds for a series of different aldehydes with NCS as the chlorine source using easily available catalysts such as L-proline amide and (2R,5R)-diphenylpyrrolidine. The α-chloro aldehydes are obtained in up to 99% yield and up to 95% ee. The synthetic utility of the enantioselective α-chlorination of aldehydes is demonstrated by transformation of the α-chloro aldehydes to the corresponding α-chloro alcohols (>90% yield) by standard reduction and further transformation to both a terminal epoxide and amino alcohol, both obtained without loss of optical purity. Oxidation of the α-chloro aldehydes followed by esterification gave optically active α-chloro esters without loss of optical purity. It is demonstrated that these optically active α-chloro esters can be converted into nonproteinogenic amino acids in overall high yields, maintaining the enantiomeric excess obtained in the catalytic enantioselective α-chlorination step. Copyright

Mechanistically Guided Design of an Efficient and Enantioselective Aminocatalytic α-Chlorination of Aldehydes

The enantioselective aminocatalytic α-chlorination of aldehydes is a challenging reaction because of its tendency to proceed through neutral intermediates in unselective pathways. Herein we report the rational shift to a highly selective reaction pathway involving charged intermediates using hexafluoroisopropanol as solvent. This change in mechanism has enabled us to match and improve upon the yields and enantioselectivities displayed by previous methods while using cheaper aminocatalysts and chlorinating agents, 80-95% less amount of catalyst, convenient temperatures, and shorter reaction times.

A general, enantioselective synthesis of 2-substituted thiomorpholines and thiomorpholine 1,1-dioxides

In the course of our drug discovery programs, we had need to access chiral, 2-substituted thiomorpholines and their oxidized congeners, thiomorpholine 1,1-dioxides. Here, we disclose a high-yielding, general protocol for the enantioselective synthesis of

Mechanistic Studies on the Organocatalytic α-Chlorination of Aldehydes: The Role and Nature of Off-Cycle Intermediates

Herein we report the isolation and characterization of aminal intermediates in the organocatalytic α-chlorination of aldehydes. These species are stable covalent ternary adducts of the substrate, the catalyst and the chlorinating reagent. NMR-assisted kinetic studies and isotopic labeling experiments with the isolated intermediate did not support its involvement in downstream stereoselective processes as proposed by Blackmond. By tuning the reactivity of the chlorinating reagent, we were able to suppress the accumulation of rate-limiting off-cycle intermediates. As a result, an efficient and highly enantioselective catalytic system with a broad functional group tolerance was developed.

Trichloromethanesulfonyl chloride: A chlorinating reagent for aldehydes

Trichloromethanesulfonyl chloride (CCl3SO2Cl), a commercially available reagent, has been found to perform efficiently in the α-chlorination of aldehydes, including its catalytic asymmetric version, under very mild reaction conditions. Under our reaction conditions, this compound outperforms typical chlorinating reagents for organic synthesis, facilitates workup and purification of the product, and minimizes the formation of toxic, chlorinated organic waste.

Enantio and diastereoselective addition of phenylacetylene to racemic α-chloroketones

In this report, we have presented the first diastereoselective addition of phenylacetylene to chiral racemic chloroketones. The addition is controlled by the reactivity of the chloroketones that allowed the stereoselective reaction to be performed at -20

Stereoselective synthesis of chiral 4-(1-Chloroalkyl)-β-lactams starting from amino acids and their transformation into functionalized chiral azetidines and pyrrolidines

Chiral short-chain α-chloroaldehydes were prepared starting from enantiomerically pure amino acids in a three-step approach, thus providing a practical synthetic alternative for known organocatalytic α-chlorination procedures. The latter aldehydes proved

General access to chiral n -alkyl terminal aziridines via organocatalysis

(Figure Presented) A three step, one-pot protocol involving enantioselective α-chlorination of aldehydes, subsequent reductive amination with a primary amine, and SN2 displacement to afford chiral N-alkyl terminal aziridines in 40-65% yield (74-87%/step) and, in most cases, >90% ee is reported.

Enantioselective -chlorination of aldehydes with recyclable fluorous (s)-pyrrolidine-thiourea bifunctional organocatalyst

A novel fluorous (S)-pyrrolidine-thiourea bifunctional organocatalyst is prepared. The catalyst shows good activity and enantioselectivity for direct -chlorination of aldehydes using N-chlorosuccinimide (NCS) as the chlorine source. It can be recovered fr

Enantioselective linchpin catalysis by SOMO catalysis: An approach to the asymmetric a-chlorination of aldehydes and terminal epoxide formation

Time for SOme MOre: For the first time SOMO (singly occupied molecular orbital) activation has been exploited to allow a new approach to the α-chlorination of aldehydes. This transformation can be readily implemented as part of a linchpin catalysis approach to the enantioselective production of terminal epoxides.