913642-87-2

Upstream product

• 69610-41-9 Boc-L-Pro-H 
• 100-58-3 phenylmagnesium bromide 
• 59936-29-7 (S)-N-(tert-butoxycarbonyl)proline methyl ester 
• 98-80-6 phenylboronic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 115186-37-3 tert-butyl (2S)-2-{[N-methoxy(N-methyl)amino]carbonyl}pyrrolidine-1-carboxylate 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 111492-61-6 (S)-2-benzoylpyrrolidine-1-carboxylic acid tert-butyl ester 
• 86953-79-9 tert-butyl pyrrolidine-1-carboxylate 
• 100-52-7 benzaldehyde 

Downstream Products

• 74936-96-2 (S)-α-<(S)-pyrrolidin-2-yl>benzyl alcohol 
• 1608091-96-8 (S)-2-((S)-azido(phenyl)methyl)-1-tritylpyrrolidine 
• 1448991-14-7 (S)-2-[(R)-azido(phenyl)methyl]-1-benzylpyrrolidine 
• 1448991-02-3 (R)-[(S)-1-benzylpyrrolidin-2-yl](phenyl)methanamine 

Relevant academic research and scientific papers

Diastereoselective Synthesis of Nonplanar 3-Amino-1,2,4-oxadiazine Scaffold: Structure Revision of Alchornedine

Herein, we report the diastereoselective synthesis of a 3-amino-1,2,4-oxadiazine (AOXD) scaffold. The presence of a N-O bond in the ring prevents the planar geometry of the aromatic system and induces a strong decrease in the basicity of the guanidine moiety. While DIBAL-H appeared to be the most efficient reducing agent because it exhibited high diastereoselectivity, we observed various behaviors of the Mitsunobu reaction on the resulting β-aminoalcohol, leading to either inversion or retention of the configuration depending on the steric hindrance in the vicinity of the hydroxy group. The physicochemical properties (pKa and log D) and hepatic stability of several AOXD derivatives were experimentally determined and found that the AOXD scaffold possesses promising properties for drug development. Moreover, we synthesized alchornedine, the only natural product with the AOXD scaffold. Based on a comparison of the analytical data, we found that the reported structure of alchornedine was incorrect and hypothesized a new one.

COMPOUND, MANUFACTURING METHOD OF COMPOUND THROUGH ASYMMETRIC MICHAEL ADDITION USING THE COMPOUND AND MANUFACTURING METHOD OF PHENIBUT USING THE COMPOUND

The present invention relates to a compound, a method of producing compounds through an asymmetric Michael addition reaction by using the same, and a method of producing a phenibut compound. Specifically, the compound of the present invention is represented by chemical formula 1. In the chemical formula 1: L represents #AAA# or #BBB# (wherein X represents sulfur or oxygen); R_1 represents hydrogen, an alkyl group having 1-5 carbons, an aryl group having 6-12 carbon atoms, or a benzyl group; R_2 represents an aryl group having 6-12 carbon atoms; R_3 represents hydrogen or an aryl group having 1-12 carbon atoms; and hydrogen in R_1, R_2, and R_3 may be each independently substituted by an alkyl group having 1-5 carbon atoms.COPYRIGHT KIPO 2018

Mechanistic interrogation of the asymmetric lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine

A fundamental mechanistic study of the s-BuLi/chiral diamine-mediated lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine is reported. We show that lithiated thiopivalamides are configurationally unstable at -78 °C. Reaction then proceeds via a dynamic resolution of diastereomeric lithiated intermediates and this accounts for the variable sense and degree of asymmetric induction observed compared to N-Boc heterocycles.

L -Proline Derived Bifunctional Organocatalysts: Enantioselective Michael Addition of Dithiomalonates to trans-β-Nitroolefins

A series of novel l-proline derived tertiary amine bifunctional organocatalysts 9 are reported, which were applied to the asymmetric Michael addition of dithiomalonates 2 to trans-β-nitroolefins 1. The reaction proceeded in high yields (up to 99%) with high enantioselectivities (up to 97% ee). The synthetic utility of this methodology was demonstrated in the short synthesis of (R)-phenibut in high yield.

l-Proline derived arylmethanamine ligands and their application in the copper-catalyzed asymmetric Henry reaction: a rare example of a Cu-complex with a dicopper tetraacetate core

A series of novel epimeric arylmethanamine ligands were synthesized from l-proline. Both epimers were subsequently examined in the copper(II)-catalyzed asymmetric Henry reaction. Product yield and stereoselectivity up to 92% ee indicated that the (S,S)-epimer was superior to the diamine with an (S,R)-configuration. An enhancement of enantioselectivity driven by the formation of a Cu(II) complex with a dicopper tetraacetate core was discovered. Two types of crystalline Cu(II) complexes were isolated, and their structures were established by X-ray analyses.

Mass Spectrometric Screening of Racemic Amine Catalysts for Enantioselective Michael Additions

In extension of a concept of Lloyd-Jones, based on the combination of a racemic catalyst with a scalemic substrate, we have recently developed a method for determining the enantioselectivity of a chiral catalyst from its racemic form by mass spectrometric screening of a non-equal mixture of two mass-labeled quasi-enantiomeric substrates. After an initial proof of principle using palladium-catalyzed allylic substitution as test reaction, we report now the successful application of this approach to the screening of chiral amines as catalysts for the enantioselective Michael addition to α,β-unsaturated aldehydes. The results confirm that our method allows fast and reliable evaluation of chiral racemic catalysts. This opens up new possibilities for investigating catalyst structures that are not easily available in enantiomerically pure form.

Boron/zinc exchange reaction in the diastereoselective arylation of N-protected L-prolinal

The diastereoselective arylation of chiral, non-racemic, N-trityl-protected L-prolinal has been investigated. The reactive aryl groups were generated by a boron/zinc exchange reaction between arylboronic acids and diethylzinc. The reactions proceeded in a highly diastereoselective fashion, and the resulting amino alcohols possessing two vicinal stereocenters were obtained in diastereomeric ratios of >20:1, regardless of the substituent at the transferable aryl group. The diastereoselectivity of the reactions is believed to be the result of an energetically favored Felkin-Anh transition state, with the competing Cram-chelation pathway precluded due to the presence of the bulky N-trityl protecting group. Copyright

Asymmetric lithiation trapping of N -boc heterocycles at temperatures above -78°C

The asymmetric lithiation trapping of N-Boc heterocycles using s-BuLi/chiral diamines at temperatures up to -20°C is reported. Depending on the N-Boc heterocycle, lithiation is accomplished using s-BuLi and (-)-sparteine or the (+)-sparteine surrogate in the temperature range -50 to -20°C for short reaction times (2-20 min). Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered functionalized N-Boc heterocycles in 47-95% yield and 77:23-93:7 er. With N-Boc pyrrolidine, trapped products can be generated in ～90:10 er even at -20°C.

Investigation of bispidines as the stoichiometric ligand in the two-ligand catalytic asymmetric deprotonation of N-Boc pyrrolidine

A range of achiral bispidines have been synthesized and evaluated as the stoichiometric ligand in the two-ligand catalytic asymmetric deprotonation of N-Boc pyrrolidine. ARKAT USA, Inc.

Asymmetric deprotonation using s -BuLi or i -PrLi and chiral diamines in THF: The diamine matters

The solution structures of [6Li]-i-PrLi complexed to (-)-sparteine and the (+)-sparteine surrogate in Et2O-d10 and THF-d8 at -80 °C have been determined using 6Li and 13C NMR spectroscopy. In Et2O, i-PrLi/(-)-sparteine is a solvent-complexed heterodimer, whereas i-PrLi/(+)-sparteine surrogate is a head-to-tail homodimer. In THF, there was no complexation of (-)-sparteine to i-PrLi until ≥3.0 equiv (-)-sparteine and with 6.0 equiv (-)-sparteine, a monomer was characterized. In contrast, the (+)-sparteine surrogate readily complexed to i-PrLi in THF, and with 1.0 equiv (+)-sparteine surrogate, complete formation of a monomer was observed. The NMR spectroscopic study suggested that it should be possible to carry out highly enantioselective asymmetric deprotonation reactions using i-PrLi or s-BuLi/(+)-sparteine surrogate in THF. Hence, three different asymmetric deprotonation reactions (lithiation-trapping of N-Boc pyrrolidine, an O-alkyl carbamate, and a phosphine borane) were investigated; it was shown that reactions with (-)-sparteine in THF proceeded with low enantioselectivity, whereas the corresponding reactions with the (+)-sparteine surrogate occurred with high enantioselectivity. These are the first examples of highly enantioselective asymmetric deprotonation reactions using organolithium/diamine complexes in THF.