353268-59-4

Upstream product

• 37577-07-4 Norpseudoephedrine 
• 100-52-7 benzaldehyde 
• 492-39-7 (1S,2S)-2-amino-1-phenylpropanol 
• 492-41-1 (1R,2S)-norephedrine 
• 40626-29-7 Acutrim 
• 37577-28-9 (1S,2R)-(+)-norphedrine 
• 117037-25-9 tert-butyl [(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]carbamate 
• 125073-84-9 (2S,4R,5R)-4-Methyl-2,5-diphenyl-oxazolidine 
• 125073-95-2 (2R,4R,5R)-4-Methyl-2,5-diphenyl-oxazolidine 
• 492-39-7 2-amino-1-phenylpropan-1-ol 

Downstream Products

• 125073-95-2 (2R,4R,5R)-4-Methyl-2,5-diphenyl-oxazolidine 
• 125073-84-9 (2S,4R,5R)-4-Methyl-2,5-diphenyl-oxazolidine 

Relevant academic research and scientific papers

Asymmetric Epoxidation of Unfunctionalized Olefins Using Novel Chiral Dihydroisoquinolinium Salts as Organocatalysts

Abstract: Two new non-racemic chiral dihydroisoquinolinium salts with N-substituents bulkier than a methyl group have been synthesized from (1S,2R)-norephedrine. These salts were used to catalyze asymmetric epoxidation of a series of prochiral olefins. One of the two new catalysts provided higher enantioselectivities (up to 66% ee) than the reference salt containing an N-methyl substituent.

Stereoselective synthesis of γ-lactams from imines and cyanosuccinic anhydrides

A reaction between imines and anhydrides has been developed with chiral disubstituted anhydrides and chiral imines. The synthesis of highly substituted γ-lactams with three stereogenic centers, including one quaternary center, proceeds at room temperature in high yield and with high diastereoselectivity in most cases. Enantiomerically pure alkyl-substituted anhydrides proceed with no epimerization, thus providing access to enantiomerically pure penta-substituted lactam products.

Catalytic asymmetric addition of diethylzinc to aldehydes via chiral, non-racemic β-hydroxy and β-methoxy salicylhydrazone catalysts

(1S,2S)-Pseudoephedrine and (1S,2S)-pseudonorephedrine have been converted to their corresponding hydrazines and condensed with either o-salicylaldehyde or 2-hydroxy-1-naphthaldehyde to afford a series of β- hydroxysalicylhydrazones that have been employed in the asymmetric addition of diethylzinc to 2-naphthaldehyde in up to 56% ee. In addition to this, the Ephedra hydrazines were also condensed with the o-hydroxyacetophenone derivative to form related hydrazones. The use of these corresponding hydrazones in the asymmetric addition reaction with the diethylzinc did not yield improved enantioselectivities. Finally, Enders' hydrazine was used as a chiral scaffold for the synthesis of β-methoxysalicylhydrazones. These compounds were employed in the asymmetric addition of diethylzinc to a variety of aromatic aldehydes with enantiomeric excesses as high as 68% ee.

N-Pyridylmethylephedrine derivatives in the catalytic asymmetric addition of diethylzinc to aldehydes and diphenylphosphinoylimines

N-Pyridylmethyl-substituted Ephedra derivatives were synthesized by either direct alkylation or reductive alkylation of (1R,2S)-norephedrine, (1S,2S)-pseudo norephedrine, and (1R,2S)-ephedrine. These derivatives were then employed in asymmetric addition reactions with diethylzinc and aldehydes and diphenylphosphinoylimines. The use of the diastereomers from the Ephedra family allowed for a systematic evaluation of the contribution of the N-pyridylmethyl.

β-Amino alcohols derived from (1R,2S)-norephedrine and (1S,2S)-pseudonorephedrine as catalysts in the asymmetric addition of diethylzinc to aldehydes

A family of N-alkylnorephedrine and N-alkylpseudonorephedrine derived ligands were prepared and applied in the asymmetric alkylation of benzaldehyde using diethylzinc. The absolute configuration of the addition product was directed primarily by the benzylic position of the Ephedra alkaloid, while the magnitude of the enantiomeric ratio was heavily influenced by the nitrogen substituent. However, sterically demanding substituents at the nitrogen position caused the enantioselectivity to be the same for the two diastereomeric systems. Among the ligands that were prepared, it was determined that the N-cyclooctylpseudonorephedrine derivative 7b yielded the highest enantiomeric ratios (87.5:12.5 to 91.0:9.0) when applied in the catalytic asymmetric addition of diethylzinc to aldehydes.

The use of benzamide derivatives of secondary amines for stereochemical studies by circular dichroism

The benzamide chromophore is widely used as a Cottonogenic derivative of primary amines for stereochemical studies by circular dichroism. The assignments based on the exciton chirality method are reliable since the benzamide group has well-defined geometry and conformation. A recent report U.D. Chisholm, J. Golik, B. Krishnan, J.A. Matson, D.L. Van Vranken, J. Am. Chem. Soc. 1999, 121: 3801-3802) claimed a caveat in the application of the exciton chirality method to benzamides derived from secondary amines. By the use of benzoyl derivatives of amino alcohols (1-4) and diamines (5, 6) of known absolute configuration we demonstrate that the 250-210 nm range exciton Cotton effects due to secondary and tertiary benzamides are generally of opposite sign. The origin of such disparity is traced to different conformational equilibria of the amide C-N bond in secondary and tertiary benzamides, as shown by semiempirical molecular modelling and NMR data. This feature can be useful in the determination of absolute configuration by analysis of the CD spectra due to exciton coupling of tertiary benzamides.

(β-amino alcohol)(arene)ruthenium(II)-catalyzed asymmetric transfer hydrogenation of functionalized ketones - Scope, isolation of the catalytic intermediates, and deactivation processes

The asymmetric transfer hydrogenation of functionalized ketones with (β-amino alcohol)(arene)RuII catalysts using 2-propanol as the hydrogen source has been studied. The structure of the catalyst has been systematically screened using a wide variety of [(η6-arene)RuCl2]2 complexes and β-amino alcohols R1CH(OH)CHR2NHR3, some of which were specifically designed for optimized performance, e.g. (1S,2R)-N-(4-biphenylmethyl)norephedrine (9ο). The efficiencies of the catalytic combinations have been evaluated in the reduction of β-oxo esters and ketones bearing heteroatoms at the α-position. The catalyst precursor [{η6-p-cymene}{η2-N,O-(9ο)}RuCl] (35), the 16-electron true catalyst [{η6-p-cymene}{η2-N,O-(9ο1-) }Ru] (36), and the hydride [{η6-p-cymene}{η2-N,O-(9ο)}RuH] (37) involved in the reduction process have been isolated, characterized by NMR and ESI-MS, as well as by X-ray crystallography in the case of 35, and their reactivities have been investigated. The results reveal two general trends regarding this catalytic process: (1) the apparent reaction rate and the enantioselectivity are largely controlled by the nature of the amine functionality of the chiral ligand and the arene ring of the RuII precursor; (2) side reactions occur between the ketone substrate and the active catalytic species that affect the concentration of the latter and consequently the apparent rate; the formation of inactive (β-diketonato)RuII complexes is demonstrated in the case of β-oxo esters.

Oxygen atom transfer from a chiral oxaziridinium salt. Asymmetric epoxidation of unfunctionalized olefins

The synthesis of an optically pure oxaziridinium salt from (1S,2R)-(+)- norephedrine and the study of the asymmetric oxygen transfer reactions from this reagent to unfunctionalized olefins are described.

Phospho-transfer catalysis on the asymmetric hydrophosphonylation of aldehydes

We report here a precise, in situ 31P{1H}-NMR method of assaying enantiopurity of α-hydroxyphosphonate esters, the products of the carbonyl hydrophosphonylation (Pudovik) reaction. This method is based upon a diazaphospholidine chiral derivatising agent (CDA) which satisfies all of the criteria for a precise assay; (i) derivatisation of α-hydroxyphosphonate esters is both rapid and clean, (ii) kinetic resolution is absent and (iii) 31P{1H} chemical shift dispersions are excellent (> 5ppm). Calibration of this assay has been achieved by cross-referencing the 31P{1H}-NMR signals obtained for the CDA-derivatised ester of (MeO)2PC=O)CHPh(OH) to optical rotation measurements from scalemic material obtained upon lipase catalysed hydrolysis (F-AP 15, Rhizopus oryzae) of (MeO)2P(=O)CHPh(OAc). Analysis of NMR chemical shift and coupling parameters for a closely related series of derivatised α-hydroxyphosphonate esters support further configuration assignments on the basis of inference. We report also on the configurational stability of α-hydroxyphosphonate esters in the presence of acids, organonitrogen bases and metal salts. 2H-labelling and carbonyl crossover experiments reveal that low levels of epimerisation (α) of α-hydroxyphosphonate esters is possible under certain conditions of catalysis and within certain limits. A design strategy for the construction of catalyst systems in the Pudovik reaction is outlined based upon a combination of Lewis acidic (E) and Lewis basic (N) sites. Four types of catalyst are outlined, members of two distinct Classes I and II according to the nature of the acid and base sites, along with our investigations of representative examples of each Class. A variety of Class I.1 systems based on β-amino alcohols (one hydrogen bonding E site and one organonitrogen N site), have been assayed in the model reaction between (MeO)2P(O)H and PhCHO. Results suggest that catalysis of the Pudovik reaction is clean and efficient in certain cases but that catalytic activity is strongly dependent upon the nature of the basic (N) nitrogen centre. Moreover, only low levels ( 50% more strongly (K11 0.53 mol-1 dm3) than dimethyl-H-phosphonate (K11 0.34 mol-1 dm3, 298 K) and to catalyse the hydrophosphonylation reaction between these two substrates with a second order rate constant comparable to that of triethylamine (both k2 5.9 × 10-2 mol-1 dm3 h-1, 293 K). However, one of the major limitations of this model is that competitive product inhibition dominates after some 15 turnovers (75% completion). Model studies reveal that hydrophosphonylation catalysis via a nitrogen Lewis base is accelerated up to 10-fold upon the introduction of [Zn(OSO2CF3)2] as co-catalyst. Consequently, Class II.1 systems employ metal salts [Zn(OSO2CF3)2] as Lewis acidic E sites and chiral co-catalysts capable of binding to the metal and also acting as Lewis basic N sites. Such systems catalyse the addition of (MeO)2P(O)H to PhCHO cleanly with modest turnover numbers (2P(O)H to PhCHO to afford (MeO)2P(O)CHPh(OH) with an average turnover rate (over a 1 h reaction time at 298 K) of 115 h-1 compared to ca. 1 h-1 for NEt3 under analogous conditions. Chiral variants are proposed.

Stereoselective synthesis of β-lactams by condensation of titanium enolates of 2-pyridyl thioesters with imines bearing a chiral auxiliary

Several amines have been tested as chiral auxiliaries in the stereoselective synthesis of β-lactams by condensation of the titanium enolates of 2-pyridyl thioesters with chiral imines. The amines were selected among the following classes of compounds: ben