61739-41-1

Upstream product

• 90-81-3 (S,S)-(+)-pseudoephedrine 
• 299-42-3 (R,R)-(-)-pseudoephedrine 
• 299-42-3 ephedrine 
• 50-98-6 ephedrine hydrochloride 
• 67069-59-4 N-methyl-[(1S,2R)-(2-phenyl-1-methyl-2-trimethylsilyloxy)]ethylamine 

Downstream Products

• 149650-19-1 (2R,4S,5R)-2-(2-Methoxyphenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine 
• 146601-29-8 <(1R,2S)-O,N-ephedrine>P(=O)H 
• 146601-32-3 (4S,5R)-2-(tert-Butyl-dimethyl-silanyloxy)-3,4-dimethyl-5-phenyl-[1,3,2]oxazaphospholidine 
• 146601-33-4 (4S,5R)-3,4-Dimethyl-5-phenyl-2-triethylsilanyloxy-[1,3,2]oxazaphospholidine 
• 32018-63-6 dimethylamino-2 dimethyl-3,4 phenyl-5 oxazaphospholane-1,3,2 
• 146601-31-2 (4S,5R)-3,4-Dimethyl-5-phenyl-2-triphenylsilanyloxy-[1,3,2]oxazaphospholidine 
• 89878-06-8 2-ethoxy-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine 
• 149650-18-0 (2R,4S,5R)-2-(2-Methoxyphenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine 2-oxide 
• 130818-07-4 (S_P)-(-)-N-<(1S,2R)-2-Hydroxy-1-methyl-2-phenylethyl>-N-methyl-P-(2-methoxyphenyl)-P-phenylphosphinamide 

Relevant academic research and scientific papers

Enantiodivergent synthesis of P-chirogenic phosphines

Several approaches for the enantiodivergent synthesis of P-chirogenic mono- and diphosphines are described, using ephedrine methodology and phosphine borane chemistry. Firstly, both enantiomers of a tertiary phosphine can be obtained starting from the same oxazaphospholidine borane complex, prepared from (+)-ephedrine, when changing the order of addition of the organolithium reagents during the synthetic pathway. The second approach is based on the chlorophosphine boranes, which react with an organolithium reagent, to afford the corresponding phosphines with inversion of configuration. In the case where the chlorophosphine borane reacts with the t-butyl lithium reagent, a metal-halogen exchange occurs to afford the corresponding phosphide borane with retention of the configuration. The reaction of the phosphide borane with an alkyl halide leads to the same phosphine, but with the opposite configuration. Another approach depends on the diastereoselective preparation of the starting oxazaphospholidine borane complex from (-)-ephedrine, which leads according the case, to either one or the other enantiomer of a phosphine. Finally, the synthesis of (R,R)- and (S,S)-1,2-bis(methylphenylphosphino)ethane is also demonstrated using both enantiomers of the P-chirogenic diphosphinite diborane, which simultaneously allows the introduction of alkyl- or aryl substituents on the phosphorus atoms. In summary, these approaches show the great efficiency of the "ephedrine methodology" for the enantiodivergent synthesis of P-chirogenic mono- and diphosphines, and bearing alkyl or aryl substituents.

New approach to the synthesis of phosphorodichloridites, phosphorochloridites, and trialkyl phosphites

Different trivalent organophosphorus esters such as phosphorodichloridites, phosphorochloridites, and mixed trialkyl phosphites have been easily synthesized in good yields using a HCl-catalyzed reaction of the corresponding chlorophosphine and alkoxytrimethylsilane by mutual exchange of the alkoxy and chlorine ligand pIIICl/ROSiR′3; exchange reaction). Chemoselectivity of the exchange reaction with primary and secondary alkoxytrimethylsilanes, as well as with alkoxytrimethylsilanes and thioalkoxytrimethylsilanes, respectively, has also been examined. It has been also found that the substitution reaction of chlorophosphines with secondary amine occurs more rapidly than the exchange reaction with ROSiR′ 3.

Oxazaphospholidine-oxide as an efficient ortho-directing group for the diastereoselective deprotonation of ferrocene

Ortho-lithiation of (2R,4S,5R)-3,4-dimethyl-2-ferrocenyl-5-phenyl[1,3,2] oxazaphospholidine 2-oxide 2 was carried out with diastereoselectivity of >99%, affording a new and efficient way for introducing planar chirality into the ferrocene backbone. Various electrophiles were used to quench the lithiated species, showing the wide applicability of the new ortho-directing group and its potential to generate ligands for use in asymmetric catalysis.

An oxazaphospholidine approach for the stereocontrolled synthesis of oligonucleoside phosphorothioates

The stereocontrolled synthesis of oligodeoxyribonucleoside phosphorothioates (PS-ODNs) using nucleoside 3′-O-oxazaphospholidine derivatives as monomer units is described. 2-Chloro-1,3,2-oxazaphospholidine derivatives were prepared from six kinds of enantiopure 1,2-amino alcohols and used for the phosphitylation reactions of 5′-O-protected nucleosides. A detailed study of these reactions revealed that the diastereoselectivity of the reaction depended on the structure of the enantiopure 1,2-amino alcohol, the reaction temperature, and the amine used as a scavenger of HCI. In addition, ab initio molecular orbital calculations for the 2-chlorooxazaphospholidine derivatives were carried out to elucidate the mechanism of these diastereoselective phosphitylation reactions. The LUMO of the 2-chloro-5-phenyloxazaphospholidine derivatives on the phosphorus atom was found to be almost orthogonal to the P-CI bond. This LUMO may be involved in the phosphitylation reactions with predominant retention of the P-configuration. A series of dialkyl(cyanomethyl)ammonium salts were developed and used as activators for the condensation reactions of the diastereopure nucleoside 3′-O-oxazaphospholidines with 3′-O-protected nucleosides. In the presence of the new activators, the reactions proceeded rapidly to give the corresponding dinucleoside phosphite triesters. The diastereoselectivity of the condensation reaction did not depend on the counteranion but on the structure of the dialkyl(cyanomethyl)amine. In the presence of the activator, which consists of a relatively small dialkyl(cyanomethyl)amine, the condensation proceeded with excellent diastereoselectivity. After sulfurization and deprotection, diastereopure (Rp)- and (Sp)-dinucleoside phosphorothioates were obtained in excellent yields. The present methodology was also applied to the solid-phase synthesis of stereoregulated PS-ODNs. all-(Rp)-[TPS]3T, all-(Sp)-[TPS]3T, all-(Rp)-d[GPSAPSCPS]T, and all-(Rp)-[TPS]9T were synthesized on a highly cross-linked polystyrene resin.

Synthons for oligonucleotide synthesis

The invention provides new reagents and processes for synthesizing oligonucleotides, including stereoselective oligonucleotide synthesis. In a first aspect, the invention provides novel monomer synthons for the synthesis of oligonucleotides. Monomer synthons according to this aspect of the invention are useful in the synthesis of oligonucleotides and can be used in place of the well known beta-cyanoethyl phosphoramidite monomer synthon in the phosphoramidite synthesis procedure. Certain monomer synthons according to this aspect of the invention are useful in this procedure for producing oligonucleotides having defined stereochemistry. In a second aspect, the invention provides processes for synthesizing monomer synthons according to the invention, including diastereomerically enriched or purified monomer synthons. In the processes according to this aspect of the invention, the chemical reactions are stereoretentive so that the products of each reaction retain the same stereoconfiguration as their precursor reagent. In a third aspect, the invention provides processes for synthesizing oligonucleotides using the well known phosphoramidite approach. In the processes according to this aspect of the invention, any of the monomer synthons according to the invention is used in place of the conventional beta-cyanoethyl phosphoramidite.

A Novel Nucleoside Phosphoramidite Synthon Derived from 1R,2S-Ephedrine

The stereoselective synthesis of the nucleoside phosphoramidite 6 by reaction of the chiral oxazaphospholidine 4 with 5'-DMT-T is reported.The novel phosphoramidite synthon, 6, is stereoselectively converted to 8 by oxidative sulfurization with 1.The oxaz

Preparation of Enantiomerically Pure Phosphine Oxides by Nucleophilic Displacement Chemistry using Oxazaphospholidines

The synthesis of enantiomerically pure triaryl- and diarylvinyl-phosphine oxides from PCl3 by three sequential nucleophilic displacements at phosphorus is demonstrated.A single diastereoisomer of the P-chlorooxazaphospholidine 4 is treated with an arylmagnesium halide to effect displacement of chloride.The major stereoisomer is formed with retention of configuration.After oxidation to the phosphine oxide with tert-butyl hydroperoxide, a second Grignard reaction leads to regiospecific and stereospecific P-O ring cleavage so that a second aryl group is introduced withretention of configuration.For the final step, the P-N bond is subjected to acid-catalysed methanolysis, previously shown to occur with inversion of configuration, followed by P-OMe displacement with a third arylmagnesium halide.The overall yield of triarylphosphine oxide is up to 29percent for the cited five steps.Simple methoxyaryl or 2-naphthyl residues are employed to demonstrate the methodology, which permits the multigram-scale preparation of this class of compound in >/= 94percent e.e.The stereochemical course of the nucleophilic displacements with arylmagnesium halides is consistent with a model in which the organomagnesium reagent is complexed to the oxo-group and attacks phosphorus cis-to it in a direction defined by both electronic and steric factors.

New, Chiral Silylated Organophosphorus(III) Reagents: Syntheses and Applications in the Asymmetric Phosphorylation of Aldehydes

The new silylated organophosphorus(III) compounds, (1R,2S)-(O,N-ephedrine)POSiR3 (R3=Ph3, t-BuMe2, Et3) have been synthesised and shown to react with benzaldehyde to afford the phosphonate esters (1R,2S)-(O,N-ephedrine)P(=O)CHPh(OSiR3) with good stereosel

Stereochemistry of Substitution at Trico-ordinate Phosphorus

A series of reactions of ring-substituted 1,3,2-dioxaphospholanes, 1,3,2-oxazaphospholanes, 1,2-oxaphospholes, and phosphetanes bearing the leaving groups Cl, OR, or NR2 on phosphorus, with the nucleophiles HCl, MeO-, MeOH, PhOH, Me2NH, Et2NH, and 5NH have been studied.N.m.r. signals (1H and 31P) from reactant and product diastereoisomers have been assigned, and the stereochemistry of the substitution reactions have been determined by 31P n.m.r. monitoring.The outcome varies from complete inversion to complete lack of stereoselectivity.During the initial stages many of the non-selective reactions proceed with predominant inversion, and most of the results may be interpreted by assuming that the actual substitution step occurs with inversion, and that the lack of stereoselectivity is due to competing isomerizations of products or reactants.Exceptions are certain reactions where the leaving group is Cl; these appear to involve a non-selective substitution step.

PENTACO-ORDINATE PHOSPHORUS COMPOUNDS BY NUCLEOPHILIC ADDITION TO ACTIVATED ALKENES AND ALKYNES IN THE PRESENCE OF ALCOHOLS AND PHENOLS

The reactions of a variety of trico-ordinate phosphorus compounds, ArnP(OR)3-n (n= 1 or 2), and cyclic analogues, with acrylonitrile, ethyl acrylate or ethyl phenylpropiolate and alcohols or phenols in low polarity media gives rise to a wide range of pentaco-ordinate phosphorus compounds.Attempts to extend this synthetic route to phosphoranes containing P-N or P-S bonds met with no success.