Organocatalytic synthesis of α-hydroxy and α-aminophosphonates

A new and highly flexible procedure is described for the synthesis of α-amino- and α-hydroxy phosphonates. In the presence of a catalytic amount of oxalic acid (10 mol %), trimethyl phosphite reacts with aldehydes or imines (generated in situ from an aldehyde and an amine) to yield the corresponding coupled products in good yield.     

Conia-ene annulation of the α-cyano β-TMS-capped alkynyl cycloalkanone system and its synthetic application

Under catalysis with ZnI(2), an effective annulation process of ω-silylacetylenic α-cyano ketones, leading to the formation of various bicyclic frameworks characterized with a TMS-containing methylenecyclopentane ring, has been developed.     

Silylene transfer to α-keto esters and application to the synthesis of γ-lactones

Disubstituted α-hydroxy acids have been synthesized by metal-catalyzed silylene transfer to α-keto esters. A range of substituents are tolerated in the transformation with the exception of branched groups at the vinylic position. The α-hydroxy acid products can be converted into γ-lactones using a variety of lactonization conditions.     

Design and synthesis of α-carboxy phosphononucleosides

Rhodium catalyzed O-H insertion reactions employing α-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an α-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.     

Regiospecific synthesis of α-chloro- and α-fluoro-1,2-diones

α-Chloro-1,2-diones and α-fluoro-1,2-diones were prepared from the corresponding α-chloroaldimines by a sequence of reactions involving cyanation to α-cyanoenamines, α-halogenation to form α-chloro- or α-fluoroimidoyl cyanides and addition of organolithium reagents across the nitrile moiety, followed by acidic hydrolysis. All steps are straightforward and occur without side reactions finally leading to regiospecifically chlorinated and fluorinated 1,2-diones in good yields.     

One pot synthesis of novel α,β-dichloro-β-trifluoromethylated enones and their application to the synthesis of trifluoromethylated heterocycles

Trifluoropropynyllithium was reacted with 1 equiv of Weinreb benzamides in THF at −78 to 0 °C, followed by treatment with 4 equiv of trifluoromethanesulfonyl chloride to give α,β-dichloro-β-trifluoromethylated enones 1 in 61-68% yield. The reactions of 1a with substituted amidines or hydrazines in refluxing 1,4-dioxane-CH₃CN afforded trifluoromethylated chloropyrimidines 3 and chloropyrazoles 6 in 58-98% yields. The microwave-assisted coupling reactions of 3 with substituted phenylstannane and allylstannane in refluxing CH₃CN in the presence of Pd(PPh₃)₄ provided the corresponding phenyl and allyl substituted pyrimidines 4 in 89-98% yields.     

A straightforward synthesis of both enantiomers of α-vinylalanine and α-ethynylalanine

This report describes the synthesis of enantiomerically pure (S)- and (R)-α-vinylalanines and (S)- and (R)-α-ethynylalanines, four quaternary α-amino acids, using a straightforward synthetic route and starting from (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinals.     

The synthesis and applications of α-zirconium phosphate

The synthesis of α-ZrP with a range of crystallinity is of high importance due to the different requirements in various applications.Nanosized crystalline α-ZrP is typically obtained by refluxing amorphous ZrP in concentrated H₃PO₄ solutions.Microcrystalline α-ZrP are obtained by direct precipitation in the presence of either HF or oxalic acid which are used as complexing agents for zirconium.These larger crystals are useful as ion-exchangers in column-type applications as ...     

Neat synthesis and antioxidant activity of α-aminophosphonates

A simple, efficient, and environmentally benign method for a three-component reaction of an amine, an aldehyde and diethyl phosphite catalyzed by Amberlyst-15 has been developed to afford α-amino phosphonates in high yields and short reaction times under solvent-free reaction conditions using microwave irradiation. The major advantages of the present method are inexpensive, ecofriendly and reusable catalyst and also studied their antioxidant activity of synthesized compounds.     

Stereoselective allylation of α-hydroxy aldimines and its application to the formal synthesis of (−)-β-conhydrine

Stereoselective allylation of N-p-methoxyphenyl (PMP)-substituted α-hydroxy aldimines is described. Several Lewis acids (BF₃·OEt₂, SnCl₄, TiCl₄, ZnCl₂, and MgBr₂·OEt₂) were employed to mediate the allylation reactions. The addition of the allyl group generates a new stereocenter and affords the syn vicinal amino alcohol. Formal synthesis of (?)-β-conhydrine (1) was accomplished via syn-selective allyl addition to N-PMP-substituted α-hydroxy aldimine.     

Diastereoselective α-alkylation of β-hydroxy sulfoxides and its application to the synthesis of (+)- and (3)-disparlure

α-Alkylation of the dianions of β-hydroxy sulfoxides proceeds with high 1, 2-asymmetric induction to give threo-α-alkyl-β-hydroxy sulfoxides. The utility of the present reaction was demonstrated in the asymmetric synthesis of (+)- and (3)-cis-7, 8-epoxy-2-methyloctadecanes (disparlure).     

New synthetic route to N-tocopherol derivatives: synthesis of pyrrolopyridinol analogue of α-tocopherol from pyridoxine

A new synthetic route to pyrrolopyridinol antioxidants from easily accessible pyridoxine was developed which includes phase-transfer catalytic alkylation and intramolecular Cu(I)-catalyzed amination as key steps.     

Convenient synthesis of fluoroalkyl α- and β-aminophosphonates

Addition of both alkyl phosphites and phosphonate α-carbanions to N-substituted aldimines derived from fluoroalkyl aldehydes presents a convenient method for synthesis of fluoroalkyl α- and β-aminophosphonates in good yield (55-86%) under mild conditions.     

Diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines

The diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines is reported. These molecules are synthesized by formation of sulfinyl imine followed by diastereoselective addition of a diphenylphosphine sulfide. The product N-sulfinyl α-aminophosphine sulfides can be converted to phosphines through removal of the sulfur by reaction with Raney nickel. Hydrolysis of the sulfinyl group provides an amine that can then be attached to other ligands or structural scaffolds.     

Dibenzylaminoacetates as useful synthetic equivalents of glycine in the synthesis of α-amino-β-hydroxyacids1

The stereochemical course of three new simple methodologies for the preparation of α-amino-β-hydroxyacids starting from dibenzylaminoacetates as synthetic equivalents of glycine is described. While the aldol-type condensation via lithium enolates gave results highly dependent on the aldehyde employed, producing in some cases diastereoselectivities up to 5:1 for the anti isomers, the acid-catalysed aldol condensation of silyl ketene acetals yielded predominantly syn adducts with selectivities from 5:1 to 32:1. Finally the acylation-reduction procedure gave the best results in terms of yields and stereoselectivities, affording syn isomers with excellent induction (⩾ 13 : 1).