New Routes to β-Iminophosphonates,Phosphineoxides, and Sulfides

Abstract

Two synthetic methods leading to β-iminophosphonates, phosphineoxides, and sulfides 2 are reported. The first method involves the reaction of imines with chlorophosphines and phosphites followed by oxidation or sulfurization. The second one utilizes the reaction of imines with diethylchlorophosphate and thiophosphate. The stereochemistry of the obtained products is discussed, and their structure is confirmed by NMR (¹H, ³¹P, ¹³C) and IR spectroscopies, and by mass spectrometry.

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GRAPHICAL ABSTRACT      

New Routes to the Synthesis of Mes

New　Routes　to　the　Synthesis　of　Mes...     

Synthesis of Some New 1,3,2-Oxazaphosphinine, 1,3,2-Diazaphosphinine,Acyclic, and/or Cyclic α-Aminophosphonate Derivatives Containing the Chromone Moiety

The synthesis of some new 1,3,2-oxazaphosphinine 18, 1,3,2-diazaphosphinine 19, acyclic, and cyclic α-aminophosphonate derivatives 3–17 containing the chromone moiety have been achieved via reaction of 3-(phenyliminomethyl)chromone (1), 3-(phenylaminomethylene)-2-hydroxychromanone (4), and/or 3-(phenylamino-methylene)-2-(phenylamino)chromanone (5) with diethyl phosphite, tris(2-chloroethyl)phosphite, and phenylphosphonic dichloride. Structures of the products were verified on the basis of their elemental analyses, IR, ¹H, and ³¹P NMR spectral data.     

A Catalytic Method for the Enantioselective Synthesis of α-Quaternary Ketones, α-Ketoesters and Aldehydes

A practical method for the efficient and enantioselective preparation of versatile ketones and aldehydes that contain an α-quaternary stereocenter is described. Reactions utilize simple carboxylic acid or ester starting materials, a monodentate chiral phosphine, and afford a variety of aryl, alkenyl, alkynyl, and alkyl-substituted ketone and aldehyde products in 25–94 % yield and 90 : 10 to >99 : 1 enantiomeric ratio. Reactions proceed by acyl substitution with in situ formed chiral allylic nucleophiles, and display selectivity and conversion dependence on a protic additive. The utility of the approach is demonstrated through several product transformations.     

Improved Synthesis of Cyclic α-Hydrazino Acids of Five- to Nine-Membered Rings and Optical Resolution of 5,6,7-Membered Ring Hydrazino Acids

Synthesis of cyclic α-hydrazino acids of five- to nine-membered rings has been described. Di-tert-butyl or dibenzyl malonate was used as starting materials instead of diethyl malonate, which was used in our first report. Deprotection of tert-butyl or benzyl ester of the final compounds was much easier than that of ethyl or methyl esters. Overall yield of these acids were 39, 50, 47, 52, and 51%, respectively. These acids were then converted to the diastereomers either via the formation of peptides with L-phenylalanine methyl ester or via the formation of esters (for five- to seven-membered rings) with L-2-phenylalaninol. All diastereomers were separated except the nine-membered ring by flash chromatography. Hydrolysis of diastereomeric esters generated the optically pure five-, six- and seven-membered cyclic α-hydrazino acids. In this process, both the enantiomers have been isolated and the chiral auxiliary L-2-phenylalaninol was recovered. Absolute stereochemistry was determined from x-ray crystallographic analysis.     

Synthesis of (+)- and (−)-Tetrabenazine from the Resolution of α-Dihydrotetrabenazine

Abstract

Tetrabenazine (1) was reduced with NaBH₄ to α-dihydrotetrabenazine (2) and then resolved with di-p-toluoyl-L-tartrate and di-p-toluoyl-D-tartrate to subsequently give (+)- and (?)-α-dihydrotetrabenazine. The enantiomers were oxidized under Swern conditions to prepare samples of (+)-tetrabenazine and (?)-tetrabenazine. The samples were optically pure by chiral HPLC analysis.     

Synthesis of α-Oxoketene CyclicO,S and S,S Acetals

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New Methodology for the Synthesis of α,α-difluoroketones

A new methodology is described for the synthesis of α,α-difluorinated ketones by the addition of organolithium reagents to α,α-difluoro-N-methoxy-N-methyl amides (Weinreb amides).     

Design,Synthesis, and Antiviral Activity of α-Aminophosphonates Bearing a Benzothiophene Moiety

Abstract

A series of α-aminophosphonates containing a benzothiophene moiety was designed and synthesized. All synthesized compounds were confirmed by ¹H NMR, ¹³C NMR, ³¹P NMR, infrared spectroscopy, and elemental analysis. The half-leaf method was used to determine the in vivo efficacy of α-aminophosphonates bearing a benzothiophene moiety against the tobacco mosaic virus (TMV). Bioassay results showed that all compounds exhibited certain anti-TMV activity at 500 μg/mL concentration. Compound 2f exhibited a curative effect of up to 48.1% against TMV, which was almost similar to that obtained from the standard ningnanmycin (51.9%).

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

Preparation of Acyclic N-Acyl-N,O-acetals by Decarboxylation of N-Protected α-Amino Acids and Studies of Asymmetric Amidoalkylation with Trimethylsilyl Cyanide

Oxidative decarboxylation of N-acyl-α-amino acids with lead tetra-acetate followed by treatment with methanol provides a facile method for preparation of acyclic N-acyl-N,O-acetals, which can be used in asymmetric α-amidoalkylation reactions using trimethylsilyl cyanide as nucleophile.     

The Application of the Trichloroacetimidate Method to the Synthesis of α-D-Gluco- and α-D-Galactopyranosides

Abstract

The trichloroacetimidate method has been applied to the construction of α-d-galacto- and α-d-glucopyranosides. The readily available β-trichloroacetimidates of 2,3,4,6-tetra-O-benzyl-d-galacto- and glucopyranose (1-β and 3-β, respectively) have been employed in glycosidations with several monosaccharides (either A, B, C or D) under varying experimental conditions. With the galactose derivative 1-β as a donor and each of the monosaccharides A-D as acceptors, the corresponding disaccharides 1A-1D, were obtained in high yield and with good α-stereoselectivity when employing diethyl ether as solvent and either trimethylsilyl- or tert-butyldimethylsilyl trifluoro-methane sulphonate as catalyst. Glycosidations with the glucose derivative 3-β, as donor, and with the monosaccharide acceptors A, B or D, gave the corresponding disaccharides 3A, 3B and 3D, in high yield but with somewhat lower α-diastereoselectivity than observed with the galactose derivative 1-β. The stereochemical outcome of the reactions is rationalised in terms of possible reaction mechanisms.     

Enantioselective Synthesis of Cyclopropanone Equivalents and Application to the Formation of Chiral β-Lactams

Cyclopropanone derivatives have long been considered unsustainable synthetic intermediates because of their extreme strain and kinetic instability. Reported here is the enantioselective synthesis of 1-sulfonylcyclopropanols, as stable yet powerful equivalents of the corresponding cyclopropanone derivatives, by α-hydroxylation of sulfonylcyclopropanes using a bis(silyl) peroxide as the electrophilic oxygen source. This work constitutes the first general approach to enantioenriched cyclopropanone derivatives. Both the electronic and steric nature of the sulfonyl moiety, which serves as a base-labile protecting group and confers crystallinity to these cyclopropanone precursors, were found to have a crucial impact on the rate of equilibration to the corresponding cyclopropanone. The utility of these cyclopropanone surrogates is demonstrated in a mild and stereospecific formal [3+1] cycloaddition with simple hydroxylamines, leading to the efficient formation of chiral β-lactam derivatives.     

Enantioselective, NHC-Catalyzed Annulations of Trisubstituted Enals and Cyclic N-Sulfonylimines via α,β-Unsaturated Acyl Azoliums

All aboard please! A new reaction of enals and cyclic sulfonylimines, as the nucleophiles(!), is the first highly enantioselective NHC-catalyzed annulation of trisubstituted enals. The catalytically generated α,β-unsaturated acyl azolium undergoes a reaction with the enamine tautomer of the imine via an aza-Claisen rearrangement as the key C?C bond-forming step. High yields and enantioselectivities were achieved using β-, α,β-, and β,β'-substituted enals.     

Catalytic Enantioselective Reactions Part 7. Synthesis of New β-Aminoalcohols Derived from α-D-Glucose as Chiral Catalysts for the Catalytic Enantioselective Addition of Diethylzinc to Aldehydes

A series of new 1, 2-O-isopropylidene-3-O-methyl-6-deoxy-6-N, N-dialkylamino-α-D-glucofuranoses 1 and 1, 2-O-isopropylidene-3, 6-dideoxy-6-N, N-dialkylamino-α-D-glucofuranoses 1′ were prepared from α-D-glucose and their enantiose-lectivities compared as chiral catalysts for the ethylation of benzaldehyde and heptanal with diethylzinc.     

Synthesis of the Methyl, 1-Octyl,and D-Trifluoro-Acetamidophentlethyl α-Glycosides of 3,6-Di-O-(α-D-Galactopyranosyl)-D-Glucopyranose and an Acyclic Analogue Thereof

Abstract

The title trisaccharides were synthesized from a common trisaccharide thioglycoside derivative, which was, in turn, prepared from monosaccharide thioglycoside precursors. An acyclic analogue, methyl 3-O-(α-D-galacto-pyranosyl)-6-O-[(2′-hydroxyethyl)oxymethyl]-α-D-glucopyranoside, which carries a 2′-hydroxyethyloxymethyl group in place of the 6-O-galactosyl residue, was also synthesized.     

One-Pot, Three-Component Coupling Approach to the Synthesis of α-Iminocarboxamides

A one-pot, three-component coupling was accomplished via the nucleophilic addition of an alkylsamarium(III) species to isocyanides and the subsequent addition of the resultant imidoyl samarium(III) species to isocyanates under mild conditions for the formation of α-iminocarboxamides. The developed sequential C-C bond-forming procedure enabled the rapid synthesis of the α-iminocarboxamides in good to excellent yields from readily available starting materials.     

Synthesis of α-alkoxyalkyltributyllead compounds via the reaction of tributylplumbyllithium with α-chloroethers,and the conjugate addition of tributylplumbyllithium to enones

α-Alkoxyalkyltributylleads 1 were prepared from the reaction of tributylplumbyllithium with α-chloroethers 2. This procedure is more convenient than the conventional method which involves transmetallation from the corresponding α-alkoxyalkyltrialkyltin. Tributylplumbyllithium was also used for the synthesis of β-oxo-organolead 4.     

Organocatalytic Enantioselective Pictet–Spengler Reaction of α-Ketoesters: Development and Application to the Total Synthesis of (+)-Alstratine A

We report herein an asymmetric Pictet–Spengler reaction of α-ketoesters. In the presence of a catalytic amount of simple alanine-derived squaramide and p-nitrobenzoic acid, reaction of tryptamines with methyl 2-oxoalkanoates afforded the corresponding 1-alkyl-1-methoxycarbonyl tetrahydro-β-carbolines (THBCs) in high yields and ee values. A primary kinetic isotope effect (KIE=4.5) using C2-deteurium-labelled tryptamine indicates that rearomatization through deprotonation of the pentahydro-β-carbolinium ion could be the rate- and enantioselectivity-determining step. A concise enantioselective total synthesis of (+)-alstratine A, a hexacyclic cagelike monoterpene indole alkaloid, featuring this reaction as a key step, was subsequently accomplished. Remeasurement of the [a]_D value of the natural product indicates that natural alstratine A is dextrorotatory rather than levorotatory as it was initially reported in the isolation paper.     

Organocatalytic Approach to (S)-1-Arylpropan-2-ols: Enantioselective Synthesis of the Key Intermediate of Antiepileptic Agent (−)-Talampanel

An efficient organocatalytic route for the preparation of enantioselective synthesis of (S)-1-arylpropan-2-ols derivatives, including the key intermediate of antiepileptic agent (?)-talampanel is described. The key steps involved are L-proline-catalyzed asymmetric α-aminooxylation of aldehydes and regioselective tosylation of diols followed by reduction.