Mechanism of the reaction of N-p-tosylsulphilimine and related compounds with thiophenolate ion

The reaction of alkyl aryl N-p-tosylsulphilimines with thiophenolate ion was found to afford quantitatively the sulphide that arises by an S_N2 like reaction on the carbon atom adjacent to the tri-valent sulphur atom. This reaction was also found to proceed smoothly with such compounds as sulphoxides and sulphones and sulphoxmanes. The kinetic study on the reaction between aryl methyl N-p-tosylsulphilimine with thiophenolate ion in DMF reveals that the reaction is of second order, namely, first order with respect to each thiophenolate ion and the sulphilimine. The enthalpy and entropy of activation for the reaction are ΔH^≠ = ?17· kcal/mol and ΔS^≠ = ?5·7 eu respectively. The effect of substituents in the reaction, p-XC₆H₄⁺(^?SO₂C₆H₄Y-p)CH₃ + p-ZC₆H₄SK is nicely correl with Hammett σ values giving ?_x = + 2·4, ?_y = + 1·2 and ?_z = ?1·8 respectively. Meanwhile, a marked steric retardation by a bulky alkyl group in alkyl phenyl N-p-tosylsulphilimine is observed. Furthermore, from the stereochemical study of the reaction using an optically active sec-octyl phenyl N-p-tosylsulphilimine with thiophenolate ion it is concluded that the reaction proceeds via a typical S_N2 process on α-carbon atom attached to the tri-valent sulphur atom.     

Racemization of sulfinic esters with trichloroacetic anhydride

Both alkane- and arene-sulfinates undergo racemization and oxygen exchange reaction with trich-loroacetic anhydride. The rate of racemization of (?)menthyl (?)p-toluenesulfinate was found to be twice that of oxygen exchange, suggesting the reaction involves a Walden inversion. When reaction was carried out in benzene, the rate of racemization was found to be first order with respect to both sulfinic ester and trichloroacetic anhydride. The substituent effect is large (p = ?1.53) suggesting that the initial acylation is the rate-determining step. The rate of racemization was found to be retarded by the addition of perhaloacetic acid while very small catalytic effect of mercuric chloride was observed.     

Configurational Stability of Optically Active Dichloromethyl p‐Tolyl Sulfoxide and Its Anionic Species: Experimental and Theoretical Study

Racemization of optically active dichloromethyl p‐tolyl sulfoxide took place at −78°C in the presence of potassium bis(trimethylsilyl)amide (KHMDS), while the same racemization did not occur under reflux in toluene in the absence of KHMDS. Density functional theory calculations suggested that the pyramidal inversion at the sulfur center was unlikely to be involved in the racemization mechanism. An anionic species of the sulfoxide was found to be gradually converted into chlorobis(p‐tolylsulfinyl)methane and dichlorocarbene. We propose a racemization mechanism mediated by achiral potassium p‐toluenesulfenate and chloro(p‐tolylsulfinyl)methylene. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:131–137, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21074     

MECHANISM OF THE REACTION OF DIPHENYL N-BROMOSULFILIMINE WITH SULFIDES,PHOSPHINES AND TERTIARY AMINES

Abstract

The mechanism of the reactions of diphenyl N-bromosulfilimine (I) with such nucleophiles as sulfides, phosphines and tertiary amines was investigated. In the presence of water, (I) reacts with sulfides or phosphines to afford the corresponding sulfoxides or the phosphine oxides in moderate yields; however, the reaction with tertiary amine gave only the N-t-aminosulfilimine derivative. The effect of ring size in the reaction with cyclic sulfides suggests that the reaction proceeds via initial bromine transfer from the nitrogen atom to the sulfur atom of the cyclic sulfides followed by S_N2 type substitution of bromide on the sulfur atom of the cyclic sulfide with the sulfilimino group. The phosphine oxide obtained in the reaction of (I) with optically active methyl n-propyl phenyl phosphine was racemized but retained a small portion of the optical activity. In the case of tertiary amines, even 1,4-diazabicyclo-(2,2,2)-octane (DABCO), in which the back side of the nitrogen atom is blocked, reacted smoothly to afford the corresponding ammonium salts, suggesting the reaction to be of S_N2 type on the nitrogen atom of the sulfilimine.     

SYNTHESIS AND TRANSFORMATIONS OF OPTICALLY ACTIVE α-PHOSPHORYL SULPHOXIDES

Abstract

As part of a continuing studies of α-phosphoryl sulphoxides, racemic dimethylphosphorylmethyl p-tolyl sulphoxide (1) was prepared and resolved into optical isomers. Sulphoxide (+)-1 with the R chirality at sulphur was synthesized stereospecifically by treatment of (?)-menthyl p-tolylsulphinate with dimethylphosphorylmethyllithium. This communication describes some transformations of optically active 1.     

Stereoregularity of poly(isopropyl acrylate) and its racemization during hydrolysis

The diad tacticity of poly(isopropyl acrylate) was measured from the β-proton absorptions of poly(isopropyl acrylate-α,β-d₂) obtained with a 100 MHz NMR spectrometer, and temperature dependence of the tacticity of the polymers obtained by radical polymerization was determined. Enthalpy and entropy differences between isotactic and syndiotactic addition for poly(isopropyl acrylate) were calculated to give the following values: Δ(ΔS) = 0.7 eu; Δ(ΔH) = 0.51 kcal/mole. In the hydrolysis of poly(isopropyl acrylate-α,β-d₂), it was found that the rate of hydrolysis of poly(isopropyl acrylate) was dependent on the molecular weight rather than on the tacticity. As for the rate of racemization during hydrolysis, the rate for syndiotactic polymer was much faster than that for the isotactic polymer. The exchange reaction of deuterium at α-position with hydrogen occurred in all the polymers during hydrolysis reaction.     

Optishift PMR spectroscopic studies on some quinoxaline amino esters and dipeptides

Optishift pmr spectral measurements on a series of N-(2-quinoxaloyl)α-amino esters and the C₃-CH₃ analogues indicate that their L-isomers are optically pure. Such measurements also show that the Eu atom in Eu(tfc)₃ preferentially complexes with the amide carbonyl. Similar optishift pmr studies on model quinoxaline-dipeptide esters reveal that the amino-terminal α-amino acid suffers appreciable racemization during the coupling process with triphenylphosphite-pyridine, whereas no detectable racemization is observed with diphenylphosphoryl azide. A Bystrov's model is suggested for the quinoxaline-dipeptide-Eu complexes studied. The benzylic protons of phenylalanine and the isopropyl methyls in their quinoxaline derivatives show signal splitting due to diastereotopy in the presence of Eu(tfc)₃.     

First Isolation and Stereochemistry of Optically Active Telluroxides

Optically active telluroxides 1 and 2 were isolated for the first time by means of medium-pressure liquid chromatography using an optically active column. Absolute configuration of the telluroxides (+)-1 and (+)-2 was determined to be R based on their specific rotations and circular dichroism spectra. The configurational lability and mechanism for racemization via an achiral hydrate were clarified by kinetic study and isotope tracer experiment.     

Stereo- and Site-Selectivity in the Reaction of Chiral Episelenonium Ion with Carbon Nucleophile

Abstract

There are two important aspects in the reaction of chiral episelenonium ion (episelenonium ion bearing chiral carbon in the three-membered ring) with carbon nucleophile; namely, (1) whether the chiral carbon racemizes during the reaction or not, and (2) the carbon nucleophile attacks the carbon atom (carbophilic attack) or selenium atom (selenophilic attack) in the three-membered ring. When carbon nucleophile such as alkenyl silyl ethers, trimethylsilyl cyanide, and allyltrimethyl-silane are employed, steric protection of the selenium atom by the attachment of tri-tert-butylphenyl (TTBP) group to the selenium atom is inevitable to avoid both of the racemization of the chiral carbon atom and selenophilic attack of the carbon nucleophile. When aromatic compounds are employed as carbon nucleophile, on the other hand, selenophilic attack is rarely observed irrespective of the nature of the aryl group on the selenium atom and introduction of electron withdrawing group into the aryl group on the selenium atom is effective to retard the racemization of the chiral carbon atom.     

The racemization of an optically active sulfilimine and optically active aminosulfonium salts

The racemization of an optically active sulfilimine and optically active aminosulfonium salts was kinetically measured. The mechanism of the racemization of optically active sulfilimine (?)-1 has been established. The activation parameters for the racemization of (?)-1 and (?)-7 were calculated. A plausible pathway for the decomposition of (?)-6, (?)-7 and (?)-8 with tetra-n-butylammonium bromide in the presence of methyl ethyl ketone to provide 3-p-tolylthio-2-butanone 22 is proposed.     

Efficient dynamic kinetic resolution of secondary alcohols with a novel tetrafluorosuccinato ruthenium complex

Dynamic kinetic resolution (DKR) of a series of secondary alcohols has been conducted with a novel dinuclear ruthenium complex, bearing tetrafluorosuccinate and (rac)-BINAP ligands as the racemization catalyst. Novozym 435 has been used as the enzyme, and isopropyl butyrate as the acyl donor. Five substrates underwent DKR successfully: an aliphatic and an aromatic secondary alcohol, an aromatic alcohol with an electron-withdrawing substituent on the phenyl ring, an aromatic alcohol bearing an electron-donating substituent on the ring and a heteroaromatic secondary alcohol. The catalyst performed optimally at 70 °C. Typically the reaction reached complete conversion within 1 day with 0.1 mol % of racemization catalyst relative to the substrate. The addition of the ketone corresponding to the substrate stabilizes the active Ru complex and, therefore, increases the rate of the reaction.     

Phosphacyclophanes Derived from Hydroquinone and 4,4'-Dihydroxybiphenyl

The first representatives of linear phosphocyclophanes were prepared starting from hydroquinone or 4,4'-dihydroxybiphenyl and phosphorous triamides. The reaction course is influenced by the structures of the aromatic diol and alkyl substituents in the phosphamide moiety. The phosphorus atom readily enters redox reactions and complexation. The complexing power of the aromatic fragments of the synthesized molecules is lower than that of classical p-cyclophanes.     

Stabilizing effect of intramolecular lewis base toward racemization of optically active selenoxides

2‐(Methylchalcogenomethyl)diphenyl selenoxides 1 and 2‐{2′‐(N,N‐dimethylamino)ethyl}phenyl alkyl (or aryl) selenoxides 2 , which were expected to be stabilized toward racemization by intramolecular coordination, were synthesized and optically resolved into their enantiomers on an optically active column using high‐performance liquid chromatography. Relationship between the absolute configurations and the chiroptical properties of the enantiomers was clarified by comparing with those of sulfur analogues. Stabilities toward racemization of optically active selenoxides 1a and 1b were nearly equal to that of 2‐{(N,N‐dimethylamino)methyl}diphenyl selenoxide and mesityl phenyl selenoxide. The rates of racemization for optically active selenoxides 2 were found to be faster than that of 2‐{(N,N‐dimethylamino)methyl}phenyl alkyl (or aryl) selenoxides. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:301–311, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20299     

Effets de Substituants en Série Diazolique et Diazinique-1,3—Etude par Résonance Magnétique Nucléaire du Carbone-13

We have recorded the ¹³C n.m.r. spectra of thiones and thioethers in the 1,3-diazole and 1,3-diazine series with various alkyl substituents at the nitrogen atoms. Some analogous oxygen containing heterocycles were also examined. We have shown that in the thiocarbonylated compounds the thiol ? thione equilibrium is displaced towards the thione form, but that ¹³C n.m.r. gives only qualitative results. In the sulphur containing derivatives the isopropyl group is in a fixed conformational position because of the steric hindrance of the sulphur atom. Substitution by a tert-butyl group leads to unexpected γ values. We ascribe this phenomenon to ring deformation or to variations in the valence angles of the substituted nitrogen atoms.     

Isolation of stable enantiomerically pure telluroxides and their stereochemistry

Optical resolution of kinetically and thermodynamically stabilized diaryl telluroxides possessing bulky substituents (rac-1a-d) and amino group (rac-2a-c), respectively, by liquid chromatography using optically active columns yielded stable enantiomerically pure telluroxides. The absolute configurations of the optically active telluroxides were determined by comparing their specific rotations and CD spectra with those of sulfur or selenium analogues. The kinetics for the racemization of optically active telluroxides in solution was studied, and it was found that kinetic and thermodynamic stabilization were very effective preventing the racemization of telluroxides. The stabilization energy of telluroxides by intramolecular coordination of the amino group to the tellurium atom was estimated to be ca. 5 kcal mol-1 by variable temperature 1H NMR measurement. The mechanism for the racemization of optically active telluroxides was studied by an isotope experiment using H2(18)O, and the results indicated that optically active telluroxides underwent racemization via an achiral tetracoordinated hydrate.     

Optically active polymers of 3-alkylmalic acids: Contribution of the bioconversion for diversifying the chiral precursors

The need for new optically active monomers and polymers is conducive to the setting up of stereospecific synthesis routes starting from chiral precursors. The biomass can be considered as a major source for extracting such biomolecules aimed at chemoenzymatic transformation and further polymerization. Due to its versatility, ß-methylaspartate ammonia-lyase, from cell-free extracts of Clostridium tetanomorphum, has been used in the bioconversion of alkylfumarates into optically active pure 3-alkylaspartic acids with alkyl=methyl, ethyl, isopropyl. These amino acids have been transformed in several steps into optically active benzyl 3-alkylmalolactonates leading to semi-crystalline polyesters. 3-Methylaspartic acid includes two chiral centers and the racemic compound containing the four stereoisomers can be prepared by a multiple step synthesis. The ability of ß-methylaspartase to catalyse both syn- and anti-elimination of ammonia from natural 3-methylaspartic acid has been expressed to retain one stereoisomer and this bioconversion is a preparative method for obtaining unnatural stereoisomers. Moreover, the catalytic hydrogenolysis of the benzyl α,ß-substituted ß-lactone yields stable 3-alkylmalolactonic acid which can be coupled with functional alcohols and copolymerized. At last the introduction of (2S)-3,3-dimethyl-2-butanol, using Rhodotorula glutinis as microorganism in a biological synthesis step, as chiral ester pendant group, has conducted to optically active polyesters with very high melting transition temperatures. The combination of bioconversion and chemical synthesis is a very useful tool for building hydrolyzable functionalized polyesters required for temporary applications.     

Organocatalytic Asymmetric Formation of Steroids

A novel and simple one‐step approach for the construction of optically active steroids in a highly stereoselective manner by using organocatalysis is presented. The reaction of (di)enals with cyclic dienophiles in the presence of a TMS‐protected prolinol catalyst leads to the construction of important 14 β‐steroids. This new reaction allows an easy access to optically active steroids with a variety of substituents in the A ring in high yields and up to greater than 99 % ee. The reaction has been extended to include the construction of B‐ and D ‐homosteroids as well as steroids containing heteroatoms in the B ring. The angular substituent at C13 can be varied and alkyl, ester, and sulfone functionalities are introduced with excellent stereoselectivities. Simple synthetic procedures provide access to a range of naturally occurring steroids such as estrone and related analogues.     

Synthesis and chiroptical properties of optically active photochromic methacrylic polymers bearing in the side chain the (S)-3-hydroxypyrrolidinyl group conjugated with the trans-azoaromatic chromophore

Novel optically active polymethacrylates, namely poly[(S)-3-methacryloyloxy-1-(4-azobenzene)pyrrolidine] and poly[(S)-3-methacryloyloxy-1-(4′-nitro-4-azobenzene)pyrrolidine], have been synthesized by radical polymerization of the corresponding monomers, prepared in turn through a synthetic route preserving the asymmetric center by any racemization reaction. These homopolymers are characterized by the presence in the side chain of an optically active pyrrolidinyl ring linked to the trans-azoaromatic system through the nitrogen atom. The optical activity of the polymers in solution appears much higher than that observed with the low molecular weight models, purposely synthesized for comparison. Circular dichroism spectra of the synthesized products demonstrated that, in solution, the macromolecules assume highly homogeneous conformations with a prevailing chirality to a larger extent with respect to analogous systems previously investigated. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3257–3268, 1999     

Operationally convenient asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid: Part I: Enantioselective biomimetic transamination of isopropyl 4,4,4-trifluoro-3-oxo-butanoate

DBU-catalyzed asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid via enantioselective biomimetic transamination of isopropyl 4,4,4-trifluoro-3-oxobutanoate with (R)- and (S)-phenylethylamine has been developed. The effect of the base concentration of the reaction rate and stereochemical outcome has been systematically studied. The key reaction step, DBU-catalyzed 1,3-proton shift transfer was found to be highly enantioselective (>95% ee). However, due to some racemization of the intermediate Schiff base under the highly basic reaction conditions leads to the final product of lower enantiomeric purity.     

Reaction of o-carboxyphenyl sulfoxides with acetic anhydride : Kinetic studies on the neighboring group effect of ortho-carboxyl group in the oxygen exchange and Pummerer reactions

Kinetic studies on the concurrent oxygen exchange and racemization reactions and Pummerer reaction of o-carboxyphenyl sulfoxides with acetic anhydride were carried out. In the reaction of o-carboxyphenyl phenyl sulfoxide, ortho-carboxyl group was found to enhance the rates of both oxygen exchange and racemization about 180 times, and the rate of racemization was nearly twice that of oxygen exchange. In the reaction of alkyl o-carboxyphenyl sulfoxides, an intramolecular Pummerer reaction took place to give 3,1-benzoxathian-4-one derivatives, and the Pummerer reaction was accelerated about 140 times that of the usual unassisted Pummerer reaction of aryl methyl sulfoxide. A very small deuterium kinetic isotope effect (k_H/k_D = 1.07 with trideuterated-methyl o-carboxyphenyl sulfoxide) and the rate-enhancing effect of α-alkyl group were also noticed. The markedly large rate-enhancement of both oxygen exchange and the Pummerer reactions is undoubtedly caused by the neighboring group participation of carboxyl group in the rate-determining intramolecular acylation of sulfinyl O atom.