Diastereotopic Protons Research Articles

Stereochemistry of the conversions of L-threonine and D-threonine into 2-oxobutanoate by the L-threonine and D-threonine dehydratases of Serratia marcescens.

dl[3‐2H]Threonine, l‐[3‐2H]threonine, (2RS,3S)‐2‐amino[3‐2H1] butanoic acid, (2RS,3S) 2‐amino[3‐3H1]butanoic acid and dl‐2‐amino[3‐14C]butanoic acid were synthesised. l‐[3‐2‐H]Threonine was converted into l‐[4‐2H1]isoleucine by Serratia marcescens strain IHr313. (2RS,3S)‐2‐Amino[3‐2‐H1]butanoic acid was converted into l‐[4‐4‐H1]isoleucine by S. marcescens strain 149. Analysis by 220‐MHz NMR spectroscopy of the labelled l‐isoleucine produced showed that the same diastereotopic hydrogen at C‐4 was labelled in each experiment, proving that, during the conversion of l‐threonine into 2‐oxobutanoate mediated by biosynthetic l‐threonine dehydratase, the hydroxyl group at C‐3 was replaced by hydrogen with retention of configuration. S. marcescens strain 149 lacks l‐threonine dehydratase but possesses an inducible d‐threonine dehydratase. This strain converted dl‐[3‐2H]threonine into dl‐[4‐2H1]isoleucine with the deuterium located in the diastereotopic C‐4 hydrogen derived from the 3 pro‐R hydrogen of 2‐aminobutanoic acid. This result proved that during the conversion of d‐threonine into 2‐oxobutanoate mediated by d‐threonine dehydratase, the hydroxyl group at C‐3 is replaced by hydrogen with retention of configuration. These results also prove that the protonation at C‐3 of the proposed enamine intermediate in the transformations catalysed by threonine dehydratase is under enzymatic control. The present results, taken in conjunction with the independent assignment of the signals in the 220‐MHz NMR spectrum of l‐isoleucine due to the diastereotopic protons at C‐4, prove that during the ethyl migration step in l‐isoleucine biosynthesis, the configuration at the migrating centre is retained.

Pmr characterization of diastereomeric forms of 6- and 7-membered cyclic compounds bearing two equivalent chiral atoms

meso and dl diastereomeric pairs of cyclic compounds with geminal probe groups in suitable position were analysed by PMR: anisochronism of diastereotopic probe protons was used for assignment of configuration; moreover, analysis of ring proton signals gave information on conformational features.

Unequal primary kinetic isotope effects in the base-catalysed H–D exchange of diastereotopic protons

Primary kinetic isotope effects have been measured for the base-catalyzed exchange reaction of 4′,1″-dimethyl-1,2,3,4-dibenzcyclohepta-1,3-diene-6-one, 1. It was found that the isotope effects kH/kT and kD/kT for the faster exchanging protons (13.6 and 3.8 respectively) are significantly larger than the corresponding values for the slower exchanging protons (4.6 and 1.6 respectively). These differences could result from truly unequal isotope effects due to transition state differences or intrusion of a second pathway for exchange of the less reactive proton in the dedeuteration reaction. The data appear to support the latter interpretation. The secondary deuterium isotope effect was found to be 1.18.

On the relationships between 18O-transfer, diastereotopic selectivity, and asymmetric induction in an intramolecular Pummerer reaction

The cyclization of benzyl 2-carboxyphenyl sulfoxide (1) to 2-benzylbenzoxathiane-6-one (2) has been examined by a combination of 18O-labelling of the sulfoxide oxygen, stereoselective deuterium labelling in the benzylic position, and the use of optically active compounds. With dicyclohexylcarbodiimide (DCC) as the cyclizing agent, the reaction proceeds with 55.8% retention of the sulfoxide oxygen, 57.8% preference for abstraction of one of the diastereotopic methylene protons, and it produces a 61.4/38.6 mixture of enantiomers. It is proposed that all three experimental observables are controlled by the competition between initial attack of the DCC upon the sulfoxide oxygen and upon the carboxyl group, and a mechanism is proposed for the reaction which clarifies the relationship between these observables. In agreement with earlier work by Stridsberg and Allenmark, DCC affords 2 having the opposite sign of rotation from 1, and acetic anhydride affords 2 having the same sign of rotation as 1. Asymmetric induction in the latter reaction is significantly less than with DCC because of competing epimerization at sulfur, but the origin of the differences in the sign of rotation of 2 under the different conditions has been clarified by the finding that there is less than 40% retention of the sulfoxide oxygen with acetic anhydride as the reagent.

1H‐, 31P‐ and 13C‐NMR spectra of some 2‐arylsulphonylamido‐2‐thiono‐5‐methyl‐1,3,2‐dioxaphospholanes

AbstractSome 2‐arylsulphonylamido‐2‐thiono‐5‐methyl‐1,3,2‐dioxaphospholanes (1), containing two chiral centres, give NMR spectra in which splittings of the 1H and 13C signals of the 5‐methyl substituent and of the 31P signal indicate that they exist in an approximately 70:30% ratio of two racemic mixtures, Z and E respectively, diastereomeric to each other. These splittings were invariably observed for compounds 1a, containing a monosubstituted sulphonylamido group (Y = H) and various substituents at position 4′ of the aryl group, X = H, CH3, OCH3, F, CI and Br. The methylenic protons in position 4 of the phospholane ring are diastereotopic and therefore magnetically non‐equivalent. Benzene‐induced shifts were measured for the Z isomers of compounds 1a, X = H, F and for compound 1b, containing an N‐disubstituted sulphonylamido group (Y = CH3) and X = H; the tentative interpretation of these shifts places the more shielded diastereotopic methylene proton on the same side of the ring as the 5‐methyl substituent. The HP and HH coupling constants indicate that the preferred conformation of the dioxaphospholane ring should be a ‘twisted envelopey’ shape with the 5‐methyl substituent in the equatorial position.

Conformational analysis of methylsuccinic acid by 1H NMR spectroscopy and circular dichroism

The pH-dependence of the 1H NMR and Circular Dichroism (CD) spectra of 2-methylsuccinic acid was investigated. Both spectra undergo dramatic changes between pH 4 and 6, where both carboxylic groups become ionized. From the coupling constants of the tertiary proton with the assigned 1 diastereotopic methylene protons, it is concluded that below pH 4 the syn-clinal ( 2) and above pH 6 the anti-periplanar ( 1) conformation of methylsuccinic acid prevail. The diesters of methylsuccinic acid also assume mainly the syn-clinal conformation ( 2). The pH-dependence of the CD spectra is discussed in terms of conformation and/or ionization effects.

Pmr characterization of diastereomeric forms of acyclic compounds bearing two equivalent chiral atoms in 1,5-positions

Assignment of configurations to diastereomeric pairs was based on anisochronism of diastereotopic protons of suitable probe groups, at various distances from both chiral centers.

AN NMR STUDY OF THE PROTONS IN α-ALKYLTHIOSULFOXIDES, RS(O)CH2SR

Abstract By means of nmr studies, including lanthanide shift experiments, the two ‘R's’ in Structure (I) (a, R = Methyl; b, R = tert-Butyl) have been assigned. The alkyl group at lower field in each case is attributed to the one adjacent to the sulfoxide. The diastereotopic protons in (Ia) are less well resolved than those in (Ib), and their separation is concentration-dependent, an observation suggesting the importance of association in (Ia). On the basis of a simple conformational analysis, the diastereotopic protons in (Ib) can be assigned in relationship to the chiral sulfoxide center.

ChemInform Abstract: KINETIC ACIDITY OF DIASTEREOTOPIC PROTONS IN SULFONIUM IONS. A TRANSITION STATE CONFORMATIONAL EFFECT

Chemischer InformationsdienstVolume 9, Issue 16 Preparative Organic Chemistry ChemInform Abstract: KINETIC ACIDITY OF DIASTEREOTOPIC PROTONS IN SULFONIUM IONS. A TRANSITION STATE CONFORMATIONAL EFFECT G. BARBARELLA, G. BARBARELLASearch for more papers by this authorP. DEMBECH, P. DEMBECHSearch for more papers by this authorA. GARBESI, A. GARBESISearch for more papers by this authorF. BERNARDI, F. BERNARDISearch for more papers by this authorA. BOTTONI, A. BOTTONISearch for more papers by this authorA. FAVA, A. FAVASearch for more papers by this author G. BARBARELLA, G. BARBARELLASearch for more papers by this authorP. DEMBECH, P. DEMBECHSearch for more papers by this authorA. GARBESI, A. GARBESISearch for more papers by this authorF. BERNARDI, F. BERNARDISearch for more papers by this authorA. BOTTONI, A. BOTTONISearch for more papers by this authorA. FAVA, A. FAVASearch for more papers by this author First published: April 18, 1978 https://doi.org/10.1002/chin.197816088Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume9, Issue16April 18, 1978 RelatedInformation

Towards a complete account of the exchange chemistry of a diastereotopic proton pair. I. Base-catalyzed enolization–exchange of 2-norbornanones; on the rate controlling factors

We report the rates of base-catalyzed hydrogen isotope exchange of the exo and endo protons in a series of 2-norbornanones. The exo:enclo rate ratios for 4-methyl-substituted 2-norbornanones 3 and 6 are less than the rate ratios of the 4-demethyl analogs 2 and 5. Therefore, a methyl group is not a useful torsional-effect probe. This is supported by an analysis which established that the small difference in the torsional strain (0.45 kcal) between eclipsed vicinal hydrogens and an eclipsed vicinal methyl and hydrogen would only resuit in a maximum twofold increase in the rate ratio. The decrease in the exo:endo rate ratio is a consequence of the electron-donating effect of a methyl group which affects the exo rate to a greater degree. Introduction of a strain-inducing exo methylene group at C(5) and C(6) in the norbornyl system does not produce a significant change in the exchange rates. The average increase of 7.9 and 2.6 in the exo and endo rates, respectively, in enones 4, 5, and 6 over the ketones 1, 2, and 3 are explicable by an inductive effect. Thus, homoallylic stabilization of the developing carbanion is not important.Through application of a new mechanistic criterion which involves a log–log plot of the exo and endo exchange rate constants, we establish, for the bicyclic ketones, that charge transfer to oxygen is greater in the transition state for endo deprotonation.

Kinetic acidity of diastereotopic protons in sulfonium ions. A transition state conformational effect

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic acidity of diastereotopic protons in sulfonium ions. A transition state conformational effectG. Barbarella, P. Dembech, A. Garbesi, F. Bernardi, A. Bottoni, and A. FavaCite this: J. Am. Chem. Soc. 1978, 100, 1, 200–202Publication Date (Print):January 1, 1978Publication History Published online1 May 2002Published inissue 1 January 1978https://doi.org/10.1021/ja00469a033RIGHTS & PERMISSIONSArticle Views178Altmetric-Citations13LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (410 KB) Get e-Alerts Get e-Alerts

Synthesis and magnetic resonance studies of some phosphinous acids, phosphorylacetic acids, and some of their coordination compounds

The synthesis of phosphorylacetic acids, RR′P(O)CH 2COOH, where R = C 6H 5 and R′ = OC 2H 5, C 2H 5, i-C 3H 7, n-C 4H 9, sec-C 4H 9 and C 6H 5, from the appropriate phosphinous acids, several of which are previously unreported, is discussed. 31P nuclear magnetic resonance spectra are reported for the phosphinous acids, RR′P(O)H, the phosphorylacetic acids and the metal derivatives of the phosphinous acids, RR′POM, where M in Na or MgBr, which are intermediates in the synthesis. The diastereoisomers of Ph sec-BuP(O)H exhibit different 31P NMR spectra. Diastereotopic protons of the phosphinous acids and phosphorylacetic acids do not exhibit complex PMR spectra, whereas the diastereotopic methyl groups of the isopropyl compounds do. Some metal complexes of the phosphorylacetic acids are reported.

On the mechanisms of acid-catalyzed enolization and hydrogen isotope exchange of cyclic ketones

The acid-catalyzed hydrogen isotope exchange of norcamphor 1 in DOAc–DCl–D2O is shown to follow the general theory (4) for exchange of a diastereotopic proton pair α to a carbonyl group. That is, the less reactive proton undergoes exchange via two channels. Through an analysis of a combination of the rate data for acid-catalyzed bromination and the pKBH+ values for a series of cyclic and bicyclic ketones, we establish that the reactivity order in the former is controlled by ketone basicity and not, as has been suggested previously, by angle strain developed in a very enol-like transition state.

Direct Measurement of the Rates of Ionic Dissociation by Dynamic NMR Technique. Dissociation of α-Chlorodibenzyl Sulfides

Abstract Exchange processes of diastereotopic protons of α-chlorodibenzyl sulfides were observed by means of dynamic nuclear magnetic resonance. Polar effects of solvents and substituent effects on the ease of the exchange process of protons in p,p′-disubstituted α-chlorodibenzyl sulfides indicate that the process occurs with the dissociation of the compounds into benzylic cations and chloride ion. It is possible to measure the rates of ionic dissocation by observing the change in the line shape of signals in 1H NMR spectra. The scope of the method is discussed.

Highly stereoselective H–D exchange of diastereotopic protons in 4′,1″-dimethyl-1,2,3,4-dibenzylcyclohepta-1,3-diene-6-one

The rates of base-catalyzed H–D exchange of the diastereotopic methylene protons adjacent to the carbonyl group in the title compound have been measured in methanol-O-d. Sodium methoxide as catalyst produced a rate ratio of 73:1. Reasons for the large increase in stereoselectivity over that encountered in the exchange of 4-tert-butylcyclohexanone are proposed.

Evidence on internal return from isotope effects in the hydrogen-deuterium exchange of benzyl sulfoxides. A caveat re-interpretation of isotopic exchange rates

Measurements were made of the primary isotope effects k/sub H//k/sub T/ and k/sub D//k/sub T/ in the isotopic exchange of each diastereotopic proton of benzyl methyl sulfoxide and of two of the benzylic protons of the bridged biaryl sulfoxide. NMR, low voltage mass spectroscopy and tritium assays were used to determine the isotope content and the proportions of the diastereomers. Evidence of internal return was observed for the exchange reaction for the biaryl sulfoxide in tert-butyl alcohol-O-d. (DDA)

Diastereotope Methylenprotonen und Methylgruppen in 2-Substituierten 1,6-Methano [10] Annulenen

Abstract The double magnetic non equivalence of the diastereotopic methylene protons resp. geminal methyl groups of 2-substituted 1,6-methano [10]annulenes were observed in five solvents. It was found that ΔνAB for one of the two methylene groups were much smaller than ΔνA ‘B’ for the other and that ΔνA‘B’ was much more solvent dependent than ΔνAB. ΔνA “B” for the bridge protons varied very little with the solvent used.

A new approach to the synthesis of ‘chiral’ glycine

The stereospecific coordination of N-benzylglycinate ion in ΔR-(N-benzylglycinato) bis(ethylene-diamine) cobalt(III) chloride has been determined by X-ray crystallographic analysis, rotatory dispersion and 1H NMR spectroscopy. The chiral glycinato-N and Co centres influence the relative rates of exchange of the diastereotopic glycine methylene protons in basic solution (pH 10·5 with Na 3PO 4inD 2O) and a synthesis supposedly of S-(N-benzyl)- 2- 2H glycinate ion ≈ 80% optical purity) has been achieved.

Chirale Butadiene, 6. Behinderte Rotation an penta‐ und hexasubstituierten Butadienen – Stützeffekte

A series of hexasubstituted butadienes of type A was prepared representing (E,E)-1,2,3,4-tetrachloro-5-methoxy-1,3-pentadienes (7) substituted by different terminal residues R. 1H n.m.r. data of diastereotopic methylene protons served to determine the barriers of rotation around the central CC single bond of the butadienes A. The considerable dependence of this barrier (ΔGmath image = 12.8–21.1 kcal/mole) upon the size of the terminal substituents R ist discussed in terms of a buttressing effect of these groups.

ChemInform Abstract: N‐ALKYLAZETIDINE‐2‐CARBOXYLIC ESTERS

Abstractα,γ‐Dibrom‐buttersäureester (II) und primäre Amine (I) reagieren in Acetonitril in Gegenwart von Triäthylamin zu 1‐Alkyl‐azetidin‐2‐carbonsäureestern (III).