Steric Course Of Reaction Research Articles

The Steric Course of SE2 Reactions of Unstabilized α-Aminoorganolithiums: Distinguishing between SET and Polar Mechanisms

The competing mechanisms that determine the steric course of electrophilic aliphatic substitution reactions (SE2) of configurationally stable, unstabilized α-aminoorganolithiums are compared. The steric course of the reaction of lithiated pyrrolidines and piperidines with electrophiles is variable, such as when comparisons are made between two electrophiles and a single organolithium, or between two organolithiums and a single electrophile. The possible pathways considered are single electron transfer (SET) and competing polar substitutions (SE2ret vs SE2inv). Catalysis of organolithium racemization by the electrophile was eliminated as a possible source of racemic products. When the products are completely racemic, our evidence suggests that SET is the most likely mechanism; when polar pathways are operative, stereoselectivities vary from 75 to 100%, and may be invertive or retentive at the carbanionic carbon, depending on the electrophile.

Steric substituent constant Ωs based on molecular mechanics calculation. II. Directionally weighted steric constants and their application to the analysis of the steric course of reactions

AbstractThe directionally weighted steric substituent constant Ωjk was introduced to evaluate the anisotropic steric hindrance effect to the reaction centre. The correlation of the rates with a series of directionally weighted Ωjk is useful for characterizing the feature of steric effect. The difference between the hydrolyses of carboxylic esters and carboxamides was shown by this method.

The reaction of acetyliron [( η5-C 5H 5)Fe(CO)(PPh 3)(COCH 3)] with sugar aldehydes. New synthesis of deoxysugars

Aldol reactions of sugar aldehydes ( 5 – 13) with enolate 2 of racemic and both enantiomeric forms of acetyliron were investigated. The steric course of reactions depended strongly on the counterions used. High stereocontrol was achieved with the following cations: tin(II), diethylaluminum(I), zirconium(IV) and the triethylaluminum-containing cation. Matched pairs, particularly with the pentose- and hexose-derived aldehydes, yielded the corresponding aldol products with very high stereoselectivities. Products of aldol reactions were decomplexed with N-bromosuccinimide in methanol. From aldols 14a-d – 18a-d stereoisomeric methyl 2-deoxypentonates and 2-deoxyhexonates were obtained and their configuration was determined. Aldols obtained from acetyliron anion ( 2) and pentose- and hexose-derived aldehydes 8 – 13 led after decomplexation to pairs of stereoisomeric methyl 6-deoxy(7-deoxy)-hept(oct)uronates. These products were separated and their configuration was assigned on the basis of chemical transformations to free 6-deoxyheptoses. In case of D- and L-arabino aldehydes ( 9 and 10)-because of low stability of products - the configuration was assigned by the synthesis of a model compound. A regularity was found in the 1H NMR spectra of methyl 6-deoxy-hepturonates connecting coupling constants J α,β and J α′, β of the methylene protons with the configuration of the β-carbon atom.

On the distribution of the diastereomers of the structural elements in lignins: the steric course of reactions mimicking lignin biosynthesis

Stereochemical studies on the formation of the diastereomers of arylglycerol-β-aryl ether structures during lignin biosynthesis have been carried out with model compounds. The addition of water to quinone methides of the β-syringyl ether type gives arylglycerol β-syringyl ethers with a predominance of the erythro isomer when the pH of the medium is low. Since erythro forms of arylglycerol β-syringyl ethers are prevalent in hardwood lignins, this indicates that the pH of the medium in which lignin biosynthesis occurs is lower than has been assumed until now. Equilibration studies with non-phenolic model compounds of the arylglycerolβ-guaiacyl ether and β-syringyl ether types under acidolysis conditions indicate that the erythro predominance observed in the syringyl ethers in lignins does not correspond to equilibrium conditions. A remarkable resistance to acidolysis is observed in the model compounds of etherified syringylglycerol β-syringyl ether type.

The Stereoselective Hydrogenation of Nepetalactoles. The Role of C1 Alkoxyl Groups on the Stereoselectivity

The stereoselective hydrogenation of nepetalactol and its derivatives was examined. From the stereochemical outcome and the conformational analyses of starting materials, it was concluded that, in the hydrogenation of nepetalactols, the most important factor which determined the steric course of reaction is the configuration of C1 position which carries the alkoxyl group

Phospholipids chiral at phosphorus. Stereochemical mechanism of reactions catalyzed by phosphatidylinositide-specific phospholipase C from Bacillus cereus and guinea pig uterus

(Rp)- and (Sp)-1,2-dipalmitoyl-sn-glycero-3-thiophosphoinositol (DPPsI) were synthesized as a mixture and their configurations assigned on the basis of the stereospecific hydrolysis catalyzed by phospholipase A2 (PLA2) from bee venom. PLA2 is known to be stereospecific to the Rp isomer of 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC) and 1,2-dipalmitoyl-sn-glycero-3-thiophosphoethanolamine (DPPsE). Since the configurations of (Rp)- and (Sp)-DPPsI correspond to those of (Sp)- and (Rp)-DPPsC, respectively, due to a change in priority, the isomer specifically hydrolyzed by PLA2 was assigned to (Sp)-DPPsI. The DPPsI analogues were then used to probe the mechanism and to elucidate the steric course of the reaction catalyzed by phosphatidylinositide-specific phospholipase C (PI-PLC) from Bacillus cereus and for both isozyme I and isozyme II of PI-PLC from guinea pig uterus. It was found that the Rp isomer of DPPsI is the preferred substrate for all three PI-PLCs. Thus PI-PLC shows the same stereospecificity as phosphatidylcholine-specific PLC (PC-PLC), which prefers the Sp isomer of DPPsC. The ratio of the two products inositol 1,2-cyclic phosphorothioate (cIPs) and inositol phosphorothioate (IPs) was not significantly perturbed by the use of phosphorothioate analogue for all three PI-PLCs, which implies that IPs is not produced by enzyme-mediated ring opening of cIPs and supports a parallel pathway for the formation of both products. In order to elucidate the steric course of the cyclization reaction, exo and endo isomers of cIPs were synthesized and their absolute configurations at phosphorus were determined by nuclear magnetic resonance and other techniques. It was found that exo-cIPs is the product produced by all three PI-PLCs. Thus the steric course of the conversion DPPsI to cIPs catalyzed by all three PI-PLCs was inversion of configuration at phosphorus. These results taken together suggest that the reaction catalyzed by PI-PLC most likely proceeds via direct attack by the 2-OH group to generate the cyclic product, and parallelly by water to generate the noncyclic inositol phosphates, without involving a covalent enzyme-phosphoinositol intermediate.

Asymmetrische Michael‐Additionen. Stereoselektive Alkylierung chiraler, nicht racemischer Enolate durch Nitroolefine. Herstellung enantiomerenreiner γ‐Aminobuttersäure‐ und Bernsteinsäure‐Derivate

Asymmetric Michael‐Additions. Stereoselective Alkylation of Chiral, Non‐racemic Enolates by Nitroolefins. Preparation of Enantiomerically Pure γ‐Aminobutyric and Succinic Acid DerivativesChiral, non‐racemic lithium enolates (E,F,G) of 1,3‐dioxolan‐4‐ones, methyl 1,3‐oxazolidin‐4‐carboxylates, methyl 1,3‐oxazolin‐4‐carboxylates, 1,3‐oxazolidin‐5‐ones, and 1,3‐imidazolidin‐4‐ones derived from (S)‐lactic acid (2a), (S)‐mandelic acid (2b), and (S)‐malic acid (2c), or from (S)‐alanine (10), (S)‐proline (11), (S)‐serine (12), and (S)‐threonine (13), are added to nitroolefins. Michael adducts (3–9, 14–18) are formed (40–80%) with selectivities generally above 90% ds of one of the four possible stereoisomers. Conversions of these nitroalkylated products furnish the α‐branched α‐hydroxysuccinic acids 28 and 29, the α‐hydroxy‐γ‐amino acid 25, the α,γ‐di‐amino acid 32, the substituted γ‐lactames 19–22, and the pyrrolidine 23. The relative and absolute configuration of the products from dioxolanones and nitropropene are derived by chemical correlation and NOE measurements indicating that the steric course of reaction is to be specified as 1k, ul‐1,3. The mechanism is discussed.

Michael additions catalysed by cinchona alkaloids bound via their vinyl groups to preformed crosslinked polymers

Cinchona alkaloids have been satisfactorily bound via their vinyl groups to crosslinked polymers containing thiol residues. The products have been used to catalyse one or more of the following Michael additions: the additions of (1) thio-p-cresol, (2)p-chlorothiophenol, and (3) thiobenzoic acid to cyclohex-2-en-1-one, and (4) of toluene-α-thiol to 2-nitrostyrene. The steric course of reactions (1)–(3) is dominated by the configurations of C-8 and C-9 in the alkaloids, but the nature of the C-3 group does have an effect and this probably explains why the optical yields obtained using the polymer-supported catalysts were lower than those obtained using the free alkaloids. The optical yields obtained in reaction (4), though small, did not follow this pattern. The polymers afforded higher optical yields than the free alkaloids and, in one case, the predominant enantiomer was of opposite configuration.

Factors determining steric course of enzymic glycosylation reactions: glycosyl transfer products formed from 2,6-anhydro-1-deoxy-D-gluco-hept-1-enitol by alpha-glucosidases and an inverting exo-alpha-glucanase.

Glycosyl transfer products were formed from 2,6-anhydro-1-deoxy-D-gluco-hept-1-enitol (heptenitol) by purified alpha-glucosidases from Candida tropicalis and rice and by an inverting exo-alpha-glucanase (glucodextranase) from Arthrobacter globiformis. The products were structurally defined through 1H and 13C NMR (nuclear magnetic resonance) spectra of their crystalline per-O-acetates in comparison with those of authentic methyl 1-deoxy-alpha- and methyl 1-deoxy-beta-D-gluco-heptuloside. 1-Deoxy-alpha-D-gluco-heptulosyl-(2 leads to 7)-heptenitol and 1-deoxy-alpha-D-gluco-heptulosyl-(2 leads to 7)-D-gluco-heptulose were produced by both the Candida alpha-glucosidase and the glucodextranase; 1-deoxy-alpha-D-gluco-heptulosyl-(2 leads to 5)- and 1-deoxy-alpha-D-gluco-heptulosyl-(2 leads to 7)-D-gluco-heptuloses by the rice alpha-glucosidase. These results, together with our earlier findings of sterospecific hydration of heptenitol catalyzed by the same enzymes [Hehre, E. J., Brewer, C. F., Uchiyama, T., Schlesselmann, P., & Lehmann, J. (1980) Biochemistry 19, 3557-3564], show the inadequacy of the long-accepted notion that carbohydrase-catalyzed reactions always lead to retention (or always lead to inversion) of substrate configuration. In particular, the finding that glucodextranase forms transfer products of alpha configuration and a hydration product of beta configuration from the same substrate provides a clear example of the functioning of acceptors rather than donor substrates in selecting the steric course of reactions catalyzed by a glycosylase. The circumstances under which acceptor cosubstrates might be expected to show this significant effect are discussed. The opportunity presumably would exist whenever carbonium ion mediated reactions are catalyzed by glycosylases that provide oppositely oriented approaches of different acceptors to the catalytic center.

The Unambiguous Specification of the Steric Course of Asymmetric Syntheses

AbstractThe nomenclature of organic chemistry has not kept pace with the staggering advances made in asymmetric syntheses over the last 15 years. Efforts to specify the steric course of stereoselective reactions by use of the terms erythro and threo, and by other descriptors have led to ambiguous notation and consequently to an almost Babylonic confusion. We propose here a method, based on the CIP‐(Cahn‐Ingold‐Prelog) system, for the unambiguous specification of the steric course and the product configuration of diastereoselective reactions. The reflection‐invariant relative topicity of approach of reactants is defined as like (lk) and unlike (ul) if the corresponding descriptor pairs are Re*, Re*. or R*, Re*, and Re*, Si*, or R*, Si*, respectively. The descriptor pair notations (lk and ul) of reactants disclose related steric courses of reactions more often than do the relative configurations of their products, for which the configurational notation l=R*, R* and u=R*, S* is proposed. The advantage of specifying the relative topicity is demonstrated by means of a series of recent examples of importance to the synthetic organic chemist taken from the literature and from our own work.

Steric course of reaction catalyzed by the enoyl acyl-carrier-protein reductase of Escherichia coli.

The steric course of the reaction catalyzed by Escherichia coli enoyl acyl-carrier-protein reductase was studied. 1. trans-2-[2-2H1]Decenoic and trans-2-[3-2H1]decenoic acids were synthesized and converted to the corresponding decenoyl thiol esters with CoA or acyl carrier protein. These deuterium-labeled decenoyl thiol esters were incubated with purified enoyl acyl-carrier-protein reductase in the presence of NADPH or NADH. 2. The unlabeled trans-2-decenoyl thiol esters were incubated with enoyl acyl-carrier-protein reductase in the presence of (4S)-[4-2H1]NADH. The unlabeled decenoyl thiol esters were also incubated with the enzyme in 2H2O. The decanoic acids formed in the above incubations were extracted and subjected to the action of acyl-CoA oxidase, which had been previously shown to catalyze the anti elimination of the pro-2R and pro-3R hydrogens of acyl-CoA. The resulting products, 2-decenoyl-CoAs, were converted to methyl esters and their deuterium contents were analyzed by gas chromatography/mass spectrometry. The results suggested that the reduction catalyzed by E. coli enoyl acyl-carrier-protein reductase occurs by a syn addition of hydrogen via a 2-Re, 3-Si attack on the double bond.

The steric course of the reaction of ethylene oxide with hydrogen halides in the gas phase

The steric course of the gas-phase reaction of trans-[2H2]ethylene oxide with HF, HCl, and HBr was investigated in order to test experimentally a mechanistic proposal based on ab initio calculations involving a concerted syn-opening mechanism. In contrast with this proposal the reactions with HCl and HBr take place entirely with anti-opening of the ring to give erythro-2-chloro- and 2-bromo[1,2-2H2]ethanol. The reaction of ethylene oxide with gaseous HF yields only 5% 2-fluoroethanol, 37% dioxan, oligomers and polymers being the main products. An improved method for the conversion of cis- and trans-[2H2]ethylene into the corresponding epoxides is described.

The Influence of the Shape of the Substrate on the Steric Course of Reactions Catalysed by a Dehydrogenase Dependent on Nicotinamide-Adenine Dinucleotide

The Influence of the Shape of the Substrate on the Steric Course of Reactions Catalysed by a Dehydrogenase Dependent on Nicotinamide-Adenine Dinucleotide

Stereoselectivity of the elimination reactions of 2,3-dihalobutanes and 2-bromobutane over alkaline earth metal oxides and alumina

Abstract The stereochemistry ( anti or syn mode) of dehydrohalogenation of 2,3-dibromo-butane, 2,3-dichlorobutane and 2-bromobutane over MgO, CaO, SrO and Al 2 O 3 was determined by use of a pulse technique from the products of the diastereomeric isomers of each compound at 100–250 °C. The elimination of hydrogen halide proceeded selectively by anti mode over fresh surface of these oxides below 200 °C for dibromobutane and below 250 °C for dichlorobutane, reflecting the surface basicity. Anti mode was also favored in the case of 2-bromobutane at about 100 °C. However, due to the alteration of surface basicity by hydrogen halide formed, the stereoselectivity decreased with repeated pulses. Present results agree with the idea deduced previously in the case of silica gels that the acid-base properties of catalyst and substrate are the prime factor controlling the steric course of reactions. Stereochemistry of debromination and halogen-substitution reactions of dibromobutane, the accompanying reactions, was also determined to be anti mode and retention, respectively.

The stereochemistry of thiane oxidation : Participation of neighboring groups

Thianes not containing 4-OH or 4-CO groups are oxidized by wet bromine predominantly to equatorial thiane 1-oxides. The reaction is assumed to proceed by way of an equatorial electrophilic attack by hypobromous acid at the S atom. An electronic interpretation is given of the steric course of electrophilic reactions at the S atom in thianes. With thianes containing 4-OH or 4-CO groups, oxidation to thiane 1-oxides by wet bromine or by t-butyl hypochlorite resulted in a reversal of the usual stereospecificities of these reagents. A two step process involving participation by the 4-substituents is given to account for the different steric course of the reactions in these cases.

Stereoselectivity of the elimination reactions of alkyl halides over silica gel and alkali-treated silica gel

The stereochemistry ( anti or syn mode) of dehydrohalogenation of 2-bromobutane, 2,3-dichlorobutane and 2,3-dibromobutane over various solid acids and bases, such as silica gel and alkali salt-impregnated silica gels, at 95–300 °C was determined from the products of the diastereomeric isomers of each compound. The steric course of dehydrobromination of 2-bromobutane at low temperatures was mainly anti mode over KOHSiO 2, K 2CO 3SiO 2 and syn mode over SiO 2. At high temperatures, syn elimination was the favored mode over most catalysts studied. The reactions of 2,3-dihalobutanes proceeded by anti elimination over those solid surfaces. From the variation in the stereochemical reactions of the catalysts and reactants, the ease of β-proton elimination, which increases with the acidity of β-proton and basicity of solid, was found to be the prime factor determining the steric course of reaction. The reaction mechanism is discussed on the basis of the stereochemistry, isotope effects and the relative reactivity of various alkyl halides.

Chloroboration and allied reactions of unsaturated compounds II. Haloboration and phenylboration of acetylenes; and the preparation of some alkynylboranes

Selected haloboranes, BX 1X 2X 3 (X 1Cl or Br, and X 2 and X 3 are either = X 1 or Ph), generally reacted with acetylenes (HCCH, BuCCH, PhCCH, or PhCCPh) to afford (2-halo- or 2-phenylalkenyl)boranes, depending on the nature of the acetylene. The products were characterised by acetolytic protodeboration, alcoholysis, and by their infrared spectra. For unsymmetrical acetylenes. Markownikoff addition was demonstrated; the steric course of reaction is trans for acetylene but is believed to be cis for at least some of the substituted acetylenes. Reactivity increases with high acceptor strength of borane and high nucleophilicity of the acetylene. Chloro- and organoboration of acetylenes is evidently a thermodynamically-controlled process, in contrast to hydroboration. Some of the reactions are of potential application for synthesis of α-substituted styrenes and their derivatives. Two alkynylboranes have been obtained from haloboranes and lithioacetylenes.

Electrophilic Substitution at Saturated Carbon. VII. Steric Course of Reactions that Involve Breaking Carbon-Oxygen Bonds1

Electrophilic Substitution at Saturated Carbon. VII. Steric Course of Reactions that Involve Breaking Carbon-Oxygen Bonds¹

Steric course of reactions of steroids.

Der sterische Verlauf von Reaktionen an einem gegebenen Kohlenstoffatom des Steroidgerustes hangt von Hinderungseffekten ab, welche innerhalb des van der Waalsschen Radius des betreffenden Kohlenstoffatoms wirken. Diese Effekte werden daher als intraradiale bezeichnet. Eine zweite Klasse von Effekten, die als extraradiale zu definieren sind, beeinflussen den sterischen Verlauf von Reaktionen funktioneller Substituenten, wie z. B. von Azetylgruppen oder Carboathoxylgruppen, am Sterinkern.