Stereoelectronic Requirements Research Articles

The structures of some sulphur-stabilized carbanions and stereoelectronic requirements for the formation of α-sulphonyl carbanions

Relatively few structure determinations of α-sulphonyl stabilized carbanions have been reported. The salient features of these are summarized and discussed in the light of the X-ray crystal structures of the potassium salt from bis(methylsulfonyl)-3-(2,6-dimethoxypyridyl)sulfonylmethane (5), the carbon acid bis(methylsulphonyl-4-(1,3-dimethoxyphenyl)sulphonylmethane (6), the triethylammonium salt of 2-methylsulphonyl-2-phenylthio-1-(3-pyridyl)-1-ethanone (7), the carbon acid 2-methyl-sulphonyl-2-phenylthio-1-phenylethanone (8), and its triethylammonium salt (9). Results of these structure determinations show that the α-sulphonyl carbanion has a significantly shorter −C—SO2 bond distance than the free sulphone, but that the S—O bond distances are essentially unchanged. The coordination about the carbanionic carbon atoms is planar; these atoms can be described as interacting with the sulphur atoms in an ylid-like manner, with a barrier to rotation about the −C—SO2 bond. The sulphonyl oxygen atoms do interact to a significant degree with the counterion, but there is no close contact between the counterion and the carbanionic carbon atom. A comparison of the structures of 6 and 5, or of 8 and 9, permits an assessment to be made concerning the stereoelectronics of deprotonation reactions on carbon atoms adjacent to sulphones.

Reactions of carbamyl radicals: intramolecular hydrogen abstraction reactions

ω-Phenylalkyl-N-methylcarbarnyl radicals undergo intermolecular addition to 3,3-dinethylbut-l-ene in preference to intramolecular hydrogen abstraction. Methyl N-(ω-phenylalkyl) carbanyl radicals and methyl N-pentylcarbamyi radicals readily abstract hydrogen through a six membered transition state or a seven membered transition state if the hydrogen is beniylic. The selectivities are interpreted in terms of the electrophilicity of the radical and the stereo-electronic requirements of hydrogen abstraction reactions.

Mechanism and stereoelectronic effects in the lysozyme reaction.

Lysozyme occupies a special place in the history of enzymology as the first enzyme to have its three-dimensional crystal structure elucidated by Phillips and co-workers in 1965. The crystallography, and much biochemical work, revealed three factors likely to be important for the mechanism of action: catalysis by the carboxyl group of Glu-35, catalysis by the ionized carboxyl group of Asp-52, and the conformation of the bound polysaccharide substrate. The work of the last 20 years has defined likely roles for the catalytic groups, but discussion of the conformational question came to a head only very recently with the suggestion that the fundamental stereoelectronic requirements of the glycoside-cleavage reaction might be decisive. Recent work on all three interlinked factors are reviewed.

Molybdenum-stabilized carbanions: a novel decyanation reaction with stereoelectronic requirement suggesting participation of the η3-allyl–Mo(CO)2(cp)(cp =η5-C5H5) moiety in stabilizing neighbouring carbanions

Carbanions stabilized by a nitrile group are readily generated in the presence of an η3-allyl–Mo(CO)2(cp)(cp =η5-C5H5) group, by treatment of complexes (5) with lithium di-isopropylamide, and undergo regio- and stereo-specific reaction with suitable electrophiles; a novel decyanation reaction is observed when (5) is treated with butyl-lithium, resulting in the generation of carbanion species (15), which also undergoes regio- and stereo-controlled reaction with electrophiles.

Total Synthesis of (±)‐Clovene. On the Stereoelectronic Requirements of the α‐Alkynone Cyclisation

AbstractThe synthesis of the sequiterpenoid tricyclic hydrocarbon (±)‐cleovene (1) by application of the α‐alkynone cyclisation is described. The starting bicyclic carboxylic acid 2 was obtained from ethyl 3‐methyl‐2‐oxocyclohexane‐1‐carboxylate by modified known methods (24%) and converted to the α‐alkynone 3 (86%). The thermolysis of 3 in the gas phase at 620° selectively produced the tricyclo[6.3.1.01,5] dodecenone 4 (80%) which was converted to 1 (37%) by conventional procedures. The selectivity of the α‐alkynone cyclisation is discussed in terms of the stereoelectronic requirements (coplanarity factor) of the carbene insertion. In order to throw further light on the importance of this factor, the (1‐adamantyl) alkynone 16 was synthesised from adamantane‐1‐carboxylic acid (78%) and subjected to thermolysis at 620°. Since this led to the tetracyclo[6.3.1.1.13,10.03,7]tridecenones 17 and 18 (together 72%), we conclude that the planar carbene insertion transition state, while preferred, is not a stringent requirement.

Photooxygenation Reactions of 4-Flavanols and Benzylic-type Alcohols

Abstract On irradiation in benzene under oxygen atmosphere cis- and trans-4-flavanols gave flavanones with significant structural effects on the yield: A high cis/trans selectivity and enhancement effect by electron-donating substituents. A series of benzylic-type alcohols showed similar substituent effects. The structure-reactivity relationships were explained in terms of the stereoelectronic requirements for favorable overlapping of intermediates. In order to infer the active oxidant species, the above photoreactions were compared with the oxidations by singlet oxygen and superoxide ion. The involvement of superoxide ion or its related species such as electron transfer complex R+····O2−· was suggested. The effects of additives and solvents were also investigated.

A reaction pathway for transimination of the pyridoxal 5'-phosphate in D-serine dehydratase by amino acids.

Transimination of the enzyme-linked cofactor by an amino acid is the first chemical transformation in the reactions catalyzed by pyridoxal 5'-phosphate-requiring enzymes. In this work, stopped flow fluorimetry was used to characterize the kinetics of transimination of the cofactor in D-serine dehydratase by several amino acids. The results of these studies indicate that transimination is a multistep process, the first step of which is probably formation of a noncovalent complex between the enzyme and the amino acid. D-Serine dehydratase was found to exhibit considerable specificity in the transimination reaction. Furthermore, the enzyme was shown to facilitate the transimination reaction with amino acids and inhibit transimination of the bound cofactor by amines lacking a carboxylate group. A reaction pathway was proposed for the transimination process which accounts for the specificity of the enzyme and indicates the changes in the conformation of the bound cofactor as dictated by the stereoelectronic requirements of the transimination reaction.

ChemInform Abstract: STUDIES ON INTRAMOLECULAR ALKYLATION. XII. STEREOCHEMICAL ASPECTS OF THE PREPARATION OF β,Γ‐UNSATURATED ALDEHYDES FROM THE (2,3)‐SIGMATROPIC REARRANGEMENT OF AMMONIUM YLIDES

AbstractEine sigmatrope Umlagerung des Allylammoniumylids (I), verbunden mit einer sauren Hydrolyse des entstehenden Gemisches isomerer Umlagerungsprodukte (II), liefert in hoher Ausb. ein Gemisch diastereomerer ungesättigter Aldehyde, in dem das trans‐Isomere (III) mit äquatorial stehender Formylgruppe stark überwiegt.

Intramolecullar alkylation of phenols. Part 4. Base-catalysed cyclisation of phenolic enones. Scope and limitations

The phenolic enones (4), (5), (8), (9), and (13) cyclise readily under acidic conditions. However, neither these nor the thin-substituted phenols (11a), (13a), (14a), and (15a) closed under basic conditions. Involvement of unfavourable equilibria is disproved. Comparison is made with related successful cyclisations of the saturated ketone (38) and aldehyde (39). Preliminary results suggest that strict stereo-electronic requirements are necessary for enone ring closure and that these conditions are not met in base-catalysed 5-Endo- and 6-Endo-Trigonal ring closures of the phenols of general type (2; n= 0 and n= 1).

Synthesis, structure, and reactions of secosteroids containing a medium-sized ring. Part 17. Structure–reactivity relationship in the solvolysis of 5,10-secosteroidal 3-tosylates

Kinetic measurements of the solvolysis of (Z)-3α- and (Z)-3β-, and (E)-3α- and (E)-3β-tosyloxy-5,10-secocholest-1(10)-en-5-ones in buffered aqueous acetone (90 : 10 v/v) reveal that the (Z)-3α-, (E)-3α-, and (E)-3β- tosylates are solvolysed according to a first-order rate law (the relative rates being ca. 1 : 3 : 8), while the (Z)-3β-ester, under the same conditions, reacts at a much slower rate by a complex mechanism, the kinetics of which are best approximated by a second-order law. These data and product analysis indicate that the former three esters are solvolysed with considerable double bond participation [resulting in the case of the (E)-3-esters in intramolecular cyclopropane ring closure], and that this interaction is unimportant for the (Z)-3β-tosylate. On the basis of conformational analysis of the starting tosylates and stereoelectronic requirements for homoallylic interaction, a possible mechanistic pathway for these solvolyses is proposed.

The selectivity of attack by the hydroxyl radical on myoinositol, and the importance of stereoelectronic factors upon radical rearrangement: an electron spin resonance conformational-analysis study

E.s.r. spectroscopy has been employed to show that the reaction of ·OH with the model substrate myoinositol is unselective; at pH 4, e.s.r. signals of all possible radicals produced by C–H abstraction are detected. A conformational analysis based on the hyperfine splittings is presented. The rates of acid-catalysed rearrangement of the radicals have been measured; the radical with an axial β-hydroxy-group is shown to lose water with a rate constant (ca. 3 × 106 dm3 mol–1 s–1) which is considerably greater than those of the radicals with only equatorial β-hydroxy-groups. This is interpreted in terms of a significant stereoelectronic requirement for rearrangement.

ChemInform Abstract: OCTAHYDRO‐7(1H)‐QUINOLONES. VII. A STEREOSELECTIVE SYNTHESIS OF CIS,TRANS‐DECAHYDRO‐3H,8H‐BENZO(I,J)QUINOLIZINE‐3,8‐DIONE

AbstractDie intramolekulare Alkylierung des Lactams (I) liefert ein Gemisch der cyclischen Verbindungen (II) und (III).

Mechanism of the reaction of papain with substrate-derived diazomethyl ketones Implications for the difference in site specificity of halomethyl ketones for serine proteinases and cysteine proteinases and for stereoelectronic requirements in the papain catalytic mechanism

Mechanism of the reaction of papain with substrate-derived diazomethyl ketones Implications for the difference in site specificity of halomethyl ketones for serine proteinases and cysteine proteinases and for stereoelectronic requirements in the papain catalytic mechanism

ChemInform Abstract: STEREOELECTRONIC FACTORS IN THE BINDING OF SUBSTRATE ANALOGUES AND INHIBITORS TO PURINE NUCLEOSIDE PHOSPHORYLASE ISOLATED FROM HUMAN ERYTHROCYTES

Several aspects of the stereoelectronic requirements of substrates of human erythrocytic purine nucleoside phosphorylase (E.C. 2.4.2.1) were elucidated providing the following information: (a) the N1 position cannot have a nonhydrogen substituent; (b) the 5'-OH group must be present for catalytic activity to be exhibited but is not an essential functional group for inhibitory action to be observed; (c) on the C8 position groups larger than -NH2 or -Br cannot be accommodated; (d) the syn-glycosyl conformation (i.e., 8-bromoguanosine) is acceptable but may not be an absolute requirement for phosphorolysis; (e) among nucleic base inhibitors methylation at N3, N7, or N9 vastly decreases the inhibitory properties as does a nitrogen in lieu of C-H in the 8 position. The results clearly indicate that this enzyme differs in its stereoelectronic requirements from the Escherichia coli enzyme.

ChemInform Abstract: SYNTHESIS OF AZAPOLYCYCLIC COMPOUNDS BY THE AMINIUM RADICAL ROUTE: REARRANGEMENTS OF C‐NITROSO COMPOUNDS AND THEIR STEREOELECTRONIC REQUIREMENTS

AbstractNach Literatur wurde Allylbromid mit Cyclopentadien zum 2‐endo‐Brommethyl‐bicyclohepten umgesetzt (Gesamtausb 70.5%, mit etwa 30% exo‐Isomerem), das mit Methylamin, danach mit Distickstofftetroxid zum Nitrosamin (I) umgesetzt wurde.

ChemInform Abstract: NUCLEOPHILIC ADDITION TO A TRIPLE BOND: PRELIMINARY AB INITIO STUDY

Preliminary ab initio, calculations (minimal basis set STO-3 G) suggest that the preferred direction of approach of a nucleophilic centre towards a CC triple bond makes an obtuse angle (∼120°) with this bond. The stereoelectronic requirements for nucleophilic addition to triple bonds and to ketones are thus rather similar.

Octahydro-7(1H)-quinolones. VII. A stereoselective synthesis of cis,trans-decahydro-3H,8H-benzo[i,j]quinolizine-3,8-dione.

The conversion of 1-(3-chloropropyl)-cis-decahydroquinoline-2, 7-dione (3) into decahydro-3H, 8H-benzo [i, j] quinolizine-3, 8-diones (12a and 12b) was accomplished with retention of the parent stereochemistry. The stereochemistry of the tricyclic system was assigned from chemical and physical evidences. It was postulated that this successful ring closure in the cis ring system resulted from easy fulfilment of the stereoelectronic requirement, for intramolecular alkylation in 3, much reduced as compared to that for N-acrylyl-cis-octahydro-7 (1H)-quinolone (1b).

Synthesis of azapolycyclic compounds by the aminium radical route: rearrangements of C-nitroso compounds and their stereoelectronic requirements

The aminium radicals generated from the photolysis of N-nitroso-endo-2-methylamino-methylbicyclo[2.2.1]hept-5-en and N-nitroso-endo-2-methylaminomethylbicyclo[2.2.2]oct-5-ene cyclize at the C-6 position, since the relevant reacting centers can achieve excellent orbital overlap with minimum molecular motion in comparison to the alternative cyclization path at the C-5 position. The photolysis of the former compound gave a C-nitroso compound which underwent a series of unusual intramolecular cleavages, deoximations, and redox reactions during the work-up. Stereoelectronic requirements for these intramolecular reactions are discussed. Thermolysis of N-chloro-endo-2-methylaminomethylbicyclo[2.2.2]oct-5-en in methanol also gave the product with azaisotwistane skeleton.

Mechanism of the reaction of papain with substrate-derived diazomethyl ketones. Implications for the difference in site specificity of halomethyl ketones for serine proteinases and cysteine proteinases and for stereoelectronic requirements in the papain catalytic mechanism.

The reactions of papain (EC 3.4.22.2) with substrate-derived diazomethyl ketones reported by Leary, Larsen, Watanabe & Shaw [Biochemistry (1977) 16, 5857--5861] are unusual in that (i) these reagents fail to react with low-molecular-weight thiols and (ii) the rate of reaction with the papain thiol group does not decrease to near-zero values across a pKa of 4 as the pH is decreased. Existing data are shown to suggest an interpretation involving neighbouring-group participation via transient thiohemiketal formation, rate-determining protonation by imidazolium ion and alkylation on sulphur via a three-membered cyclic transition state. Implications for (a) the difference in site-specificity exhibited by halomethyl ketones in their reactions with serine proteinases and cysteine proteinases and (b) stereoelectronic requirements in the mechanism of papain-catalysed hydrolysis are discussed. The possibility of two tetrahedral intermediates between adsorptive complex and acyl-enzyme is indicated.

Nucleophilic Addition to a Triple Bond; Preliminary ab initio study

AbstractPreliminary ab initio, calculations (minimal basis set STO‐3 G) suggest that the preferred direction of approach of a nucleophilic centre towards a CC triple bond makes an obtuse angle (∼120°) with this bond. The stereoelectronic requirements for nucleophilic addition to triple bonds and to ketones are thus rather similar.