Β-carbon Atom Research Articles

Unusual Reactivity of (Vinylimino)phosphoranes and Their Utility in the Preparation of Pyridine and Dihydropyridine Derivatives.

New reactions of (vinylimino)phosphoranes with aldehydes involving an initial nucleophilic attack of the beta-carbon atom of the vinyl side chain on the carbonyl carbon atom are reported. Iminophosphorane 4 derived from ethyl beta-azidoacrylate reacts with substituted cinnamyl aldehydes to give a mixture of 2-arylpyridine and 4-styryldihydropyridine derivatives, whereas the reaction with substituted benzaldehydes provides 4-aryldihydropyridine derivatives. However, the iminophosphorane 16 derived from the diethyl azidofumarate reacts with cinnamyl aldehydes through the expected aza-Wittig fashion to give 4-arylpyridine derivatives after dehydrogenation of the resulting dihydropyridine.

Versatile synthesis of L-α-amino acids stereospecifically labelled on the β-carbon atom

Inversion of the stereochemistry at the α-centre of stereospecifically labelled samples of (2S)-isoserine ( 7) using a sequence involving an intramolecular substitution reaction has allowed synthesis of the stereospecifically labelled aziridines ( 19) to be completed. These are synthons for a very versatile preparation of L-amino acids which are stereospecifically labelled at the β-carbon atom.

The palladium-catalysed vinylic substitution of vinyl triflates with β-substituted-α,β-unsaturated carbonyl compounds. An application to the synthesis of cardenolides

Vinyl triflates react with β-substituted-α,β-unsaturated aldehydes, ketones, and esters in the presence of catalytic amounts of Pd(OAc)2 and an exeess of KOAc, omitting phosphine ligands, to give vinylic substitution products in good to high yield with high regioselectivity. The added vinyl unit is preferentially linked to the β-carbon atom. As to the stereochemistry, vinylic substitution products contain the carbonyl group on the same side of the preexisting β-substituent. The use of KOAc has been proved to be superior both to tertiary amines and to carbonatc or bicarbonatc bases with or without the addition of salts such as LiCl and n-Bu4NCl. The application of the reaction to the synthesis of a cardenolide derivative is reported. Depending on the nature of β-substituted-α,β-unsaturated carbonyl compounds, the reaction can produce hydrovinylation (formal conjugated addition) products.

Initiating Systems for Nitroxide-Mediated “Living” Free Radical Polymerizations: Synthesis and Evaluation

A variety of initiating systems for the preparation of macromolecules by nitroxide-mediated “living” free radical procedures have been prepared and evaluated. The systems can be divided into two classes, unimolecular initiators in which alkylated TEMPO (2,2,6,6-tetramethylpiperidinyloxy) derivatives dissociate to provide both the initiating radical and the stable radical, and bimolecular systems in which a traditional free radical initiator, such as BPO or AIBN, is used in conjunction with TEMPO. For the unimolecular initiators it was found that an α-methyl group is essential for “living” character, while a variety of substituents could be placed on the phenyl ring or the β-carbon atom without affecting the efficiency of the unimolecular initiator. It was also found that the rate of polymerization is approximately the same for both the unimolecular and corresponding bimolecular systems; however, the unimolecular initiators afforded better control over molecular weight and polydispersity.

Asymmetric Michael Addition of Malonate Anions to Prochiral Acceptors Catalyzed by l-Proline Rubidium Salt

l-Proline rubidium salt catalyzes the asymmetric Michael addition of malonate anions to prochiral enones and enals. This method can be applied to a wide range of substrates to give adducts with a predictable absolute configuration: (S)-adducts from (E)-enones/enals and (R)-adducts from cyclic (Z)-enones. Both the secondary amine moiety and the carboxylate moiety are critical for the catalytic activity and asymmetric induction. Varying the countercation also affects the reaction course. High enantiomeric excesses were attained when di(tert-butyl) malonate was added to (E)-enones in the presence of CsF. The stereochemistry of the Michael reaction indicates that asymmetric induction takes place via enantioface discrimination involving the acceptor α-carbon atom rather than the β-carbon atom.

ビタミンＢ１２モデル錯体を触媒とした有機電解反応

Vitamin B12-dependent enzymes, involving the cobalt species as a catalytic center, mediate various isomerization reactions accompanied by carbon-skeleton rerragements. In order to simulate the catalytic functions of vitamin B12 as excerted in the hydrophobic active sites of enzymes concerned, we have been dealing with hydrophobic vitamin B12 derivatives which have ester groups in place of the peripheral amide moieties of the naturally occurring vitamin B12. In this work, the carbon-skeleton rearrangements as mediated by hydrophobic vitamin B12 derivatives were investigated under elec-trochemical conditions. The controlled-potential electrolyses of alkyl halides with various electronwithdrawing groups were carried out, and the electrochemical carbon-skeleton rearrangements proceeded effectively via formation of anionic intermediates. These reactions can be also applied to the ring-expansin reactins. We have carried out the electrolysis of an alkyl halide having two ester groups and one phenyl group on the β-carbon atom in the presence of a catalytic amount of the hydrophobic vitamin B12. The migration of the pheny group was observed under the conditions forming a radical intermediate. The ester-migrated product was detected under the conditions forming an anionic intermediate. This is the first successful example in selecting a migrating group by electroylsis potential. We have also prepared a strapped hydrophobic vitamin B12 in order to change the enantioselectivity. The controlled-potential electrolysis of a racemic alkyl halide having phenyl, methoxy, and carboxylic ester groups on the same carbon atom was carried out. The simple hydrophobic vitamin B12 tends to bind S-enantiomers more favorably. On the other hand, strapped hydrophobic vitamin B12 acts to bind R-enantiomers more favorably. These results suggested that the stability of alkylated complexes was dominated the enantioselectivity of reduction products.

Flash Photolytic Generation of Primary, Secondary, and Tertiary Ynamines in Aqueous Solution and Study of Their Carbon-Protonation Reactions in That Medium

A group of nine phenylynamines (PhC⋮CNH2, PhC⋮CNHCH(CH3)2, PhC⋮CNHC6H11, PhC⋮CNHC6H5, PhC⋮CNHC6F5, PhC⋮CN(CH2)5, PhC⋮CN(CH2CH2)2O, PhC⋮CN(CH2CH2CN)2, and PhC⋮CN(CH3)C6F5) were generated in aqueous solution by flash photolyic decarbonylation of the corresponding phenylaminocyclopropenones, and the kinetics of their facile decay in that medium were studied. This decay is catalyzed by acids for all ynaminesprimary, secondary, and tertiaryand also by bases for primary and secondary ynamines. Solvent isotope effects and the form of acid−base catalysis show that the acid-catalyzed path involves formation of keteniminium ions by rate-determining proton transfer to the β-carbon atoms of the ynamines. The ions generated from primary and secondary ynamines then lose nitrogen-bound protons to give ketenimines, and the ketenimines obtained from secondary ynamines are hydrated to phenylacetamides, whereas that from the primary ynamine tautomerizes to phenylacetonitrile. Keteniminium ions formed from tertiary ynamines ...

1H nuclear magnetic resonance and molecular orbital studies of 2-formylstyrene. Three significant nonplanar conformers at 300 K

The 1H nuclear magnetic resonance spectra of 2-formylstyrene, from dilute solutions in CS2–C6DI2 and acetone-d6, are analyzed to yield precise chemical shifts and spin–spin coupling constants. The long-range coupling constants imply a conformational distribution in which the O-trans conformer is 55% abundant in both polar and nonpolar environments. They also imply that the vinyl group, on average, is twisted out of the aromatic plane to a much larger extent than in styrene. The 6-31G* basis set gives an ab initio potential for the torsion of the vinyl moiety with a relatively deep minimum at 38° out-of-plane, for the O-cis conformer. For the O-trans conformer, two minima are found, one at 45° and another at 129.6°. Essentially the same potential is obtained with the 6-31G** basis. The latter corresponds to a close approach of the hydrogen atom of the formyl group and π orbitals or the β-carbon atom of the olefinic side chain. This local minimum is interesting in terms of a hypothesis used to explain the photochemistry of the molecule. The long-range coupling constants are consistent with the conformational properties calculated for the free molecule; they also indicate no significant difference between the conformational behaviour of the molecule in the two solvents. A proximate coupling constant of −0.16 Hz exists between the formyl and methine (α) protons. The latter is strongly deshielded in the presence of the formyl group, so that it becomes even less shielded than some of the aromatic protons. Keywords: 1H NMR, 2-formylstyrene (o-vinylbenzaldehyde); long-range spin–spin coupling constants, 2-formylstyrene; conformations, three nonplanar of 2-formylstyrene; molecular orbital calculations, conformations of 2-formylstyrene.

Synthetic Applications of Vinyliminophosphoranes Based on the Reactivity of the Vinyl Side Chain. Preparation of Dihydropyridines

New reactions of vinyliminophosphoranes with aldehydes involving an initial nuclcophilic attack of the β-carbon atom of the vinyl side chain on the carbonylic carbon atom is reported. The resulting bctaines undergo either intra- or intermolecular cyclization to give pyridines or dihydropyridines.

Synthetic applications of vinyliminophosphoranes based on the reactivity of the vinyl side chain. Preparation of dihydropyridines

New reactions of vinyliminophosphoranes with aldehydes involving an initial nuclcophilic attack of the β-carbon atom of the vinyl side chain on the carbonylic carbon atom is reported. The resulting bctaines undergo either intra- or intermolecular cyclization to give pyridines or dihydropyridines.

Synthesis of glutamate agonists and anatagonists by a ring switching strategy

Our ring switching strategy for synthesis of compounds with structural features consistent with activity at glutamate receptors has been modified to prepare L-alanine derivative substituted at the β-carbon atom with six-membered heteroaromatic rings. The pyrimidinone ( 11, R = R 1 = R 2 = H ) has been shown to be a glutamate agonist and the compound ( 13) to be an antagonist.

Gas chromatography of styrene oligomers using a curie-point pyrolyzer

A Curie-point pyrolyzer directly coupled to a capillary gas Chromatograph was applied to analyze the volume effects of stereoisomers on the chromatography of 2,4-diphenylpentane as a model compound of a styrene dimer, and finally of those of styrene oligomers. It was found that the retention time for the meso-isomer of 2,4-diphenylpentane appeared to be advanced and significantly far apart from that of the racemo-isomer. In the case of styrene oligomers prepared with n-butyllithium as the initiator, the n-butyl group coupled to the β-carbon atom to the styrene terminal unit was stable even at 590 °C, and corresponding peaks for the 1-mer, 2-mer, 3-mer and 4-mer were detected, in addition to the well-recognized peaks assigned to the dimer and the trimer.

The hydration of mesitylketene in aqueous solution: detection of acid catalysis for an aromatic ketene

Mesitylketene was generated flash photolytically in aqueous solution by the photo-Wolff reaction of 2,4,6-trimethyldiazoacetophenone and also by rearrangement of mesitylynol obtained through photodecarbonylation of mesitylhydroxycyclopropenone, and rates of hydration of this ketene were measured in dilute perchloric acid, sodium perchlorate, and sodium hydroxide solutions as well as in concentrated sodium perchlorate and perchloric acid solutions. In dilute solution only an uncatalyzed reaction and a sodium-hydroxide-catalyzed process were observed, both of which could be attributed to nucleophilic attack, by water and by hydroxide ion, respectively, at the ketene carbonyl carbon atom. In concentrated sodium perchlorate solutions, a mild decrease in reaction rate with increasing salt concentration was observed, as expected on the basis of decreasing water activity and a consequent slowing of the uncatalyzed reaction. A similar mild decrease was found in perchloric acid solutions up to [Formula: see text] but this then gave way to a rate increase that became dominant above [Formula: see text] This appearance of acid catalysis indicates a change in reaction mechanism from nucleophilic attack of water to an electrophilic process involving rate-determining protonation on the β-carbon atom of the ketene group. Analysis of the acid-catalyzed reaction rate by the Cox–Yates method gives the catalytic coefficient [Formula: see text] This, when compared with [Formula: see text] for ketene itself, shows that the mesityl group retards acid-catalyzed hydration by a factor of 2200, and consequently the acid-catalyzed reaction of this, and other aromatic ketenes as well, becomes apparent only under strongly acidic conditions. Keywords: mesitylketene, ketene hydration, acid catalysis, Cox–Yates excess acidity correlation.

Rhodium(II) acetate-catalysed decomposition of 2-diazo-3-oxobutanamides derived from L-phenylalanine

In order to developed a practical method for alkylating α-amino acids at the α- or β-carbon atom by intramolecular carbene CH insertion, a series of diazoamides 3a–e was synthesized and subjected to rhodium(II) acetatecatalysed decomposition. The N-benzyl derivative 3a gave mainly the azetidinones 4a and 5a, resulting from a carbene CH insertion into the N-benzyl group. The N-diphenylmethyl derivative 3c yielded, upon treatment with rhodium(II) acetate, the azetidinone 5c, the imine 6c, the cycloheptapyrrolidinone 7c as well as the desired pyrrolidinone 8c (12% yield) the latter resulting from an alkylation of the L-phenylalanine framework at the β-carbon atom.

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.

The first study on 2′,5′-dideoxynucleosidyl radicals formed from the anaerobic photolysis of 2′,5′-dideoxynucleosidylcobalamins by the ESR spin-trapping technique

Anaerobic photolysis of coenzyme B 12(Ia) and its four analogues of 2′,5′-dideoxynucleosidylcobalamins (Ib → Ie) containing 2′,5′-dideoxycytidyl, 2′,5′-dideoxyuridinyl, 2′,5′-dideoxyadenosyl, and 5′-deoxythymidyl groups (R) as axial ligands in the presence of t-nitrosobutane (tNB) in H 2O, DMSO, and DMF affords the spin-trapped nitroride radicals Bu tN(Ȯ)R (IIa → IIe) and B 12r. This result reveals anaerobic Co IIIC homolysis for Ib → Ie, as for coenzyme B 12. The spectra of all Bu tN(Ȯ)R radicals show 1:1:1:1 quartet and line width alternations were observed due to two unsymmetrical conformers caused by a chiral β-carbon atoms. Magnetic nuclei on the α and β-carbon atoms produce informative secondary and third structures of nitroxide radicals. The effects of the solvent and temperature on ESR spectra and parameters were rationalized.

Catalytic asymmetric Michael addition of nitroalkane to enone and enal

L-Proline rubidium salt catalyzes the asymmetric Michael addition of nitroalkanes to enones and an enal. ( R)-Adducts were obtained from cyclic ( Z)-enones and ( S)-adducts from acyclic ( E)-enones. Bu 3SnH treatment of the products replaced the nitro group with hydrogen atom. The overall transformation allows the asymmetric alkylation of enones at the β-carbon atom.

New synthetic applications of vinyliminophosphoranes based on the reactivity of the vinyl side chain

New reactions of vinyliminophosphoranes involving either the β-carbon atom of the vinyl side chain as nucleophilic center or the α-carbon as electrophilic center are described

Nonnatural amino acid yields improved drugs

Chemists from Texas A&M University, College Station, have used a severely constrained analog of an amino acid to make a peptide that has higher biological activity and resistance to degradation than the natural peptide. This substitution of nonnatural for natural amino acids is one approach that medicinal chemists are using to invent peptide drugs of superior efficacy and bioavailability. Texas A&M organic chemistry professor Kevin Burgess told the Division of Organic Chemistry at the ACS national meeting in San Diego that his work with graduate students Kwok-Kan Ho, Chun-Yen Ke, and Dong Yeol Lim uses methionine (Met) that has an extra methylene group, -CH 2 -, between the α- and β-carbon atoms. The extra methylene group ties the normal straight-chain molecule back into a cyclopropane. The researchers nickname the resulting 1-amino-2-methylthiomethylcyclopropanecarboxylic acid E-cyclo-Met, because the amino and methylthiomethyl groups are trans to one another. They also use the name (2S,3S)-cyclo-Met, re...

Kinetics and mechanism of hydrolysis of tyrphostins

The rates of hydrolysis of RG 14620, a tyrphostin, have been determined at pH values between 1 and 10. The log k-pH profile shows the rate of the hydrolysis is proportional to the concentration of hydroxide ion above pH 5. In the acidic pH region, the profile shows a curve with a maximum between pH 2 and 3. The presence of a maximum has been interpreted in terms of a change from the rate-determining formation of a tetrahedral addition intermediate on the basic side of the maximum to the rate-determining cleavage of the intermediate on the acidic side. This interpretation is supported by the observations that the reaction is catalyzed by chloroacetate buffer at pH 3.2 and that the catalytic constants for the buffer decrease with an increasing buffer concentration at pH values in the range of 2.26–2.79. The non-linearity is due to the uncatalyzed cleavage of the intermediate which becomes partially rate-determining at higher buffer concentrations. The effect of variation in the polar nature of phenyl substituents at the β-carbon atom of the tyrphostin is in accord with the hydrolysis mechanism.