Open-chain Intermediate Research Articles

Tunable “In-Chain” and “At the End of the Branches” Methyl Acrylate Incorporation in the Polyolefin Skeleton through Pd(II) Catalysis

The synthesis of functionalized polyolefins through coordination–insertion polymerization is a highly challenging reaction. The ideal catalyst, in addition to showing a high productivity, has to be able to control the copolymer microstructure and, in particular, the way of the polar vinyl monomer incorporation. In this contribution, we modified the typical Brookhart’s catalyst by introducing in the fourth coordination site of palladium a hemilabile, potentially bidentate ligand, such as a thiophenimine (N–S). The obtained cationic Pd(II) complexes, [Pd(Me)(N–N)(N–S)][PF6], generated active catalysts for the ethylene/methyl acrylate (MA) copolymerization leading to the desired copolymer with a different incorporation of the polar monomer depending on both the reaction medium and the N–S ligand. Surprisingly enough, the produced copolymers have the inserted acrylate both at the end of the branches (T(MA)) and in the main chain (M(MA)) in a ratio M(MA)/T(MA) that goes from 9:91 to 45:55 moving from dichloromethane to trifluoroethanol (TFE) as a solvent for the catalysis and varying the N–S ligand. The catalytic behavior of the new complexes was compared to that of the parent compound [Pd(Me)(N–N)(MeCN)][PF6], highlighting the fact that when the copolymerization is carried out in trifluoroethanol, this complex is also able to produce the E/MA copolymer with MA inserted both in the main chain and at the end of the branches. Accurate NMR studies on the reactivity of the precatalyst [Pd(Me)(N–N)(MeCN)][PF6] with the two comonomers allowed us to discover that in the fluorinated solvent, the catalyst resting state is an open-chain intermediate having both the organic fragment, originated from the migratory insertion of MA into the Pd–Me bond, and the acetonitrile coordinated to palladium and not the six-membered palladacycle typically observed for the Pd-α-diimine catalysts. This discovery is also supported by both DFT calculations and in situ NMR studies carried out on [Pd(Me)(N–N)(N–S)][PF6] complexes that point out that N–S remains in the palladium coordination sphere during catalysis. The open-chain intermediate is responsible for the growth of the copolymer chain with the polar monomer inserted into the main chain.

Study of Mass Spectra of Some Indole Derivatives

In the work, a study of mass fragmentation routes by the electron-impact mass spectrometry data has been examined for two open chain intermediates of indole derivatives and two pyrroloquinolines. By the isolation of open chain intermediate and the mass spectra, the structures of pyrroloquinoline have been confirmed.

The Role of the Amino Acid-Derived Side Chain in the Preorganization of C2-Symmetric Pseudopeptides: Effect on SN2 Macrocyclization Reactions

A family of pseudopeptidic macrocycles containing non-natural amino acids have been synthesized. The macrocyclization reaction has been studied experimentally and computationally, demonstrating the key role of both the amino acid side chain and the catalytic bromide anion. The bromide anion acts as an external template assisting the folding of the open-chain precursor in a proper conformation. Computations revealed that in the presence of the anion, the effect of the side chain on the energy barrier for the macrocyclization is very small. However, the effect on the conformational equilibria of the open-chain precursors is very important. Overall, the stabilization of those conformation(s) in which the two reactive ends of the open-chain intermediate are located at short distances from each other with the correct orientation is the critical parameter defining the success of the macrocyclization. The best yield was found for the compound containing cyclohexylalanine, for which the computationally-predicted most stable conformer in the presence of Br(-) has a proper preorganization for cyclization. The remarkable agreement obtained between experiments and theory reveals that the computational approach here considered can be of great utility for the prediction of the behavior of other related systems and for the design of appropriate synthetic routes to new macrocyclic compounds.

ChemInform Abstract: Synthesis of 1‐Aryl‐4‐(3‐nitrophenylmethylene)‐6‐ [(1Z)‐2‐arylvinyl]‐3H‐1,3,5‐triazin‐2‐ones.

AbstractThe formation of title compounds (IV) is assumed to proceed via Michael type addition, followed by aminolysis of the oxadiazine to an unstable open chain intermediate which undergoes dehydrative cyclization to (IV).

Tin(iv) catalyzed d-galacturonic acid anomerization

A comparative kinetic study of anomerization between the four main forms (alpha/beta-pyranosides and alpha/beta-furanosides) of D-galacturonic acid (GalAH(2), 1) and tin(IV) complexed D-galacturonate ([Sn(CH(3))(2)(GalA)(H(2)O)(2)], 2) in D(2)O, is reported. Important differences are shown by pD vs. mutarotation rate profiles of 1 and 2. Coordination, in fact, causes: i) a spectacular increase of the rate due to kinetic template assistance of the carboxylic tail holding the metal in close proximity to the reactive centre and ii) a change in the dependence of the rate on the pD. Entropic and enthalpic factors contribute to the huge activation energy decrease in 2. Anomerization rates of the complexed ligand are determined by 2D-EXSY cross-peak integration. Analysis of up to twelve direct and reverse rate constants in the pD range 7.0-2.5 evidences ring size memory, and at least one reaction path which bypasses the aldehydo open chain intermediate. Solvent oxygen atom incorporation into the ligand is, at pH 4.5, about ten fold faster when catalyzed by the metal, and proves that the metal-assisted nucleophilic attack of water on the anomeric carbon atom cannot significantly contribute to mutarotation rates that are thousands of times faster.

The [C6H10]•+ Hypersurface: the Parent Radical Cation Diels−Alder Reaction

Various possible reaction pathways between ethene, 1, and butadiene radical cation (cis-, 2, trans-, 11) have been investigated at different levels of theory up to UCCSD(T)/DZP//UMP2(fc)/DZP and with density functional theory at B3LYP/DZP. A stepwise addition involving open chain intermediates and leading to the Diels−Alder product, the cyclohexene radical cation, 6, (path A) was found to have a total activation barrier ΔG298≠ = 6.3 kcal mol-1 and a change in free Gibbs energy, ΔG298, of −33.5 kcal mol-1. On the E° potential energy surface, all transition states are lower in energy than separated 1 + 2, the exothermicity ΔE = −45.6 kcal mol-1. A more direct path B could be characterized as stepwise with one intermediate only at the SCF level but not at electron-correlated levels and hence might actually be a concerted strongly asynchronous addition with a very small or no activation barrier (UCCSD(T)/DZP//UHF/6-31G* gives a ΔG298≠ of 0.8 kcal mol-1). The critical step for another alternative, the cyclobutanation−vinylcyclobutane/cyclohexene rearrangement, is a 1,3-alkyl shift which involves a barrier (ΔG298≠) only 1.7 kcal mol-1 higher than that of path A for both cis-, 2, (path C) and trans-butadiene radical cation, 11 (path D). However, from the 1 + 11 reactions, ring expansion of the vinylcyclobutane radical cation intermediate, 14, to a methylene cyclopentane radical cation, 16, (path E) requires an activation only 1.3 kcal mol-1 larger than for path D. While cis/trans isomerization of free butadiene radical cation requires a high activation (24.9 kcal mol-1), a reaction sequence involving addition of ethene (to stepwise give an open chain intermediate 13 and vinyl cyclobutane radical cation, 10) has a barrier of only 3.5 kcal mol-1 (ΔG298≠). This sequence also makes ethene and butadiene radical cations to exchange terminal methylene groups.

An efficient β-turn directed cyclization of simple peptidomimetics

Chiral polyaza[n]para- and metacyclophanes are easily assembled starting from the appropriate bis(bromomethyl)arene and diamides obtained from aminoacids and alkylidenediamines. The corresponding ortho-derivatives could not be obtained. Molecular dynamics calculations suggest that those results can be explained through the participation of a β-turn like structure in the open chain intermediate, which is only important for para- and meta-derivatives.

Semiempirical and ab initio transition state calculations for the transformation of N-acetyltetrazoles into corresponding 1,3,4-oxadiazoles

The transformation of 2-acetyl-5-substituted-tetrazoles into the corresponding 1,3,4-oxadiazoles was studied with the mopac semiempirical and gaussian ab initio methods. Two mechanisms, one with two transition states and the other with three, were elucidated by mopac. The first mechanism supported by PM3 and MNDO has a two-step, almost concerted, mechanism for the elimination of a nitrogen molecule from the tetrazole ring and formation of the oxadiazole product from an open-chain intermediate through carbon C 5 and acetyl oxygen bond formation. The second mechanism supported by AM1 and MINDO/3 breaks the elimination of the nitrogen molecule into two steps: first breaking the N 4-C 5 and then the N 2-N 3 bonds. Even when the AM1 and MINDO/3 transition state structures were optimized by PM3 and MNDO, the obtained transition states present only one bond breaking. The HF/STO-3G and HF/3-21G ab initio methods agree with the first mechanism where two bonds are breaking almost simultaneously. Despite the disagreement in the mechanism of the nitrogen elimination, the transition state that presents the product formation from open-chain intermediates is quite similar for all methods studied. The semiempirical calculation of this transition state is possible only if it is assumed that it has biradical character. The activation energies calculated by PM3 seem to be insensitive to the nature of the substituents.

Ring Contraction of a Cyclic Seven-membered Ketene Imine

A cyclic ketene imine prepared from 2,2,4,4-tetramethyl-3-thioxocyclobutanone S-methylide and 2,3-bis(trifluoromethyl) fumaronitrile rearranges to the isomeric thiolane. The high dependence of the rate on solvent polarity and the steric course are in accordance with an open-chain zwitterionic intermediate

Synthesis and properties of the cyclopentapeptide desthiomalformin

Desthiomalformin, cyclo- d-alanyl- d-alanyl- l-valyl- d-leucyl- l-isoleucyl, was synthesized by conventional methods. Cyclization of the open chain intermediate through the azide produced the cyclopentapeptide in short reaction time and in high yield and was not accompanied by cyclodimerization. The extreme readiness of the pentapeptide azide to form a cyclic structure can be attributed to the presence of alternating d and l residues in the sequence, a feature that should result in reverse turns stabilized by intramolecular hydrogen bonds. Thus the open chain intermediate could have a preferred cyclic conformation. Desthiomalformin has high thermal stability; it can be sublimed in vacuo without decomposition. It lacks, however, the biological activity of its parent compound, malformin.

Synthesen der Nonactinsäure

AbstractTwo stereoselective syntheses of nonactic acid I, the building block of the macrotetrolide antibiotic nonactin are described. The characteristic cis‐configuration of the 2,5‐substituents on the tetrahydrofuran ring of I is obtained in the first synthesis by catalytic hydrogenation of the furan derivative X. This key intermediate possesses the carbon skeleton and correct distribution of oxygen functions for conversin into nonactic acid. It is synthesized by an electrophilic substitution of 2‐acetonylfuran (VI) with the N‐cyclohexyl‐N‐propenyl nitrosonium ion (V) generated from the corresponding α‐chloronitrone (VII) and silver fluoroborate, followed by hydrolysis and oxidation of the aldehyde group.The second synthesis starts with a diol already having the correct configuration of the side chain that contains the hydroxyl group. For this purpose threo‐1‐octen‐5,7‐diol (XV) is synthesized from acetylacetone in two steps. Oxidative cleavage of the terminal double bond of this threo‐diol yields an aldehyde which is converted by a Wittig reaction, with the carbanion, obtained from diethyl α‐methoxycarbonylethyl phosphonate, into the open chain intermediate, 2‐methyl‐6,8‐dihydroxy‐2‐nonenoic acid methylester (XVIII). Base‐catalyzed cyclisation of this α,β‐unsaturated dihydroxy ester yields the methyl ester of nonactic acid (I) as the main product.

Formation of pyrazoles from 1,3,4-oxadiazolium salts

1,3,4-Oxadiazolium salts react with ethyl cyanoacetate in the presence of triethylamine to yield 1-substituted 3-aminopyrazole-4-carboxylic esters. An open-chain intermediate has been isolated and a mechanism is proposed involving initial attack at C-2 of the oxadiazole ring. The reaction was extended to the synthesis of 3-aminopyrazole-4-carbonitriles, ethyl pyrazole-4-carboxylates, 4-acylpyrazoles, and a 3-acetoxypyrazole from oxadiazolium salts and malononitrile, β-ketonic esters, β-diketones, and ethyl malonate, respectively. Application of these reagents to oxadiazolo[3,2-a]pyridinium salts gave derivatives of pyrazolo[1,5-a]pyridine.