Density functional studies on the Pauson--Khand reaction.

The Pauson--Khand reaction represents a one-step Co(2)(CO)(8)-catalyzed synthesis of cyclopentenone through [2 + 2 + 1] assembly of one molecule each of alkene, alkyne, and carbon monoxide. Density functional studies (B3LYP/631LAN) on the reaction pathway of the Pauson--Khand (PK) reaction reported here for the first time provides valuable information on the structures and energetics of various intermediates and transition states. The PK reaction consists of olefin insertion, CO insertion, and reductive elimination steps. The olefin insertion step was found to be an irreversible step that determines the stereo- and regiochemistry of the overall reaction. The following steps are low activation energy processes and reversible. The bond-forming events occur only on one of the two metal atoms, while the second metal atom not only acts as an anchor that fixes the metal cluster to the organic substrate but also exerts electronic influences on the reaction at the first atom.     

Study of the reaction between 1,5-naphtalene diisocyanate and polycaprolactone in different solvents

The reaction between polycaprolactone and 1,5-naphtalene diisocyanate has been investigated in solvents with different dielectric constants and hydrogen bonding powers (toluene, ethyl acetate, ethyl methyl ketone), and in the same solvents with the addition of a catalytic amount of dimethyl sulfoxide (DMSO). The reaction was considered to proceed over two steps, the reaction of the first NCO group being faster. The course of the reaction was measured by titration of the unreacted NCO groups, ¹H- and ¹³C-NMR spectroscopy, and size exclusion chromatography. By titration only the overall reaction order and reaction rate constants could be determined. DMSO accelerated the reaction in all three solvents, which was explained by the stabilization of the activation complex by DMSO. Both steps of the reaction could be specified by NMR spectroscopy. The ratio between the reaction rate constants for the first and the second step decreased with the increased hydrogen bonding strength of the solvent and with DMSO. By SEC only the reaction of the first NCO group could be determined due to the low resolution for higher molar mass reaction products with a broad distribution. The values obtained for the first step reaction rate constants were in good agreement with NMR values. © 1995 John Wiley & Sons, Inc.     

About the Leuckart reaction of chiral 2-norbornanones bearing electron-withdrawing groups: reaction of bridgehead triflates and triflamides

The mechanism of the Leuckart reaction of 3,3- and 7,7-dimethyl-2-oxo-1-norbornyl triflates and triflamides, synthesised by us starting from (1R)-camphor and (1R)-fenchone, has been studied. Strikingly, the electron-withdrawing capacity of the bridgehead substituents has demonstrated not to be enough to control the Wagner-Meerwein rearrangement during the course of the reaction, so that only both enantiomers of a 3,3-dimethylnorbornanediamine derivative have been obtained as final products. As a result, the total synthesis of these interesting chiral compounds has been optimised and shortened until three overall steps starting from (1R)-fenchone.     

Enantiospecific total synthesis of the sarpagine related indole alkaloids talpinine and talcarpine as well as the improved total synthesis of alstonerine and anhydromacrosalhine-methine via the asymmetric Pictet-Spengler reaction

The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has been accomplished from D-(+)-tryptophan in 13 steps (11 reaction vessels) in 10% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3and anhydromacrosalhine-methine 4 in 12% and 14% overall yield, respectively. A convenient synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (-)-N(a)-H, N(b)-benzyl tetracyclic ketone 15a via the asymmetric Pictet-Spengler reaction on a multihundred-gram scale has been developed. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and the intramolecular rearrangement to form ring-E and an N(b)-benzyl/N(b)-methyl transfer reaction also served as key steps. This general approach can now be utilized for the synthesis of macroline/sarpagine related indole alkaloids and their antipodes for biological screening.     

Synthesis of the dysiherbaine tetrahydropyran core employing a tethered aminohydroxylation reaction

A stereocontrolled and scalable synthesis of an advanced intermediate of the dysiherbaine tetrahydropyran core has been achieved in 11 steps and 27% overall yield. The key feature of this synthetic approach is the application of the Donohoe tethered aminohydroxylation reaction to install the amino diol and establish the four contiguous syn stereocenters on the tetrahydropyran ring.     

De novo synthesis of oligosaccharides using a palladium-catalyzed glycosylation reaction

The natural all d- and/or unnatural all l-1,4- and 1,6-oligosaccharides were synthesized from furan alcohols using a palladium-catalyzed glycosylation reaction. The 1,4- and 1,6-alpha-manno-disaccharides were achieved in seven total steps starting from chiral furan alcohols. Similarly, 1,4- and 1,6-alpha-manno-trisaccharides were also synthesized in nine total steps. Key to the overall efficiency of this process was the use of highly diastereoselective palladium-catalyzed glycosylations, reductions, and dihydroxylations.     

New synthetic strategy for preparation of the anticoagulant drug Rivaroxaban via an asymmetric Henry reaction

A new synthetic approach towards the anticoagulant drug (S)-Rivaroxaban was described. This reaction sequence involved six steps overall, starting from commercially available and inexpensive N-(4-aminophenyl)morpholin-3-one. The stereogenic centre was introduced by an asymmetric Henry reaction catalysed by the complex of copper(II) acetate and (2R,5S)-2-(pyridine-2-yl)imidazolidine-4-one with 87% ee. The individual reaction steps proceeded with high yields and did not require any unusual or expensive reagents.     

Total synthesis of (+)-acanthodoral by the use of a Pd-catalyzed metal-ene reaction and a nonreductive 5-exo-acyl radical cyclization

[reaction: see text] The first total synthesis of the antibiotic acanthodoral (1) has been achieved from 3-methyl-2-cyclohexen-1-one in 19 steps in 2.1% overall yield. The synthesis features the use of a Pd-ene reaction in the presence of CO to form the endocyclic alkene 8, a nonreductive acyl radical cyclization reaction, and a ring contraction reaction by the Wolff rearrangement. (+)-Acanthodoral has also been synthesized starting from (+)-S-2,2-dimethyl-6-methylenecyclohexanecarboxylic acid.     

An interpretation of the kinetics of ethylene oxidation over silver based on separate studies of kinetics of the reaction steps

The kinetics of the separate reaction steps, corresponding to the stepwise redox mechanism of ethylene oxidation over silver, was studied. The results are used for the interpretation of the kinetics of overall catalytic reactions by taking into account an influence of the adsorption of oxygen on the surface properties of silver.     

气相芳香亲电取代反应研究进展

对气相芳香亲电取代反应的一般机理、小碎片正离子的亲电取代反应特性、反应中间体结构及质子在芳香环内和芳香环间的迁移反应作了评述。     

Total synthesis of (-)-martinellic acid via radical addition-cyclization-elimination reaction

The asymmetric total synthesis of martinellic acid, the first pyrrolo[3,2-c]quinoline alkaloid found in nature, is described. Three key steps in our synthesis of (-)-martinellic acid are the Bu(3)SnH-promoted radical addition-cyclization-elimination (RACE) reaction of an oxime ether with an alpha,beta-unsaturated ester to generate the pyrrolo[3,2-c]quinoline core, a chemoselective lactam carbonyl reduction, and guanidinylation under Mitsunobu reaction conditions. The key radical cyclization has also been investigated by using SmI(2). (-)-Martinellic acid was synthesized from commercially available methyl 4-bromo-3-methylbenzoate in fewer steps than previous syntheses and in an improved overall yield.     

Synthesis of (+)-sch 642305 by a biomimetic transannular Michael reaction

[reaction: see text] The synthesis of (+)-Sch 642305 (1) has been completed in 17 steps in 1.6% overall yield. Transannular Michael reaction of 2b with NaH in THF provided cyclohexenone 23 stereospecifically. Heating 23 in TFA/CDCl(3) provided a 3:1 equilibrium mixture of 23 and 25, which was hydrolyzed to give (+)-6-epi-Sch 642305 (24) and (+)-Sch 642305 (1), respectively.     

A concise total synthesis of (+/-)-alantrypinone by a novel hetero-Diels-Alder reaction

[reaction: see text] An efficient total synthesis of (+/-)-alantrypinone (1) and its 17-epi isomer (17) has been accomplished employing a novel aza-Diels-Alder reaction as the key step. The reaction sequence comprises 8 steps starting from anthranilic acid and proceeds in 13.5% overall yield. An interesting anionic equilibration between 1 and its epimer 17 has also been discovered.     

An efficient sequential reaction process to polysubstituted indolizidines and quinolizidines and its application to the total synthesis of indolizidine 223A

The reaction of iodides 1 with delta-chloropropylamines 5 in MeCN assisted with K2CO3 undergoes a sequential S(N)2/Michael addition/SN2/SN2 reaction process to give polysubstituted indolizidines and quinolizidines. Using this method, indolizidine 223A is synthesized from 2-ethyl-2-hexenoic acid in 12 linear steps and 14.5% overall yield. [Reaction: see text]     

Kinetics of the reaction of atomic fluorine with phosphorous trifluoride: ESR determination

The reaction rate constant of the addition of atomic fluorine to excess PF₃ was determined by fast flow ESR measurements to be (8.6 ± 0.6) × 10¹² cm³ mole^?1 s^?1 at 300 K. The stoichiometry of the overall reaction of F with PF₃ was 2:1. Finite difference calculations simulating several reaction mechanisms suggest that the reaction occurs in two consecutive addition steps, F + PF₃ = PF₄ and F + PF₄ = PF₅. Assuming this mechanism is correct, the rate constant for the second reaction would be approximately (1.2 ± 0.2) × 10¹³ cm³ mole^?1 s^?1.     

Kinetic isotope effects in complex reaction networks: formic acid electro-oxidation.

The determination of kinetic isotope effects (KIEs) for different reaction pathways and steps in a complex reaction network, where KIEs may affect the overall reaction in various different ways including dominant and minority pathways or the buildup of a reaction-inhibiting adlayer, is demonstrated for formic acid electrooxidation on a Pt film electrode by quantitative electrochemical in situ IR spectroscopic measurements under controlled mass-transport conditions. The ability to separate effects resulting from different contributions--which is not possible using purely electrochemical kinetic measurements--allows conclusions on the nature of the rate-limiting steps and their transition state in the individual reaction pathways. The potential-independent values of approximately 1.9 for the KIE of formic acid dehydration (CO(ad) formation) in the indirect pathway and approximately 3 for the CO(ad) coverage-normalized KIE of formic acid oxidation to CO2 (direct pathway) indicate that 1) C-H bond breaking is rate-limiting in both reaction steps, 2) the transition states for these reactions are different, and 3) the configurations of the transition states involve rather strong bonds to the transferred D/H species, either in the initial or in the final state, for the direct pathway and--even more pronounced--for formic acid dehydration (CO(ad) formation).     

Procedures for a fast separation of berkelium from complex mixtures of reaction products

Two procedures are described for fast separations of berkelium from complex mixtures of reaction products arising from heavy ion reactions, such as¹⁸O+²⁴⁸Cm. The first procedure uses a combination of several extraction steps with a final separation on a cation exchanger, the second procedure starts with an anion exchange column which is followed by multiple extractions in different media. The elements separated in the different steps were analyzed and overall decontamination factors are given.     

Multiple rate-determining steps for nonideal and fractal kinetics

We show that the kinetic model of a single rate-determining step in a reaction mechanism can be extended to systems with multiple overall reactions for which the elementary reactions obey nonideal or fractal kinetics. The following assumptions are necessary: (1) The system studied is either closed or open, but no constraints exist preventing the evolution toward equilibrium. (2) Elementary reactions occur in pairs of forward and backward steps. (3) The kinetics of the elementary steps are either nonideal or fractal and are compatible with equilibrium thermodynamics. (4) The number of reaction routes is identical with the number of rate-determining steps. If these hypotheses are valid, then the overall reaction rates can be explicitly evaluated: they have a form similar to the kinetic equations for the elementary reactions and the apparent reaction orders and fractal coefficients can be expressed analytically in terms of the kinetic parameters of the elementary reactions. We derive a set of relationships which connect the equilibrium constants of the reaction routes, the corresponding overall rate coefficients, and the stoichiometric numbers of the rate-determining steps. We also derive a set of generalized Boreskov relations among the apparent activation energies of the forward and backward overall processes, the corresponding reaction enthalpies, and the stoichiometric coefficients of the rate-determining steps. If the elementary reactions obey fractal kinetics, the same is true for the rate-determining steps. The fractal exponents of the forward and backward overall reactions are linear combinations of the fractal exponents of the fractal elementary reactions. Similar to the theory of single rate-determining steps, our approach can be used for selecting suitable reaction mechanisms from experimental data.     

Automated derivation of reaction rules for the EROS 6.0 system for reaction prediction

The purpose of the EROS 6.0 system is to predict the products of chemical reactions and to model reaction mechanisms. This is accomplished by elementary reaction steps that are selected through the rules that constitute the knowledge base of the EROS 6.0 system. These rules are derived by methods of machine learning. The learning process is based on reaction in data bases. An overview of the EROS 6.0 system is given and the structure of the knowledge as well as the generation of reaction rules are described.     

Synthesis of porphobilinogen via a novel ozonide cleavage reaction

Porphobilinogen lactam methyl ester (3a) has been prepared in seven steps, and approximately 20-30% overall yield, beginning with furfurylamine (4a).(24) Hydrolysis of 3a following the literature procedure then gave porphobilinogen (1). A key intermediate in our synthesis of 3a is the 7-oxonorbornene derivative 7a, which was derived from 4a utilizing a tandem Johnson ortho ester Claisen rearrangement followed by intramolecular Diels-Alder cyclization (five steps, 55-65%).(24) Interesting steric accelerating effects were observed in this sequence. Conversion of 7a to 3a was then accomplished employing a novel ozonide cleavage/oxidation reaction, which generated tetrahydrofurans 16a, 32, and 33 in the proper oxidation state for direct aminolysis to pyrrole 3a. A mechanism is proposed for the ozonide cleavage/oxidation that accounts for the observed stereoselectivity of this step.