A theoretical study of thermal [1,3]-sigmatropic rearrangements of 3-trimethylsilyl-1-pyrazoline: concerted vs. stepwise mechanisms

Possible reaction mechanisms of 1,3-silyl and 1,3-hydrogen thermal rearrangements of trimethylsilyl-1-pyrazoline and its model systems were theoretically explored using B3LYP, MP2, CR-CCSD(T), CASSCF(6,5), and MRMP2(6,5) theories. Nitrogen substitution at the center position of allylic moiety turned out to have a special stabilizing effect on diradical intermediates, allowing a stepwise pathway. This substitutional effect was attributed to the nitrogen lone pair electrons, which form strong pi-conjugations with diradicals. The second nitrogen substitution at the terminal allylic position selectively reduces the reaction barrier of antarafacial retention pathway, creating a competition between concerted and stepwise channels. The introduction of a five-membered ring imposes ring strain on the allylic moiety and increases steric hindrance, allowing no antarafacial channels. The combined effect of the nitrogen substitution and the five-membered ring further removes the possibility of concerted reaction pathways. Therefore 1,3-silyl migrations of 3-trimethylsilyl-1-pyrazoline were found to occur only through stepwise mechanisms, implying that the Woodward-Hoffmann rule is not operative. The 1,3-hydrogen migration also occur via a stepwise mechanism; however, it would not occur easily because its reaction barrier is much higher than that of 1,3-silyl migrations. Current study shows that a stepwise mechanism can be the dominant reaction pathway of some particular [1,3]-sigmatropic rearrangements.     

Ruthenium-catalyzed [1,n]-metallotropic shift (n = 3, 5) of alkynyl carbene complex intermediates

The ruthenium-catalyzed isomerization of diynes and triynes involving propargyl carboxylate moieties affords dienynes and dienediynes, respectively. The [1,n]-metallotropic shift (n = 3, 5) (carbene walk) of in situ generated alkynyl carbene complexes has been proposed for the catalytic isomerization reaction.     

The mechanism and regioselectivity of the ene reactions of nitroso compounds: a theoretical study of reactivity,regioselectivity, and kinetic isotope effects establishes a stepwise path involving polarized diradical intermediates

A theoretical study of the mechanisms of ene reactions of nitroso compounds has been completed, using UB3LYP, CASPT2, UCCSD(T) and UQCISD(T) methods. Stepwise paths through polarized diradical intermediates are always preferred. These intermediates have unusual properties, involving high rotational barriers about formally single bonds, which permit them to maintain stereochemical relationships. The diradicals may exchange the RNO moiety between the two ends of the alkene via an aziridine N-oxide. The aziridine N-oxide cannot be accessed directly from reactants and cannot lead directly to ene products. It is therefore an innocent by-stander in the way proposed by Singleton for the aziridinium imide in the ene reactions of triazolinediones. A detailed analysis of the electronic structure of the polarized diradicals is given. The kinetic isotope effects measured in a Stephenson isotope effect test have been reproduced. These kinetic isotope effects are consistent with a mechanism in which partitioning of the polarized diradical between cyclization to an aziridine N-oxide and H-abstraction to ene product takes place, and in which the formation of the polarized diradical is to some extent reversible. Finally, calculated regioselectivities reproduce those observed experimentally.     

Studies on alkylation of bicyclo[2.2.2]octenones and 3,3-sigmatropic shift: synthesis of advanced cis-decalins

A stereoselective method for alkylation of bicyclo[2.2.2]octenones and their 3,3-sigmatropic shift leading to cis-decalins containing various types of appendages is described. A simple and convenient method for the introduction of a butenyl chain onto the bicyclooctenones employing 1,4-dibromobutane as an equivalent of 4-bromobutene, was developed.     

Mechanistic twist of the [8+2] cycloadditions of dienylisobenzofurans and dimethyl acetylenedicarboxylate: stepwise [8+2] versus [4+2]/[1,5]-vinyl shift mechanisms revealed through a theoretical and experimental study

Recently, it was reported that both dienylfurans and dienylisobenzofurans could react with dimethyl acetylenedicarboxylate (DMAD) to give [8+2] cycloadducts. Understanding these [8+2] reactions will aid the design of additional [8+2] reactions, which have the potential for the synthesis of 10-membered and larger carbocycles. The present Article is aimed to understand the detailed mechanisms of the originally reported [8+2] cycloaddition reaction between dienylisobenzofurans and alkynes at the molecular level through the joint forces of computation and experiment. Density functional theory calculations at the (U)B3LYP/6-31+G(d) level suggest that the concerted [8+2] pathway between dienylisobenzofurans and alkynes is not favored. A stepwise reaction pathway involving formation of a zwitterionic intermediate for the [8+2] reactions between dienylisobenzofurans that contain electron-donating methoxy groups present in their diene moieties and DMAD has been predicted computationally. This pathway is in competition with a Diels-Alder [4+2] reaction between the furan moieties of dienylisobenzofurans and DMAD. When there is no electron-donating group present in the diene moieties of dienylisobenzofurans, the [8+2] reaction occurs through an alternative mechanism involving a [4+2] reaction between the furan moiety of the tetraene and DMAD, followed by a [1,5]-vinyl shift. This computationally predicted novel mechanism was supported experimentally.     

Phase transfer catalysis in N-alkylations of the pharmaceutical intermediates 5H-dibenz[b,f]azepine and 5H-10,11-dihydrodibenz[b,f]azepine

The two title compounds were alkylated under very mild phase-transfer-catalysis conditions. Differences in reactivities of the two heterocyclic nucleophiles, and in the reactivities of various alkyl halides are discussed.     

A DFT study of the thermal, orbital symmetry forbidden, cyclophanediene to dihydropyrene electrocyclic reaction. Predictions to improve the dimethyldihydropyrene photoswitches

The orbital symmetry forbidden thermal electrocyclic equilibria between a series of cyclophanedienes and dimethyldihydropyrenes (CPD<==>DDPs) were studied using density functional theory (DFT). These reactions are important not only because of their fundamental interest but also in how they restrict the potential utility of the DDP photoswitches by limiting the thermal lifetime of the CPDs. The transition states (TSs) for these reactions could not be modeled using restricted DFT (RB3LYP) but were located using unrestricted DFT (UB3LYP). Each TS possesses significant biradical character as indicated by their spin contaminated wave functions, S2 not = 0. Specific substitution by nitrile or trifluoromethyl group(s) is predicted to strongly affect the magnitude of the activation barriers for these reactions. In particular, replacing the internal methyl groups of the CPDs/DDPs with nitrile groups is predicted to have the maximum effect and to raise the activation barriers and lifetimes of the CPDs considerably.     

Development of a new Lewis acid-catalyzed [3,3]-sigmatropic rearrangement: the allenoate-Claisen rearrangement

A new Lewis acid-catalyzed Claisen rearrangement has been developed that allows the stereoselective construction of beta-amino-alpha,beta,epsilon,zeta-unsaturated-gamma,delta-disubstituted esters from simple allylic amines and allenoate esters. This reaction, which is contingent upon the use of Lewis acid, can be conducted with a range of metal salts (Yb(OTf)3, AlCl3, Sn(OTf)2, Cu(OTf)2, MgBr2.Et2O, FeCl3, Zn(OTf)2) with catalyst loadings as low as 5 mol %. This catalytic process provides access to a diverse range of beta-amino-alpha,beta,epsilon,zeta-unsaturated-gamma,delta-disubstituted esters in high yield and with excellent levels of diastereoselectivity for a series of allyl pyrrolidines (R1 = H, Me, i-Pr, Ph, NR2 = pyrrolidine, piperidine, NMe2; >/=81% yield, >/=94:6 syn:anti) and allenoate esters (R2 = H, Me, i-Pr, Ph, allyl, NPht, Cl; >/=75% yield, >/=91:9 syn:anti). The capacity of this new Claisen rearrangement to provide catalytic access to elusive structural motifs has also been demonstrated in the stereospecific formation of quaternary carbon bearing frameworks arising from geranyl- and neryl pyrrolidine (>/=93% yield, >98:2 dr).     

Thermal rearrangement of 3H-pyrroles by competitive [1,5]-sigmatropic shifts,and the reversibility of the 3H- to 2H-pyrrole interconversion

3-Ethoxycarbonyl-3H-pyrroles are converted via thermal (l,5]-ester shifts to the isomeric lH-pyrrole-4- and N-esters. Isolable intermediate 2H-pyrroles are converted into the same products, and also into the 3H-pyrroles, demonstrating conclusively the reversibility of the 3H- to 2H-pyrrole interconversion.     

Concerted rearrangement versus heterolytic cleavage in anionic [2,3]- and [3,3]-sigmatropic shifts. A DFT study of relationships among anion stabilities,mechanisms, and rates

The anionic [2,3] sigmatropic Wittig rearrangements of deprotonated 4-hetera-1-pentenes and the anionic [3,3] sigmatropic Cope rearrangements of 3-substituted-1,5-hexadienes were explored by using density functional theory calculations. While the deprotonated anionic 3-hydroxy-1,5 hexadiene (2a), 3-thiohydroxy-1,5-hexadiene (2c), and 3-formamidyl-1,5-hexadiene (2d) Cope substrates undergo concerted rearrangements, the deprotonated anionic 3-amino-1,5-hexadiene (2b) and 3-methyl-1,5-hexadiene (2e) Cope substrates follow nonconcerted cleavage/recombination pathways. We have also found that the gas-phase Wittig (1a), aza-Wittig (1b), and carba-Wittig (1c) reactions proceed via nonconcerted cleavage/recombination pathways. These results are compared with previous results on the Cope rearrangements of deprotonated anionic 3-hydroxy-1,5-hexadiene and 3-amino-1,5-hexadiene anions. A previously established model that heterolytic and homolytic bond dissociation energies can be used to predict how anionic amino- and oxy-Cope substrates will react is generalized to account for the reactivity of other Cope substrates as well as for the Wittig rearrangements. There is also a relationship between the basicity of the anionic substituent in the Cope rearrangement and the reaction pathway: the more basic the substituent anion, the less stable it is, and the more likely it is that cleavage will occur. A first step toward studying these reactions in solution was also taken by calculating energetics for some of the rearrangements with a lithium counterion present.     

Designing an Apparently Orbital-Symmetry-Forbidden [3s,5s]-Sigmatropic Shift through Transition-State Complexation and Stereoelectronic Effects

The [3s,5s]-sigmatropic shift is an example of an orbital-symmetry forbidden pericyclic reaction that is outcompeted by the allowed [3s,3s]-sigmatropic shift. Density functional theory calculations are used to show that Pd^II-complexed systems with strategically placed substituents engaging in key stereoelectronic effects can select for the [3s,5s] process, thereby outcompeting both orbital-symmetry-allowed [3s,3s]- and [3s,5a]-shifts.     

Synthesis of thiopyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines

<正>Reactions of the 6-hydroxy-thiopyrano[3,4-c]pyridine-5-carbonitrile derivative 1 withα-halo-carbonyl compounds gave the ortho-substituted intermediates 2a-c which were converted into furo[2,3-b]thiopyrano[4,3-d]pyridines 3a-c by fusion of a furan moiety under basic conditions.Further cyclization of 3a-c led to a fusion of a pyrimidine ring,yielding the tetracyclic products 6,7 and 8.In addition,condensation of 6 with various aromatic aldehydes afforded the corresponding imines 9a,b.Mannich reaction of 7 gave products 10a,b.     

PMO[KIT-5]-n: synthesis of highly ordered three-dimensional periodic mesoporous organosilicas with Fm3m symmetry

Divalent surfactant [CH3(CH2)15N(CH3)2(CH2)3N(CH3)3]2+ - 2Br- (C16-3-1) was used as a structure directing agent (SDA) for the synthesis of highly ordered periodic mesoporous organosilicas (PMOs) with cubic Fm3m symmetry from 1,2-bis(triethoxylsilyl)ethane (BTEE) under basic conditions.     

Barrier to 1,3-sigmatropic shift in odd electron ions. A MINDO/3 study of H,OH, CH3 and C6H5 migration

Critical energies for 1,3-R sigmatropic migrations (R?H, OH, CH₃ and C₆H₅) have been calculated by means of the MINDO/3 method. This investigation was carried out for the system [RCH₂CH?CH₂]^+˙ and the results indicated that hydroxyl group migration is energetically favoured (critical energy = 53 kJ mol^?1). Calculations are also presented for [3-buten-2-ol]^+˙ isomerizations. The lowest energy pathway is related to the [2-buten-1-ol]^+˙; the corresponding critical energy for OH migration is equal to 33 kJ mol^?1 in this case.     

Broken orbital symmetry and the description of valence hole states in the tetrahedral [CrO4]2− anion

The localization of ligand-based valence holes in the tetrahedral complex ion [CrO₄]^2? in a crystalline environment is studied by SCF calculations on the hole states, with progressively less restrictions on the spatial symmetry of the molecular orbitals. The final wavefunctions are obtained by constructing, from the symmetry broken SCF solutions, wavefunctions that exhibit again the proper transformation properties under the operations of T _d . The crystal environment of the [CrO₄]^2? anion is represented by a point charge model. In contrast with the situation for core hole states, the projection afterwards into T _d symmetry is important. The final ionization energies, which are obtained from projected C _3v adapted SCF solutions, are reduced considerably (?3 eV) with respect to the T _d ΔSCF results, but the ordering of the states has not changed essentially. The calculated ionization energies compare favourably with results of XPS experiments on Na₂CrO₄. The evaluation of the energies of projected symmetry broken SCF solutions requires the calculation of hamiltonian matrix elements between determinantal wavefunctions built from mutually non-orthogonal orbital sets. An efficient method for the calculation of such matrix elements is presented.     

Unexpected reactions of [60]fullerene involving tertiary amines and insight into the reaction mechanisms

Thermal reactions of [60]fullerene with amino acid ester hydrochlorides and triethylamine in o-dichlorobenzene at reflux afforded pyrrolidinofullerene derivatives containing the CH(3)CH moiety and originating from triethylamine through an unusual C-N bond cleavage. Detailed investigation of these thermal reactions resulted in the discovery of unprecedented reactions between C(60) and tertiary amines and of reactions of C(60) with tertiary amines and aldehydes, giving cyclopentafullerene derivatives with high stereoselectivity. Plausible reaction mechanisms for the product formation involving the uncommon C-N bond cleavage of tertiary amines were proposed on the basis of extensive experimental results.     

Interplay of orbital symmetry and nonstatistical dynamics in the thermal rearrangements of bicyclo[n.1.0]polyenes.

CASSCF and CASPT2 calculations have been carried out on some of the thermal rearrangements of bicyclo[2.1.0]pentene (BCP), bicyclo[4.1.0]hepta-2,4-diene (BCH), bicyclo[6.1.0]nona-2,4,6-triene (BCN), and 9,9-dicyanobicyclo[6.1.0]nona-2,4,6-triene (DCBCN). In addition, experiments have been conducted to determine the stereoselectivity and temperature dependence of the nondegenerate rearrangement of 9,9-dicyanobicyclo[6.1.0]nona-2,4,6-triene-exo-15N. The calculations and experiments allow a consistent picture to be drawn for these reactions. The principal conclusions are as follows. (1) The ring-walk rearrangements of BCP, BCN, and DCBCN are pericyclic reactions occurring with a strong preference for inversion of configuration at the migrating carbon. However, the ring-walk rearrangement of BCH is a nonpericyclic reaction. (2) The rearrangement of DCBCN to 9,9-dicyanobicyclo[4.2.1]nona-2,4,7-triene occurs with a preferred stereochemistry corresponding to a 1,3 migration with retention. However, this reaction is not a pericyclic process; the stereoselectivity is probably of dynamic origin. (3) Cyano substituents can significantly reduce the activation energy for a reaction occurring via a singlet biradical, but they do not necessarily cause the intermediate to sit in a deeper local minimum on the potential energy surface.