Synthesis of functionalised cyclohexadienes through addition of lithiated phosphine borane complexes to benzonitriles

Functionalised 1,3- and 1,4-cyclohexadienes have been prepared through dearomatisation of benzonitriles by sequential conjugate addition of -lithium alkyl(diphenyl)phosphine borane in the presence of HMPA and capture of the intermediate anion with protonating and alkylating reagents.     

Highly enantioselective reaction of lithiated N-Boc-thiazolidine: a new chiral formyl anion equivalent

Reaction of lithiated N-Boc-thiazolidine with various aldehydes in the presence of (-)-sparteine afforded the products with up to 93% ee. The reaction was confirmed to proceed through a dynamic thermodynamic resolution pathway. Each diastereomeric alcohol could be converted to the corresponding optically active 1,2-ethanediols.     

Synthesis of polycyclic benzonitriles via a one-pot aryl alkylation/cyanation reaction

A norbornene-mediated palladium-catalyzed tandem alkylation/cyanation sequence is described in which an alkyl-aryl bond and a nitrile-aryl bond are formed in one pot. A variety of sterically hindered, five-, six-, and seven-membered ring benzonitriles were synthesized in good yields from easily accessible starting materials.     

An unexpected pathway of the reaction of lithiated 1,1-dimethylallene with isopropyl isothiocyanate

The reaction of lithiated 1,1-dimethylallene with isopropyl isothiocyanate gives 3a,4,5,5a-tetrahydro-4,4,5a-trimethyl-2-methylthio-3H-cyclobuta[b]pyrrole resulting from cyclization of the intermediate 2,7-dimethyl-4-methylthio-3-azaocta-2,4,6-triene. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 865–867, April, 1997.     

Electrolyte-concentration and ion-size dependence of excited-state intramolecular charge-transfer reaction in (alkylamino)benzonitriles: steady-state spectroscopic studies

Steady-state spectroscopic studies have been performed with three intramolecular charge-transfer molecules, 4-(1-azetidinyl)benzonitrile (P4C), 4-(1-pyrrolidinyl)benzonitrile (P5C), and 4-(1-piperidinyl)benzonitrile (P6C), in ethyl acetate and acetonitrile in presence of lithium perchlorate (LiClO(4)) at room temperature to investigate the effects of electrolytes on excited-state intramolecular charge-transfer reaction. Electrolyte-concentration and ion-size dependences of several spectroscopic properties such as quantum yield, absorption and emission transition moments, radiative and nonradiative rates, and changes in reaction free energies associated with LE --> CT conversion have been determined for these molecules and reported. For P4C, quantum yield decreases by a factor of approximately 7 at the highest electrolyte concentration relative to that in pure ethyl acetate whereas it is a factor of approximately 4 for both P5C and P6C. However, in acetonitrile with 1.0 M LiClO(4), quantum yield reduces to almost half of that in the pure solvent. Formation of a charge-transfer (CT) state is found to be strongly favored over the locally excited (LE) state as the electrolyte (LiClO(4)) concentration is increased, electrolyte effects being more pronounced in ethyl acetate than in acetonitrile. Relative to pure ethyl acetate, reaction free energy change (-DeltaG(r)) increases by a factor of approximately 5, approximately 4, and approximately 2 for P4C, P5C, and P6C, respectively, at 2.5 M LiClO(4) in this solvent. -DeltaG(r) for P4C exhibits a change in sign (from negative to positive) upon addition of electrolyte in ethyl acetate. In acetonitrile, however, these changes are within a few percent, except for P4C where it is about 4 times greater at 1.0 M LiClO(4) than that in pure acetonitrile. The electrolyte-induced total red shift of the CT band of these TICT molecules is 3 times higher in ethyl acetate than in acetonitrile. Although both the quantum yield and CT emission peak frequency decrease linearly with the increase in ion size, -DeltaG(r) remains largely insensitive. Further studies using a nonreactive probe (coumarin 153) in concentrated electrolyte solutions also show qualitatively similar results.     

Electrolyte-concentration and ion-size dependence of excited-state intramolecular charge-transfer reaction in (alkylamino)benzonitriles: time-resolved fluorescence emission studies

Time-resolved studies with three intramolecular charge-transfer molecules 4-(1-azetidinyl)benzonitrile (P4C), 4-(1-pyrrolidinyl)benzonitrile (P5C), and 4-(1-piperidinyl)benzonitrile (P6C) in ethyl acetate in presence of LiClO(4) indicate that the average reaction time for LE --> CT conversion increases at low electrolyte concentration and then decreases to become comparable and even lower than that in the pure solvent. Except for Mg(2+), the average reaction time decreases linearly with the ion size in perchlorate solutions of ethyl acetate. The observed electrolyte-concentration dependence of the average reaction time for these molecules agrees well with the predictions from the theory of Zwan and Hynes [Chem. Phys. 1991, 152, 169] in the broad barrier overdamped limit with barrier frequency, omega(b) approximately 2 x 10(12) s(-1).     

Synthetic approach to substituted cyclopropanes based on the coupling reaction of lithiated chloroalkyloxazolines with Fischer carbene complexes

Regioselective addition of lithiated oxazoline 2a, easily available from 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline 1a (LDA, THF, -98 degrees C), to alpha,beta-unsaturated Fischer carbene complexes 3 afforded cyclopropylcarbene complexes 4 as sole diastereoisomers. Exposure of carbene complexes 4a-c (M = Cr) to air and sunlight gave cyclopropane carboxylate derivatives 5a-c. A plausible mechanistic explanation is proposed. Moreover, when lithiated oxazoline 2b was generated from 1b in the presence of the carbene complex 3a,b, the oxazolinylcyclopropane carboxylates 6a,b formed as a 1:1 mixture of diastereoisomers. Chiral lithiated oxazoline 2c added regioselectively and diastereoselectively to chromium complexes 3a,b and to tungsten complexes 3d,e, leading, after oxidation of the metal fragment, to esters 7a,b with good diastereoselectivity (dr = 4:1). The reaction of lithiated oxazoline 2d with chromium complex 3b and tungsten complex 3e proceeded less diastereoselectively, furnishing, in both cases, after oxidation, the ester 7c as a 3:2 diastereoselective mixture.     

Structural and rate studies of the 1,2-additions of lithium phenylacetylide to lithiated quinazolinones: influence of mixed aggregates on the reaction mechanism

The 1,2-addition of lithium phenylacetylide (PhCCLi) to quinazolinones was investigated using a combination of structural and rate studies. (6)Li, (13)C, and (19)F NMR spectroscopies show that deprotonation of quinazolinones and phenylacetylene in THF/pentane solutions with lithium hexamethyldisilazide affords a mixture of lithium quinazolinide/PhCCLi mixed dimer and mixed tetramer along with PhCCLi dimer. Although the mixed tetramer dominates at high mixed aggregate concentrations and low temperatures used for the structural studies, the mixed dimer is the dominant form at the low total mixed aggregate concentrations, high THF concentrations, and ambient temperatures used to investigate the 1,2-addition. Monitoring the reaction rates using (19)F NMR spectroscopy revealed a first-order dependence on mixed dimer, a zeroth-order dependence on THF, and a half-order dependence on the PhCCLi concentration. The rate law is consistent with the addition of a disolvated PhCCLi monomer to the mixed dimer. Investigation of the 1,2-addition of PhCCLi to an O-protected quinazolinone implicates reaction via trisolvated PhCCLi monomers.     

Catalytic antibodies for complex reactions: hapten design and the importance of screening for catalysis in the generation of catalytic antibodies for the NDA/CN reaction

Success in generating catalytic antibodies as enzyme mimics lies in the strategic design of the transition-state analog (TSA) for the reaction of interest, and careful development of screening processes for the selection of antibodies that are catalysts. Typically, the choice of TSA structure is straightforward, and the criterion for selection in screening is often binding of the TSA to the antibody in a microtiter-plate assay. This article emphasizes the problems of TSA design in complex reactions and the importance of selecting antibodies on the basis of catalysis as well as binding to the TSA. The target reaction is the derivatization of primary amines with naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide ion. The desired outcome is selective catalysis of formation of the fluorescent derivative in preference to nonfluorescent side-products. In the study, TSA design was directed toward the reaction branch leading to the fluorescent product. Here, we describe a microtiter plate-based assay that is capable of detecting antibodies showing catalytic activity at an early stage. Of the antibodies selected, 36% showed no appreciable binding to any of the substrates tested, but did show catalytic activity in derivatizing one or more of the amino acids screened. In contrast, only two out of 77 clones that showed binding did not show catalysis. Thus, in this complex system, observation of binding is a good predictor of the presence of catalytic activity, and failure to observe binding is a poor predictor of the absence of catalytic activity.     

HMPA promotes retro-aldol reaction, resulting in syn-selective addition of lithiated 1-naphthylacetonitrile to aromatic aldehydes

In HMPA-THF solution, lithiated 1-naphthylacetonitrile undergoes highly syn-selective addition to aromatic aldehydes, providing the first access to such syn-aldols. Syn-selectivity is also observed with two other arylacetonitriles. Aldolate equilibration and crossover experiments demonstrate that HMPA promotes retro-aldol reaction and that aldol diastereoselectivity under these conditions is thermodynamically controlled.     

The generation of gem-difluoroallyllithium by the transmetalation reaction

3,3-Difluoroallyltrimethyltin was prepared by reaction of chlorodifluoromethane with the ylide reagent Ph₃PCHCH₂SnMe₃$\text{gem}$-Difluoroallyllithium, which was generated by the reaction of $\text{n}$-butyllithium with 3,3-difluoroallyltrimethyltin in THF at ?95°, was of very limited stability at that temperature. However, $\text{in}$$\text{situ}$ procedures and alternate incremental addition procedures allowed its application in the synthesis of 1,1-difluoroallylsilanes from chlorosilanes and of CH₂CHCF₂C(OH)-Et₂ from 3-pentanone.     

Selective hydrogenation of fatty oils on alloyed Ni?Al catalysts. II. Optimal reaction conditions

The previously suggested kinetic model permits to predict that maximum selectivity towards olein is attained under the limiting diffusional resistance with respect to hydrogen. This conclusion is confirmed by the experimental data obtained in a fixed catalyst bed reactor. Some recommendations to intensify industrial processes are given.

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Unexpected course of the reaction of aromatic aldehydes on lithiated N,N-dimethyl o-(3-quinolyl)carbamate

The reaction of aromatic aldehydes with N,N-dimethyl O-(3-lithioquinolyl)carbamate produces 4-(dimethyl-aminomethyl)3-hydroxyquinolines via a new rearrangement.