New developments in the Peterson olefination reaction

Noteworthy developments of the Peterson olefination reaction are reviewed. Evidence for both concerted and stepwise mechanisms for the Peterson olefination reaction is presented. The strong affinity of the oxygen anion for the silyl moiety is emphasised when the Peterson olefination reaction takes preference over both the Julia and Wittig reactions in the presence of S- and P-stabilised silyl carbanions. Cerium-mediated Peterson methylenation reactions are discussed.     

Dual Ligand‐Enabled Nondirected C−H Olefination of Arenes

The application of the Pd‐catalyzed oxidative C?H olefination of arenes, also known as the Fujiwara–Moritani reaction, has traditionally been limited by the requirement for directing groups on the substrate or the need to use the arene in large excess, typically as a (co)solvent. Herein the development of a catalytic system is described that, through the combined action of two complementary ligands, makes it possible to use directing‐group‐free arenes as limiting reagents for the first time. The reactions proceed under a combination of both steric and electronic control and enable the application of this powerful reaction to valuable arenes, which cannot be utilized in excess.     

Synthesis and Application of Tetraphosphane Ligands in Rhodium‐Catalyzed Hydroformylation of Terminal Olefins: High Regioselectivity at High Temperature

A new class of substituted tetraphosphane ligands has been developed and applied in the rhodium‐catalyzed regioselective hydroformylation of terminal olefins. The high regioselectivity (linear selectivity is above 97 % for 1‐octene and 1‐hexene) at high temperature (140 °C) shown by these tetraphosphane ligands is remarkable considering the low regioselectivity commonly observed under similar reaction conditions when other bisphosphane analogues are used. The steric and electronic effects of substituents on the diarylphosphane moiety have also been examined.     

A synthesis of trisubstituted alkenes by a Ru-catalyzed addition

Catalyzed by ruthenium trisacetonitrile hexafluorophosphate 4, the Alder-ene type reaction of alkenes and internal alkynes provides an effective way to synthesize trisubstituted alkenes. Unlike most typical olefination protocols, this reaction is atom economical, and affords trisubstituted alkenes with defined olefin geometry. The regioselectivity can be explained invoking a steric argument based on the proposed mechanism. The first C-C bond formation generally involves sterically less hindered carbons of the alkenes and alkynes. Modest to very high regioselectivity can be achieved depending on the steric difference of the two substituents of alkynes.     

Highly efficient Peterson olefination leading to unsaturated selenoamides and their characterization

The Peterson olefination of aromatic aldehydes with an alpha-silyl selenoacetamide proceeded smoothly with high stereoselectivity to give E-alpha,beta-unsaturated selenoamides in good to high yields. The reaction with aldehydes bearing alkenyl and dienyl groups gave the corresponding selenoamides bearing dienyl and trienyl groups, but the stability of the products depended on the substituents on the aromatic ring. X-ray molecular analysis disclosed that the alpha,beta,gamma,delta-unsaturated selenoamides had a nearly planar structure. In the (77)Se NMR spectra, signals were observed in the region greater than 130 ppm depending on the substituents on the aromatic ring, whereas the (1)J coupling constant between the carbon atom and the selenium atom was almost independent of the substituents. A linear relationship was observed between the chemical shifts in the (77)Se NMR spectra and Hammet sigma parameters, and this correlation was retained even when one or two alkenyl groups were introduced to alpha,beta-unsaturated selenoamides, although it became less sensitive.     

Attraction or Repulsion? London Dispersion Forces Control Azobenzene Switches

Large substituents are commonly seen as entirely repulsive through steric hindrance. Such groups have additional attractive effects arising from weak London dispersion forces between the neutral atoms. Steric interactions are recognized to have a strong influence on isomerization processes, such as in azobenzene‐based molecular switches. Textbooks indicate that steric hindrance destabilizes the Z isomers. Herein, we demonstrate that increasing the bulkiness of electronically equal substituents in the meta‐position decreases the thermal reaction rates from the Z to the E isomers. DFT computations revealed that attractive dispersion forces essentially lower the energy of the Z isomers.     

Z-selective synthesis of alpha,beta-unsaturated amides with triphenylsilylacetamides

With the purpose of developing a method of preparing Z-alpha,beta-unsaturated amides, the Peterson reaction of the (triphenylsilyl)acetamide Ph(3)SiCH(2)COX (1, X = NBn(2); 3, X = NMe(2)) with various aldehydes was examined. The reaction of aromatic aldehydes gave selectivities up to >97:3. It was found that the selectivity was a function of the electronic nature of the aromatic ring and higher Z selectivity was attained with electron-rich aldehydes. With aliphatic aldehydes selectivities up to 92:8 were achieved, and unlike with analogous phosphorus reagents, less sterically hindered aldehydes gave higher Z selectivity. Also, 3, which has a smaller amide group than 1, tended to give rise to higher selectivity. A comparison with the reaction of trimethylsilyl analogues revealed the significance of the phenyl substituents on the silyl group.     

Double ring-closing metathesis reaction of nitrogen-containing tetraenes: efficient construction of bicyclic alkaloid skeletons and synthetic application to four stereoisomers of lupinine and their derivatives

The double ring-closing metathesis reaction of nitrogen-containing tetraenes was studied. The selectivity of the fused/dumbbell-type products can be controlled by the electronic/steric effects of the substituents attached to the C[double bond]C bonds and the s-cis/s-trans conformational ratios of the substrates. This methodology has also been successfully applied to the enantioselective synthesis of four stereoisomers of lupinine and their derivatives.     

Stereoselective peterson alkoxycarbonylmethylenation reaction of substituted cyclohexanones

In contrast to previous results the Peterson olefination reaction of substituted cyclohexanones with metallotrimethylsilylacetates (1) affords moderate to high stereoselectivity.     

Stereoselective synthesis of enediynes and enynes by condensation of aldehydes with γ-(trialkylsilyl)allenylboranes

Enediynes and enynes with high geometric purity were synthesized by treating acetylenic and simple aldehydes with γ-(tert-butyldimethylsilyl)allenylborane 2a followed by the elimination step of the Peterson olefination reaction.     

Total Synthesis of the Tiacumicin B (Lipiarmycin A3/Fidaxomicin) Aglycone

Tiacumicin B (lipiarmycin A3, fidaxomicin) is an atypical macrolide antibiotic which is used for the treatment of Clostridium difficile infections. Tiacumicin B is also a potent inhibitor of Mycobacterium tuberculosis, but due to its limited oral bioavailability is unsuitable for systemic therapy. To provide a basis for structure–activity studies that might eventually lead to improved variants of tiacumicin B, we have developed an efficient approach to the synthesis of the tiacumicin B aglycone. The synthesis features a high‐yielding intramolecular Suzuki cross‐coupling reaction to effect macrocyclic ring closure. Key steps in the synthesis of the macrocyclization precursor were a highly selective, one‐pot Corey–Peterson olefination and an ene–diene cross‐metathesis reaction. Depending on the reaction conditions, the final deprotection delivered either the fully deprotected tiacumicin B aglycone or partially protected versions thereof.     

Structure-reactivity correlations in the reaction of ethyl bromoacetate with aliphatic carboxylate ions

The second-order rate constants at three different temperatures have been determined for nucleophilic substitution reactions of ethyl bromoacetate with various substituted aliphatic carboxylate ions (XCH₂COO⁻) in 90% acetone-10% water (v/v) mixture and the activation parameters have been evaluated. The rate data have been analysed in terms of electronic and steric effects by using various single and multi-parameterequations. Analysis of the results shows that localized and steric effects are more important than the delocalized effect. The regression coefficient of the inductive component is negative indicating that inductively electron-releasing substituents accelerate the reaction and electron-withdrawing substituents retard it. The steric component corresponds to the reaction being subject to steric acceleration by the substituents. The per cent steric effect has been calculated. The Br?nsted type correlation is fair, and theβ _N value has been determined.     

Steric effects of polar substituents evaluated in terms of energy by means of isodesmic reactions

Steric effects of various polar and some charged groups were estimated on sterically crowded cyclopropane cis-1,2-bis derivatives 2 or 3, in which the variable substituent is in the proximity of a t-butyl group or of a methyl group. The steric energy was evaluated with reference to the pertinent mono derivatives, that is as reaction energy of an isodesmic reaction, in which the crowded compound is formally synthesized from simple derivatives. Energies were calculated within the framework of the density functional theory at level B3LYP/6-311+G(d,p)//B3LYP/6-311+G(d,p) for 11 dipolar and 5 charged substituents. Interaction of charged substituents is not only steric (destabilizing) but also inductive (stabilizing). The steric effects evaluated in this way differ distinctly from the standard steric constants derived purely from the van der Waals radii of the substituents.     

Iridium‐Catalyzed Silylation of Five‐Membered Heteroarenes: High Sterically Derived Selectivity from a Pyridyl‐Imidazoline Ligand

The steric effects of substituents on five‐membered rings are less pronounced than those on six‐membered rings because of the difference in bond angles. Thus, the regioselectivities of reactions of five‐membered heteroarenes that occur with selectivities dictated by steric effects, such as the borylation of C?H bonds, have been poor in many cases. We report that the silylation of five‐membered‐ring heteroarenes occurs with high sterically derived regioselectivity when catalyzed by the combination of [Ir(cod)(OMe)]₂ (cod=1,5‐cyclooctadiene) and a phenanthroline ligand or a new pyridyl‐imidazoline ligand that further increases the regioselectivity. The silylation reactions with these catalysts produce high yields of heteroarylsilanes from functionalization at the most sterically accessible C?H bonds of these rings under conditions that the borylation of C?H bonds with previously reported catalysts formed mixtures of products or products that are unstable. The heteroarylsilane products undergo cross‐coupling reactions and substitution reactions with ipso selectivity to generate heteroarenes that bear halogen, aryl, and perfluoroalkyl substituents.     

Synthesis of vinylindoles and vinylpyrroles by the Peterson olefination or by use of the Nysted reagent

Vinylindoles and vinylpyrroles were prepared from their corresponding aldehydes or ketones using the Peterson olefination, or by use of the Nysted reagent, a commercially available gem‐dimetallic compound. The two methods provide efficient and convenient access to these useful heterocyclic 1,3‐diene systems. J. Heterocyclic Chem., (2011).     

β-Olefination of 2-alkynoates leading to trisubstituted 1,3-dienes

A phosphine-mediated olefination of 2-alkynoates with aldehydes forming 1,3-dienes with high E-selectivity and up to 88% yield is described. Reaction conditions are optimized and reactions are demonstrated for various aryl, alkyl, and alkenyl aldehydes and for ethyl 2-alkynoates with different substituents in the δ-position. Proof of concept is shown for the generation of a β,γ-unsaturated lactone by intramolecular olefination, and furthermore the use of the generated 1,3-dienes in the Diels-Alder reaction has been demonstrated.     

Boron‐Containing Polycyclic Aromatic Hydrocarbons: Facile Synthesis of Stable,Redox‐Active Luminophores

Herein we show that replacing the two meso carbon atoms of the polycyclic aromatic hydrocarbon (PAH) bisanthene by boron atoms transforms a near‐infrared dye into an efficient blue luminophore. This observation impressively illustrates the impact of boron doping on the frontier orbitals of PAHs. To take full advantage of this tool for the targeted design of organic electronic materials, the underlying structure–property relationships need to be further elucidated. We therefore developed a modular synthesis sequence based on a Peterson olefination, a stilbene‐type photocyclization, and an Si–B exchange reaction to substantially broaden the palette of accessible polycyclic aromatic organoboranes and to permit a direct comparison with their PAH congeners.     

Boron‐Containing Polycyclic Aromatic Hydrocarbons: Facile Synthesis of Stable,Redox‐Active Luminophores

Herein we show that replacing the two meso carbon atoms of the polycyclic aromatic hydrocarbon (PAH) bisanthene by boron atoms transforms a near‐infrared dye into an efficient blue luminophore. This observation impressively illustrates the impact of boron doping on the frontier orbitals of PAHs. To take full advantage of this tool for the targeted design of organic electronic materials, the underlying structure–property relationships need to be further elucidated. We therefore developed a modular synthesis sequence based on a Peterson olefination, a stilbene‐type photocyclization, and an Si–B exchange reaction to substantially broaden the palette of accessible polycyclic aromatic organoboranes and to permit a direct comparison with their PAH congeners.     

Silenes as novel synthetic reagents: synthesis of diols and lactones from simple alkyldienes

Aryl substituted silenes can be generated by a modified Peterson olefination reaction and trapped in situ to afford silacycles with high diastereoselectivity. These silacycles can be elaborated by ‘Fleming-Tamao’ type oxidation to provide access to functionalized diols and lactones.     

Temperature‐responsive Catalyst for the Coupling Reaction of Carbon Dioxide and Propylene Oxide

The selective synthesis of polypropylene carbonate (PPC) and cyclic propylene carbonate (CPC) from coupling reaction of CO₂ and propylene oxide (PO) is a long term pursuing target. Here we report that a temperature controllable porphyrin aluminum catalyst using 5,10,15,20‐tetra(1,2,3,4,5,6, 7,8‐octahydro‐1,4:5,8‐dimethanoanthracen‐9‐yl)porphyrin as ligand, once in conjunction with suitable onium salt, achieved single cycloaddition or copolymerization reaction. Only cycloaddition reaction happened at temperature above 75 °C to produce 100% CPC, whereas copolymerization became dominant to afford PPC with selectivity over 99% at 25 °C, and the obtained PPC showed over 99% carbonate linkage and 92% head‐to‐tail structure. Based on systematic analysis of the electronic and steric feature in the porphyrin ligand, it was found that the electronic feature of the substituent in porphyrin ligand was decisive for PPC selectivity, porphyrin ligand bearing strong electron‐donating substituents displayed a significantly reduced tolerance towards increased temperature with respect to PPC formation. Therefore, temperature‐responsive catalyst could be designed by suitable modification in porphyrin ligand, and such accurate synthesis of target product by one catalyst may create a useful and facile platform for selective PPC or CPC production.