Mechanistic analysis of the photocycloaddition of silyl-tethered alkenes

The photochemistry of substituted cinnamyloxy silanes has been examined in both cyclohexane and acetonitrile solvents. Alkene isomerization occurs in addition to cycloaddition. Fluorescence quantum yields and excited singlet state lifetimes have been determined for each compound. We have used the information in order to better understand the regio- and stereoselectivity of photocycloaddition between silyl-tethered cinnamyl groups. This study allows us to conclude that the 2 + 2 photocycloaddition between alkenes is not a Woodward-Hoffmann orbital symmetry controlled event. The most consistent explanation for the excellent regio- and stereoselectivity is that the photocycloaddition is conformationally controlled.     

Neighboring group participation of phosphine oxide functionality in the highly regio- and stereoselective iodohydroxylation of 1,2-allenylic diphenyl phosphine oxides

Two sets of reaction conditions were established to enable the highly regio- and stereoselective iodohydroxylation of 1,2-allenylic diphenyl phosphine oxides, yielding (E)-2-iodo-3-hydroxy-1-alkenyl diphenyl phosphine oxides with very high stereoselectivity. The scope of this reaction was examined extensively. Notably, studies on the reactivity of optically active substrates indicated that the axial chirality in the starting allenes may be efficiently transferred to the center chirality of the products with no discernible loss of enantiopurity. Due to the importance of phosphine-containing compounds, both as reagents and ligands, this reaction shows potentials in organic synthesis. Investigations using ESI-MS technology on the (18)O-labeled product, which was prepared using (18)O-water as the solvent, indicated that the (18)O atom was bound to phosphorus in the final product and the oxygen atom of the hydroxyl comes from the phosphinyl functionality of the allene reactant. These results provided solid evidence for the formation of a five-membered cyclic intermediate from the neighboring group participation of the diphenylphosphinyl group. To the best of our knowledge, this is the first time that the neighboring group participation of this type of group was observed.     

An X- (X= I, Br)-triggered ring-opening coupling reaction of cyclopropenes with organic halides

Polyfunctionalized (E)-alk-1-enyl halides 3 were efficiently synthesized in high yields via a novel regio- and stereoselective X- (X = I or Br)-triggered ring-opening coupling reaction of cyclopropenes 1 with organic halides 2.     

Sulfinyl group as an intramolecular nucleophile: synthesis of bromohydrins from beta-methyl-gamma,delta-unsaturated sulfoxides with high 1,2-asymmetric induction

Bromohydrins have been prepared from beta-methyl-gamma,delta-unsaturated sulfoxides with high regio- and stereoselectivity. The reaction proceeds via neighboring group participation of the sulfinyl moiety with inversion of sulfoxide configuration as proven by an (18)O labeling study and X-ray crystallography.     

Ionic liquid media resulted in more efficient regio- and stereoselective aminohalogenation of cinnamic esters

The ionic liquid, butylmethylimidazolium tetrafluoroborate ([Bmim][BF4]), was found to be superior to classical organic solvents for the metal catalyzed regio- and stereoselective aminohalogenation of cinnamic esters. The aminohalogenation reaction of cinnamic esters with p-TsNCl₂ proceeded at a faster rate (within 12 h) in the presence of a reduced amount of catalyst (CuOTf, 6.0 mol %). Good yields (76-82%) and excellent regio- and stereoselectivity (one isomer) were achieved for eight examples.     

Light-mediated transformations of olefins into alcohols: reactions of hydroxyl radicals with cycloalkenes

Reactions of hydroxyl radicals, generated by photodecomposition of hydrogen peroxide in acetonitrile, with a wide variety of cycloalkenes have been examined. The results show that the major reaction is the addition of hydroxyl radicals to the less substituted end of the double bond, furnishing the secondary alcohols. The reactivity pattern and the observed regio- and stereoselectivity clearly reveal that the steric parameters associated with the substrates play a dominant role in directing the addition reactions. More importantly, this study led to the development of a new methodology for the facile conversions of olefins essentially into secondary alcohols, and includes a few examples which demonstrate the potential of the method.     

Highly Stereoselective and Efficient Hydrosilylation of Terminal Alkynes Catalyzed by

With [RuCl(2)(p-cymene)](2) as a catalyst, extremely high regio- and stereoselectivity was observed in the hydrosilylation reaction of various terminal alkynes under mild conditions to afford beta-(Z)-vinylsilanes in excellent yields. A dramatic directing effect was also observed when alkynes having a hydroxyl group at the beta position to the triple bond were employed as a substrate, and in these cases regioisomeric alpha-vinylsilanes were generated with excellent selectivity.     

Microwave-assisted reactions in heterocyclic compounds with applications in medicinal and supramolecular chemistry

Microwave irradiation has been successfully applied in organic chemistry. Spectacular accelerations, higher yields under milder reaction conditions and higher product purities have all been reported. Indeed, a number of authors have described success in reactions that do not occur under conventional heating and modifications in selectivity (chemo-, regio- and stereoselectivity) have even been reported. Recent advances in microwave-assisted combinatorial chemistry include high-speed solid-phase and polymer-supported organic synthesis, rapid parallel synthesis of compound libraries, and library generation by automated sequential microwave irradiation. In addition, new instrumentation for high-throughput microwave-assisted synthesis continues to be developed at a steady pace. The impressive speed combined with the unmatched control over reaction parameters justifies the growing interest in this application of microwave heating. In this review we highlight our recent advances in this area, with a particular emphasis on cycloaddition reactions of heterocyclic compounds both with and without supports, applications in supramolecular chemistry and the reproducibility and scalability of organic reactions involving the use of microwave irradiation techniques.     

Cyclopropenes and methylenecyclopropanes in 1,3-dipolar cycloaddition reactions

The review considers the main results of the cycloaddition reactions involving cyclopropenes and methylenecyclopropanes, the compounds bearing strained three-membered rings and, respectively, endo- and exocyclic double bonds. The main attention is focused on the reactions of these compounds with 1,3-dipoles (nitrones, azomethine imines, azomethine ylides, carbonyl ylides, etc.), which gave complex heterocyclic systems with high regio- and stereoselectivity.

     

Asymmetric 1,3-dipolar cycloaddition of N-metalated azomethine ylides to methyl (S)-2-(p-tolylsulfinyl)acrylate. Synthesis of optically pure 2,4,5-trisubstituted 2,5-dihydro-1H-pyrroles

The first 1,3-dipolar reaction of azomethine ylides with optically pure vinyl sulfoxide are reported. The presence of the sulfinyl group increase the reactivity of the acrylate moiety as a dipolarophile, and the reactions evolve with complete regio- and endo-selectivities. Nevertheless, mixtures of the two diastereoisomers 4 and 5 (75-88% de) resulting from the anti dipole/s-cis dipolarophile and syn dipole/s-trans dipolarophile approaches, respectively, are obtained. The stereoselectivity can be controlled by using THF or MeCN as solvents or by changing the reaction temperature in MeCN. After separation of the cycloadducts, optically pure 2,5-dihydro-1H-pyrroles are easily obtained by pyrolytic desulfinylation.     

Effect of hexafluorobenzene on the photophysics of pyrene

Absorption and fluorescence spectroscopy studies reveal the formation of a weak complex between pyrene and C(6)F(6) even in very dilute systems. The complex affects the photophysics of pyrene and reveals a combination of static and dynamic-quenching phenomena in both polar and nonpolar solvents. The results are supported by computational studies that shed light on the structure of the complex and the interactions involved and suggest that ground and excited-state interactions are of comparable magnitude; the association is believed to be driven by quadrupolar interactions. Understanding these interactions in solution is important for applications that aim at controlling the regio- or stereoselectivity of organic reactions.     

A regio- and stereoisomeric study of allylic alcohol fluorination with a range of reagents

A range of dehydroxyfluorination reagents was reacted with separate diastereoisomers of a chiral allylic alcohol to explore both the regio- and stereoselectivity ratios of direct versus allylic fluorination. The allylic alcohol stereoisomers gave the same predominant fluorinated diastereoisomer indicating that the reaction proceeds with a significant S_N1 component via an allylic carbocation intermediate, which is quenched by fluoride ion, predominantly from the least hindered face. None of the reagents displayed very high regio- or stereoselectivity, although in all cases the allylic fluorination products predominated.     

A facile highly regio- and stereoselective preparation of N-tosyl allylic amines from allylic alcohols and tosyl isocyanate via Palladium(II)-catalyzed aminopalladation-beta-heteroatom elimination

The high regio- and stereoselectivity have been obtained from the allylic substitution reaction catalyzed by palladium(II) species. From allylic alcohols, one-pot reaction with tosyl isocyanate followed by palladium(II)-catalyzed allylic substitution gives N-tosyl (E)-allylic amines in high yield. The substitution occurs only at the gamma-position of the 1- or 3-substituted allylic alcohols.     

An experimental and computational investigation of the Diels-Alder cycloadditions of halogen-substituted 2(H)-pyran-2-ones

[reaction: see text] Diels-Alder reactions of 3- and 5-halo-subsituted 2(H)-pyran-2-ones with both electron-rich and electron-deficient dienophiles afford stable and readily isolable bridged bicyclic lactone cycloadducts. These cycloadditions proceed with excellent regioselectivity and very good stereoselectivity. In contrast, Diels-Alder reactions of 4-halo-subsituted 2(H)-pyran-2-ones afford cycloadducts which are very prone to loss of bridging CO(2) and the subsequent formation of barrelenes ([2.2.2]cyclooctenes). Furthermore, these cycloadditions proceed with only moderate regio- and stereoselectivity. For both series of the 3- and 5-halo-subsituted 2(H)-pyran-2-ones and 4-halo-subsituted 2(H)-pyran-2-ones, the reactivity patterns do not significantly change between the halogens. The regio- and stereochemical preferences of the cycloadditions of halo-substituted 2(H)-pyran-2-ones are investigated computationally. Calculations were carried out on the transition states leading to the four possible regio- and stereoisomeric cycloadducts by using density functional theory (B3LYP/6-31G). These studies allow prediction of the regio- and stereoselectivity in these reactions which are broadly in line with experimental observations.     

Microwaves in organic synthesis. Thermal and non-thermal microwave effects

Microwave irradiation has been successfully applied in organic chemistry. Spectacular accelerations, higher yields under milder reaction conditions and higher product purities have all been reported. Indeed, a number of authors have described success in reactions that do not occur by conventional heating and even modifications of selectivity (chemo-, regio- and stereoselectivity). The effect of microwave irradiation in organic synthesis is a combination of thermal effects, arising from the heating rate, superheating or "hot spots" and the selective absorption of radiation by polar substances. Such phenomena are not usually accessible by classical heating and the existence of non-thermal effects of highly polarizing radiation--the "specific microwave effect"--is still a controversial topic. An overview of the thermal effects and the current state of non-thermal microwave effects is presented in this critical review along with a view on how these phenomena can be effectively used in organic synthesis.     

Enantioselective synthesis of the carbocyclic nucleoside (-)-abacavir

An enantiopure β-lactam with a suitably disposed electron withdrawing group on nitrogen, participated in a π-allylpalladium mediated reaction with 2,6-dichloropurine tetrabutylammonium salt to afford an advanced cis-1,4-substituted cyclopentenoid with both high regio- and stereoselectivity. This advanced intermediate was successfully manipulated to the total synthesis of (-)-Abacavir.     

A novel approach to the taxane BC ring system through formation of alpha-ketol by oxidative removal of the phenylsulfonyl group with subsequent in situ oxidation

Cis-fused bicyclo[6.4.0]dodecene 11 was converted into taxane BC ring system 21 in three steps; transformation of the phenylsulfonyl group to an alpha-hydroxy carbonyl group by the treatment with potassium hexamethyldisilazide (KHMDS) and triethyl phosphite under oxygen atmosphere, followed by reductive elimination of the hydroxyl group of alpha-ketol moiety, and inversion of ring juncture. Epimerization of the sulfonyl group of 11 was indispensable for the first oxidation process (17 --> 18) and the second oxidation of 12 leading to hydroxylation at the alpha-position of the carbonyl group proceeded with high regio- and stereoselectivity to give 13. On the other hand, reaction of the cross-conjugated compound 5 with KHMDS at 0 degrees C brought about a complete reorganization of molecular framework to provide the compound 7 in which the five-membered ring and the conjugated seven-membered ring were connected through a single bond.     

Conformationally flexible chiral supramolecular catalysts for enantioselective Diels-Alder reactions with anomalous endo/exo selectivities

The potential of supramolecular catalysts to realize anomalous regio- and/or stereoselectivity in organic synthesis is highly attractive. To date, there have been a few examples of non-polymeric and non-covalent chiral supramolecular catalysts that induce practical enantioselectivity. In this regard, a metal-organic framework (MOF) may be one of the most important techniques for constructing conformationally rigid supramolecular catalysts. However, it is not easy to use the MOF technique to fine-tune a much more precise cage in catalysts for anomalous purposes. To establish high catalytic activity with anomalous regio- and/or stereoselectivity, in principle, an artificial cage should be conformationally flexible, like an active pocket in an enzyme with an induced-fit function. In this feature article, we focus on the anomalous endo/exo-selective Diels-Alder reaction, and overview the development of the successive catalysts including our recent highly active, conformationally flexible, and chiral supramolecular catalysts. The evolution from 'ready-made' single-molecule catalysts to 'tailor-made' supramolecular catalysts could offer not only high enantioselectivity but also high anomalous endo/exo-selectivities due to substrate-specific characteristics, as with enzymes.     

Palladium-catalyzed and organozinc-promoted synthesis of dienes from allylic esters possessing an acyloxy or alkoxy group

Organozinc and a Pd catalyst promoted formation of dienes from allylic esters possessing a leaving group such as acyloxy and alkoxy groups next to the allyl moiety. The reaction proceeded with high regio- and stereoselectivity when applied to secondary allylic substrates.     

Regio- and stereoselective cycloadditions of cyclic nitrones to maleic diamide forced in a peptide: synthesis of potent ligands of human NK-2 receptor

The regioselectivity and the stereoselectivity induced by relatively small peptidomimetic maleic diamide 1 in cycloaddition reactions with cyclic nitrones 2-5 was studied. The high regio- and stereoselectivity observed, sensibly increased by nonpolar solvents, was the effect of a double-asymmetric induction produced by the nitrone substituent on the pseudopeptidic tether. A new class of potent human tachykinin NK-2 receptor ligands was synthesized.