Aryl-substituted alkenes

Another important type of reactivity of palladium, namely oxidative addition to Pd(0), is the foundation for several methods of forming carbon-carbon bonds. Aryl126 and alkenyl127 halides react with alkenes in the presence of catalytic amounts of palladium to give net substitution of the halide by the alkenyl group. The reaction, known as the Heck reaction,128 is quite general and has been observed for simple alkenes, aryl-substituted alkenes, and substituted alkenes such as acrylate esters, vinyl ethers, and A-vinylamides.129... 

Heck reaction, palladium-catalyzed cross-coupling reactions between organohalides or triflates with olefins (72JOC2320), can take place inter- or intra-molecularly. It is a powerful carbon-carbon bond forming reaction for the preparation of alkenyl- and aryl-substituted alkenes in which only a catalytic amount of a palladium(O) complex is required. 

With aryl-substituted alkenes, the aryl ketone is the major product. 

Many chiral diphosphine ligands have been evaluated with regard to inducing enantioselectivity in the course of the hydroformylation reaction [25,26]. However, a real breakthrough occurred in 1993 with the discovery of the BI-NAPHOS ligand by Takaya and Nozaki [65]. This was the first efficient and rather general catalyst for the enantioselective hydroformylation of several classes of alkenes, such as aryl alkenes, 1-heteroatom-functionalized alkenes, and substituted 1,3-dienes, and is still a benchmark in this area [66,67]. But still a major problem in this field is the simultaneous control of enantio-... 

An extensive array of chiral phosphine ligands has been tested for the asymmetric rhodium-catalyzed hydroboration of aryl-substituted alkenes. It is well known that cationic Rh complexes bearing chelating phosphine ligands (e.g., dppf) result in Markovnikoff addition of HBcat to vinylarenes to afford branched boryl compounds. These can then be oxidized through to the corresponding chiral alcohol (11) (Equation (5)) ... 

In the course of investigation into new C-C bond formation processes, Hiyama has developed an efficient nickel-catalyzed arylcyanation of alkynes.67 The addition reaction of an aryl-CN bond to alkyne affords aryl-substituted alkene nitrile in good yield. Good regioselectivity is reported in the case of unsymmetrical alkynes with two sterically different substituents. 

In addition to /3-H elimination, olefin insertion, and protonolysis, the cr-metal intermediate has also proved to be capable of undergoing a reductive elimination to bring about an alkylative alkoxylation. Under Pd catalysis, the reaction of 4-alkenols with aryl halides affords aryl-substituted THF rings instead of the aryl ethers that would be produced by a simple cross-coupling mechanism (Equation (126)).452 It has been suggested that G-O bond formation occurs in this case by yy/z-insertion of a coordinated alcohol rather than anti-attack onto a 7r-alkene complex.453... 

Ionic hydrogenations of C=C bonds generally work well only in cases where a tertiary or aryl-substituted carbenium ion can be formed through protonation of the C=C bond. Alkenes that give a tertiary carbenium ion upon protonation include 1,1-disubstituted, tri-substituted and tetra-substituted alkenes, and each of these are usually hydrogenated by ionic hydrogenation methods in high yields. 

The titanocene catalyst 41 was used to hydrogenate a range of aryl-substituted alkenes (Fig. 30.16, Table 30.12) [28]. 

Isomerization of 1,3-dienes (12, 36).3 The 1,5-hydrogen shift in isomerization of 1,3-dienes catalyzed by (naphthalene)Cr(CO)3 (1) can be used for synthesis of aryl-substituted exocyclic alkenes, which are not readily available by coupling of aryl halides with exocyclic vinyl halides. 

Acetoxylation proceeds mostly via the radical cation of the olefin. Aliphatic alkenes, however, undergo allylic substitution and rearrangement predominantly rather than addition [224, 225]. Aryl-substituted alkenes react by addition to vic-disubstituted acetates, in which the dia-stereoselectivity of the product formation indicates a cyclic acetoxonium ion as intermediate [226, 227]. In acenaphthenes, the cis portion of the diacetoxy product is significantly larger in the anodic process than in the chemical ones indicating that some steric shielding through the electrode is involved [228]. 

Elimination to yield alkenes can be induced thermally or by treatment with acids or bases (for one possible mechanism, see Figure 3.39) [138,206]. Less common thermal demetallations include the thermolysis of arylmethyloxy(phenyl)carbene complexes, which can lead to the formation of aryl-substituted acetophenones [276]. Further, (difluoroboroxy)carbene complexes of molybdenum, which can be prepared by treating molybdenum hexacarbonyl with an organolithium compound and then with boron trifluoride etherate at -60 °C, decompose at room temperature to yield acyl radicals [277]. 

Insertion of aUcynes into aromatic C-H bonds has been achieved by iridium complexes. Shibata and coworkers found that the cationic complex [Ir(COD)2]BF4 catalyzes the hydroarylation of internal alkynes with aryl ketones in the presence of BINAP (24) [111]. The reaction selectively produces ort/to-substituted alkenated-aryl products. Styrene and norbomene were also found to undergo hydroarylation under similar condition. [Cp IrCl2]2 catalyzes aromatization of benzoic acid with two equivalents of internal alkyne to form naphthalene derivatives via decarboxylation in the presence of Ag2C03 as an oxidant (25) [112]. 

The cross-coupling reaction of diaryl tellurides with alkenes in MeOH in the presence of Pd " catalyst, EtjN and AgOAc as oxidant, gives the corresponding aryl-substituted (Z)-aUcenes in good yields. ... 

These intrazeolite singlet oxygen ene reactions have synthetic potential because the cis effect observed in solution is suppressed in the zeolite [13]. Consequently, allylic hydroperoxides which are inaccessible by other routes may be available via this new technology. For example, photo-oxidations of aryl-substituted alkenes, 7, in sensitizer-doped NaY react to generate the allylic hydroperoxides as the major or exclusive product [17]. In contrast, in solution, the hydroperoxides are formed in only 5-20% yields, with 2-1-2 and 4-1-2 adducts dominating the reaction mixtures. In the case of 2-methyl-5-phenyl-2-hexene, 8, the regio-selectivity for 8b and 8c improved from 47% to 94% and the diastereoselectivity from 10% to 44% as the reaction is moved from solution into the zeolite [18] ... 

Three types of photoextrusion reactions have been identified in the irradiation of aryl-substituted 1,3,2-dioxathiolane 2-oxides [5 1-1-2 4-2] cycloelimination to produce a carbonyl compound, a carbene and sulfur dioxide extrusion of sulfur dioxide accompanied by a pinacol-like rearrangement to yield an aldehyde or ketone and extrusion of sulfur trioxide to give an alkene <72JOC2589>. Sensitization and quenching experiments indicate that a singlet state is responsible for the cycloelimination reaction, whereas the rearrangement and sulfur trioxide extrusion reactions arise from a triplet state <82JCR(S)175>. 

Like the parent compound (1), alkyl- and/or aryl-substituted 1,2,3-trioxolanes can be generated only at low temperatures by the cycloaddition of ozone to alkenes. The concerted nature of the cycloaddition is reflected in the stereochemistry of the products observed aliphatic cis alkenes afford only cis 4,5-dialkyl-1,2,3-trioxolanes, and the analogous trans alkenes yield only trans 4,5-dialkyl-... 

The simple peptide, used in stoichiometric amounts, can convert a variety of aryl-substituted alkenes to the corresponding cyclopropane with good to excellent enantioselectivities (Figure 8). 

An alternate approach has been developed by Charette and coworkers in which chiral iodomethylzinc phosphates were prepared and tested in the cyclopropanation of unfunctionalized alkenes. Although these reagents were not sufficiently reactive to convert aryl-substituted alkenes (such as indene) to the corresponding cyclopropane, they reacted nicely with protected aryl-substituted allylic and homoallylic alcohols (equation 92) °. Several 3,3 -disubstituted binols were tested and ligand 23 stood out as being the most effective with this class of compounds. The active reagent in this case is a chiral iodomethylzinc phosphate. 

The epoxidation procedure developed by Yian Shi of Colorado State University has become one of the workhorses of enantioselective synthesis. That work has been based around trans and trisubstituted alkenes. Professor Shi has now developed (Tetrahedron Lett. 2004,45, 8115) an efficient protocol for the enantioselective epoxidation of aryl-substituted cis alkenes such as 6. 

Ni(II) complexes of cyclam and oxocyclam derivatives catalyze the epoxidation of cyclohexene and various aryl-substituted alkenes with PhIO and NaOCl as oxidants, respectively. In the epoxidation catalyzed by the Ni(II) cyclam complex using PhIO as a terminal oxidant, the high-valent nickel- complexes (e.g., LNiin-0, LNi=0, LNiin-0-... 

The scope and limitations of the Lewis acid-catalyzed additions of alkyl chlorides to carbon-carbon double bonds were studied.51 Since Lewis acid systems are well-known initiators in carbocationic polymerizations of alkenes, the question arises as to what factors govern the two transformations. The prediction was that alkylation products are expected if the starting halides dissociate more rapidly than the addition products.55 In other words, addition is expected if the initial carbocation is better stabilized than the one formed from the dissociation of the addition product. This has been verified for the alkylation of a range of alkyl-and aryl-substituted alkenes and dienes with alkyl and aralkyl halides. Steric effects, however, must also be taken into account in certain cases, such as in the reactions of trityl chloride.51... 

Dioxacyclohexanes can be produced in excellent yields from aliphatic or aryl-substituted alkenes.64 Dilute sulfuric acid at or above room temperature with paraformaldehyde appears to give the best results. Dioxane-water or acetic acid as solvent was found to afford increased yields in the Prins reaction of arylalkenes. 

A unique example,80 the reduction via transfer hydrogenation of aryl-substituted alkenes, is facilitated by A1C13 ... 

Cpsymmetric organolanthanide complexes exhibit moderate to good enantioselectivities in the hydrogenation and deuteration of styrene and 2-phenyl-1-butene.433 Cationic iridium-phosphanodihydrooxazole complexes are more efficient catalysts for the asymmetric hydrogenation of unfunctionalized aryl-substituted alkenes. The best catalyst (42) gives high yield (>99%) and excellent enantioselectivity (97% ee) in the hydrogenation of ( )-l,2-diphenyl-l-propene 434... 

Cyano-substituted ethylenes react in a different way with aliphatic ketones. The orientation of photochemical cycloaddition (4.661 is the opposite of that found for electron-rich alkenes, and the reaction is highly stereoselective (4.69) in the early stages. These processes involve the formation and subsequent decay of an excited complex (exciplex) from the (n,n ) singlet state of the ketone and the alkene. Aryl ketones undergo intersystem crossing so efficiently that such a singlet-state reaction is rarely observed, but the reaction of a benzoate ester with an electron-rich alkene 14.70 rnay well be of this type, with the ester acting as electron-acceptor rather than electron-donor. 

A study of the scope of the reaction has shown that mono- and disubstituted alkenes and, particularly, aryl-substituted alkenes are the best substrates. Various limitations have been noted, some not unexpected (sensitivity to steric effects), others quite surprising (complex reactivity of cyclohexenes). Nevertheless, the exceptionally high stability of the reagent should make it available from the shelf, and in appropriate cases its use is to be considered as an alternative to the Simmons-Smith reaction. 

In relation to enzymic cytochrome P-450 oxidations, catalysis by iron porphyrins has inspired many recent studies.659 663 The use of C6F5IO as oxidant and Fe(TDCPP)Cl as catalyst has resulted in a major improvement in both the yields and the turnover numbers of the epoxidation of alkenes. 59 The Michaelis-Menten kinetic rate, the higher reactivity of alkyl-substituted alkenes compared to that of aryl-substituted alkenes, and the strong inhibition by norbornene in competitive epoxidations suggested that the mechanism shown in Scheme 13 is heterolytic and presumably involves the reversible formation of a four-mernbered Fev-oxametallacyclobutane intermediate.660 Picket-fence porphyrin (TPiVPP)FeCl-imidazole, 02 and [H2+colloidal Pt supported on polyvinylpyrrolidone)] act as an artificial P-450 system in the epoxidation of alkenes.663... 

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