Phenyl/methyl-substituted alkenes

TABLE 20. Comparative reactivity of cyclopropyl-, phenyl- and methyl-substituted alkenes (R R C=CH2) in acid-catalyzed hydrations... 

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] ... 

Only two examples of the synthesis pyrimidoazocines have been described. In Ref. 82JHC1257, a three-stage synthesis of a new heterocycle system, pyrimido[5,4-c]benz[l]azocine, has been proposed. Condensation of 4-methyl-2-phenyl-5-pyrimidincarboxylate (112) with 3,4-dimethoxy-6-nitrobenzaldehyde (113) led to the substituted alkene 114, which, after catalytic hydrogenation of the nitro group on Raney nickel and subsequent intramolecular cyclization of product 115, was converted into pyrimidobenz[l]azocine 116 (Scheme 32). 

Phenyl hydroperoxide, C-O distance, 103 (y-Phenylhydroperoxides, nucleophiUc substitution cyclization, 234-5 1 -Phenyl-3-methyl-3-butene, intrazeohte photooxygenation, 874-5 Phenyl substituted alkenes, photooxidation site selectivity, 839-42... 

Azine approach. 4,5-Dihydro-6//- 1,2-oxazine 2-oxides undergo 1,3-dipolar cyclo-addition reacting with appropriately substituted alkenes and alkynes to form isoxazolo-[2,3-Z>][l,2]oxazines. With styrene as the dipolarophile in the reaction with the oxazine (87), the product (88) with cis methyl and phenyl groups is formed. With acrylonitrile and methyl acrylate, some trans isomer is formed, but the cis isomer is predominant. The rings are always c/s-fused (77IZV211). 

The frontier orbital picture for a simple nitrone is shown in Fig. 6.38, where we can see that the easy reactions will be dipole-LU-controlled with X-substituted alkenes and dipole-HO-controlled with Z-substituted alkenes. In practice, phenyl, alkoxy, and methoxycarbonyl substituents speed up the cycloadditions. Any substituent on the carbon atom of the dipole introduces a steric element in favour of the formation of the 5-substituted isoxazolidines 6.238. The selectivity with monosubstituted alkenes is in favour of this regioisomer, decisively so with C- and X-substituents, but delicately balanced with Z-substituents, since the HOMO of the dipole is not strongly polarised. With methyl crotonate, both adducts have the methyl group on the 5-position and the ester group on the 4-position. 

The reaction rate of the addition decreased on going from phenyl-substituted alkenes to mono-, di-, and trisubstituted alkenes. A preference for E double bonds over Z double bonds was exhibited by the monoimido complex 1. Complete regioselectivity was observed with mono-and trisubstituted alkenes and gmi-disubstituted alkenes, since the C-N bond is formed exclusively at the least substituted alkene carbon, for example of 1-methyl- and 1-phenylcyclo-hexene. However, for 1,2-disubstituted alkenes the regioselectivity depended on the substrate70,71. Unexpectedly, benzylic amination was predominant in the reaction mixtures derived from 1-phenylpropenes and 1,2-dihydronaphthalene (Tabic 5). 

The photochemistry of more complex and highly substituted alkenic partners has been studied. In 1978, Hartmann and coworkers reported the photocycloaddition of 4-oxazolin-2-one with acetone, used as a photosensitizer in the reaction of 4-oxazolin-2-one with alkenyl and alkynyl partners, to form oxe-tane (44). Recently, Scharf has described the photochemistry of 3-acetyl-2,3-dihydio-2,2-dimcthyloxa-zole (45). Irradiation of (45) in the presence of acetophenone produced the oxetane (46) with the phenyl group endo (17%), in addition to 21% of a ring-opened derivative. The stereoselectivity is in agreement with the high exo carboxyl selectivity observed in the photocycloaddition of methyl phe-nylglyoxylate with 2,2-dimethyl-1,3-dioxole to produce oxetane (47). 

In the original study by Peterson, the alkenation procedure was found to be compatible with sulfur and phosphorus substitution. The alkenation reaction has been tqrplied successfully to a variety of substituted alkenes. Because of the aiuon-stabilizing nature of the thiophenyl, the p-hydroxysiliuie is not isolated and the elimination to the alkene takes place directly to form a 1 1 mixture of ( )- and (Z)-isomers. Ager studied the reaction of the lithio anions of phenyl (trimethylsilyl)methyl sulfides (318) with a variety of carbonyl compounds (equation 72). Yields of this process were good, and addition occurred even with enolizable substrates. This reaction was extended to vinyl sulfones. In contrast to the sulfide case, the substituted sulfone silyl anion behaves as a base, leading to undesired enolization. The best yields were observed for the case where R is a hydrogen or phenyl. 

The olefins investigated were 1,1-diphenylethylene, stilbene, styrene, 2-methyl-propene, 2,3-dimethyl-2-butene, butadiene, pentadiene, and isoprene. The phenyl-substituted alkenes were chosen because the spectra of the expected carbonyl oxides are well known, the alkyl-substituted because of their relevance in tropospheric chemistry. 

Nitrones or aci-nitro esters react with alkenes to give in some cases A/-substituted isoxazolidines and in others 2-isoxazolines. When the intermediate isoxazolidines were observed, a number of procedures transformed them into the 2-isoxazolines. Acrylonitrile and phenyl rzcf-nitrone esters produced an A/-methoxyisoxazolidine. Treatment with acid generated a 2-isoxazole while treatment with base generated an oxazine (Scheme 118) (68ZOR236). When an ethoxycarbonyl nitrone ester was reacted with alkenes, no intermediate isoxazolidine was observed, only A -isoxazolines. Other aci-mtro methyl esters used are shown in Scheme 118 and these generate IV-methoxyisoxazolidines or A -isoxazolines which can be further transformed (72MI41605). 

The mechanism of the reaction is unknown. The stereospecificity observed with (E)- and (Z)-l-methyl-2-phenylethylene points to a one-step reaction. The very low Hammett constant, -0.43, determined with phenylethylenes substituted in the benzene ring, excludes polar intermediates. Yields of only a few percent are obtained in the reaction of aliphatic alkenes with (52). In the reaction of cyclohexene with (52), further amination of the aziridine to aminoaziridine (99) is observed. Instead of diphenylazirine, diphenylacetonitrile (100) is formed from diphenylacetylene by NH uptake from (52) and phenyl migration. 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

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