Aromatic compounds alkenylation

The reactions of the second class are carried out by the reaction of oxidized forms[l] of alkenes and aromatic compounds (typically their halides) with Pd(0) complexes, and the reactions proceed catalytically. The oxidative addition of alkenyl and aryl halides to Pd(0) generates Pd(II)—C a-hondi (27 and 28), which undergo several further transformations. 

The transmetallation of various organometallic compounds (Hg, Tl, Sn, B, Si, etc.) with Pd(II) generates the reactive cr-aryl, alkenyl, and alkyl Pd compounds. These carbopalladation products can be used without isolation for further reactions. Pd(II) and Hg(II) salts have similar reactivity toward alkenes and aromatic compounds, but Hg(II) salts form stable mercuration products with alkenes and aromatic rings. The mercuration products are isolated and handled easily. On the other hand, the corresponding palladation products are too reactive to be isolated. The stable mercuration products can be used for various reactions based on facile transmetallation with Pd(II) salts to generate the very reactive palladation products 399 and 400 in rim[364,365]. 

Tetrahalobenzynes, however, react with a variety of aromatic compounds to afford tetrahalobenzobarrelene derivatives in good yields, frequently in the range of 55 to 75%. The dehalogenation of a variety of alkenyl chlorides with alkali metals in tetrahydrofu-ran containing tert-butyl alcohol suggested this approach to the dechlorination of tetrachlorobenzobarrelenes. 

Although the Heck reaction may be efficiently employed for synthesis, it has its limits that should not go unmentioned the Heck reaction can not—at least not intermolecularly—couple alkenyl triflates (-bromides, -iodides) or aryl triflates (-bromides, -iodides) with metal-free aromatic compounds in the same way as it is possible with the same substrates and metal-free alkenes. The reason is step 4 of the mechanism in Figure 16.35 (part II). If an aromatic compound instead of an alkene was the coupling partner the aromaticity with this carbopallada-tion of a C=C double bond would have to be sacrificed in step 4. Typically, Heck reactions can only be run at a temperature of 100 °C even if they proceed without any such energetic effort. This is why this additional energetically demanding loss of aromaticity is not feasible. 

Arylboronic esters (Figure 5.39) and arylboronic acids (Figure 5.40) can also react with unsaturated electrophiles, which cannot be introduced in one step into metal-free aromatic compounds these reactions are with alkenyl bromides, iodides, and triflates... 

For the preparation of conjugated alkynes, one can alkenylate or arylate alkynes according to Section 13.3.4. Alternatively, metallated alkenes or metallated aromatic compounds also may be alkynylated, but this option will not be pursued further. We merely mention in passing that bromoalkynes and iodoalkynes are suitable alkynylat-ing agents and that these can be obtained in a one-step reaction from terminal alkynes ... 

One of the things the Heck reaction cannot do, at least not in an intermolecular fashion, is couple alkenyl triflates (bromides, iodides) with metal-free aromatic compounds,... 

Alkenyl and aryl derivatives of transition metals are generally more stable than the corresponding alkyl derivatives. This has been attributed to the unsaturated groups being able to accept charge from the metal via tt orbitals. This process should be enhanced by the introduction of fluorine or fluorocarbon groups into the alkene or aromatic compound. 

Oxidations by oxygen and catalysts are used for the conversion of alkanes into alcohols, ketones, or acids [54]-, for the epoxidation of alkenes [43, for the formation of alkenyl hydroperoxides [22] for the conversion of terminal alkenes into methyl ketones [60, 65] for the coupling of terminal acetylenes [2, 59, 66] for the oxidation of aromatic compounds to quinones [3] or carboxylic acids [65] for the dehydrogenation of alcohols to aldehydes [4, 55, 56] or ketones [56, 57, 62, 70] for the conversion of alcohols [56, 69], aldehydes [5, 6, 63], and ketones [52, 67] into carboxylic acids and for the oxidation of primary amines to nitriles [64], of thiols to disulfides [9] or sulfonic acids [53], of sulfoxides to sulfones [70], and of alkyl dichloroboranes to alkyl hydroperoxides [57]. 

Aromatic substitution The profile of group-directed o-substitution of aromatic compounds with alkenyl and alkynylsilanes varies with the Ru catalyst. 

An analogous vinylketene intermediate (127, see Schemes 57 and 59) as proposed for the Dotz reaction has been assumed in the so-called cyclobutenedione methodology [161]. The key intermediate is a 4-aryl or 4-alkenyl substituted 2-cyclobutenone (128) that can be obtained e.g. by the reaction of the 3-cyclo-butene-1,2-dione (129) with the appropriate lithium reagent or Stille coupling with 4-chloro-3-cyclobutenone. Thermal cyclobutenone ring opening to the vinylketene 130 followed by electrocyclization furnishes the highly substituted aromatic compound 131 (see Scheme 59). 

Activated aromatic compounds can be alkenylated with (Z)-2-bromo-l-(5-nitro-2-thi-enyl)ethylene in the presence of aluminum chloride to form (392) <86CCC il27>. 

The Catellani s alkylation-alkenylation sequence using norbomene offers a useful synthetic method for 2,6-dialkylated 1-substituted benzenes. Lautens applied the reaction to the synthesis of fused aromatic compounds using ort/jo-substituted iodobenzenes and bromoalkenes. Reaction of o-iodotoluene (11) with ethyl 6-bromo-2-hexenoate (13) afforded the benzocarbocycle 14 via monoalkylation and intramolecular Heck reaction. It is important to use tri-2-furylphosphine (1-3) as a ligand [4]. Similarly the 2,5-disubstituted 4-benzoxepine 17 was obtained in 72% yield by the reaetion of 1-iodonaphthalene (15) with the unsaturated bromo ester 16 [5]. 

This section deals with a unique new methodology for the synthesis of selectively substituted aromatic compounds. Two examples of twofold (Eq. 1) or single ortho alkylation (Eq. 2) of aryl iodides occurring with temporary incorporation of norbomene accompanied by an alkenylation reaction are presented in Scheme 1. 

The palladium(II)-assisted alkenylation of aromatic compounds has also been applied to the synthesis of heterocycles. A novel synthesis of pyrido[3,4-d] pyrimidines, pyrido[2,3-d]pyrimidines and quinazolines was developed by Hirota et al. [18] employing the palladium(ll)-promoted oxidative coupling of uracil derivatives and alkenes. l,3-Dimethyluracil-6-carboxaldehyde dimethylhydrazone (22), 6-dimethylaminomethylenamino-l,3-dimethyluracil (24) and ( )-6-(2-dimethylaminovinyl) uracil (26) all reacted with methyl acrylate in the presence of stoichiometric Pd(OAc)2, producing pyrido[3,4-ii]pyrimidine 23, pyrido[2,3-if]pyrimidine 25 and quinazoline 27, each apparently arising from direct arylation, 6ti electrocycliza-tion, and elimination of dimethylamine, in 67%, 89% and 64% yields respectively (Scheme 9.3). 

The cross-coupling of boron compounds with aryl or alkenyl halides (Suzuki coupling) was used for the preparation of polycyclic aromatic compounds in a biphasic reaction medium. For example, 2-bromobenzonitrile and 4-methylphenylboronic acid gave 4-methyl-2"-cyanobiphenyl in good jdeld with Pd/TPPTS catalyst at 80°C in a toluene-ethanol-aqueous Na2C03 solvent mixture (Scheme 37). The product, isolated by phase separation, was free of metal or ligand impurities and the catalyst could be recycled in the aqueous phase (208). 

The use of ionic liquids as solvents dramatically increased the catalytic activity of Sc(OTf)3, and it exhibited unusually high activity for Friedel-Crafts alkylation of aromatic compounds with linear or cyclic olefins in imidazolium-based hydrophobic ionic liquids such as [EMIm]SbF6, [BMIm]PF6, and [HMIm]PF6. It should be noted that no reaction occurred in common organic solvents, water and hydrophilic ionic liquids [45]. This kind of activity enhancement of Sc (OTf) 3 by means of ionic liquid solvents was also observed in the Friedel-Crafts alkenylation of arenes with alkynes [46]. 

Reoxidant in Palladium-Catalyzed Reactions. Cu(OAc)2 has been used as a reoxidant in the Wacker oxidation (CH2=CH2 + 02- CHsCHO) and in the Pd(OAc)2-catalyzed alkenylation of aromatic compounds with alkenes (eq 17). Pd(OAc)2 and Cu(OAc)2 are effective catalysts for the reactions... 

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